                 In the United States Court of Federal Claims
                                    OFFICE OF SPECIAL MASTERS
                                             No. 17-250V
                                           (to be published)

*************************                                                Chief Special Master Corcoran
NEONA MARTIN, on behalf of the *
ESTATE OF JOSEPH JAMES MARTIN, *
                               *                                         Filed: July 17, 2020
                Petitioner,    *
                               *                                         Influenza vaccine; Death;
           v.                  *                                         Pathology findings; Bacterial
                               *                                         respiratory infection; Cytokine
SECRETARY OF HEALTH AND        *                                         production; Non-infectious
HUMAN SERVICES,                *                                         inflammation; Timeframe
                Respondent.    *
                               *
*************************

Milton Clay Ragsdale, IV, Ragsdale LLC, Birmingham, AL, for Petitioner.

Catherine Stolar, U.S. Dep’t of Justice, Washington, DC, for Respondent.


                                       ENTITLEMENT DECISION1

        On February 21, 2017, Neona Martin, on behalf of the estate of Joseph Janes Martin (her
deceased husband), filed a petition seeking compensation under the National Vaccine Injury
Compensation Program (“Vaccine Program”).2 Petitioner alleged that Mr. Martin died on February
26, 2015, as a result of an influenza (“flu”) vaccine he received on February 5, 2015. Petition (ECF
No. 1) at 1. An entitlement hearing in the matter was held February 3–4, 2020 in Washington, D.C.

        For the reasons stated in greater detail below, I deny an entitlement award in this matter.
Petitioner has not established that Mr. Martin’s death three weeks post-vaccination more likely

1
  This Decision will be posted on the Court of Federal Claims’ website in accordance with the E-Government Act of
2002, 44 U.S.C. § 3501 (2012)). This means that the Decision will be available to anyone with access to the
internet. As provided by 42 U.S.C. § 300aa-12(d)(4)(B), however, the parties may object to the Decision’s inclusion
of certain kinds of confidential information. Specifically, under Vaccine Rule 18(b), each party has fourteen days
within which to request redaction “of any information furnished by that party: (1) that is a trade secret or commercial
or financial in substance and is privileged or confidential; or (2) that includes medical files or similar files, the
disclosure of which would constitute a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b). Otherwise, the
whole Decision will be available to the public. Id.
2
 The Vaccine Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660,
100 Stat. 3758, codified as amended at 42 U.S.C. §§ 300aa-10 through 34 (2012) [hereinafter “Vaccine Act” or “the
Act”]. Individual section references hereafter will be to § 300aa of the Act (but will omit that statutory prefix).
than not was caused in any part by the flu vaccine, or that the vaccine could be fatal in the manner
alleged. The tragedy of his sudden death is far more likely attributable to his pre-vaccination health
condition, and/or an intercurrent bacterial lung infection that went undiagnosed until after his
death.

I.        Factual Background

           Mr. Martin’s Pre-Vaccination Condition
            Mr. Martin, a retired Army veteran, was 53 years old when he received the flu vaccine
    at a Veterans Affairs (“VA”) facility in Huntsville, Alabama, on February 5, 2015. Ex. 1 at 1;
    Ex. 5 at 115-16; Ex. 9 at 1. He was not in good health at the time, and suffered from a number
    of comorbidities – in particular a history of poorly-controlled diabetes mellitus. His diabetes had
    caused secondary diabetic neuropathy and retinopathy, as well as a diabetic foot ulcer in 2014.
    Ex. 5 at 1–243, 611–63; Ex. 7 at 178–485. Mr. Martin’s past medical history also included
    hypertension, hyperlipidemia, chronic diarrhea, service-related disabilities, and kidney disease.
    Ex. 5 at 1–243, 611–63; Ex. 7 at 178–485.

           In addition to the above, the record establishes that Mr. Martin had recently begun having
    syncopal episodes. Thus, on December 12, 2014 (about ten weeks before his death), Mr. Martin
    went to the Huntsville Hospital emergency room after a syncopal episode at a gun range, where
    he reported that he “woke up [o]n the floor,” with “no idea what [had] happened.” Ex. 7 at 204.
    Mr. Martin also noted at this time that he had been experiencing similar episodes over the prior
    three weeks. Id. At the ER, Mr. Martin had a normal CT scan but an abnormal EKG, plus a high
    glucose reading. Id. at 205, 208, 224. Indeed, the EKG determination included the finding
    “septal infarct, age undetermined”—which suggested the possibility that Mr. Martin had
    previously suffered an undiagnosed heart attack sometime in the past. Id. at 224.3

            At a later doctor’s visit in January 2015 at the Birmingham VA Hospital, Mr. Martin’s
    primary care physician (“PCP”) confirmed Mr. Martin’s ongoing diabetes and notably high
    glucose levels, which were at that time measured at 414 mg/dl—well in excess of the normal
    range (70–110 mg/dl). Ex. 5 at 129–30. Mr. Martin also reported some recent incidents of chest
    pain, and he displayed an increased heart rate that treaters deemed the product of dehydration
    attributable to “uncontrolled diabetes.” Id. at 128.

           The following month, on February 3, 2015, Mr. Martin had a telehealth consultation
    with a VA nurse for his diabetes. Ex. 5 at 123–25. Two days later, on February 5, 2015, he
    followed up with his PCP, who deemed Mr. Martin “in complete denial of his disease.” Id. at
    112, 113–22. At that time, Mr. Martin continued to have dizziness, but reported no further


3
 As one of Respondent’s experts, Dr. Kathleen Collins, noted at hearing, “septal infarction . . . is another word for a
heart attack.” Tr. at 299.

                                                           2
    episodes of syncope. Id. at 118–20. It was at that follow-up visit that Mr. Martin received the
    flu vaccine in question. Id. at 115–16.4

            The parties dispute whether the flu vaccine was contraindicated for Mr. Martin.
    Petitioner has maintained that it was, but relies on a hospital record prepared after Mr. Martin’s
    death. Ex. 7 at 154. This particular record thus does not shed light on whether, as of the time the
    vaccine was administered, Mr. Martin’s PCP had such concerns (and does not elaborate on how
    or why this alleged contraindication came up at this time). By contrast, the record from the
    February 5, 2015 date of vaccination states that Mr. Martin verbally “denie[d] contraindications
    to the influenza vaccine,” including any prior allergic reaction to egg protein. Ex. 5 at 115
    (emphasis added). In addition, it appears from the filed record that Mr. Martin had received the
    flu vaccine in previous years, without complaint or reported reaction. See, e.g., id. at 241–43
    (flu vaccine administered in October 2013, after Mr. Martin verbally denied contraindications).
    I ultimately find that the record preponderates against a determination that the flu vaccine was
    contraindicated by any medical treater, although my overall analysis does not turn on this fact.5

           February 2015 and Circumstances of Mr. Martin’s Death

       There are few records for the period between the date of vaccination and the days
immediately prior to Mr. Martin’s death. There is no independent record evidence that Mr. Martin
experienced an immediate reaction to the February 2015 vaccination, or any arguably-related
symptoms within a few days later. The last medical record created before the date of Mr. Martin’s
death is a February 24, 2015 telemedicine nurse consultation note regarding his uncontrolled
diabetes. Ex. 5 at 101–10. (It appears from these records that Mr. Martin could remotely transmit
blood sugar readings to VA treaters for monitoring, and could also communicate with caregivers
by phone). But nothing in these records disclose Mr. Martin’s condition at the time (beyond his
blood sugar readings), or whether his overall health was different in tenor from what he had
previously experienced. Id. at 101–22. Indeed, Mr. Martin appears to have been asked some
questions about his functionality or health problems as part of the February 24th telemedicine
consultation, but identified no recent flare-ups. Id. at 108–09.

         Petitioner, however, has alleged in witness statements filed in this case that within three
to five days after receiving the vaccine at issue, Mr. Martin “became ill” with “flu-like
symptoms,” including “chills, headaches, body aches, dizziness, weakness, diarrhea, nausea and
vomiting.” See Ex. 10 (Affidavit of Neona Martin, dated November 17, 2017 (ECF No. 13-1)) at
1. Petitioner also proposes that in this time period Mr. Martin “likely experienced a fever, based

4
  According to the medical records Mr. Martin received the inactivated influenza vaccine. Ex. 5 at 115. At the time of
injection Mr. Martin was counseled on regarding precautions, risks, and benefits of the vaccine. Id. He also received
the “CDC Influenza Vaccine (Inactivated/IIV) Information Statement 2014-2015.” Id.
5
 Petitioner has also not offered evidence in this case to establish that the flu vaccine is generally contraindicated for
persons with diabetes. In fact, evidence filed in this matter supports the contrary.

                                                           3
on the chills and sweating episodes I observed,” complained of feeling worse than he had before,
and that these symptoms progressed to the date of his death. Id. She further explains that
Petitioner’s ability to see a doctor in some of this time period was limited due to hazardous winter
travel conditions for the area in which they lived. Id.

         On February 26, 2015, at 4:49 a.m., Mrs. Martin called 911 after finding Mr. Martin
 unresponsive, pulseless, and apneic in their bathroom. Ex. 6 at 3–7; Ex. 5 at 482. In
 subsequently-created witness statements as well as in contemporaneous reports to emergency
 first responders, Petitioner has maintained that Mr. Martin had not recently felt well, told her
 early on the morning in question he felt dizzy and was coughing, then went to the bathroom
 where she found him a few minutes later. Ex. 10 at 1, Ex. 6 at 7, Ex. 7 at 10. She specified in
 subsequent hospital records that Mr. Martin had been experiencing cold symptoms for a few
 days prior to this incident. Ex. 7 at 10; see also Ex. 5 at 342–43 (patient was sick with cold for
 “few days” with “recent cold symptoms”); Ex. 5 at 405 (“[w]ife said that [Mr. Martin] woke up
 feeling dizzy, went to the bathroom . . . Wife said that he has been sick w/ cold for days”).

       Mrs. Martin attempted to perform CPR while waiting for EMS personnel to arrive. Ex. 6
 at 3–7. When such personnel arrived at 5:07 a.m., Mr. Martin remained unresponsive, pulseless,
 and apneic. See id.; Ex. 5 at 340–41; Ex. 7 at 10–11. EMS attempted to resuscitate Mr. Martin,
 which required suctioning vomit out of his airways, then took him to Huntsville Hospital
 emergency room. Ex. 6 at 3–6, 7. EMS records deemed Mr. Martin’s breathing apneic. Id. at 4.
 Upon arrival, it was determined that Mr. Martin’s blood glucose level was 671 mg/dL (far higher
 than his also-elevated reading the month before). Ex. 5 at 432. ER records reported that Mr.
 Martin had suffered cardiac arrest. Ex. 7 at 9.

        A battery of labs diagnostics were performed on Mr. Martin. See Ex. 7 at 10. For example,
 his temperature on arrival was 92.5 degrees, his heart rate swung from 80 bpm and 111 bpm
 between periods of pulselessness, and his blood pressure fluctuated from high to low. Id. Chest
 X-rays showed Mr. Martin had pneumonia in the upper right lobe of his lungs. Id. And his white
 blood cell count was notably elevated (a 19.8 reading, in comparison to normal values of 4.8 to
 10.8). Ex. 5 at 437.

        While in the ER, Mr. Martin experienced several additional episodes of cardiac arrest
 with asystole and, following multiple resuscitation attempts, was pronounced dead at
 approximately 9:30 a.m. on February 26, 2015. Ex. 4 at 1; Ex. 5 at 323, 340; Ex. 7 at 6, 10, 48–
 49; Ex. 8 at 1. The treating physician proposed that the cause of Mr. Martin’s cardiac arrest was
 unknown, but that it was “likely secondary to sepsis due to pneumonia versus undiagnosed
 coronary artery disease with history of diabetes mellitus.” Ex. 5 at 341; Ex. 7 at 11. The death
 certificate identifies the cause of death as “cardiac arrhythmia.” Ex. 4 at 1.




                                                 4
       Autopsy Report

       An autopsy was performed the next day (February 27, 2015) by Dr. L. Allen Perkins, a
 pathologist at Huntsville Hospital. See generally Ex. 8. Dr. Perkins noted that Mr. Martin’s
 airways were clear of debris and foreign material. He also observed “fungal organisms
 highlighted on GMS special stain associated with food particles most likely secondary to agonal
 aspiration” (meaning gasping at the time of death), although he deemed these findings
 postmortem in nature rather than part of the etiology of Mr. Martin’s death. Id. at 1, 4.

       In addition, Dr. Perkins took tissue from the lung and sent it to a laboratory, but found an
 absence of “significant histopathologic abnormality.” Ex. 8. at 4. However, he did observe
 neutrophilia within the airways of both lungs. Id. From this, Dr. Perkins listed bilateral
 bronchopneumonia as the first part of his pathological diagnosis, emphasizing it in his summary
 as well, although his report did not ultimately designate it as his primary conclusion. Id. at 1.
 The pathology report did not otherwise propose that the flu vaccine Mr. Martin received three
 weeks or so prior was causal of his death—nor did any other of the medical treaters who attended
 to him on February 26th.

II.    Expert Witness Testimony

       A.      Petitioner’s Experts

               1.       Dr. Alan Levin – Dr. Levin, an immunologist with some pathology training,
was Petitioner’s first expert to testify at trial, and also offered two expert reports. Tr. at 33–104;
Report, dated November 27, 2017, filed as Ex. 11 (ECF No. 13-2) (“Levin Rep.”); Report, dated
November 14, 2018, filed as Ex. 23 (ECF No. 21-3) (“Levin Supp. Rep.”). He opined that Mr.
Martin’s health issues made him susceptible to an aberrant innate immune response, leading to and
causing his death. Tr. at 35. That response was driven by the flu vaccine, and mediated through
what Dr. Levin deemed a “noninfectious inflammatory process.” Id. at 93.

         Dr. Levin is a board-certified immunologist and pathologist. Levin CV at 1–2, filed Nov.
27, 2017, as Ex. 12 (ECF No. 13-3); Tr. at 34. He earned his B.S. in Chemistry from the University
of Illinois, Champaign-Urbana in 1960, his M.S. in biochemistry from the University of Illinois in
1963, and his M.D. from the University of Illinois in 1964. Levin CV at 1. In 1995, however, Dr.
Levin earned his J.D. from Golden Gate University. Id. Dr. Levin now spends most of his time on
the practice of law—about 95 percent of his time since the mid-1990s. Tr. at 54–55 He has not
taught medicine or pathology in over 20 years and focuses on environmental toxicology. Id. at 59.
Dr. Levin is not boarded in anatomic pathology, but performed an autopsy about three years ago
and “reviews histological slides on a regular basis.” Id. at 61–62. He regularly testifies as a
Program expert, but admitted that one of his opinions had been excluded in a civil case outside the



                                                  5
Vaccine Program.6 See also Id. at 64 (Dr. Levin admitting that a federal district court judge had
referred to him as a “junk scientist”).

         The scientific basis for Dr. Levin’s opinion was rooted in the nature of the immune
response that vaccines engender. The body’s immune system is best understood, he maintained, as
a “mechanism of biological response modification,” and includes several arms. Tr. at 37, 38. There
is the initial innate response, followed by an adaptive response. Id. at 38. For healthy individuals,
the innate response is usually thought not to be “antigen-specific” (meaning reactive to the specific
antigen of the presenting wild virus or vaccine), although Dr. Levin observed that science was
beginning to see that the initial response does have the capacity to “remember” subsequent
presentations of a previously-encountered antigen and to react accordingly. Id. at 41. The
subsequent adaptive response, however, is well-understood to be more directed at the antigen in
question, and through vaccination can be “trained” to look for and attack foreign antigens to which
it has been previously exposed. Id. at 42.

        In Dr. Levin’s view, the immune system’s response to both wild infections and vaccines
will invariably involve cytokines—messenger immune cells. Tr. at 35–36, 38. The cytokines that
react to a wild infection or vaccine, he reasoned, also cause symptoms through inflammation that
can make a person feel unwell (i.e. fever, aches, malaise, etc.). Id. at 38. This response is worsened,
and more dangerous, in susceptible individuals. Id. at 39. Although some such individuals might
not find that a vaccine creates any ill-feeling, for others it will produce an overreaction resulting
in harmful sequelae (although such a reaction is more likely with a wild viral infection than
vaccination). Id. at 43. Elderly individuals, Dr. Levin maintained, can particularly suffer from the
effects of a prolonged cytokine-driven inflammatory response. Id. at 53; S. Mohanty et al.,
Prolonged Proinflammatory Cytokine Production in Monocytes Modulated by Interleukin 10 After
Influenza Vaccination in Older Adults, 211 J. Infect. Diseases 1174–84 (2015), filed as Ex. 28
(ECF No. 38-1) (“Mohanty”).

        Mohanty sought to “better understand the effects of aging innate immune responses to the
trivalent inactivated influenza vaccine.” Mohanty at 1180. To do so, the study considered the in
vivo immune response, before and after receipt of the flu vaccine, of a 67-patient population—36
of whom were older than 65, while the remainder were between the ages of 21 and 30—looking
at levels of different cytokines (pro and anti-inflammatory) and monocytes (white blood cells)
before vaccination and then at days two, seven and 28 post-vaccination. Id. at 1176, 1180.
Mohanty’s authors observed an increase in inflammatory monocytes in both age groups in days
two to seven, returning to baselines by day 28—thus suggesting that the flu vaccine can have a
stimulating impact on the innate immune response. Id. at 1180. They also observed a comparable


6
 See Avila v. Willitis Environmental Remediation Trust, No. C 99-3941 SI., 2008 WL 360858, at *16 (N.D. Calf. Feb.
6, 2008) (excluding Dr. Levin’s opinion because it failed to comply with the reliability standards of Daubert and Fed.
R. Evid. 702).

                                                          6
increase in cytokine production, although the younger group evidenced a higher level by day 28,
and the older studied individuals demonstrated a “delayed increase” at day seven. Id. at 1181. In
addition, the older studied population showed a “marked age-associated increase” in the
production of anti-inflammatory cytokines over all time periods, which Mohanty’s authors felt
contributed to the impaired vaccine response that older individuals often experience (and which
vaccine manufacturers have attempted to address through high-dose or adjuvanted vaccines). Id.
at 1183. Mohanty said nothing about the purported pathologic effects of the flu vaccine in any of
the studied populations, and did not observe a chronic increase in the kinds of pro-inflammatory
cytokines most associated with post-vaccination malaise.

        Vaccines, Dr. Levin maintained, must invoke an inflammatory response if they are to cause
later immunity to the pathogen at issue. Tr. at 38–39. In this case, the flu vaccine was the most
likely cause of Mr. Martin’s condition and death, because of the degree to which it encouraged
harmful inflammation. No other pathogen was found, Dr. Levin noted, leaving the vaccine as the
“only logical explanation” for what befell Mr. Martin. Id. at 36. Dr. Levin also referenced VAERS
reports7 revealing, by his research, nearly 700 instances in which an individual reported pneumonia
after the flu vaccine. Id. at 85–87; Levin Rep. at 4. He did not, however, substantiate his purported
VAERS findings in either of his reports. See Levin Supp. Rep. at 3; Tr. at 89–91.

        Dr. Levin further proposed that Mr. Martin’s susceptibility to an aberrant immune response
was evidenced not only by his existing health issues, but by the fact (as Mrs. Martin testified) that
in 2013 Mr. Martin appeared to have experienced an aberrant response to a prior flu vaccine
(although this conclusion was derived solely from Petitioner’s allegations rather than from record
evidence). Tr. at 39. In 2015, however, the reaction was worse, given Mr. Martin’s age and the
extent of his diabetes. Id. at 40. Although Dr. Levin seemed to deny that in this case the vaccine’s
wild virus components “caused” the flu, given their inactivated nature, he did allow for the
possibility that “the virus could replicate and cause symptoms,” although ultimately he relied on
the innate immune reaction leading to a cytokine response as the true driving mechanism herein
for the pathologic process that resulted in Mr. Martin’s death. Id. at 49–50.

