COVID-19 No "Worse" than The Flu?

It is very common these days for people with varying motivations to make the argument that that COVID-19 the current pandemic caused by the SARS-CoV-2 virus is no worse than seasonal influenza.  After presenting that premise, the conclusions are typically that there is really no reason to implement social distancing, stay at home orders, and all of the additional precautions currently in place to prevent the spread of the virus.

The important qualifier here is the need to include how deaths from both illnesses are estimated.  The CDC is very clear that it does not know the exact number of influenza deaths each year but it estimates them from statistical models. This is nothing new and they have been using this procedure for decades.  The reasons include the fact that influenza deaths are not reportable at a national level, although pediatric influenza deaths are.  It is also not possible to know if influenza is the proximate cause of death because the death may occur weeks later as a result of a secondary infection or an exacerbation of a chronic medical condition by the influenza infection.  In these cases, influenza may not be listed as a secondary infection.  Finally - not everyone who dies from an influenza-like illness (ILI) has influenza and not everyone who dies from ILI is tested for influenza. The influenza death estimates are not based on death certificates for that reason.  

There is considerable variability in mortality estimates based on the model being used.  A description of their current methodology and its limitations is available at this link.   There is a similar limitation of COVID-19 related deaths and the CDC has a specific reporting procedure suggested for that process.  CDC clinical criteria and lab testing is further specified to determine if COVID-19 is an underlying cause of death. COVID-19 can be reported as "probable" or "presumed" based on clinical judgment.  Three examples are given in the linked document in how to fill out the death certificate. The main difference is that COVID-19 mortality depends on deaths certificates and influenza mortality does not.  At least for now.

Looking at the CDC death rate estimates for influenza over time looks like this (click to enlarge any graphic):

But looking at the raw data based on death certificates looks like this:

Looking at the typical influenza season going from 2019 (week 43) to 2020 (week 15) shows that the raw death certificate data for pneumonia is 90,369 and for influenza it is 7,591.   


The argument typically is made looking at disease mortality and the raw number of deaths are not used. The CDC and other agencies report rates per 100,000 to correct for differences in population.  The current mortality rate for COVID-19 as of today is shown below - even though the lead graphic illustrates that deaths are continuing to increase at this point.:


COVID -19 Deaths  CDC Page

Total Deaths: 37,158

Death Rate/100,000: 11.3

First Case January 21,