        On cross examination, Dr. Levin admitted that certain articles he had offered to substantiate
his contention that kinds of excessive inflammation could be driven by the immune system rather
than directly by infection (via “cytokine storms,” for example)8 said nothing about how a vaccine

7
  VAERS (the Vaccine Adverse Event Reporting System) “accepts and analyzes reports of adverse events (possible
side effects) after a person has received a vaccination. Anyone can report an adverse event to VAERS. . . . . VAERS
is a passive reporting system, meaning it relies on individuals to send in reports of their experiences to CDC and FDA.
VAERS is not designed to determine if a vaccine caused a health problem, but is especially useful for detecting unusual
or unexpected patterns of adverse event reporting that might indicate a possible safety problem with a vaccine.” About
VAERS, HHS, https://vaers.hhs.gov/about.html (last visited June 30, 2020).
8
 In partial substantiation for the more general assertion about the harmful impact of excessive cytokine upregulation,
Dr. Levin’s first report included a citation to a website (www.cytokinestorm.com) that he claimed was probably

                                                          7
could be responsible for such an aberrant process. Tr. at 79–80; J. Bordon et al., Understanding
the Role of Cytokines and Neutrophil Activity and Neutrophil Apoptosis in the Protective Versus
Deleterious Inflammatory Response in Pneumonia, 17 Int’l J. Infect. Diseases 76–83 (2013), filed
as Ex. 17 (ECF No. 13-8) (“Bordon”). Thus, while an article like Bordon does discuss the role of
“cytokine dysregulation” in the “toxic inflammatory response” brought on by a bacterial
pneumonia infection, it does not at all comment on how a vaccine could induce such a pathologic
process. Bordon at 81. Dr. Levin also admitted that other than some lab testing suggesting Mr.
Martin was experiencing an inflammatory process at the time of death, he could not point to record
proof that cytokines generated through an immune response in reaction to vaccination three weeks
before were causal in this case, although he favored that conclusion. Tr. at 80–81.

        Dr. Levin agreed that support for his contention that cytokine levels could remain high for
several weeks post-vaccination was derived from in vitro studies involving repeated stimulation
with additional doses of vaccine—unlike what Mr. Martin had experienced. Tr. at 81–82; see also
E. Bernstein et al., Cytokine Production After Influenza Vaccination in a Healthy Elderly
Population, 16 Vaccine 18:1722-31 (1998), filed as Ex. 19 (ECF No. 13-10) (“Bernstein”).
Bernstein tested blood samples from a group of 270 elderly individuals who had received the flu
vaccine, and some of its analysis involved a five-day stimulation of those samples with additional
amounts of the vaccine. Bernstein at 1724. Bernstein ultimately (and somewhat contrary to
Petitioner’s causation theory) concluded that the overall elderly response to receipt of the flu
vaccine was not sufficiently robust to induce protection against the wild virus—not that the flu
vaccine had a pathologic impact that could cause persistent cytokine-derived inflammation for
days after vaccination. Id. at 1730.

        Another article only established cytokine elevation peaking within 12 hours of receipt of
the flu vaccine—far shorter a timeframe than the facts of this case. Tr. at 83–84; N. Chatziandreou
et a., Macrophage Death Following Influenza Vaccination Initiates the Inflammatory Response
that Promotes Dendritic Cell Function in the Draining Lymph Node, 18 Cell Reports 2427–40
(2017), filed as Ex. 15 (ECF No. 13-6) (“Chatziandreou”). Chatziandreou’s focus was the
performance of certain innate immune system-oriented cells called macrophages, and their role
helping stimulate post-vaccination inflammation necessary for an adaptive response to a vaccine,
but found that increases in relevant pro-inflammatory cytokine levels was far more time-limited
than proposed in Petitioner’s causation theory. Chatziandreou at 2429–30. And the literature cited
in Dr. Levin’s report did not directly support his contention that the flu vaccine could instigate a
“cytokine storm” sufficient to cause immune system-mediated harm, but instead only explored the
harmful nature of a cytokine storm once it comes into being. Tr. at 84–85; J. Boomer et al., The
Changing Immune System in Sepsis, 5 Virulence 1:45–56 (2014), filed as Ex. 16 (ECF No. 13-7)

created by the National Institutes of Health (Tr. at 101), although the one-page site appears mainly to promote
treatments for the condition, and its authors are not disclosed. The website also says nothing about how a vaccine
might initiate a cytokine storm.


                                                        8
(“Boomer”) (discussing the hyper-response of a cytokine storm in reaction to ongoing sepsis, and
the causes of immune-suppression that inhibit the immune system under such circumstances).

        Besides the causation theory offered, Dr. Levin commented on the pathology evidence. He
noted the presence of inflammatory cells (specifically neutrophils) in Mr. Martin’s lungs,
something that in his view would not have occurred simply due to aspiration of food particles
associated with vomiting. Tr. at 47. In Dr. Levin’s opinion, these neutrophils evidenced the
existence of inflammation in Mr. Martin’s respiratory airways that was “pneumonia-like,” and
would in most circumstances be deemed evidence of an infectious process, but in his view probably
the product of an earlier post-vaccination, non-infectious innate response driven by cytokines
(produced in turn via an immune response) best characterized as pneumonitis. Id. at 47, 68, 92, 93.
Otherwise, the pathology findings identified no specific pathogen that might have been causal
herein, strengthening in Dr. Levin’s view the conclusion that Mr. Martin died from a dysregulated
immune process. Id. at 48, 52, 53.9 But the noninfectious inflammation that Dr. Levin posited had
occurred could also have made Mr. Martin more susceptible to an infectious process as well. Id.

         In so maintaining, Dr. Levin discussed whether the autopsy evidence from Mr. Martin’s
lungs established the existence of an infectious bronchopneumonia (as Respondent’s expert Dr.
Vargas has proposed—and as Dr. Levin himself had seemed to accept in his report). See Levin
Rep. at 4 (“the most probable cause of [Mr. Martin’s] cardiac arrest was hypoxia associated with
his bronchial pneumonia”).10 Dr. Levin maintained, to the contrary, that this diagnostic proposal
was made by the pathologist who initially considered Mr. Martin’s lung tissue showings without
all of the necessary information, including microbiology findings. Tr. at 49. He also disputed that
the lung tissue evidence established aspiration pneumonia (in which case Mr. Martin would have
developed an infection due to aspiration of food particles after choking), arguing that “it takes
days” to develop sufficient inflammatory cells in the lungs to cause that process. Id. at 53.

       Dr. Levin agreed, however, that the lung tissue slides he reviewed did suggest the presence
of a bacterial infection, although the failure to identify a pathogen, in his mind, made that less


9
  Respondent pointed out through cross examination, however, that literature Petitioner had filed indicated that a
specific pathogen for pneumonia was identified in less than 50 percent of cases. Tr. at 72–73; S. Sethi, Community-
Acquired       Pneumonia,        Merck        Manuals,       https://www.merckmanuals.com/professional/pulmonary-
disorders/pneumonia/community-acquired-pneumonia (last visited July 13, 2020), filed as Ex. 18 (ECF No. 13-9) at
1. In response, Dr. Levin tried to maintain that the issue of identification of pathogen was largely dependent on the
medical/scientific “sophistication” of the treaters looking for it, although he added he was “not going to argue with
somebody who says there was an organism” that here could explain Mr. Martin’s diagnosed bronchopneumonia. Tr.
at 73.
10
  On cross examination, Respondent questioned Dr. Levin about his review of the pathologic slides prepared from
Mr. Martin’s lung tissue samples, and the photo he included of one of them in his report. Tr. at 65–69; Levin Rep. at
3. He claimed to agree with the pathology findings in the autopsy (which reasonably can be read to favor
bronchopneumonia as an explanatory diagnosis). Tr. at 66.


                                                         9
likely. Tr. at 67–68. He also admitted that the actual autopsy report (Ex. 8) had (and thus contrary
to his assertions) incorporated the microbiology and other findings that he claimed had not been
considered, but still had reached the determination that bronchopneumonia was the correct
diagnosis. Ex. 8 at 1; Tr. at 69–70. But Dr. Levin relied on a distinction between “the time the
report was issued” and “the time the [diagnostic] decision was made” to defend his claim that the
proposed bronchopneumonia diagnosis contained in the pathology report had been arrived at on
the basis of incomplete information. Tr. at 70–71.

         Dr. Levin also proposed that the overall timeframe of Mr. Martin’s alleged illness and then
death—with onset of initial symptoms three to five days after vaccination, and death two to three
weeks later—was medically acceptable. Tr. at 43. In fact, Dr. Levin seemed to embrace the idea
that Mr. Martin developed the pneumonitis that may explain his death “within probably hours” of
receipt of the vaccine, despite the lack of record evidence for that specific conclusion, although he
later seemed to revert to the concept that onset was actually days later (consistent with Petitioner’s
testimony). Id. at 87, 88. To illustrate grounds for the timeframe aspects of his claim, Dr. Levin
used Reye’s syndrome (an illness that predominantly affects children) 11 as a comparison, noting
that, in reaction to aspirin given to children to fight a viral infection, cytokines released by the liver
ultimately impact the brain and cause secondary symptoms not directly attributable to the initial
viral infection. Tr. at 44. This kind of immune-mediated process could occur in a timeframe of a
few days. Id. It would not, however, necessarily also be fatal in that same period.

        Significantly, Dr. Levin admitted that even though he proposed some kind of aberrant
cytokine response, the flu vaccine “was probably a very weak cytokine producer,” and hence this
(plus Mr. Martin’s overall unhealthy condition as well as unique genetic makeup) worked in
tandem to draw out the timeframe from initial onset to progression of symptoms and then death
two to three weeks later. Tr. at 45–46. He also asserted that Mohanty supported the timeframe at
issue, observing that it demonstrated a “sustained innate immune engagement” of up to 28 days
after immunization, and that the same persistence was possible with inactivated vaccines like the
one Petitioner received. Mohanty at 1181; Tr. at 98–99.

                2.      Dr. Allan Goldstein – Dr. Goldstein, an internist and pulmonologist, also
testified on Petitioner’s behalf, and prepared two reports as well. Tr. at 104–61; Report, dated
October 30, 2018, filed as Ex. 21 (ECF No. 21-1) (“Goldstein Rep.”); Report, dated December 23,
2019, filed as Ex. 39 (“Supp. Goldstein Rep.”). He proposed that the flu vaccine caused an
inflammatory process that likely created the conditions for a secondary infection in Mr. Martin’s
lungs, sufficient to produce the bronchopneumonia that led to his death. Tr. at 137–38; Goldstein

11
   Reye’s syndrome is “a rare, acute, sometimes fatal disease of childhood, characterized by recurrent vomiting and
elevated serum transaminase levels, with distinctive changes in the liver and other viscera; an encephalopathic phase
may follow with acute brain swelling, disturbances of consciousness, and seizures. It most often occurs as a sequela
of chickenpox or a viral upper respiratory infection.” Dorland’s Medical Dictionary Online,
https://www.dorlandsonline.com/dorland/definition?id=111287 (last visited July 1, 2020).

                                                        10
Rep. at 2.

        Dr. Goldstein earned his M.D. from Ohio State University in 1965. Goldstein CV, filed on
November 15, 2018 as Ex. 22 (ECF No. 12-2), at 1. He is board certified in internal medicine and
specializes in pulmonary disease—not infectious disease or pathology. Id.; Tr. at 131–32. His
practice is currently focused on occupational pulmonary disease. Tr. at 105. Dr. Goldstein also
works as an expert in occupational and workers compensations pulmonary disease evaluations,
and some litigation where the nature of a person’s condition is disputed. Id. at 105–06, 127. He
has treated patients with lung issues, including pneumonia, in his clinical practice, many of whom
were HIV/AIDS patients.12 Id. at 105–06. Besides his clinical practice, Dr. Goldstein was a
professor of medicine at Grandview Hospital but stopped teaching eight to nine years ago, and
research was never part of his professorial activities. Id. at 128–29.

        Dr. Goldstein’s opinion largely arose from what the medical records revealed about Mr.
Martin’s health (from the time he received the vaccine until his death), plus some articles provided
to him by counsel as well as Petitioner’s testimony. Tr. at 133–36. He noted first that Mr. Martin
was reported to have had a reaction in 2013 to the flu vaccine (based on Mrs. Martin’s testimony),
exemplified by flu-like symptoms, and then a similar reaction in February 2015 within three to
five days of receipt of the vaccine. Id. at 109, 111. This kind of post-vaccination reaction was
common, in Dr. Goldstein’s experience,13 although usually unreported since vaccine-induced
malaise typically went away. Id. at 111–14. Dr. Goldstein did not maintain, however, that this
reaction was evidence of a vaccine-caused flu infection, and added that opining on such
immunologic topics was outside his area of expertise. Tr. at 143–44.

        Thereafter (and through a process that Dr. Goldstein admitted he lacked the expertise to
opine upon), some kind of “inflammation related to the vaccine” took hold in Mr. Martin’s lung.
Tr. at 112, 148. Evidence of the inflammation was provided by the autopsy/pathology report,
which revealed neutrophils in his airways and the proposed diagnosis of bronchopneumonia. Id.
at 110, 112. This bronchopneumonia in turn revealed the existence of a secondary infectious
process, likely bacterial in nature, that the record corroborated through evidence such as Mr.
Martin’s white blood cell count measured at the time of his death. Id. at 137, 138. Dr. Goldstein
discounted the possibility that the infection was de novo, arguing that the “entire clinical picture”
relevant to Mr. Martin suggested he was already sick before any bacterial infectious process began,
although he could not totally discount the alternative possibility. Id. at 139, 155. He differentiated


12
  On cross examination Dr. Goldstein conceded that the HIV/AIDS patients he treated for pneumonia would have
been more susceptible to infectious pneumonia “in theory.” Tr. at 132.
13
   Dr. Goldstein’s second report limits the commonality of this reaction to “elderly or weakened” patients. Supp.
Goldstein Rep. at 2; Tr. at 145–46. He also agreed in his testimony that he had witnessed such a reaction in only a
handful of patients, none of whom were hospitalized or had developed a secondary pneumonia akin to what is alleged
in this case. Tr. at 145–47.

                                                        11
Mr. Martin’s earlier symptoms beginning three to five days post-vaccination from what later
happened to him, maintaining the earlier symptoms corroborated the secondary character of the
bacterial lung infection. Id. at 140–41. He acknowledged, however, that all of Mr. Martin’s
symptoms unfolded within the time of year in which flu and respiratory infections are most
common. Id. at 141.

        The allegedly vaccine-caused inflammation, Dr. Goldstein maintained, likely reduced Mr.
Martin’s resistance to an infection attributable to bacteria normally present in the lungs but which
a person would in most cases naturally resist. Tr. at 112, 113, 159–60. Thus, the
bronchopneumonia that may have been observed after Mr. Martin’s death (and in fact may have
caused it) was likely secondary to vaccine-induced inflammation. Id. at 110, 115. Dr. Goldstein
did not, however, accept that Mr. Martin might have experienced a noninfectious pneumonitis due
to aspiration of food particles, maintaining that a single instance of aspiration from coughing or
choking would not be enough to produce the extensive evidence from the pathology slides, and
there was not any history of chronic aspiration otherwise. Id. at 123–24.

         Dr. Goldstein also maintained (although the subject was beyond his expertise) that the flu
vaccine could cause the kind of noninfectious pulmonary condition Mr. Martin is alleged to have
experienced. He noted that the vaccine’s package insert (which does not appear to have been filed
in this case) allowed that safety determinations derived from testing trials did not mean that
reactions might not still be observed in a clinical practice. Tr. at 107–08. He also proposed that
literature established how even an inactivated flu vaccine could increase later susceptibility to a
respiratory infection. Tr. at 116–18; B. Cowling et al., Increased Risk of Noninfluenza Respiratory
Virus Infections Associated with Receipt of Inactivated Influenza Vaccine, 54 Clin. Infect. Diseases
12:1778–83 (2012), filed as Ex. 29 (ECF No. 38-2) (“Cowling”).

        Cowling was a study involving 115 children (aged six to 15 years) whose health courses
were monitored over a nine-month period after receiving the trivalent inactivated flu vaccine,
compared to a subsection of that group that had not been vaccinated. Cowling at 1778. The subjects
were tested for 19 different non-influenza respiratory viruses (and hence not bacterial-oriented
illnesses like pneumonia) in that timeframe. Id. at 1778, 1780. Cowling’s authors did observe an
increased risk of viral respiratory infection thereafter when comparing recipients of the vaccine to
an unvaccinated portion of the test group, although the increased risk was most frequently observed
in the late winter/early spring of the time period at issue (and thus “after the peak in seasonal
influenza activity”). Id. at 1780. Cowling’s authors opined that the flu vaccine might have reduced
the studied sample’s “nonspecific immunity” to other kinds of viral infections, and that the
duration of this diminished response might persist for two to four weeks post-vaccination, but also
that the reliability of their findings was limited by the small sample size and low number of
confirmed infections. Id. at 1780–81; Tr. at 154.



                                                12
        Other articles, Dr. Goldstein maintained, also established that the flu vaccine could cause
or induce an interstitial lung disease. Tr. at 121–22.14 But, as Respondent pointed out through
cross-examination, some such literature was inapposite. Tr. at 150–54. One such article, for
example, involved only a single-patient case study, in which an 82-year old man received a dose
of the H1N1 flu vaccine, and within two weeks began to experience bloody sputum
(distinguishable from Mr. Martin’s presentation) that was associated with an acute lung injury. E.
Satoh et al., Acute Lung Injury Accompanying Alveolar Hemorrhage Associated with Flu
Vaccination in the Elderly, 54 Intern. Med. 3193–96 (2015), filed as Ex. 32 (ECF No. 38-5)
(“Satoh”), at 3193. The studied individual had suffered a similar injury the year before, however,
and also ten days prior to seeking treatment, although he had received an antibiotic as well closer-
in-time to the more recent injury. Satoh at 3192–93; Tr. at 150–51.

        In another such item, an elderly individual already suffering from chronic obstructive
pulmonary disease presented to emergency treaters with fever, malaise, and other symptoms a
week before receiving an inactivated flu vaccine. P. Pornsuriyasak et al., Acute Respiratory Failure
Secondary to Eosinophilic Pneumonia Following Influenza Vaccination in an Elderly Man With
Chronic Obstructive Pulmonary Disease, 26 Int’l. J. Infectious Diseases 14–16 (2014), filed as
Ex. 33 (ECF No. 38-6) (“Pornsuriyasak”), at 14–15. But the form of pneumonia at issue was
eosinophilic15—which is distinguishable from bronchopneumonia, and is something Mr. Martin
was never proposed to have experienced. Tr. at 152–53. Indeed, Dr. Goldstein admitted that
Pornsuriyasak had specifically noted that the flu vaccine was recommended for patients susceptible
to or suffering from chronic obstructive pulmonary disease. Pornsuriyasak at 14; Tr. at 152–53.

        Mr. Martin’s history (in particular his diabetes and secondary sequelae) were also likely
contributory to a susceptibility to infection after vaccine-induced inflammation. Tr. at 109–10,
114, 119–20. Indeed, his diabetes made him immune-compromised. Id. at 156. And rather than the
flu vaccine “making its way from the skin through the body into the lungs,” Mr. Martin had likely
experienced a “general body reaction” to the vaccine. Id. at 119. While the reaction took a few
days to manifest, Mr. Martin (who is alleged to have hesitated in seeking treatment immediately
before his death, due to inclement winter weather) was, in Dr. Goldstein’s estimation, like other
patients he had seen who had experienced a systemic reaction to a vaccine rather than the vaccine
directly attacking the impacted organ. Id. at 120. Although such reactions were not common, they
could still occur. Id. at 120–21.


14
  Dr. Goldstein additionally maintained he had previously treated patients with an interstitial lung disease, and also
asserted that it was more often than not non-infectious in origin. Tr. at 133.
15
  “Eosinophilic pneumonia comprises a group of lung diseases in which eosinophils (a type of white blood cell)
appear in increased numbers in the lungs and usually in the bloodstream.” Joyce Lee, Eosinophilic Pneumonia, Merck
Manuals, https://www.merckmanuals.com/home/lung-and-airway-disorders/interstitial-lung-diseases/eosinophilic-
pneumonia (last visited July 13, 2020). Allergic reactions, certain medications, parasites, and fungi are thought to
cause eosinophilic pneumonia. Id.

                                                         13
        At the same time, however, Dr. Goldstein acknowledged that the medical history in this
case complicated Petitioner’s arguments about the centrality of the flu vaccine in causing Mr.
Martin’s death. For example, Dr. Goldstein allowed that Mr. Martin’s comorbidities might have
caused him to suffer a heart attack on February 26, 2015, although he pointed out that the pathology
record did not suggest this had occurred. Tr. at 141. In fact, Dr. Goldstein agreed, Mr. Martin had
been deemed likely to have experienced a prior myocardial infarction, as evidenced by testing
after his December 2014 syncopal episode. Id. at 142. And if the record better supported the
conclusion that Mr. Martin’s death was triggered by another such event, then it would be unlikely
a flu vaccine administered three weeks before had caused it. Id. at 141. Dr. Goldstein also accepted
the significance of Mr. Martin’s extremely high glucose levels at the time he arrived at the hospital
on February 26th, noting that such a reading alone would be grounds for immediate treatment if
not full in-patient admission. Id. at 158.

        Ultimately, Dr. Goldstein opined, the flu vaccine Mr. Martin received was the most likely
cause of his subsequent condition and death. But in so opining, he placed considerable weight on
the temporal association of vaccination and evidence of Mr. Martin’s progressive health
deterioration to exclude the possibility of an intercurrent infection (although he also deemed
significant the prior report of a reaction in 2013). Tr. at 122–23, 155. Dr. Goldstein also defended
the timeframe in which (according to Petitioner) Mr. Martin first began to experience flu-like
symptoms three to five days post-vaccination, although he did not question that (as Respondent
established in cross-examination) evidence from the Centers for Disease Control (“CDC”)
supported the conclusion that any malaise-like/nonspecific symptoms associated with receipt of
the flu vaccine would occur in less than twelve hours of vaccination, and subside in two days at
most. Id. at 149–50; Influenza Virus, in Epidemiology and Prevention of Vaccine-Preventable
Diseases 187–206 (J. Hamborsky et al., eds., 13th ed. CDC 2015), filed as Ex. Y (ECF No. 26-3)
(“Hamborsky”), at 201.

       B.      Respondent’s Experts

                1.      Dr. Sarah Vargas – Dr. Vargas is an anatomic and clinical pathologist, and
she prepared two reports and testified on behalf of Respondent. Tr. at 161-283; Report, dated April
12, 2018, filed as Ex. A (ECF No. 15-1) (“First Vargas Rep.”); Report, dated February 26, 2019,
filed as Ex. X (ECF No. 26-2) (“Second Vargas Rep.”). She maintained that Mr. Martin had most
likely experienced an infectious pneumonia that was bacterial in origin, that was unrelated to his
receipt of the flu vaccine, and that explained his sudden death, given his extensive comorbidities.
Tr. at 245–46.

       Dr. Vargas is a staff pathologist at Boston Children’s Hospital. Tr. at 166. She earned her
M.D. from the University of Vermont College of Medicine in 1994. Vargas Updated CV at 2, filed
on April 16, 2020 as Ex. BB (ECF No. 41-2). After medical school she completed her residency


                                                 14
in anatomic and clinical pathology at Brigham and Women’s Hospital in Boston. Id. at 1. Then
she completed a pediatric pathology fellowship at Children’s Hospital in Boston. Id. In her practice
she sees mostly children, but also some adults. Tr. at 167. She also performs a few autopsies per
weeks and has treated “to many to count” broncho-pneumonia cases over her career. Tr. at 168.
Besides her clinical practice she is also an associate professor of pathology at Harvard Medical
School. Tr. at 168. While delivering her testimony Dr. Vargas explained that her opinion was
mostly from her viewpoint as a pathologist, but also incorporated her clinical experience—which
is consistent with the field of pathology. Tr. 254–55.

        Dr. Vargas began her testimony by defining acute bronchopneumonia as a “histologic
pattern of pneumonia” evident microscopically, and characterized by the presence of a kind of
immune inflammatory cell called a neutrophil. Tr. at 174. The neutrophils (most commonly part
of the initial/innate immune response in reaction to a bacterial or fungal infection)16 come from
the bloodstream and into the lung’s airway lining as well as the air sacs, or alveoli, furthering an
inflammatory process. Id. at 175–76. For bronchopneumonia, the alveoli near the bronchus, or
airway, descending into the lower part of the lung, are most inflamed, making this lung component
the “epicenter of the inflammation,” but distributing in a patchy manner (meaning only in one lung,
or in a scattered manner throughout both). Id. at 176 177, 182. Lobar pneumonia, by contrast,
features “confluent” neutrophil presence over large and continuous areas of lung, filling all alveoli.
Id. at 175, 177. Dr. Vargas did not deem it necessary for a person to possess some “predisposing
factor” to develop bronchopneumonia, although certain conditions, like diabetes, could make its
development more likely. Id. at 201–02.

        Dr. Vargas opined that Mr. Martin had likely experienced acute bronchopneumonia
(although she agreed there was some evidence of confluent inflammation) attributable to some
pathogenic organism (more likely bacterial than viral). Tr. at 177, 182. She provided a complete
review of the tissue sample slides to support this opinion. Id. at 178-84. From such evidence, Dr.
Vargas observed an overall patchy distribution of neutrophils consistent with bronchopneumonia.
Id. at 178–80. Had the infection been viral in nature, there would be evidence of “lymphocytic,”
or white blood cell-oriented, inflammation, or the effects of viral replication within the cells of the
impacted organ (viral inclusion). Id. at 183–84. Dr. Vargas saw no such evidence from the slides
in question, which she felt strongly supported her conclusion. Id. at 184, 201.17

16
  Tr. at 272–73. In so explaining, Dr. Vargas contrasted the “pyogenic” propensity of bacterial or fungal infections –
the capacity to elicit inflammatory immune cells like neutrophils—with a viral infection, which she noted did not have
this propensity. Id. at 181.
17
   Dr. Vargas also took specific issue with the conclusions to be drawn from an image of a lung tissue sample slide
that was included in Dr. Levin’s first expert report, using his treatment of it to suggest deficiencies in his analysis. Tr.
at 161–63; Levin Rep. at 3. As Dr. Vargas explained, the image depicted the lung alveoli, but in her view showed no
inflammation. Tr. at 162. Dr. Levin claimed to the contrary, but Dr. Vargas felt he was erroneously pointing out blood
vessels in the photo that were “part of the expected anatomy of the lung.” Id. In addition, arrows on the photo
reproduction of the slide pointed, in Dr. Vargas’s view, not to eosinophils or inflammation, but rather to white blood

                                                            15
       Besides the tissue sample slides, Dr. Vargas maintained that the autopsy/pathology report
also supported the post-mortem bronchopneumonia diagnosis.18 She first noted that the
pathologist’s summary of findings began with bronchopneumonia, highlighting the basis for this
conclusion. Tr. at 185, 264–65. In particular, the pathologist had deemed significant the excessive
weight of Mr. Martin’s right lung—double what would normally have been expected, and also
unusually heavier than its left counterpart—and she opined that this was consistent with “a good,
well-developed pneumonia,” since the lung would have retained more fluid than normal. Id. at
186, 187.19 She agreed that the pathology report did not identify a specific pathogen responsible
for Mr. Martin’s bronchopneumonia, but felt that the circumstances overall presented “classic”
evidence20 of a bacterial pneumonia, adding that it was common not to be able to identify a
pathogen in postmortem testing. Id. at 190. In fact, it was common to discover pneumonia after
death and on autopsy, since it might take some time for the pneumonia to show up early on x-ray
(especially given the lack of sensitivity in this particular imaging technique). Id. at 196–97.

        What was known about Mr. Martin’s clinical presentation or lab findings also, in Dr.
Vargas’s view, supported the bronchopneumonia diagnosis. Bronchopneumonia would usually be
characterized by a cough, or shortness of breath, plus a variety of other flu-like symptoms (fever,
aches and chills, dizziness, etc.). Tr. at 195–96; Vargas Rep. at 6. Physical collapse without any
other presenting symptoms was also “well documented.” Tr. at 196. Here, Mr. Martin was noted
when brought to the hospital21 to be displaying abnormal breathing sounds. Id. at 196, 199–200;
Ex. 7 at 11. His elevated white blood cell count (which evidenced an ongoing inflammatory
process) as well as chest x-ray findings were also consistent with the presence of bacterial
bronchopneumonia. Id. at 196, 244; Ex. 5 at 437; Ex. 7 at 143. Dr. Vargas did not dispute (as


cells in vessels as would be expected. Id. at 163. She also felt this one individual photo did nothing to establish
“chronicity of disease,” meaning that the inflammatory process long predated Mr. Martin’s death. Id. at 181. She
therefore disputed Dr. Levin’s contention that the slide photo in any way supported Petitioner’s theory. Id.
18
   On cross examination, Dr. Vargas made specific comments about the list of other proposed diagnostic findings after
autopsy. Tr. at 264–68. She did not overall express any disagreements with the findings that relate to her opinion. Id.
at 268–69.
19
  Dr. Vargas did not, however, conclude based on the slides and written pathology findings that Mr. Martin’s illness
had progressed to acute respiratory distress syndrome, noting that the radiologic evidence did not suggest “whiteout,”
or shadows covering the images, along with the fact that there was no reported clinical symptoms consistent with
severe respiratory failure. Tr. at 187–88. The absence of air in the alveoli (due to the presence of neutrophils) would
make them appear “radiopaque,” or whiter, on imaging. Id. at 199.
20
  Dr. Vargas later emphasized that although it was never “easy” in any case to pinpoint with precision a cause of
death based on medical record and pathologic postmortem findings, this case presented based on her experience a
“satisfactory and very common explanation.” Tr. at 200.

21
   On cross-examination, Dr. Vargas agreed that the record did not suggest Mr. Martin was experiencing
bronchopneumonia in December 2014, when he suffered a syncopal episode. Tr. at 229.


                                                          16
stressed by Dr. Levin) that Mr. Martin had also displayed certain inflammation biomarkers (e.g.
an elevated sedimentation rate), but deemed them a product of his chronic diabetes and other
comorbidities rather than proof of cytokine-driven inflammatory processes due to vaccination. Id.
at 217–18.

        Bronchopneumonia was a “well-known cause of death” generally, Dr. Vargas noted, and
in this case Mr. Martin’s comorbidities increased the likelihood that it would have a fatal impact
for him. Tr. at 277 (“this was a gentleman who had many chronic diseases that were all things
[that] can be fatal or contribute to a terminal fatal event”). Thus, Mr. Martin had “major risk
factors” for a heart attack (and had even experienced an undiagnosed myocardial infarction, as
evidenced from his December 2014 EKG), along with high blood pressure. Id. at 192, 193, 202–
03, 232–33, 237. In addition, he had uncontrolled diabetes, which could exacerbate the risk to his
heart, would have rendered him immunocompromised, and could also increase the likelihood of a
respiratory infection. Id. at 193, 230–31, 237, 248–49. Mr. Martin continued in the period post-
vaccination to display high blood sugar levels. Id. at 240. She admitted, however, that not every
one of Mr. Martin’s comorbidities could be deemed contributory, or at least that she had not
identified every one as relevant or significant. See, e.g., Tr. at 235–36 (discussing significance of
retroperitoneal hematoma observed on autopsy).

        Pneumonia would interact with all of the above to the extent it compromised Mr. Martin’s
ability to “oxygenate” his blood, thereby depriving the heart of oxygen needed to function and
increasing the likelihood of arrhythmia or sudden collapse from heart failure. Tr. at 234–35. The
dehydration from diabetes could also impact the blood’s effectiveness. Id. at 194; Vargas Rep. at
7. And sepsis (which could cause low blood pressure or impact the heart in other ways) attributable
to such a bacterial infection could also result in cardiac arrest. Id. at 193–94. The medical record
establishes that sepsis was also included at Huntsville Hospital as a potential explanation for Mr.
Martin’s death. Ex. 5 at 341; Ex. 7 at 11.

        Dr. Vargas could not precisely pinpoint when Mr. Martin’s alleged bronchopneumonia
most likely began. She proposed it was likely acute, and that (based on the extent of coverage of
neutrophils from review of the lung tissue slides) it might have begun a few days before his death.
Tr. at 246, 258. She noted that evidence in support of its likely acute nature was also drawn from
the fact that there was no evidence from the tissue sample slides of immune cell “cleanup” of a
chronic/preexisting infectious process. Id. at 274–75. She also deemed significant reports from the
record that in the days immediately preceding Mr. Martin’s collapse and death, he was said not to
be feeling well. Id. at 278–79, 283. She acknowledged, however, that her report did not address
this question in any particularity. Id. at 247. She also agreed that a person with some preexisting
viral respiratory illness could later “pick up a pneumonia” 17 days after a first infection, but denied
that the record in this case demonstrated that this had occurred in Mr. Martin’s case. Id. at 255.



                                                  17
         Dr. Vargas contested Dr. Levin’s conclusion that Mr. Martin’s lung condition was
attributable to some kind of non-infectious inflammatory process that began in the three weeks
before his death. She maintained that the slides and other record evidence clearly demonstrated the
existence of neutrophils, which would typically accumulate in response to a bacterial presence in
the lung. Tr. at 203, 258–59.22 She did not read the evidence as suggesting the existence of an
interstitial pneumonia—a disease of the lung “interstitium,” or fluid-filled support structures in the
lungs,23 as opposed to the air space/bronchi, through which breathed-in air flows. Id. at 203–04.
She also disputed the possibility that Mr. Martin’s pneumonia was chronic or could have existed
from the time of his purported onset three to five days post-vaccination, noting that she saw no
such evidence from the pathology slides that would support that conclusion, and similarly rejected
the concept that it reflected some “superinfection” (meaning a secondary bacterial infection
following some prior viral infectious process). Id. at 218–19, 251–52, 256.

        Dr. Vargas also disagreed with Dr. Levin’s argument that the flu vaccine could trigger a
process ultimately culminating as a neutrophilic pneumonia akin to what she opined Mr. Martin
had experienced, maintaining that his opinion lacked medical or scientific support. Tr. at 205–06;
Second Vargas Rep. at 3. She doubted that a plausible mechanism for how this would work could
be articulated—especially when, as here, the vaccine had been intradermally administered in an
arm rather than directly into the airways. Tr. at 206. Even if a known pathogenic cause of
pneumonia, like a bacterium, were to be directly injected into the blood, it would at most cause
what she termed a “hematogenous infection” in the lung that would not spread anatomically in the
same manner as bronchopneumonia. Id. at 206–07. At bottom, Dr. Vargas said she did not “think
that a vaccine can make the lungs fill up with neutrophils.” Id. at 210.24

        Dr. Goldstein’s report and opinion were similarly rejected by Dr. Vargas as unpersuasive
and medically unreliable. Id. at 207–09. Dr. Vargas took particular issue with Dr. Goldstein’s
contentions about the nature of the immune response to the flu vaccine, explaining that although
vaccines could instigate some “systemic” reaction beyond the situs of administration (i.e., body
aches or other more wide-spread symptoms), they did not have a “pathway” to the lung airways
sufficient to cause a pneumonia-like reaction. Id. at 209–210. She also argued that the literature
(primarily case studies) Dr. Goldstein offered to suggest an association between vaccines and
certain kinds of pneumonia was distinguishable, mostly because the precise kind of pneumonia at

22
  Dr. Vargas did admit that there were circumstances where neutrophils might be produced in response to a
noninfectious process, but ultimately (and relying on the pathology findings in this case) opined that “it’s hard to
imagine that it’s anything but [in reaction to] bacteria.” Tr. at 258, 259–60.
23
     Dorland’s Illustrated Medical Dictionary 939, 1451 (33d ed. 2020) (hereinafter Dorland’s).
24
   Dr. Vargas also disputed that there was any evidence that Mr. Martin had experienced an eosinophilic pneumonia
(in which clusters of eosinophils, a kind of disease-fighting white blood cell distinct from neutrophils, lead to abscesses
in the alveolar spaces), and thus literature offered by Petitioner suggesting vaccines could cause this pneumonia variant
did not bear on the case. Tr. at 210–12.

                                                           18
issue did not reflect what Mr. Martin had experienced, or because the illnesses at issue were not
bacterial in nature. Id. at 212–17.

         On cross examination, Dr. Vargas was asked about the evidence (mostly obtained from
Petitioner’s testimony, but also reflected in contemporaneous records from incidents like the EMT
visit) that Mr. Martin had not felt well for some part of the approximately three-week timeframe
between vaccination and death. Dr. Vargas acknowledged that it did appear for some of this period
that Mr. Martin was “feeling poorly,” with a variety of flu-like symptoms (e.g., chills, body ache,
GI-related problems). Tr. at 240–41. She also accepted that Mr. Martin had likely begun to feel
such symptoms sometime after vaccination, although she contested whether these symptoms were
necessarily indicative of the acute respiratory pneumonia that was observed in his autopsy,
reflective alone of a respiratory infection, or began as early as Petitioner has alleged. Id. at 250–
51, 253, 271–72. She did, however, agree that a 17-day time course was consistent with a
“superinfection,” although she reiterated that she saw no evidence from the pathology report and
slides that Mr. Martin had experienced a chronic infectious process of any kind before his
pneumonia likely began. Id. at 252.

                2.       Dr. Kathleen Collins – Dr. Collins, an infectious disease and immunology
expert, also testified for Respondent in support of the expert reports she prepared. Tr. at 284–411;
Report, dated April 13, 2018, filed as Ex. I (ECF No. 16-1) (“Collins Rep.”); Report, dated
February 20, 2019, filed as Ex. W (ECF No. 26-1) (“Supp. Collins Rep.”). She opined that Mr.
Martin’s death was attributable to his comorbidities coupled with a likely bacterial-in-origin
bronchopneumonia, rather than to the flu vaccine. Tr. at 308, 380.

        Dr. Collins specializes in microbiology, immunology, and infectious disease—she is board
certified in infectious disease but she is not a per se immunologist. Tr. at 287–88, 293. She earned
her M.D. and Ph.D. in molecular biology and genetics from Johns Hopkins School of Medicine in
1993; Tr. at 285. Subsequently, Dr. Collins served as a postdoctoral fellow in Dr. David
Baltimore’s25 laboratory at MIT from 1996 to 1998. Collins Updated CV at 1, filed on January 29,
2020 as Ex. CC (ECF No. 41-3); Tr. at 286. There she conducted research on “understanding the
cell-mediated immune response to viral infections. Tr. at 286. Dr. Collins currently teaches
immunology and virology at the University of Michigan. Id. at 287–88. She sees patients (among
whom are pneumonia patients) for about four weeks out of the year total, although this time is
often broken up into shorter periods. Id. at 288, 363. Dr. Collins also works with the National
Institutes of Health on vaccine development. Id. at 292–93.

        From the filed record, Dr. Collins made several observations bearing on her ultimate

25
  Dr. David Baltimore is an American Biologist and 1975 Nobel laureate for his work in virology. David Baltimore,
The Nobel Prize, https://www.nobelprize.org/prizes/medicine/1975/baltimore/biographical/ (last visited July 7, 2020);
see also Tr. at 286.


                                                        19
opinion. Although Petitioner asserts that Mr. Martin’s prior exposure to the flu vaccine resulted in
a reaction, Dr. Collins observed no evidence of an allergic response that would have suggested to
treaters that he should not receive it in the future. Tr. at 294–95. Indeed, the vaccine was not
specifically contraindicated for him by treaters, and the records revealed Mr. Martin had positively
answered treater questions about his ability to tolerate it. Id. at 295. In Dr. Collins’s view, the flu
vaccine was particularly appropriate for a diabetic person like Mr. Martin, who was likely not to
respond well to wild viral infections. Id. at 296.

        Dr. Collins then went on to evaluate Mr. Martin’s overall medical history in 2014 and 2015.
He consistently displayed high blood sugar levels, establishing that his diabetes was uncontrolled.
Tr. at 299–300. Dr. Collins highlighted the different complications from his diabetes, including
his 2014 foot infection—a common presentation of diabetes, and revealing poor circulation
coupled with a dysfunctional immune response. Id. at 298. The antibiotics he took for the infection
resulted in a renal failure complication that same year. Id. Then, toward the end of 2014, Mr.
Martin had some syncopal events, and in the medical work-up that followed his undiagnosed heart
attack was revealed. Id. at 299. The records in Dr. Collins’s reading suggested treaters felt his
syncope could be a product of diabetes-associated dehydration (which resulted in abnormally low
blood pressure). Id. at 300–01. Efforts to better explain the constellation of symptoms that Mr.
Martin displayed were cut short by his death. Id. at 301–02.

        Dr. Collins next pointed out the record from Mr. Martin’s VA telehealth visit with a nurse
on February 24, 2015. Tr. at 302–03; Ex. 5 at 101–10. Although Petitioner has alleged that by this
time Mr. Martin felt sick and had desired more direct medical intervention, the notes from the
telehealth meeting only recorded that he was experiencing lower back and hip pain (which Dr.
Collins understood from the record to be a chronic concern), and also (based on a checklist) ran
down a number of other symptoms and conditions. Tr. at 302–43. Dr. Collins felt the record should
have revealed some instances of complaints of the flu-like symptoms if in fact Mr. Martin had
been experiencing them at the time. Id. at 303.

        The other records from the day of Mr. Martin’s death were, in Dr. Collins’s reading,
consistent with Petitioner’s assertions about the immediate circumstances of the morning of
February 26, 2015. Tr. at 304. Thus, Mr. Martin had been “sick with a cold” a few days prior to
his collapse, although immediate ER tests established an exceedingly high blood sugar reading.
Id. at 305. Dr. Collins opined this finding was relevant to Mr. Martin’s heart stopping, as it was
further proof of the intensity of his diabetes and the impact it would have had on his blood pressure
and circulation. Id. at 306. The pathology evidence about fluid and lung congestion due to
neutrophils further suggested the impact on oxygenation of the blood, which would in her view
also have affected his heart function. Id. The lung findings as of this point were also different from
x-rays taken at the time of Mr. Martin’s syncopal event in December 2014, further highlighting
the greater risk Mr. Martin faced at the time of his death. Id. at 307.


                                                  20
        Based upon the above, Dr. Collins maintained it was likely that Mr. Martin’s death was
attributable to a “community-acquired pneumonia.” Tr. at 308; Collins Rep. at 4. She felt the
record evidence, supplied by Petitioner’s contemporaneous statements to treaters, that Mr. Martin
had been sick for a few days before “would go along with a pneumonia.” Tr. at 309–10. The
pathology report (as explained by Dr. Vargas) was also strongly consistent with this conclusion,
as was lab work performed at his arrival to the hospital suggesting a high white blood cell count
(and thus the existence of an infectious process at work). Id. at 309, 312. And emergency treaters
used an antibiotic, suggesting they too suspected a bacterial infectious process. Id. at 315–16; Ex.
7 at 119. Dr. Collins did not, however, deem the claimed symptoms that began closer in time to
vaccination as likely related, since they seemed more consistent with a GI-tract-oriented disease,
and did not describe respiratory symptoms (e.g., cough, shortness of breath, best pain, phlegm
production). Tr. at 311–12.

        Dr. Collins strongly disputed Petitioner’s assertion that Mr. Martin’s death was associated
with his receipt of the flu vaccine. She noted as a threshold matter that a person could develop
bronchopneumonia without first receiving the flu vaccine. Tr. at 314. In fact, the bacterial
infectious process necessary to result in bronchopneumonia did not require a preexisting risk
factor, and could thus affect a totally healthy person. Id. No treaters from the filed medical record
seem to have proposed the flu vaccine could have caused Mr. Martin’s death, and Dr. Collins
added that she would herself not have considered it as a possible pathologic factor. Id. at 316–17.
In addition, Dr. Collins opined that the February 5th vaccination was too remote in time to Mr.
Martin’s collapse and death to be causal. Tr. at 318. Rather, the record suggested he experienced
acute symptoms immediately around the February 26th event, with a “well-documented history”
that up until right before that day he was in usual health. Id.

        More broadly, Dr. Collins disputed the contention that the flu vaccine has ever been
reliably associated with any form of pneumonia, or true flu-like symptoms. Tr. at 330–34, 335–
37. In so maintaining, she noted that the version of the vaccine Mr. Martin had received was
inactivated, meaning its viral components could not reproduce within a cell akin to a wild virus
and cause the kind of symptoms that a wild infection would inherently provoke. Id. at 335. She
also questioned whether literature offered on this point in fact squarely supported Petitioner’s
argument. Id. at 330–31. Chatziandreou, for example, was an animal study that said nothing about
any association between the flu vaccine and respiratory diseases like pneumonia. Id. at 331.

        Dr. Collins similarly discounted other categories of evidence relied upon by Petitioner’s
experts as corroborative of causation. VAERS reports of pneumonia following receipt of the flu
vaccine, for example, only establish a temporal association between vaccine and illness, are not
consistently reported, lack scientific controls that would permit conclusions to be drawn about a
causal association, and can also fail to take into account confounding factors. Tr. at 331–33.


                                                 21
Similarly, the fact that no other possible pathogen was identified to explain Mr. Martin’s purported
infection was not meaningful in Dr. Collins’s experience—and therefore did not leave the vaccine
as the most likely explanation. Id. at 334–35. She denied as well that a vaccine could elicit
neutrophils in the lungs—adding her view that if the vaccine could damage the lungs in any way,
there would exist substantially more evidence of this occurring. Id. at 343, 345–46.

         Besides offering a direct opinion, Dr. Collins commented on aspects of the opinions offered
by Petitioner’s experts. As Dr. Collins explained, the immune system’s usual regulation of
cytokine secretion could sometimes fail (often as a result of an existing infection or some other
cause for an abnormal immune activation), resulting in overproduction of such immune cells, in
the form of a cytokine storm, and thereby causing systemic harm. Tr. at 319–20. She cited sepsis
(a bacterial infection leading to systemic inflammation throughout the body) as the kind of
accepted medical trigger for a cytokine storm. Id. at 320–21. But Dr. Levin’s arguments about the
propensity of vaccines to cause inflammatory “cytokine storm” cascades were undercut by
findings of the Institute of Medicine. Collins Rep. at 6; Tr. at 318–19; Institute of Medicine,
Adverse Effects of Vaccines: Evidence and Causality 76 (Kathleen Stratton et al., 2012), filed as
Ex. V on Apr. 16, 2018 (ECF No. 17-4) (admitting that “more subtle imbalances” of cytokines
may occur after administration of vaccines other than flu vaccine, but concluding that “no evidence
that directly or indirectly supports the oversecretion of cytokines as an operative mechanism was
found”). Dr. Collins was otherwise aware of no reliable medical or scientific literature establishing
that vaccination could cause a cytokine storm, or even play a role in the breakdown of immune
regulatory function necessary to result in it. Tr. at 320. And the record in this case did not support
the conclusion that Mr. Martin himself had experienced such an uncontrolled immune reaction (at
least in response to the flu vaccine three weeks prior to his death). Id. at 321–22.26 His preexisting
diabetes did not suggest a propensity for an overactive immune response (and if anything,
suggested a slower, less robust response). Id. at 323–24.

        Dr. Collins similarly found unpersuasive Dr. Levin’s contentions that Mr. Martin had likely
experienced an upregulation of cytokines after vaccination, and that such excessive cytokine levels
could thereafter last several weeks. She saw no such evidence of cytokine elevation in the actual
medical record. Id. at 324, 321. Dr. Collins also observed that the literature offered in support of
this contention, like Bernstein, only established that a person who had previously received the flu
vaccine (and thus was primed to respond to its antigens) could generate an immune response if re-
exposed—not that the second response would be reflected in “continuously elevated” levels of
cytokines. Id. at 325. On the contrary—the cytokines responsive to vaccination due to adaptive
immune “memory” of an earlier flu vaccine’s receipt would generally peak rapidly in any event,
and the overall robustness of immune response to receipt of the vaccine was ultimately lower in

26
   For the same reasons, Dr. Collins rejected the proposal in Dr. Levin’s first report that Mr. Martin experienced
“hypercytokinemia,” noting in particular that even a vaccine reaction that was documented would usually be localized
to the site of vaccination, and not focused on an inflammatory process in the lungs. Tr. at 322–23.


                                                        22
elderly populations. Tr. at 326; Bernstein at 1730.27

         Mohanty (the article filed by Petitioner but only addressed by Dr. Levin at hearing rather
than in his reports) did not, in Dr. Collins’s reading, support the contention that certain individuals
(the elderly or immune-compromised) would likely experience a temporally-prolonged cytokine
elevation period after vaccination. Tr. at 337–40. Dr. Collins agreed that older individuals would
mount a less-robust immune challenge to pathogen, and that the overall process of cytokine
regulation in response might take longer. Id. at 337–38. However, she noted that not all cytokines
perform the same task, and there are both pro and anti-inflammatory cytokines that are produced
as part of the immune system’s self-regulation. Id. at 338–39. Mohanty only established an overall
course for production of different types of cytokines—not that the allegedly-pathogenic effect of
initially-produced proinflammatory cytokines would inherently persist, and cause symptoms, in
the timeframe alleged by Dr. Levin. Id. at 339.28 Dr. Collins also noted that Mr. Martin was not in
the same age cohort as the older studied population in Mohanty, and that the article said nothing
at all about how a vaccine-induced inflammatory response beginning in the blood would migrate
to the lungs. Id. at 340.29

        Dr. Collins similarly disputed many of Dr. Goldstein’s expert contentions. She concurred
with Dr. Vargas (and her specific citation to CDC publications) that post-vaccination malaise could
occur, and have a flu-like appearance, but maintained that it would be short-lived. Tr. at 344–45,
398–99. She argued that certain literature Dr. Goldstein had more recently offered only suggested
that transient, cytokine-associated malaise could occur in such a brief time period—not that a
pathogenic response was likely on a longer timeframe akin to what is alleged to have occurred in
this case. Id. at 347–49; L. Christian et al., Proinflammatory Cytokine Responses Correspond with
Subjective Side Effects After Influenza Virus Vaccination, 33 Vaccine 29:3360-66 (2015), filed as
Ex. 30 (ECF No. 38-3) (“Christian”). Christian was in fact mostly concerned with evaluating (in a
population of women only) the relationship between immediate, subjective post-vaccination

27
   In so asserting, Dr. Collins noted that other literature offered by Dr. Levin to support his contention actually
underscored the rapidity of the post-vaccination cytokine peak, rather than suggested that elevated cytokine levels
would last for a long period after vaccination. Tr. at 327–30; see, e.g., K. Talaat et al., Rapid Changes in Serum
Cytokines and Chemokines in Response to Inactivated Influenza Vaccination, 12 Influenza Other Resp. Viruses 202–
10 (2018), filed as Ex. 24 (ECF No. 21-4), at 202 (cytokine levels in response to receipt of trivalent inactivated flu
vaccine administered to 20 subjects peaked in 24 hours of vaccination, with no measured cytokine sustaining in
elevated levels for more than two weeks).
28
  In fact (as Dr. Collins observed), Mohanty found that vaccines likely were less effective for older adults because of
a failure in their immune systems to regulate the overall immune response (here, through the production of anti-
inflammatory cytokines)—not that vaccines were themselves more pathogenic. Tr. at 340; Mohanty at 1183.
29
   Dr. Collins expanded on this point when asked about assertions Dr. Vargas made about the low likelihood that an
intradermally-administered vaccine would impact the respiratory system. Tr. at 341–43. An infectious process that
began through the blood would not, in Dr. Collins’s experience, appear on X-ray or other imaging the same as one
(like here) that was clearly impacting the respiratory pathways. Id. at 343.


                                                         23
complaints, like soreness at the site of administration, and subsequent inflammatory responses
(which would point to the vaccine’s effectiveness). Christian at 3366 (p. 9 of ECF No. 38-3). Dr.
Collins agreed that articles like Cowling did reliably observe an increased risk of viral (non-flu)
respiratory infections in children after receipt of the flu vaccine, but noted that its findings had not
since been updated, it offered no mechanistic explanation for causation, and it otherwise did not
offer a good comparison to Mr. Martin’s likely bacterial infection-caused bronchopneumonia. Tr.
at 349–51. And she disputed the evidentiary value of case reports offered by Dr. Goldstein to
establish causal association. Tr. at 353–54.

        On cross-examination, Dr. Collins was questioned about the extent to which her first
written report concluded (consistent with Dr. Levin’s opinion) that in fact Mr. Martin had
experienced a noninfectious pneumonitis (rather than bacterial bronchopneumonia), pointing out
language in her report supportive of that view. Tr. at 365–70; Collins Rep. at 4, 7. Dr. Collins
agreed that record evidence (in particular evidence of vomit in Mr. Martin’s mouth at the time
EMTs attempted resuscitation) did suggest the presence of “[c]hemical pneumonitis from acid
aspiration.” Tr. at 367; Collins Rep. at 7. She also admitted concluding that such a noninfectious
pneumonitis could have contributed to the events culminating in his death. Tr. at 381. However,
Dr. Collins (both in her report and testimony) also allowed for the possibility that Mr. Martin has
experienced “community-acquired pneumonia” of a bacterial origin, and ultimately deferred to Dr.
Vargas on the issue. Collins Rep. at 7; Tr. at 368–71. Her second report more clearly incorporated
Dr. Vargas’s opinion (presumably because both of Respondent’s experts’ first reports were
prepared and filed simultaneously),30 and clearly included the opinion that Mr. Martin’s respiratory
condition was in part the result of a bacterial infection, in addition to her prior discussion of the
possibility it was noninfectious. Supp. Collins Rep. at 4–5.

       Dr. Collins also was asked about the timeframe in which Mr. Martin’s pneumonia
developed, and what that said about its likely etiology. She agreed that a noninfectious pneumonitis
could occur faster than a bacterial infectious process, but denied that the approximately 15 days
from the time Mr. Martin first seemed to complain of flu-like symptoms to the date of his death
was a reasonable temporal course for development of a bacterial pneumonia. Tr. at 376–78. She
also emphasized that Mr. Martin’s history revealed that his numerous risk factors (which long
predated vaccination) were nonspecific for a respiratory condition—but the same was true of the
symptoms that Petitioner alleges he began experiencing three to five days post-vaccination, which
were somewhat consistent with his health before vaccination, or reflective of a GI-oriented
condition distinguishable from a respiratory illness like pneumonia. Id. at 382–84, 387–88.

       Dr. Collins added that she had heard and accepted Petitioner’s allegations about Mr.
Martin’s post-vaccination malaise and flu-like symptoms, but ultimately felt it most likely that (a)
the symptoms Petitioner alleged to have observed in her husband were not related to the

30
     See ECF Nos. 15-1 (Vargas Rep.) and 16-1 (Collins Rep.), dated April 12, 2018, and April 13, 2018, respectively).

                                                          24
bronchopneumonia seen from the pathology evidence, and (b) Mr. Martin’s bronchopneumonia
likely began closer in time to his death, rather than three to five-days post-vaccination. Tr. at 383,
387–89. In so opining, Dr. Collins gave some weight to the fact that Mr. Martin did not appear to
have complained of illness or malaise-like symptoms during his February 24th telehealth visit,
along with the fact that Petitioner made contemporaneous statements to first responders on the
26th that Mr. Martin had only felt unwell for a few days or a week prior to his death. Id. at 389–
90. She did agree, however, that the record from when Mr. Martin was taken to the ER mentioned
he had been “sick with [a] cold for days” (thus allowing for the possibility that the period of time
might have exceeded a week, given the indeterminate nature of “days”). Id. at 391–93; Ex. 7 at
104 (emphasis added).

       C.      Fact Witnesses

       The sole fact witness to testify in this matter was Petitioner herself. Tr. at 4–32. Her
testimony was consistent with the witness statements filed in this case, although she provided some
additional details about the circumstances of her husband’s health in February 2015.

        Petitioner recalled that Mr. Martin received vaccines “very rarely,” and that he had been
administered the flu vaccine on February 5, 2015 (a Thursday) at his doctor’s recommendation,
due to his ongoing diabetes. Tr. at 10, 11–12. (He had also received the vaccine in 2013, and had
(in Petitioner’s uncorroborated recollection) subsequently experienced flu-like symptoms for two
weeks after. Id. at 11). The evening after receiving the vaccine in February 2015, Mr. Martin
seemed fine, and into that weekend as well, with Petitioner only noticing that her husband was not
feeling well by Monday, February 9, 2015. Id. at 13–14.

        The rest of that week and into the next, Petitioner testified, Mr. Martin continued to feel
sick, with body aches, nausea, and other progressively worse symptoms, that made it impossible
for him to go out to dinner or socialize. Tr. at 14–15. Eventually, Mr. Martin phoned a VA doctor
on February 19, 2015, to seek advice on his condition, although there is no filed record of this call.
Id. at 16, 25. He thereafter continued to feel unwell, and had planned to seek in-person treatment
but was unable to do so because of a snowstorm experienced in Huntsville right around the date
of his death. Id. at 17–18. Petitioner did acknowledge Mr. Martin’s telehealth call on February 24,
2015, but suggested that call was limited to discussion of his breathing and diabetes control issues,
and thus was not sure if it presented an occasion for him also to mention his alleged other
symptoms. Id. at 29.

       On the evening of February 25, 2015, Mrs. Martin and her husband fell asleep in their home
game room while watching some movies. Tr. at 18. Early the next morning, Petitioner recalled,
Mr. Martin awoke and informed her he felt dizzy, then went to the bathroom. Id. at 18–19. After
five minutes or so, Mrs. Martin went to check on him (having heard no noises coming from the


                                                 25
bathroom), and found her husband slumped over the toilet, unresponsive. Id. at 19. She
immediately called 911 and attempted to perform CPR. Id. at 19, 20. In the process of so doing,
she observed vomit in and around his mouth, which she attempted to clean. Id. at 20–21.31 She
informed the arriving paramedics that Mr. Martin had been sick recently (and in her mind since a
few days after receiving the flu vaccine twenty days before). Id. at 21, 22. She thereafter travelled
to the hospital with the paramedics. Id. at 22.

        Mrs. Martin acknowledged her husband’s pre-existing diabetes, which she recalled had
been diagnosed in 2001. Tr. at 7–8. He took medications for it, although she could not recall the
various complications and sequelae that the record establishes Mr. Martin suffered from in
connection with his diabetes. Id. at 8. In fact, Petitioner maintained that Mr. Martin was “in good
health” prior to his vaccination, and that he attended to his health and sought medical treatment in
a seasonable manner when appropriate. Id. at 8–9. At most, Petitioner admitted that Mr. Martin
struggled to keep his blood sugar levels in control. Id. She did also acknowledge, however, Mr.
Martin’s fainting in late 2014, although she suggested it was a single occurrence. Id. at 9–10.

      III.        Procedural History

       As stated above, this case was initiated in February 2017. The filing of records was
completed that June, and Respondent’s Rule 4(c) Report opposing an entitlement award was filed
in August 2017. ECF No. 10. Thereafter, and until the winter of 2019, the parties engaged the
experts whose opinions are discussed above and filed reports from each. In February 2019, I set
this matter for hearing in February 2020, and the hearing went forward as planned. The parties
opted not to file post-hearing briefs, and the matter is now fully ripe for adjudication.

IV.          Applicable Law

             A.      Petitioner’s Overall Burden in Vaccine Program Cases

        To receive compensation in the Vaccine Program, a petitioner must prove either: (1) that
he suffered a “Table Injury”—i.e., an injury falling within the Vaccine Injury Table—
corresponding to one of the vaccinations in question within a statutorily prescribed period of time
or, in the alternative, (2) that his illnesses were actually caused by a vaccine (a “Non-Table
Injury”). See Sections 13(a)(1)(A), 11(c)(1), and 14(a), as amended by 42 C.F.R. § 100.3; §
11(c)(1)(C)(ii)(I); see also Moberly v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1321 (Fed.




31
   This allegation is also not corroborated by the medical record and was not addressed in her prehearing statements,
although Petitioner maintained merely that she was not asked to do so. Tr. at 30.


                                                         26
Cir. 2010); Capizzano v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006).32
In this case, Petitioner does not assert a Table claim.

         For both Table and Non-Table claims, Vaccine Program petitioners bear a “preponderance
of the evidence” burden of proof. Section 13(1)(a). That is, a petitioner must offer evidence that
leads the “trier of fact to believe that the existence of a fact is more probable than its nonexistence
before [he] may find in favor of the party who has the burden to persuade the judge of the fact’s
existence.” Moberly, 592 F.3d at 1322 n.2; see also Snowbank Enter. v. United States, 6 Cl. Ct.
476, 486 (1984) (mere conjecture or speculation is insufficient under a preponderance standard).
Proof of medical certainty is not required. Bunting v. Sec’y of Health & Human Servs., 931 F.2d
867, 873 (Fed. Cir. 1991). In particular, a petitioner must demonstrate that the vaccine was “not
only [the] but-for cause of the injury but also a substantial factor in bringing about the injury.”
Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344,
1352–53 (Fed. Cir. 1999)); Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1355 (Fed.
Cir. 2006). A petitioner may not receive a Vaccine Program award based solely on his assertions;
rather, the petition must be supported by either medical records or by the opinion of a competent
physician. Section 13(a)(1).

        In attempting to establish entitlement to a Vaccine Program award of compensation for a
Non-Table claim, a petitioner must satisfy all three of the elements established by the Federal
Circuit in Althen v. Sec’y of Health & Human Servs., 418 F.3d 1274, 1278 (2005): “(1) a medical
theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and
effect showing that the vaccination was the reason for the injury; and (3) a showing of proximate
temporal relationship between vaccination and injury.”

        Each of the Althen prongs requires a different showing. Under Althen prong one, petitioners
must provide a “reputable medical theory,” demonstrating that the vaccine received can cause the
type of injury alleged. Pafford, 451 F.3d at 1355–56 (citations omitted). To satisfy this prong, a
petitioner’s theory must be based on a “sound and reliable medical or scientific explanation.”
Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994). Such a theory
must only be “legally probable, not medically or scientifically certain.” Id. at 549.

        Petitioners may satisfy the first Althen prong without resort to medical literature,
epidemiological studies, demonstration of a specific mechanism, or a generally accepted medical
theory. Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1378–79 (Fed. Cir. 2009)
(citing Capizzano, 440 F.3d at 1325–26). Special masters, despite their expertise, are not

32
  Decisions of special masters (some of which I reference in this ruling) constitute persuasive but not binding
authority. Hanlon v. Sec’y of Health & Human Servs., 40 Fed. Cl. 625, 630 (1998). By contrast, Federal Circuit rulings
concerning legal issues are binding on special masters. Guillory v. Sec’y of Health & Human Servs., 59 Fed. Cl. 121,
124 (2003), aff’d 104 F. Appx. 712 (Fed. Cir. 2004); see also Spooner v. Sec’y of Health & Human Servs., No. 13-
159V, 2014 WL 504728, at *7 n.12 (Fed. Cl. Spec. Mstr. Jan. 16, 2014).

                                                         27
empowered by statute to conclusively resolve what are essentially thorny scientific and medical
questions, and thus scientific evidence offered to establish Althen prong one is viewed “not through
the lens of the laboratorian, but instead from the vantage point of the Vaccine Act’s preponderant
evidence standard.” Id. at 1380. Accordingly, special masters must take care not to increase the
burden placed on petitioners in offering a scientific theory linking vaccine to injury.

        In discussing the evidentiary standard applicable to the first Althen prong, the Federal
Circuit has consistently rejected the contention that it can be satisfied merely by establishing the
proposed causal theory’s scientific or medical plausibility. See Boatmon v. Sec’y of Health &
Human Servs., 941 F.3d 1351, 1359 (Fed. Cir. 2019); see also LaLonde v. Sec’y of Health &
Human Servs., 746 F.3d 1334, 1339 (Fed. Cir. 2014) (“[h]owever, in the past we have made clear
that simply identifying a ‘plausible’ theory of causation is insufficient for a petitioner to meet her
burden of proof.” (citing Moberly, 592 F.3d at 1322)). Petitioners otherwise always have the
ultimate burden of establishing their overall Vaccine Act claim with preponderant evidence,
regardless of what evidentiary level of evidence on the “can cause” prong is required. W.C. v. Sec’y
of Health & Human Servs., 704 F.3d 1352, 1356 (Fed. Cir. 2013) (citations omitted); Tarsell, 133
Fed. Cl. at 793 (noting that Moberly “addresses the petitioner’s overall burden of proving
causation-in-fact under the Vaccine Act” by a preponderance standard).

        The second Althen prong requires proof of a logical sequence of cause and effect, usually
supported by facts derived from a petitioner’s medical records. Althen, 418 F.3d at 1278; Andreu,
569 F.3d at 1375–77; Capizzano, 440 F.3d at 1326; Grant v. Sec’y of Health & Human Servs., 956
F.2d 1144, 1148 (Fed. Cir. 1992). In establishing that a vaccine “did cause” injury, the opinions
and views of the injured party’s treating physicians are entitled to some weight. Andreu, 569 F.3d
at 1367; Capizzano, 440 F.3d at 1326 (“medical records and medical opinion testimony are favored
in vaccine cases, as treating physicians are likely to be in the best position to determine whether a
‘logical sequence of cause and effect show[s] that the vaccination was the reason for the injury’”)
(quoting Althen, 418 F.3d at 1280). Medical records are generally viewed as particularly
trustworthy evidence, since they are created contemporaneously with the treatment of the patient.
Cucuras v. Sec’y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993).

        Medical records and statements of a treating physician, however, do not per se bind the
special master to adopt the conclusions of such an individual, even if they must be considered and
carefully evaluated. Section 13(b)(1) (providing that “[a]ny such diagnosis, conclusion, judgment,
test result, report, or summary shall not be binding on the special master or court”); Snyder v. Sec’y
of Health & Human Servs., 88 Fed. Cl. 706, 746 n.67 (2009) (“there is nothing . . . that mandates
that the testimony of a treating physician is sacrosanct - that it must be accepted in its entirety and
cannot be rebutted”). As with expert testimony offered to establish a theory of causation, the
opinions or diagnoses of treating physicians are only as trustworthy as the reasonableness of their
suppositions or bases. The views of treating physicians should be weighed against other, contrary


                                                  28
evidence also present in the record—including conflicting opinions among such individuals.
Hibbard v. Sec’y of Health & Human Servs., 100 Fed. Cl. 742, 749 (2011) (not arbitrary or
capricious for special master to weigh competing treating physicians’ conclusions against each
other), aff’d, 698 F.3d 1355 (Fed. Cir. 2012); Veryzer v. Sec’y of Dept. of Health & Human Servs.,
No. 06-522V, 2011 WL 1935813, at *17 (Fed. Cl. Spec. Mstr. Apr. 29, 2011), mot. for review
denied, 100 Fed. Cl. 344, 356 (2011), aff’d without opinion, 475 F. Appx. 765 (Fed. Cir. 2012).

        The third Althen prong requires establishing a “proximate temporal relationship” between
the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been equated to the
phrase “medically-acceptable temporal relationship.” Id. A petitioner must offer “preponderant
proof that the onset of symptoms occurred within a timeframe which, given the medical
understanding of the disorder’s etiology, it is medically acceptable to infer causation.” de Bazan
v. Sec’y of Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). The explanation for
what is a medically acceptable timeframe must align with the theory of how the relevant vaccine
can cause an injury (Althen prong one’s requirement). Id. at 1352; Shapiro v. Sec’y of Health &
Human Servs., 101 Fed. Cl. 532, 542 (2011), recons. denied after remand, 105 Fed. Cl. 353 (2012),
aff’d mem., 503 F. Appx. 952 (Fed. Cir. 2013); Koehn v. Sec’y of Health & Human Servs., No. 11-
355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr. May 30, 2013), mot. for rev. denied (Fed. Cl. Dec.
3, 2013), aff’d, 773 F.3d 1239 (Fed. Cir. 2014).

       B.      Legal Standards Governing Factual Determinations

        The process for making determinations in Vaccine Program cases regarding factual issues
begins with consideration of the medical records. Section 11(c)(2). The special master is required
to consider “all [] relevant medical and scientific evidence contained in the record,” including “any
diagnosis, conclusion, medical judgment, or autopsy or coroner’s report which is contained in the
record regarding the nature, causation, and aggravation of the petitioner’s illness, disability, injury,
condition, or death,” as well as the “results of any diagnostic or evaluative test which are contained
in the record and the summaries and conclusions.” Section 13(b)(1)(A). The special master is then
required to weigh the evidence presented, including contemporaneous medical records and
testimony. See Burns v. Sec’y of Health & Human Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (it is
within the special master’s discretion to determine whether to afford greater weight to
contemporaneous medical records than to other evidence, such as oral testimony surrounding the
events in question that was given at a later date, provided that such determination is evidenced by
a rational determination).

        Medical records that are created contemporaneously with the events they describe are
presumed to be accurate and “complete” (i.e., presenting all relevant information on a patient’s
health problems). Cucuras, 993 F.2d at 1528; Doe/70 v. Sec’y of Health & Human Servs., 95 Fed.
Cl. 598, 608 (2010) (“[g]iven the inconsistencies between petitioner’s testimony and his
contemporaneous medical records, the special master’s decision to rely on petitioner’s medical
                                                  29
records was rational and consistent with applicable law”), aff’d sub nom. Rickett v. Sec’y of Health
& Human Servs., 468 F. Appx. 952 (Fed. Cir. 2011) (non-precedential opinion). This presumption
is based on the linked propositions that (i) sick people visit medical professionals; (ii) sick people
honestly report their health problems to those professionals; and (iii) medical professionals record
what they are told or observe when examining their patients in as accurate a manner as possible,
so that they are aware of enough relevant facts to make appropriate treatment decisions. Sanchez
v. Sec’y of Health & Human Servs., No. 11-685V, 2013 WL 1880825, at *2 (Fed. Cl. Spec. Mstr.
Apr. 10, 2013); Cucuras v. Sec’y of Health & Human Servs., 26 Cl. Ct. 537, 543 (1992), aff’d, 993
F.2d at 1525 (Fed. Cir. 1993) (“[i]t strains reason to conclude that petitioners would fail to
accurately report the onset of their daughter’s symptoms”).

        Accordingly, if the medical records are clear, consistent, and complete, then they should
be afforded substantial weight. Lowrie v. Sec’y of Health & Human Servs., No. 03-1585V, 2005
WL 6117475, at *20 (Fed. Cl. Spec. Mstr. Dec. 12, 2005). Indeed, contemporaneous medical
records are generally found to be deserving of greater evidentiary weight than oral testimony—
especially where such testimony conflicts with the record evidence. Cucuras, 993 F.2d at 1528;
see also Murphy v. Sec’y of Dep’t of Health & Human Servs., 23 Cl. Ct. 726, 733 (1991) (citing
United States v. United States Gypsum Co., 333 U.S. 364, 396 (1947) (“[i]t has generally been
held that oral testimony which is in conflict with contemporaneous documents is entitled to little
evidentiary weight.”)).

        There are, however, situations in which compelling oral testimony may be more persuasive
than written records, such as where records are deemed to be incomplete or inaccurate. Campbell
v. Sec’y of Health & Human Servs., 69 Fed. Cl. 775, 779 (2006) (“like any norm based upon
common sense and experience, this rule should not be treated as an absolute and must yield where
the factual predicates for its application are weak or lacking”); Lowrie, 2005 WL 6117475, at *19
(“’[w]ritten records which are, themselves, inconsistent, should be accorded less deference than
those which are internally consistent’”) (quoting Murphy, 23 Cl. Ct. at 733)). Ultimately, a
determination regarding a witness’s credibility is needed when determining the weight that such
testimony should be afforded. Andreu, 569 F.3d at 1379; Bradley v. Sec’y of Health & Human
Servs., 991 F.2d 1570, 1575 (Fed. Cir. 1993).

        When witness testimony is offered to overcome the presumption of accuracy afforded to
contemporaneous medical records, such testimony must be “consistent, clear, cogent, and
compelling.” Sanchez, 2013 WL 1880825, at *3 (citing Blutstein v. Sec’y of Health & Human
Servs., No. 90-2808V, 1998 WL 408611, at *5 (Fed. Cl. Spec. Mstr. June 30, 1998)). In
determining the accuracy and completeness of medical records, the Court of Federal Claims has
listed four possible explanations for inconsistencies between contemporaneously created medical
records and later testimony: (1) a person’s failure to recount to the medical professional everything
that happened during the relevant time period; (2) the medical professional’s failure to document


                                                 30
everything reported to her or him; (3) a person’s faulty recollection of the events when presenting
testimony; or (4) a person’s purposeful recounting of symptoms that did not exist. Lalonde v. Sec’y
of Health & Human Servs., 110 Fed. Cl. 184, 203-04 (2013), aff’d, 746 F.3d 1334 (Fed. Cir. 2014).
In making a determination regarding whether to afford greater weight to contemporaneous medical
records or other evidence, such as testimony at hearing, there must be evidence that this decision
was the result of a rational determination. Burns, 3 F.3d at 417.

       C.      Analysis of Expert Testimony

        Establishing a sound and reliable medical theory often requires a petitioner to present
expert testimony in support of his claim. Lampe v. Sec’y of Health & Human Servs., 219 F.3d
1357, 1361 (Fed. Cir. 2000). Vaccine Program expert testimony is usually evaluated according to
the factors for analyzing scientific reliability set forth in Daubert v. Merrell Dow Pharmaceuticals,
Inc., 509 U.S. 579, 594–96 (1993). See Cedillo v. Sec’y of Health & Human Servs., 617 F.3d 1328,
1339 (Fed. Cir. 2010) (citing Terran v. Sec’y of Health & Human Servs., 195 F.3d 1302, 1316
(Fed. Cir. 1999)). “The Daubert factors for analyzing the reliability of testimony are: (1) whether
a theory or technique can be (and has been) tested; (2) whether the theory or technique has been
subjected to peer review and publication; (3) whether there is a known or potential rate of error
and whether there are standards for controlling the error; and (4) whether the theory or technique
enjoys general acceptance within a relevant scientific community.” Terran, 195 F.3d at 1316 n.2
(citing Daubert, 509 U.S. at 592–95).

         The Daubert factors play a slightly different role in Vaccine Program cases than they do
when applied in other federal judicial fora (such as the district courts). Daubert factors are usually
employed by judges (in the performance of their evidentiary gatekeeper roles) to exclude evidence
that is unreliable and/or could confuse a jury. In Vaccine Program cases, by contrast, these factors
are used in the weighing of the reliability of scientific evidence proffered. Davis v. Sec’y of Health
& Human Servs., 94 Fed. Cl. 53, 66–67 (2010) (“uniquely in this Circuit, the Daubert factors have
been employed also as an acceptable evidentiary-gauging tool with respect to persuasiveness of
expert testimony already admitted”). The flexible use of the Daubert factors to evaluate the
persuasiveness and reliability of expert testimony has routinely been upheld. See, e.g., Snyder, 88
Fed. Cl. at 742–45. In this matter (as in numerous other Vaccine Program cases), Daubert has not
been employed at the threshold, to determine what evidence should be admitted, but instead to
determine whether expert testimony offered is reliable and/or persuasive.

        Respondent frequently offers one or more experts of his own in order to rebut a petitioner’s
case. Where both sides offer expert testimony, a special master’s decision may be “based on the
credibility of the experts and the relative persuasiveness of their competing theories.”
Broekelschen v. Sec’y of Health & Human Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing
Lampe, 219 F.3d at 1362). However, nothing requires the acceptance of an expert’s conclusion


                                                 31
“connected to existing data only by the ipse dixit of the expert,” especially if “there is simply too
great an analytical gap between the data and the opinion proffered.” Snyder, 88 Fed. Cl. at 743
(quoting Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997)); see also Isaac v. Sec’y of Health &
Human Servs., No. 08-601V, 2012 WL 3609993, at *17 (Fed. Cl. Spec. Mstr. July 30, 2012), mot.
for rev. denied, 108 Fed. Cl. 743 (2013), aff’d, 540 F. Appx. 999 (Fed. Cir. 2013) (citing Cedillo,
617 F.3d at 1339). Weighing the relative persuasiveness of competing expert testimony, based on
a particular expert’s credibility, is part of the overall reliability analysis to which special masters
must subject expert testimony in Vaccine Program cases. Moberly, 592 F.3d at 1325–26
(“[a]ssessments as to the reliability of expert testimony often turn on credibility determinations”);
see also Porter v. Sec’y of Health & Human Servs., 663 F.3d 1242, 1250 (Fed. Cir. 2011) (“this
court has unambiguously explained that special masters are expected to consider the credibility of
expert witnesses in evaluating petitions for compensation under the Vaccine Act”).

        Expert opinions based on unsupported facts may be given relatively little weight. See
Dobrydnev v. Sec’y of Health & Human Servs., 556 F. App’x. 976, 992–93 (Fed. Cir. 2014) (“[a]
doctor’s conclusion is only as good as the facts upon which it is based”) (citing Brooke Group Ltd.
v. Brown & Williamson Tobacco Corp., 509 U.S. 209, 242 (1993) (“[w]hen an expert assumes
facts that are not supported by a preponderance of the evidence, a finder of fact may properly reject
the expert’s opinion”)). Expert opinions that fail to address or are at odds with contemporaneous
medical records may therefore be less persuasive than those which correspond to such records. See
Gerami v. Sec’y of Health & Human Servs., No. 12-442V, 2013 WL 5998109, at *4 (Fed. Cl. Spec.
Mstr. Oct. 11, 2013), aff’d, 127 Fed. Cl. 299 (2014).

       D.      Consideration of Medical Literature

        Both parties filed medical and scientific literature in this case, but not every filed item
factors into the outcome of this decision. While I have reviewed all the medical literature submitted
in this case, I discuss only those articles that are most relevant to my determination and/or are
central to Petitioner’s case—just as I have not exhaustively discussed every individual medical
record filed. Moriarty v. Sec’y of Health & Human Servs., 844 F.3d 1322, 1328 (Fed. Cir. 2016)
(“[w]e generally presume that a special master considered the relevant record evidence even
though he does not explicitly reference such evidence in his decision”) (citation omitted); see also
Paterek v. Sec’y of Health & Human Servs., 527 F. Appx. 875, 884 (Fed. Cir. 2013) (“[f]inding
certain information not relevant does not lead to—and likely undermines—the conclusion that it
was not considered”).

       E.      Consideration of Comparable Special Master Decisions

       In reaching a decision in this case, I have considered other decisions issued by special
masters (including my own) involving similar injuries, vaccines, or circumstances. I also reference


                                                  32
some of those cases in this Decision, in an effort to establish common themes, as well as
demonstrate how prior determinations impact my thinking on the present case.

        There is no error in doing so. It is certainly correct that prior decision in different cases do
not control the outcome herein.33 Boatmon v. Sec’y of Health & Human Servs., 941 F.3d 1351,
1358–59 (Fed. Cir. 2019); Hanlon v. Sec’y of Health & Human Servs., 40 Fed. Cl. 625, 630 (1998).
Thus, the fact that another special master reasonably determined elsewhere, on the basis of facts
not in evidence in this case, that preponderant evidence supported the conclusion that vaccine X
caused petitioner’s injury Y does not compel me to reach the same conclusion in this case.
Different actions present different background medical histories, different experts, and different
items of medical literature, and therefore can reasonably result in contrary determinations.

        However, it is equally the case that special masters reasonably draw upon their experience
in resolving Vaccine Act claims. Doe v. Sec’y of Health & Human Servs., 76 Fed. Cl. 328, 338–
39 (2007) (“[o]ne reason that proceedings are more expeditious in the hands of special masters is
that the special masters have the expertise and experience to know the type of information that is
most probative of a claim”) (emphasis added). They would therefore be remiss in ignoring prior
cases presenting similar theories or factual circumstances, along with the reasoning employed in
reaching such decisions. This is especially so given that special masters not only routinely hear
from the same experts in comparable cases but are also repeatedly offered the same items of
medical literature regarding certain common causation theories. It defies reason and logic to
obligate special masters to “reinvent the wheel”, so to speak, in each new case before them, paying
no heed at all to how their colleagues past and present have addressed similar causation theories
or fact patterns. It is for this reason that prior decisions can have high persuasive value—and why
special masters often explain how a new determination relates to such past decisions.34 Even if the
Federal Circuit does not require special masters to distinguish other relevant cases (Boatmon, 941
F.3d at 1358), it is still wise to do so.




33
   By contrast, Federal Circuit rulings concerning legal issues are binding on special masters. Guillory v. Sec’y of
Health & Human Servs., 59 Fed. Cl. 121, 124 (2003), aff’d 104 F. Appx. 712 (Fed. Cir. 2004); see also Spooner v.
Sec’y of Health & Human Servs., No. 13-159V, 2014 WL 504728, at *7 n.12 (Fed. Cl. Spec. Mstr. Jan. 16, 2014).
Special masters are also bound within a specific case by determinations made by judges of the Court of Federal Claims
after a motion for review is resolved.
34
  Consideration of prior determinations is a two-way street that does not only inure to the benefit of one party. Thus,
I would likely take into account the numerous decisions finding no association between vaccination and autism when
confronted with a new claim asserting autism as an injury, and have informed such claimants early in the life of their
case that the claim was not viable for just that reason. But I would also deem a non-Table claim asserting Guillain-
Barré syndrome (“GBS”) after receipt of the flu vaccine as not requiring extensive proof on Althen prong one “can
cause” matters, for the simple reason that the Program has repeatedly litigated the issue in favor of petitioners.


                                                         33
                                                     ANALYSIS

I.       Overview of Some Prior Flu Vaccine-Death Cases

       Other petitioners have succeeded in establishing that certain vaccines, including the flu
vaccine, could contribute to an individual’s subsequent death.35 The circumstances of such cases,
however, are distinguishable from the present record. See, e.g., Halverson v. Sec’y of Health &
Human Servs., No. 15-227V, 2020 WL 992588 (Fed. Cl. Spec. Mstr. Feb. 4, 2020); Bragg v. Sec’y
of Health & Human Servs., No. 08-477V, 2012 WL 404773 (Fed. Cl. Spec. Mstr. Jan 18, 2012).

        In Halverson, for example, a petitioner successfully established that a “high dose” version
of the flu vaccine (a form often administered to the elderly) was a substantial factor in causing the
death of a 66 year-old woman four days after the vaccine’s administration. Halverson, 2020 WL
992588, at *1. The deceased individual presented with a number of comorbidities comparable to
the facts herein, such as diabetes, and had a documented history of cardiac issues. Id. at *5–9. She
also displayed immediate health degeneration the evening after receiving the vaccine. Id. at *9.
The special master ruling in the case ultimately determined that the vaccine likely interacted with
an upper respiratory infection to significantly aggravate her preexisting heart disease, leading to
cardiac arrest and death. Id. at *32. Halverson thus involved a demonstrably shorter timeframe in
which the vaccine could interact with the decedent’s preexisting health issues, plus a more potent
formulation of the flu vaccine.

        In Bragg, a petitioner successfully established that a flu vaccine caused the death of an 82
year-old man five days later. Bragg, 2012 WL 404773, at *1, *27. The deceased man presented
with some comorbidities that are also comparable to the instant case—e.g., prediabetes and
hyperlipidemia. Id. at *1. But, unlike the present case, the decedent was comparatively in far better
health, and reported walking nine miles per day and riding an exercise bike to stay in shape about
ten days before his death. Id. In addition, and similar to Halverson, the decedent in Bragg displayed
immediate health degeneration 30 minutes after receiving the vaccine, “[h]e never felt any better
but continued to get worse until he died.” Id. at *26. The special master thus found that petitioner
had proven that the flu vaccine can cause systemic inflammatory response syndrome in the elderly,
that the decedent had suffered from systemic inflammatory response syndrome, and that the injury




35
   There are also cases in which petitioners have successfully established that the flu vaccine caused GBS, which in
turn was determined to be a substantial factor in causing the injured party’s death. See, e.g., Stitt v. Sec'y of Health &
Human Servs., No. 09-653V, 2013 WL 3356791 (Fed. Cl. Spec. Mstr. May 31, 2013). But such cases provide little
guidance herein, since they involved not only circumstances in which the vaccine was alleged to be causal of a specific
and discrete illness (and in the case of GBS, an injury well-understood to be associated with the flu vaccine), but
distinguishable causal mechanisms as well.



                                                           34
occurred in a medically acceptable timeframe. See id. at *21–*26.36 Bragg thus also presents a far
more compressed timeframe than is at issue herein.

II.      Mr. Martin Likely Experienced Bronchopneumonia Caused by an Unidentified
         Bacterial Infection

        In many Vaccine Program cases, a critical first step is to determine the injury at issue—
especially when the causal theory depends directly on such a finding. Broekelschen, 618 F.3d at
1346. Here, Mr. Martin’s death is the ultimate “injury,” although Petitioner’s theory of how it
came about (non-infectious inflammation in a susceptible, immune-compromised individual) is
broad enough to encompass whatever the contributing factors causing death were. In addition,
Petitioner does not contest that Mr. Martin’s established comorbidities (in particular uncontrolled
diabetes) likely impacted his health and/or immune response. Respondent, however, has
maintained that Mr. Martin likely was experiencing a bacterial pneumonia as of his death, and a
finding on this issue does bear on the overall success of Petitioner’s causal showing, so I will
preliminary resolve this question.

        The record in this case preponderates in favor of a finding that Mr. Martin more likely than
not had experienced a bacterial infection-driven bronchopneumonia right around the time of his
death—and that this illness was integral in causing death. The records from the date of Mr.
Martin’s untimely death, plus the subsequent pathology report (which stressed the importance of
the bronchopneumonia findings), strongly support that conclusion. Dr. Vargas’s experienced and
cogent review of the lung tissue slides (and specifically what they demonstrated about evidence of
neutrophil infiltration and dissemination in Mr. Martin’s lungs) only underscored my
determination. Her explanation of what she saw from the pattern of inflammation, as well as the
very existence of neutrophils (which would more likely than not appear in response to a bacterial
infection) was persuasive. In addition, some of the other factual evidence—that Mr. Martin
displayed breathing issues right around the time of death, was coughing before his collapse, and
was reported to treaters by Petitioner to have been sick around the time of his death—all are
consistent with my conclusion.

       By contrast, the record evidence does not preponderantly establish that Mr. Martin had
been experiencing a non-infectious inflammatory process at any time between the date of
vaccination and his death, or that such a process contributed to a bacterial infection-driven
bronchopneumonia. There is no particular evidence (other than the uncorroborated claims that Mr.
Martin began to feel unwell a few days after the vaccination) that he was experiencing any such

36
  Notably, Dr. Levin was an expert witness for the Bragg petitioner. Bragg, 2012 WL 404773, at *15. He opined that
a cytokine storm caused the petitioner to develop systemic inflammatory response syndrome and later die. See id.
Here, however, and as noted in more detail below, I do not find him as credible as the special master did in that case,
and also deem his opinion on cytokine function generally not to be reliably established, at least given the evidence
presented herein.

                                                         35
prior chronic inflammation, regardless of its cause. Moreover, Dr. Levin’s interpretation of the
pathology report and tissue slides was not nearly as persuasive as Dr. Vargas’s, and his arguments
that Petitioner had likely only experienced a non-infectious pneumonitis37 was not evidentiarily
supported as the best explanation for his death.

        The fact that no particular bacterial agent was ever identified as causal does not cut against
my finding. Respondent’s experts persuasively established that this is not uncommon—a
conclusion bulwarked by Petitioner’s own literature. S. Sethi, Community-Acquired Pneumonia,
Merck               Manuals,               https://www.merckmanuals.com/professional/pulmonary-
disorders/pneumonia/community-acquired-pneumonia (last visited July 13, 2020), filed as Ex. 18
(ECF No. 13-9) at 1 (“even with testing, specific agents are identified in < 50% of cases”). Illnesses
can often have an idiopathic viral or bacterial origin, and it is well-understood in the Program that
an inability to identify the precise alternative cause of a particular post-vaccination injury does not
mean such an explanation is unlikely—any more than it means a vaccine known to have been
administered was more likely to have been causal. Zumwalt v. Sec'y of Health & Human Servs.,
No. 16-994V, 2019 WL 1953739, at *19 (“a Vaccine Program petitioner does not succeed in his
claim simply by eliminating other possible causes” (citations omitted)) (Fed. Cl. Spec. Mstr. Mar.
21, 2019), mot. for review den’d, 146 Fed. Cl. 525 (2019). The overall record best supports the
conclusion that Mr. Martin did experience bronchopneumonia, and that it played a significant role
in causing his death.

II.      Petitioner has not Carried Her Burden of Proof

         A.       Althen Prong One

        Petitioner made a number of individual plausible assertions in support of her causation
theory, but nevertheless fell short of establishing preponderantly, with reference to reliable
scientific/medical evidence, that the flu vaccine could cause, or set the stage for, death through a
noninfectious inflammatory process driven by vaccine-induced cytokines generated as part of the
innate immune response.

        Reliable science supports certain components of Petitioner’s theory. It has been reliably
established that (a) vaccines stimulate an innate immune response resulting in the production of

37
  I also did not find convincing Petitioner’s arguments that Dr. Collins conceded, in whole or even part, that a non-
infectious pneumonitis attributable to aspiration of food particles was the most likely cause of Mr. Martin’s death.
See, e.g., Pet’r’s Br. at 6–7. Unquestionably Dr. Collins mentioned pathologic findings supportive of pneumonitis in
her reports, as Petitioner observed. However, she also referenced a bacterial pneumonia, did not weight the former
over the latter, and at hearing seems to have given more weight to Dr. Vargas’s testimony on this issue. In any event,
I find based on an overall review of the evidence (which is not limited only to written expert reports) that
bronchopneumonia is the most evidentiarily-supported conclusion. This determination places greater weight on Dr.
Vargas’s testimony – as I am free to do, having heard all expert testimony, considered their reports, and weighed the
probative value overall of their opinions.

                                                         36
cytokines, including those that are proinflammatory, (b) different cytokines can be sustained at
higher-than-normal levels for different periods of time after vaccination, and (c) certain
proinflammatory cytokines are associated with some pathologic disease processes. Similarly, there
are several non-infectious respiratory diseases propelled by inflammation, such as obstructive lung
disease. Petitioner also offered some items of reliable literature, like Cowling, supporting the
conclusion that in at least some populations (though clearly not in the age cohort most relevant to
Mr. Martin) receipt of a flu vaccine can later be associated with other kinds of viral respiratory
infections (as opposed to bacterial-caused conditions, like bronchopneumonia). And Petitioner’s
experts pointed to a few case reports (a kind of evidence having some weak probative causation
value) in which a flu vaccine preceded damage to the lungs, or invoked (although it was never
corroborated with the necessary back-up documentation) VAERS reports purporting instances of
post-flu vaccine injuries resulting in death or pneumonia. It is also true that bacterial infectious
illnesses, like pneumonia, can be secondary to a viral flu infection. Hamborsky at 190.

       But this patchwork showing was not enough, collectively, to constitute preponderant
evidence that the flu vaccine could create circumstances ripe for a bacterial-initiated
bronchopneumonia occurring weeks later. First, Petitioner’s argument relies on scientifically
unreliable contentions that confuse cytokine function with expression, and that specifically assume
cytokines stimulated by vaccination readily play a pathologic role, even in the absence of an
ongoing infectious disease process. Indeed, Dr. Levin himself admitted that the inactivated form
of flu vaccine received by Mr. Martin was unlikely to cause cytokine overproduction (thus
contrasting it with the high dose form deemed to be causal in Halverson). Tr. at 45.

        Many other petitioners have similarly attempted to satisfy the first Althen prong by arguing,
as here, that the intended pro-inflammatory impact of a vaccine (to the extent the vaccine
stimulates cytokine production in order to create adaptive immune system memory of a viral
antigen) can become pathologic. But I have consistently found this argument lacking in sufficient
reliable scientific/medical support. See, e.g., Olson v. Sec’y of Health & Human Servs., No. 13-
439V, 2017 WL 3624085, at *20 (Fed. Cl. Spec. Mstr. July 14, 2017) (“it remains a speculative
issue as to whether cytokine production instigated by a single vaccine containing alum 38 would be
robust enough, and occur for long enough, to be pathogenic generally, let alone to cause” the
complained-of injury), mot. for review den’d, 135 Fed. Cl. 670 (2017), aff'd, 758 F. App'x 919
(Fed. Cir. 2018). There is a vast difference between the transient increase in cytokines that
vaccination is intended to trigger (since an innate response is required for the vaccine to have
immunogenicity) and the kind of harmful, ongoing inflammatory process that a wild infection
causes. There is an even a greater gap between transient cytokine upregulation due to vaccination


38
  Indeed, there is no adjuvant contained in the inactivated form of flu vaccine Mr. Martin received, further diminishing
the possibility of a heightened immune response in this case (since adjuvants are intended to spark a more robust
response).


                                                          37
and a true “cytokine storm”39 capable of causing critical and overwhelming systemic damage to
an individual. I have yet to be presented with evidence in a Program case linking any vaccine to
over-production of cytokines capable of becoming pathologic (at least over an extended period of
time, as here) simply due to the vaccine’s stimulation of an innate immune response—and this
case was no different.

        Second, Petitioner’s theory did not persuasively establish by a preponderance that the flu
vaccine could initiate a non-infectious inflammatory process that would unfold over time, and later
“set up” a person with a high susceptibility to experience a secondary bacterial infection of the
kind I have found Mr. Martin experienced. Although evidence was filed in this matter establishing
that non-infectious inflammatory processes exist, the evidence linking the flu vaccine – or any
vaccine – to such processes was far more limited, and mostly came from the conclusory statements
of Petitioner’s experts (whom, as discussed below, either lacked the demonstrated experiential
depth in their fields necessary to render a reliable opinion, or were unpersuasive for other reasons).
Petitioner did file some intriguing and facially-reliable items like Cowling that point to the flu
vaccine as possibly having the capacity to reduce an individual’s innate resistance to subsequent
viral respiratory infection. But these articles do not say anything about pneumonia or bacterial
infections, and are also distinguishable in terms of the studied population.

        Finally, I credit the point that a person with significant comorbidities, such as diabetes,
might well be immunocompromised, and therefore might plausibly be more likely to have
difficulty processing vaccination. But I do not find that it has been preponderantly established in
this case that the flu vaccine of the type administered would be expected to have greater pathologic
potential (and specifically could initiate a non-infectious inflammatory process under such
circumstances) for that kind of person, leading to “immunologic dissonance” as argued by
Petitioner that would set the stage for a subsequent bacterial infection. Petitioner’s Pre-Hearing
Brief, dated November 5, 2019 (ECF No. 29) (“Brief”), at 3. Indeed, much of Petitioner’s literature
stands for the opposite conclusion—that vaccines are expressly recommended for persons with
substantial comorbidities, given the greater risk of a wild viral or bacterial infection the immune-
compromised face. See, e.g., E. Bernstein et al., Cytokine Production After Influenza Vaccination
in a Healthy Elderly Population 16(18) Vaccine 1729–30 (1998), filed on Nov. 27, 2017 as Ex.
19 (ECF No. 13-10).




39
  Indeed, the ongoing COVID-19 pandemic dramatically illustrates what a true cytokine storm looks like, and its fatal
implications. Qing Ye et al., The Pathogenesis and Treatment of the ‘Cytokine Storm’ in COVID-19, 80(6) J. of
Infection 607–13 (2020). It takes an uncontrolled infectious process, resistant to the functioning of a normal immune
response, to produce wildly aberrant cytokine function sufficient to cause death.


                                                         38
        The validity of this conclusion is strengthened when the version of the flu vaccine at issue
is taken into account. Mr. Martin received a nonadjuvanted40 version of the flu vaccine, which
included inactivated viral particles that would not be able to replicate after injection. Unlike a high
dose version of the same vaccine found to be contributing to death in Halverson, here it is far less
likely that the version in question would have the same capacity, even for a person with significant
comorbidities and/or who was deemed immunocompromised.

        Petitioner’s experts were unable to rectify the deficiencies in the causation theory through
the persuasiveness or compelling character of their testimony. Dr. Levin’s overall credibility as a
trustworthy expert has been called into question in numerous prior cases—by me as well as other
special masters.41 And even if I ignore his past performance and the conclusory, non-credible
statements he has repeatedly made elsewhere, I note that his overall expertise in immunologic
matters42 (especially lacking now that his focus is on attorney work) was too lacking herein to
imbue his opinions with heft that they could not otherwise obtain from the filed medical literature.
His views on the pathology issues relevant to this case were especially outclassed by Dr. Vargas’s
far more probative and compelling testimony.

         Dr. Goldstein, by contrast, did not present the same kind of facial credibility problems, and
his testimony and opinions arose mainly from his demonstrated experience treating respiratory and
pulmonary diseases. However, Dr. Goldstein ultimately lacked the kind of specific expertise in the
immunologic issues most relevant to Petitioner’s causation theory to carry the day. The fact that
he could rely on some treating expertise in offering an opinion on the causal link in this case
between vaccination and Mr. Martin’s later death had evidentiary value, but was not enough to
carry Petitioner’s overall preponderant burden—especially in the absence of other reliable
scientific and medical evidence.

        In discussing my weighing of the evidence in this case offered in connection with the first
Althen prong, a distinction should be made between the probative value of the scientific or medical
articles discussed and filed to support the claim and expert testimony on these same subjects. It is
unquestionably the case (as I have already said above) that petitioners need not offer medical

40
   In immunology an adjuvant is “a nonspecific stimulator of the immune response, such as BCG vaccine.” Dorland’s
at 32.

 See, e.g., Bigbee v. Sec’y of Health & Human Servs., No. 06-663V, 2012 WL 1237759, at *30 (Fed. Cl. Spec. Mstr.
41

Mar. 22, 2012) (“Dr. Levin’s testimony in particular was extremely unhelpful—as would be expected from someone
who practices law 99% of the time and thus medicine 1% and has not seen a patient since 1993”).
42
  This is so even in comparison to Dr. Collins, who unquestionably does not have board certification in immunology,
and yet was able to explain the immunologic concepts at issue in this case in a more lucid and persuasive manner. Of
course, Dr. Levin today spends far more of his time (when not an expert witness) as an attorney, and his credentials
in immunology lie mainly in his educational background—they have not been honed over the years in patient practice
or research not relating to a lawsuit in which he was involved.


                                                        39
literature to prevail. Andreu, 569 F.3d at 1378–79. Thus, while literature supporting “contention
X” may be absent from a case, that fact is not disqualifying of the claim as a whole. Rather, the
total mix of evidence can easily meet the preponderant burden even where (as is usually the case,
given the rareness of injuries evaluated in the Program) there is no one item of article addressing,
let alone proving, that the vaccine in question “can cause” the relevant injury. Expert opinions can
assist petitioners in such circumstances by filling in such gaps.

       Nevertheless, I am called upon to weigh the overall evidence offered in any case, on each
Althen prong. Moreover, it is equally a black-letter concept that I need not accept an expert’s
opinion at face value.43 Snyder, 88 Fed. Cl. at 743. Rather, in properly performing my duties, I
may consider how probative such opinions are, in light of the expert’s credentials, personal
experience with the subject, and other considerations that shed light on the opinion’s reliability. I
may apply the Daubert criteria, used in other courts to evaluate the admissibility of evidence, to
determine whether an opinion is sufficiently reliable to give it significant probative weight.

        Here, I have found that Drs. Levin’s and Goldstein’s pronouncements were not persuasive
or sufficiently reliable to fill other gaps in Petitioner’s case that could not be satisfied with other
forms of evidence. I made this determination after listening to them at trial, reviewing their reports,
and weighing the reliability of their statements against other evidence, from both the medical
record and the other scientific evidence. Based on this determination, and for the reasons stated
above, Petitioner has not carried her Althen prong I burden.

         B.       Althen Prong Two

         Although (and as stated above) the evidence preponderates in favor of the conclusion that
Mr. Martin more likely than not was experiencing a bacterial bronchopneumonia around February
26, 2015, and that it played a significant role in his untimely death, I do not purport to identify the
precise cause of his death, given the swirl of contributory factors at issue. For example, the records
could be read to support cardiac arrest as the immediate cause—although I cannot ultimately
conclude that such heart issues were the product of his illness, his preexisting uncontrolled
diabetes, or some inter-relationship between the two. However, whatever the cause, the evidence
in this case does not preponderantly establish that the flu vaccine he received three weeks before
played any role at all in his death.

        The medical record preponderantly establishes at a minimum that Mr. Martin had felt sick
in the days immediately before his death, as corroborated by contemporaneous statements made

43
   Were it otherwise, there would never be any need in the Program for special masters to consider an expert’s
credibility and persuasiveness. Once a petitioner obtained an expert opinion, the first prong would be automatically
satisfied. Although many petitioners essentially embrace this standard on appeal (when they argue that a special master
has not given proper weight to an expert opinion—mainly because the special master did not accept the opinion
offered), this cannot possibly be accurate.

                                                         40
by Petitioner to emergency treaters. Mrs. Martin’s description of Mr. Martin’s condition
immediately prior to his collapse also paints a picture of an individual who did not feel well, and
may also have been experiencing some respiratory difficulties. All of the above, when
supplemented with the pathologic findings and immediate ER testing, are consistent with an
individual suffering from an undiagnosed bacteria infection-induced pneumonia, whose existing
comorbidities inhibited greatly his ability to respond positively to such negative stimulants.

        But that same record does not persuasively establish any connection between Mr. Martin’s
health at the time of his death and how he may have been after receipt of the flu vaccine
approximately three weeks before. Thus, there is no evidence that Mr. Martin experienced any
kind of close-in-time (meaning within a day or two) malaise, fever, or other reaction to the
vaccination, as even Petitioner has admitted. Br. at 9. At most, she maintains that no sooner than
three days after vaccination, Mr. Martin began feeling unwell (albeit with many symptoms that
are not specific for pneumonia)—but these assertions are wholly uncorroborated by any other
evidence, and thus amount to bare allegations that do not preponderantly establish the fact for
which they have been offered. Section 13(a)(1(B) (Program claimants cannot succeed solely on
the basis of claims “unsubstantiated by medical records or by medical opinion”). And, as Dr.
Collins noted, some of these symptoms Petitioner alleged her husband experienced (such as nausea
or diarrhea) were generally nonspecific, or described GI-associated problems that are not
precursors of a bacterial lung infection.

        In addition, the record does not corroborate that Mr. Martin felt unwell (in a way
distinguishable from his usual circumstances) for most of the period thereafter. At no time in this
period before Mr. Martin had his telehealth caregiver visit44 on February 24th (meaning no more
than two and one-half weeks from the alleged onset to the latter date) does the record reveal any
attempt even to seek treatment of any kind. The record better supports the conclusion that he felt
unwell very close in time to the date of his death—but that is consistent with him experiencing an
acute bronchopneumonia, distinguishable from his alleged condition three to five days post-
vaccination. And although I credit somewhat Petitioner’s assertion that poor winter weather may
have prevented him from seeking treatment despite a desire to do so, this overall timeframe is too
long, and too otherwise unilluminating about any flu-like symptoms he may have been
experiencing, to conclude more likely than not that he felt sick for this entire period, beginning a
few days after vaccination.45


44
  In addition, and as Respondent pointed out, Mr. Martin did not inform this telehealth treater that he did not feel
well—although given the primary purpose of that visit (which obviously from the record was focused on Mr. Martin’s
diabetes), it is reasonable to infer that he would not necessarily have expected to discuss that aspect of his health at
that time.
45
   While Petitioner correctly noted that some of the records contemporaneous with Mr. Martin’s death employed the
temporally-vague term of “days” to measure how long Petitioner had told emergency treaters he felt unwell, and while
it is true that this indeterminate term could be read to mean a period longer than a few days, I do not find that the

                                                          41
        This record thus is inconsistent with the contentions of Petitioner’s experts that Mr. Martin
began to experience a non-infectious inflammatory process a few days post-vaccination, setting
the stage for his subsequent death three weeks later. Insufficient record evidence establishes that
he was experiencing any inflammatory processes in this time period, and Dr. Vargas persuasively
opined that the pathology evidence from after death did not reveal the presence of a prior chronic
process of lung inflammation. There is no evidence of a cytokine storm-like process that was
occurring over such a lengthy period, brought on by pro-inflammatory cytokines stimulated by
vaccination.46 On the basis of this record, the evidence best supports the conclusion that
Petitioner’s death was attributable to a combination of the bronchopneumonia and his preexisting
health conditions - the pathologic effect of vaccination was not even necessary to cause the same
tragic result.

         I additionally note some other findings relevant to the second “did cause” prong. First,
Petitioner has not preponderantly established that the flu vaccine was contraindicated for Mr.
Martin. Although one record from the time of his death so suggests, the record contemporaneous
with his receipt of the vaccine at issue explicitly establishes his consent to the vaccine, and his
affirmation suggests at least his own understanding that it was not contraindicated. Ex. 5 at 115
(denying contradictions on the day flu vaccine was received); Ex. 7 at 154 (listing contradictions
to the flu vaccine 21 days after its receipt). While Mr. Martin’s consent is not equivalent to a health
assessment of the safety of the vaccine for someone in comparable poor health, it undercuts
Petitioner’s contrary assertions to some degree. The record also establishes Petitioner’s
recollection that Mr. Martin’s physician recommended receipt of the flu vaccine precisely because
of his diabetes. Tr. at 10–11. This greatly undercuts Petitioner’s other contentions about the
dangers of immunocompromised individuals like Mr. Martin receiving vaccinations (which do not
otherwise find evidentiary support, as discussed above).

        Second (and related to the latter point), Petitioner has not corroborated her contentions
(relied upon by her experts) that Mr. Martin experienced an aberrant reaction to the earlier 2013
vaccination (a point Petitioner seemed to raise in the interests of underscoring the impact the



record overall supports that interpretation, given the lack of evidence corroborating Mrs. Martin’s contention that her
husband felt flu-like for most of the three-plus week temporal interval from 2–3 days post-vaccination to his death.
46
   Indeed, as Dr. Collins noted, the best evidence in this case that Mr. Martin might have experienced a debilitating,
uncontrolled inflammatory cytokine storm of the kind Dr. Levin proposed had occurred could only be derived from
the fact that (a) treaters proposed sepsis associated with the bacterial infection causing his bronchopneumonia as
potentially explaining his cardiac arrest, and (b) certain literature filed in the case, like Boomer, associates cytokine
storms with sepsis. Ex. 5 at 341; Ex. 7 at 11; Tr. at 320–21. Yet the record does not support a finding of sepsis anytime
before right around Mr. Martin’s death—not in the two or three weeks post-vaccination. The record thus does not
allow the conclusion that the sepsis speculated to be connected to Mr. Martin’s death was in any manner vaccine-
related (even assuming that a vaccine could produce a cytokine storm—a contention not established herein).


                                                          42
vaccine may have had on him, perhaps in a challenge-rechallenge sense).47 There is no record
evidence at all confirming this assertion. Although I found Petitioner to be sincere in her testimony
overall, these specific contentions were not corroborated by independent evidence. I thus do not
find that allegations of a purported earlier vaccine reaction made a second reaction more likely,
and Petitioner’s experts did not reasonably rely on this unproven assertion in formulating their
opinions. See, e.g., Dobrydnev, 566 F. App’x at 982–83 (holding that the special master was correct
in noting that “when an expert assumes facts that are not supported by a preponderance of the
evidence, a finder of fact may properly reject the expert's opinion”) (citing Brooke Group Ltd. v.
Brown & Williamson Tobacco Corp., 509 U.S. 209, 242 (1993)). And similar to the 2015
vaccination, the record of the 2013 flu vaccine administration also memorializes Mr. Martin’s
consent and agreement that he appropriately should receive it. Ex. 5 at 241 (denying contradictions
to flu vaccine in 2013).

         C.       Althen Prong Three

       Petitioner did not establish herein that the two timeframe “legs” in this case—from
vaccination to purported onset within three to five days thereafter, and then from onset to Mr.
Martin’s death—were medically acceptable for causation purposes.

        First, the most persuasive and reliable scientific or medical literature offered in this case
supports the conclusion that post-flu vaccine malaise (reflecting a reaction to vaccination and
perhaps the effects of the proinflammatory cytokines pointed to by Petitioner’s experts) would
begin in the somewhat shorter timeframe of no more than a day or two. Centers for Disease Control
and Prevention, Epidemiology and Prevention of Vaccine Preventable Diseases 200–01 Jennifer
Hamborsky et al. eds., (2015), filed on Feb. 27, 2019 as Ex. Y (ECF No. 26-3) (pages 25–26 of
Ex. Y). Yet Mr. Martin had no demonstrated reaction at all to the vaccine in that timeframe, as
Petitioner has admitted. I also do not find that it has been preponderantly established that he ever
experienced a similar reaction to a prior receipt of the flu vaccine, such that he would have been
expected to have an even more rapid reaction after his next vaccine exposure. As a result, the
evidence is thin to begin with that the flu vaccine had begun to cause a non-infectious inflammatory
process for Mr. Martin within a few days of its administration.

       Second, even if Mr. Martin had experienced a documented, flu-like reaction closer in time
to vaccination (or if the difference between a three and two-day onset is discounted for sake of
argument), Petitioner has not offered sufficient reliable evidence to support the conclusion that the

47
   Other special masters have described “rechallenge” as follows: “[c]hallenge-rechallenge happens when a person (1)
is exposed to one antigen, (2) reacts to that antigen in a particular way, (3) is given the same antigen again, and (4)
reacts to that antigen similarly. Typically, the second reaction is faster and more severe.” Nussman v. Sec'y of Health
& Human Servs., 83 Fed. Cl. 111, 119 (Fed. Cl. 2008) (internal citations omitted) (quoting Nussman v. Sec'y of Health
& Human Servs., No. 99-500V, 2008 WL 449656, at *9 (Fed. Cl. Spec. Mstr. Jan. 31, 2008)).


                                                         43
flu vaccine could initiate a non-infectious inflammatory process, fueled by cytokine upregulation,
that would persist over a 16 to 17 day-period sufficient to play a role in causing his death later.
The evidence Petitioner’s experts relied upon to establish this point did not support the contention
that a one-time vaccination can launch the chronic production of pro-inflammatory cytokines over
such a timeframe. At best, Petitioner references Mohanty, which concludes that the production of
two kinds of pro-inflammatory cytokines (Il-6 and TNF-α) are in fact impaired in older
individuals, while Il-10 (an anti-inflammatory cytokine) is dysregulated and increases for 7–28
days post vaccination in older individuals. Mohanty at 1179, 1183. This hardly establishes the
lingering and pathologic effects of post-vaccination pro-inflammatory cytokine upregulation. And
neither of Petitioner’s experts possessed the specific, demonstrated expertise in immunologic
matters to persuasively establish such arguments in any event.48

         The other facts of the case also greatly undercut Petitioner’s contentions about timeframe.
There is no record evidence that Mr. Martin was experiencing any kind of inflammatory process,
infectious in origin or not, in the two to three-week period before his death. The nonspecific
symptoms he is alleged to have displayed also are somewhat consistent with his existing
diabetes—a proposition that was not effectively rebutted by Petitioner. And the symptoms he
arguably felt in the days before death could easily be attributed to the post-mortem
bronchopneumonia diagnosis revealed in the pathology results. The overall three-week timeframe
from vaccination to death, with no intervening evidence of medical treatment, corroborative test
results, or other objective proof consistent with Petitioner’s theories, is too long to deem medically
acceptable, given the high likelihood of other contingencies, known and unknown, that could also
have played a role in Petitioner’s death.

III.     The Flu Vaccine was not a Substantial Factor in Mr. Martin’s Death

         Because of the aforementioned timeframe issues, this case unquestionably does not present
circumstances in which I could find (based on what is often deemed a “Shyface analysis”) that the
flu vaccine was a substantial factor in Mr. Martin’s illness and death, even if the predominating
factor cannot be identified. Shyface, 165 F.3d at 1352–53. In Shyface, the Federal Circuit found
that although a child’s death was associated with a fever that could equally be attributed to both a
vaccine or E. coli infection that the child was suffering from at the time of vaccination, the fact
that one could not be established over the other as most likely causal did not preclude a recovery
for the claimant. Id. at 1351, 1353. The special master in Halverson found such reasoning
persuasive in determining that the high dose flu vaccine was causal of an individual’s death despite
the decedent’s demonstrated comorbidities. Halverson, 2020 WL 992588, at *26.

48
   Cases like Halverson, by contrast, involve a compressed timeframe of less than a week from the date of vaccination
to death, and thus a period in which it would be far more credible and persuasive that the vaccine’s intended cytokine
stimulation could negatively interact with a person’s existing comorbidities sufficient to contribute to a pathologic
process resulting in death. Halverson, 2020 WL 992588, at *1 (vaccine received four days before death).


                                                         44
        Here, by contrast, the facts are wholly different. The Halverson decedent’s vaccination
occurred far closer in time to death, and there was robust evidence of an immediate reaction or
pre-death illness, thus allowing for the possibility that the vaccine played some contributory role.
But in this case, the period from even alleged onset (no sooner than February 8, 2015) to the
morning of February 26, 2015, is too attenuated, and without suggestion of any specific medical
problems other than Mr. Martin’s ongoing struggle to control his diabetes, plus some evidence that
he might have begun to experience pneumonia symptoms right before his death. And Petitioner’s
experts did not persuasively establish that the flu vaccine could create circumstances that would
interact with a person with Mr. Martin’s comorbidities over such a several-week period,
contributing to his death even if a bacterial infection was the likely immediate cause. It cannot be
concluded here that the flu vaccine likely played any role in Mr. Martin’s death.


                                                  CONCLUSION

        Petitioner has not carried her burden of proof, and therefore she is not entitled to an award
of compensation in this case. In the absence of a motion for review filed pursuant to RCFC
Appendix B, the clerk of the court SHALL ENTER JUDGMENT in accordance with the terms
of this decision.49


         IT IS SO ORDERED.
                                                                 s/ Brian H. Corcoran
                                                                 Brian H. Corcoran,
                                                                 Chief Special Master




49
  Pursuant to Vaccine Rule 11(a), the parties may expedite entry of judgment if (jointly or separately) they file notices
renouncing their right to seek review.

                                                          45
608                                          Q. Ye, B. Wang and J. Mao / Journal of Infection 80 (2020) 607–613


panion animals and are the causes of mild and severe respiratory                 leading to more severe disease manifestations.37 It seems that
diseases in humans.7 , 8 So far, seven HCoVs that can invade                     the excessive inﬂammatory response rather than the virus titer is
humans have been identiﬁed, including the α -type HCoV-229E                      more relevant to the death of the old nonhuman primates.37 Sim-
and HCoV-NL63; the β -type HCoV-HKU1, SARS-CoV, MERS-CoV,                        ilarly, in BALB/c mice infected with SARS-CoV, disease severity in
and HCoV-OC43; and 2019-nCoV, causing the present epidemic.                      old mice is related to the early and disproportionately strong up-
According to their pathogenicity, HCoVs are divided into mildly                  regulation of the ARDS-related inﬂammatory gene signals.38 The
pathogenic HCoVs (including HCoV-229E, HCoV-OC43, HCoV-NL63,                     rapid replication of SARS-CoV in BALB/c mice induces the de-
and HCoV-HKU) and highly pathogenic CoVs (including severe                       layed release of IFN-α /β , which is accompanied by the inﬂux of
acute respiratory syndrome CoV (SARS-CoV),9 Middle East respira-                 many pathogenic inﬂammatory mononuclear macrophages.15 The
tory syndrome coronavirus (MERS-CoV) 10 , 11 and SARS-CoV-2). The                accumulated mononuclear macrophages receive activating signals
mildly pathogenic HCoVs infect the upper respiratory tract and                   through the IFN-α /β receptors on their surface and produce more
cause seasonal, mild to moderate cold-like respiratory diseases                  monocyte chemoattractants (such as CCL2, CCL7, and CCL12), re-
in healthy individuals. In contrast, the highly pathogenic HCoVs                 sulting in the further accumulation of mononuclear macrophages.
(hereinafter referred to as pathogenic HCoVs or HCoVs) infect the                These mononuclear macrophages produce elevated levels of proin-
lower respiratory tract and cause severe pneumonia, sometimes                    ﬂammatory cytokines (TNF, IL-6, IL1-β , and inducible nitric oxide
leading to fatal acute lung injury (ALI) and ARDS. The pathogenic                synthase), thereby increasing the severity of the disease. Depleting
HCoVs have high morbidity and mortality and pose a major threat                  inﬂammatory monocyte-macrophages or neutralizing the inﬂam-
to public health.12–14                                                           matory cytokine TNF protected mice from the fatal SARS-CoV in-
                                                                                 fection. In addition, IFN-α /β or mononuclear macrophage-derived
Mechanism of cytokine storm by pathogenic HCoV infection                         proinﬂammatory cytokines induce the apoptosis of T cells, which
                                                                                 further hinders viral clearance.15 Another consequence of rapid vi-
    It has long been believed that cytokines play an important                   ral replication and vigorous proinﬂammatory cytokine/chemokine
role in immunopathology during viral infection. A rapid and                      response is the induction of apoptosis in lung epithelial and en-
well-coordinated innate immune response is the ﬁrst line of de-                  dothelial cells. IFN-αβ and IFN-γ induce inﬂammatory cell in-
fense against viral infection. However, dysregulated and exces-                  ﬁltration through mechanisms involving Fas–Fas ligand (FasL) or
sive immune responses may cause immune damage to the human                       TRAIL–death receptor 5 (DR5) and cause the apoptosis of airway
body.15–17 The relevant evidences from severely ill patients with                and alveolar epithelial cells.39–41 Apoptosis of endothelial cells and
HCoVs suggest that proinﬂammatory responses play a role in the                   epithelial cells damages the pulmonary microvascular and alveo-
pathogenesis of HCoVs. In vitro cell experiments show that delayed               lar epithelial cell barriers and causes vascular leakage and alveo-
release of cytokines and chemokines occurs in respiratory epithe-                lar edema, eventually leading to hypoxia in the body. Therefore,
lial cells, dendritic cells (DCs), and macrophages at the early stage            inﬂammatory mediators play a key role in the pathogenesis of
of SARS-CoV infection. Later, the cells secrete low levels of the an-            ARDS.
tiviral factors interferons (IFNs) and high levels of proinﬂamma-                    ARDS is the leading cause of death in patients infected
tory cytokines (interleukin (IL)-1β , IL-6, and tumor necrosis fac-              with SARS-CoV or MERS-CoV.42 , 43 It is now known that sev-
tor (TNF)) and chemokines (C-C motif chemokine ligand (CCL)-2,                   eral proinﬂammatory cytokines (IL-6, IL-8, IL-1β , granulocyte-
CCL-3, and CCL-5).18–20 Like SARS, MERS-CoV infects human air-                   macrophage colony-stimulating factor, and reactive oxygen species)
way epithelial cells, THP-1 cells (a monocyte cell line), human pe-              and chemokines (such as CCL2, CCL-5, IFNγ -induced protein
ripheral blood monocyte-derived macrophages and DCs, and in-                     10 (IP-10), and CCL3) all contribute to the occurrence of
duces delayed but elevated levels of proinﬂammatory cytokines                    ARDS.44–46 These results support such points of view that, fol-
and chemokines.21 , 22 After MERS-CoV infection, plasmacytoid den-               lowing SARS-CoV infection, high virus titers and dysregulation
dritic cells, but not mononuclear macrophages and DCs,23 are in-                 of cytokine/chemokine response cause an inﬂammatory cytokine
duced to produce a large amount of IFNs.                                         storm. The inﬂammatory cytokine storm is accompanied by im-
    Serum cytokine and chemokine levels are signiﬁcantly higher                  munopathological changes in the lungs.
in patients with severe MERS than patients with mild to moderate
MERS.24 , 25 The elevated serum cytokine and chemokine levels                    The relationship between cytokine levels and disease
in MERS patients are related to the high number of neutrophils                   progression in patients
and monocytes in the patients’ lung tissues and peripheral blood,
suggesting that these cells may play a role in lung pathology.24–26                  High levels of expression of IL-1B, IFN-γ , IP-10, and monocyte
Similar phenomena have been observed in patients with SARS-CoV                   chemoattractant protein 1 (MCP-1) have been detected in patients
infection.27–34 The production of IFN-I or IFN-α /β is the key                   with COVID-19. These inﬂammatory cytokines may activate the T-
natural immune defense response against viral infections, and                    helper type 1 (Th1) cell response.47 Th1 activation is a key event
IFN-I is the key molecule that plays an antiviral role in the early              in the activation of speciﬁc immunity.48 However, unlike SARS pa-
stages of viral infection.35 , 36 Delayed release of IFNs in the early           tients, patients with COVID-19 also have elevated levels of Th2 cell-
stages of SARS-CoV and MERS-CoV infection hinders the body’s                     secreted cytokines (such as IL-4 and IL-10), which inhibit the in-
antiviral response.36 Afterward, the rapidly increased cytokines                 ﬂammatory response. The serum levels of IL-2R and IL-6 in pa-
and chemokines attract many inﬂammatory cells, such as neu-                      tients with COVID-19 are positively correlated with the severity
trophils and monocytes, resulting in excessive inﬁltration of the                of the disease (i.e., critically ill patients > severely ill patients
inﬂammatory cells into lung tissue and thus lung injury. It appears              > ordinary patients).49 Other studies have found that, compared
from these studies that dysregulated and/or exaggerated cytokine                 with COVID-19 patients from general wards, patients in the inten-
and chemokine responses by SARS-CoV-infected or MERS-CoV-                        sive care unit (ICU) display increased serum levels of granulocyte
infected cells could play an important role in pathogenesis of SARS              colony-stimulating factor, IP-10, MCP-1, macrophage inﬂammatory
or MERS.                                                                         protein-1A, and TNF-α . The above studies suggest that the cytokine
    Animal models can well elucidate the role of cytokines and                   storm is positively correlated with disease severity.47
chemokines in mediating pulmonary immunopathology after HCoV                         A report on the severe new-type coronavirus-infected pneumo-
infection. Despite of similar virus titers in the respiratory tract,             nia showed that 37 patients (71.2%) required mechanical ventila-
SARS-CoV-infected old nonhuman primates are more likely to de-                   tion, and 35 patients (67.3%) suffered ARDS. Moreover, the mortal-
velop immune dysregulation than the infected young primates,                     ity of the elderly patients with ARDS was signiﬁcantly elevated.50
                                             Q. Ye, B. Wang and J. Mao / Journal of Infection 80 (2020) 607–613                                     609


The core pathological change in ARDS is the pulmonary and inter-                 SARS-CoV infection led to adverse consequences. Early treatment
stitial tissue damage caused by nonspeciﬁc inﬂammatory cell inﬁl-                of SARS patients with corticosteroids increased plasma viral load
tration.51 Local excessive release of cytokines is the decisive factor           in non-ICU patients, resulting in the aggravation of the disease.64
that induces this pathological change and clinical manifestation.52                  In treatment of patients with COVID-19, the use of glucocorti-
In COVID-19, the inﬂammatory cytokine storm is closely related to                coids has again become a major conundrum for clinicians.68 The
the development and progression of ARDS. The serum levels of cy-                 timing of administration and the dosage of glucocorticoids are
tokines are signiﬁcantly increased in patients with ARDS, and the                very important to the outcome of the severely ill patients. A too
degree of increase is positively correlated with mortality rate.53               early administration of glucocorticoids inhibits the initiation of the
The cytokine storm is also a key factor in determining the clin-                 body’s immune defense mechanism, thereby increasing the viral
ical course of extrapulmonary multiple-organ failure.54 This par-                load and ultimately leading to adverse consequences. Therefore,
tially explains the signs of extrapulmonary organ failure (such as               glucocorticoids are mainly used in critically ill patients suffering
elevated liver enzymes and creatinine) seen in some COVID-19 pa-                 inﬂammatory cytokine storm. Inhibition of excessive inﬂammation
tients without respiratory failure, suggesting that the inﬂammatory              through timely administration of glucocorticoids in the early stage
cytokine storm is the cause of damage to extrapulmonary tissues                  of inﬂammatory cytokine storm effectively prevents the occurrence
and organs.                                                                      of ARDS and protects the functions of the patients’ organs. For
    In summary, the new-type coronavirus infection causes an in-                 patients with progressive deterioration of oxygenation indicators,
ﬂammatory cytokine storm in patients. The cytokine storm leads                   rapid imaging progress, and excessive inﬂammatory response, the
to ARDS or extrapulmonary multiple-organ failure and is an im-                   use of glucocorticoid in the short term (3–5 days) is appropriate,
portant factor that causes COVID-19 exacerbation or even death.                  and the recommended dose is no more than equivalent to methyl-
                                                                                 prednisolone 1–2 mg/kg/day.69 It should be noted that large doses
Theoretical treatment strategy with inﬂammatory cytokine                         of glucocorticoid may delay the clearance of coronavirus due to
storm                                                                            immunosuppression.

    High virus titer and the subsequent strong inﬂammatory cy-                   Intravenous immunoglobulin (IVIG)
tokine and chemokine responses are related to the high morbid-
ity and mortality observed during the pathogenic HCoV infection.                     Chen et al. analyzed the treatment of 99 Wuhan patients with
The experience from treating SARS and MERS shows that reducing                   COVID-19 and found that 27% of these patients had received IVIG
viral load through interventions in the early stages of the disease              treatment.70 IVIG therapy has the dual effects of immune substi-
and controlling inﬂammatory responses through immunomodula-                      tution and immunomodulation. Its practical application value in
tors are effective measures to improve the prognosis of HCoV in-                 treatment of COVID-19 needs conﬁrmation in future studies.
fection.55–58
                                                                                 IL-1 family antagonists
IFN-λ
                                                                                     During the cytokine storm, the three most important cytokines
    IFN-λ primarily activates epithelial cells and reduces the                   in the IL-1 family are IL-1β , IL-18, and IL-33.4 Studies that focus on
mononuclear macrophage-mediated proinﬂammatory activity of                       the inhibition of IL-1β to reduce the cytokine storm have attracted
IFN-αβ .59 In addition, IFN-λ inhibits the recruitment of neu-                   most attention. Anakinra, an antagonist of IL-1β , can be used to
trophils to the sites of inﬂammation.60 SARS-CoV and MERS-CoV                    treat the cytokine storm caused by infection. It signiﬁcantly im-
mainly infect alveolar epithelial cells (AEC). IFN-λ activates the an-           proved the 28-day survival rate of patients with severe sepsis.71
tiviral genes in epithelial cells, thereby exerting antiviral effects            There is currently no clinical experience with applying speciﬁc IL-1
without overstimulating the human immune system. Therefore,                      family blockers to treat COVID-19. Their effects need to be veriﬁed
IFN-λ may be an ideal treatment. Some studies have applied pe-                   through in vivo animal experiments and clinical trials.
gylated and non-pegylated interferons for the treatment of HCoVs,
but the eﬃcacy varied signiﬁcantly due to the application of dif-                IL-6 antagonists
ferent treatment regimens. Early administration of interferons has
certain beneﬁts in reducing viral load and improves the clinical                     Tocilizumab is an IL-6 antagonist that suppresses the function
symptoms of patients to a certain extent. However, it fails to re-               of the immune system. Currently, tocilizumab is mainly applied in
duce mortality rates.61–63 With the exception of early administra-               autoimmune diseases such as rheumatoid arthritis.72 Tocilizumab
tion, the use of interferons at other time periods will not bring                itself has a therapeutic effect on the infection-induced cytokine
more beneﬁts than placebo treatment.63                                           storm.73 Serum IL-6 level is signiﬁcantly increased in severely ill
                                                                                 patients with COVID-19. Clinical studies from China have shown
Corticosteroid therapies                                                         that Tocilizumab is effective in treating severely ill patients with
                                                                                 extensive bilateral lung lesions, who have elevated IL-6 levels. The
    Corticosteroids are a class of steroid hormones that have anti-              ﬁrst dose was 4–8 mg/kg. The recommended dosage was 400mg
inﬂammatory functions. Corticosteroids are commonly used to sup-                 with 0.9% saline diluted to 100 ml. The infusion time was more
press inﬂammation. During the 2003 SARS epidemic, corticos-                      than 1 h. For patients with poor eﬃcacy of the ﬁrst dose, an ad-
teroids were the primary means of immunomodulation. Timely ad-                   ditional dose can be applied after 12 h (the dose is the same as
ministration of corticosteroids often leads to early improvements                before), with a maximum of two cumulative dose.
such as reducing fever, relieving radiation inﬁltration of the lung,
and improving oxygenation.64–66 A retrospective study of 401 pa-                 TNF blockers
tients with severe SARS revealed that proper administration of
glucocorticoids in patients with severe SARS signiﬁcantly reduced                   TNFs are key inﬂammatory factors that trigger a cytokine storm.
the mortality rate and shortened the hospital stay. Moreover, sec-               They are attractive targets for controlling the cytokine storm. A
ondary infections and other complications rarely occurred in these               meta-analysis showed that anti-TNF therapy has signiﬁcantly im-
glucocorticoid-treated patients.67 However, there are studies show-              proved survival in patients with sepsis.74 Anti-TNF therapy has
ing that administration of corticosteroid therapy during human                   also achieved satisfactory outcomes in treatment of noninfectious
610                                          Q. Ye, B. Wang and J. Mao / Journal of Infection 80 (2020) 607–613


diseases such as atherosclerosis.75 Studies in animal models have                production of OxPL, inﬂammatory cytokines, and chemokines in
shown that TNFs contribute signiﬁcantly to acute lung injury and                 IAV-infected mice, thereby reducing death.82 Pathogenic human
impair the T cell response in SARS-CoV-challenged mice. In mice,                 coronaviruses also cause a high accumulation of OxPL in patients’
neutralization of TNF activity or loss of TNF receptor provides                  lung tissues, resulting in ALI.81 Thus, it seems that eritoran and
protection against SARS-CoV-induced morbidity and mortality.15 , 76              other OxPL inhibitors may also be able to alleviate HCoV-induced
However, it should be noted that, at least in the later stages of in-            inﬂammatory responses.
fection, TNF has not been detected in the serum of patients with
SARS. At present, TNF blockers have not been suggested in the
treatment of patients with COVID-19, but the eﬃcacy of TNF block-                Sphingosine-1-phosphate receptor 1 agonist therapy
ers in treatment of patients with COVID-19 deserves further explo-
ration.                                                                              Sphingosine-1-phosphate (S1P) is a signal lysophospholipid that
                                                                                 promotes cytokine synthesis and secretion.83 The S1P receptor
IFN-αβ inhibitors                                                                signaling pathways signiﬁcantly inhibit the pathological damage
                                                                                 induced by the host’s innate and adaptive immune responses,
    IFN-αβ limits viral replication by inducing IFN-stimulated gene.             thereby reducing the cytokine storm caused by inﬂuenza virus
However, IFN-αβ also exacerbates diseases through enhancing the                  infection.84 , 85 In mouse models of IAV infection, sphingosine-1-
recruitment and function of mononuclear macrophages and other                    phosphate receptor 1 (S1P1 ) signal transduction in respiratory en-
innate immune cells. Although an early interferon response has a                 dothelial cells modulates pathogenic inﬂammatory responses.85
protective effect on mice infected with SARS-CoV, delayed IFN-αβ                 Agonists targeting S1P1 inhibit excessive recruitment of inﬂamma-
signaling causes an imbalance of the anti-SARS-CoV immune re-                    tory cells, inhibit proinﬂammatory cytokines and chemokines, and
sponses in humans. This phenomenon indicates that the timing of                  reduce the morbidity and mortality of IAV.85 , 86 SARS-CoV-2 also
IFN treatment is crucial to the outcome of diseases. Based on these              mainly infects human lung epithelial cells and endothelial cells.
results, IFN-αβ receptor blockers or antagonists should be admin-                Therefore, S1P1 agonists may be potential therapeutic drugs for
istered in the later stages of severe disease to prevent excessive               reducing cytokine and chemokine responses in those HCoV pa-
inﬂammatory responses.16                                                         tients whose cells generated excessive immune responses. An S1P-
                                                                                 receptor modulating drug, siponimod, was approved in 2019 to
Chloroquine                                                                      treat multiple sclerosis. However, clinical trials are needed to fur-
                                                                                 ther verify whether siponimod is an ideal alternative for the treat-
   Chloroquine inhibits the production and release of TNF and IL-6,              ment of cytokine storm.
which indicates that chloroquine may suppress the cytokine storm
in patients infected with COVID-19.77 Chloroquine phosphate has
been used in the treatment of adults aged 18 to 65 in China.78 The
recommended dosage by diagnosis and treatment of new coron-                      Stem cell therapy
avirus pneumonia (trial version 7) from china is as follows: If the
weight is more than 50 kg, 500 mg each time, 2 times a day,                          As an important member of the stem cell family, mesenchy-
7 days as a treatment course; If the weight is less than 50 kg,                  mal stem cells (MSC) not only have the potential of self-renewal
500 mg each time on the ﬁrst and second days, twice a day,                       and multidirectional differentiation, but also have strong anti-
500 mg each time on the third to seventh days, once a day.                       inﬂammatory and immune regulatory functions. MSC can inhibit
                                                                                 the abnormal activation of T lymphocytes and macrophages, and
Ulinastatin                                                                      induce their differentiation into regulatory T cell (Treg) subsets and
                                                                                 anti-inﬂammatory macrophages, respectively. It can also inhibit the
    Ulinastatin is a natural anti-inﬂammatory substance in the                   secretion of pro-inﬂammatory cytokines, such as, IL-1, TNF-α , IL-
body. It protects the vascular endothelium by inhibiting the pro-                6, IL-12, and IFN-γ , thereby reducing the occurrence of cytokine
duction and release of inﬂammatory mediators. Ulinastatin is                     storms.87 , 88 At the same time, MSC can secrete IL-10, hepatocyte
widely used in clinical practice to treat pancreatitis and acute cir-            growth factor, keratinocyte growth factor and VEGF to alleviate
culatory failure. Ulinastatin reduces the levels of proinﬂammatory               ARDS, regenerate and repair damaged lung tissues, and resist ﬁ-
factors such as TNF-α , IL-6, and IFN-γ , and increases the level of             brosis.89 Therefore, many functions of MSC are expected to make
anti-inﬂammatory factor IL-10.79 These activities of ulinastatin pro-            it an effective method for the treatment of COVID-19.
mote the balance between proinﬂammatory and anti-inﬂammatory
responses in humans, thus interrupting the cytokine storm induced
by the vicious cycle of inﬂammation. Animal studies show that                    Blood puriﬁcation treatments
the anti-inﬂammatory effect of high-dose ulinastatin is equivalent
to that of hormones.80 However, unlike glucocorticoids, ulinastatin                  In addition, the blood puriﬁcation treatments currently used in
does not inhibit immune functions and is unlikely to cause seque-                clinic practice can remove inﬂammatory factors to a certain extent.
lae such as femoral head necrosis. Therefore, ulinastatin has great              Blood puriﬁcation system including plasma exchange, adsorption,
application prospects in the treatment of COVID-19.                              perfusion, blood/plasma ﬁltration, etc., can remove inﬂammatory
                                                                                 factors, block the "cytokine storm", to reduce the damage of in-
The inhibitory effect of oxidized phospholipids (OxPL)                           ﬂammatory response to the body. This therapy can be used for
                                                                                 severe and critical patients in the early and middle stages of the
   In a mouse model of inﬂuenza A virus (IAV) infection,                         disease. The artiﬁcial liver technology led by Academician Li Lan-
OxPL increases the production of cytokines/chemokines in lung                    juan can eliminate inﬂammatory factors on a large scale. This tech-
macrophages through the Toll-like receptor 4 (TLR4)–TIR-domain-                  nology has also been used to resist the cytokine storm of H7N9,
containing adapter-inducing interferon-β signaling pathway,                      and its application on COVID-19 has also achieved certain eﬃ-
thereby promoting the occurrence of ALI.81 Eritoran is a TLR4                    cacy.90 Early renal replacement therapy, which is similar to the
antagonist. It does not have direct antiviral activity but has strong            treatment principle of artiﬁcial liver technology, seems to be an
immunomodulatory functions. Eritoran effectively lowers the                      effective method to control cytokine storm.91
                                                     Q. Ye, B. Wang and J. Mao / Journal of Infection 80 (2020) 607–613                                              611




Fig. 1. Mechanism of cytokine storm in COVID-19 and potential therapy.
1 Supplement with IFN-λ to activate the innate immunity; 
                                                          2 Using immunomodulator to restore immune balance;   3 Inhibiting the production of cytokines;  4 Scavenging
cytokines; 
           5 Inhibiting mononuclear macrophage recruitment and function; 
                                                                         6 Strengthening the vascular barrier by activating of the endothelial Slit-Robo4 signal pathway.




Inhibitors of mononuclear macrophage recruitment and                                     Conclusion
function
                                                                                             Inﬂammation is an essential part of an effective immune re-
    An autopsy report of patients with COVID-19 revealed a large                         sponse. It is diﬃcult to eliminate infections successfully without
amount of inﬂammatory cell inﬁltration in the lungs of the de-                           inﬂammation. The inﬂammatory response begins with an initial
ceased.92 One potentially effective treatment approach is to reduce                      recognition of pathogens. The pathogens then mediate the re-
the recruitment of mononuclear macrophages to the site of inﬂam-                         cruitment of immune cells, which eliminates the pathogens and
mation through small interfering RNA (siRNA)-mediated silencing                          ultimately leads to tissue repair and restoration of homeosta-
of C-C chemokine receptor type 2 (CCR2), which has been demon-                           sis. However, SARS-CoV-2 induces excessive and prolonged cy-
strated by animal experiments to improve the outcome of the dis-                         tokine/chemokine responses in some infected individuals, known
ease.93 , 94 Toll-like receptor 7 (TLR7) agonists stimulate mononu-                      as the cytokine storm. Cytokine storm causes ARDS or multiple-
clear macrophages to undergo a strong inﬂammatory response at                            organ dysfunction, which leads to physiological deterioration and
the time of infection with single-stranded RNA (ssRNA) viruses                           death. Timely control of the cytokine storm in its early stage
such as HCoV. Therefore, TLR7 antagonists may be able to alleviate                       through such means as immunomodulators and cytokine antago-
the storm of inﬂammatory factors caused by SARS-CoV-2 infection.                         nists, as well as the reduction of lung inﬂammatory cell inﬁltration,
                                                                                         is the key to improving the treatment success rate and reducing
                                                                                         the mortality rate of patients with COVID-19. Fig. 1
Strengthens the vascular barrier

   Increased vascular permeability is also a hallmark change that
occurs in the process of a cytokine storm. It was found in ani-
mal infection models of sepsis and H5N1 virus that activation of                         Declaration of Competing Interest
the endothelial Slit-Robo4 pathway with drugs improved vascular
permeability, thereby reducing the occurrence of a cytokine storm                           The authors declare that they have no competing ﬁnancial in-
during infection.95                                                                      terests.
612                                                      Q. Ye, B. Wang and J. Mao / Journal of Infection 80 (2020) 607–613


Contributors                                                                                 21. Tynell J, Westenius V, Rönkkö E, Munster VJ, Melén K, Österlund P, et al. Middle
                                                                                                 East respiratory syndrome coronavirus shows poor replication but signiﬁcant
                                                                                                 induction of antiviral responses in human monocyte-derived macrophages and
    QY led the writing of the manuscript. JHM developed the ini-                                 dendritic cells. J Gen Virol 2016;97(2):344–55 PubMed PMID: 26602089. Epub
tial concept and framework for the manuscript and oversaw the                                    2015/11/24. eng.
drafting of the manuscript. All authors contributed to the content,                          22. Zhou J, Chu H, Li C, Wong BH-Y, Cheng Z-S, Poon VK-M, et al. Active replication
                                                                                                 of Middle East respiratory syndrome coronavirus and aberrant induction of in-
drafting, and critical review of the manuscript.                                                 ﬂammatory cytokines and chemokines in human macrophages: implications for
                                                                                                 pathogenesis. J Infect Diseases 2014;209(9):1331–42 PubMed PMID: 24065148.
                                                                                                 Epub 2013/09/24. eng.
Funding
                                                                                             23. Scheuplein VA, Seifried J, Malczyk AH, Miller L, Höcker L, Vergara-Alert J,
                                                                                                 et al. High secretion of interferons by human plasmacytoid dendritic cells
   This study was supported by Zhejiang University special scien-                                upon recognition of Middle East respiratory syndrome coronavirus. J Virol
                                                                                                 2015;89(7):3859–69 PubMed PMID: 25609809. Epub 2015/01/21. eng.
tiﬁc research fund for COVID-19 prevention and control.
                                                                                             24. Kim ES, Choe PG, Park WB, Oh HS, Kim EJ, Nam EY, et al. Clinical progression
                                                                                                 and cytokine proﬁles of middle east respiratory syndrome coronavirus infection.
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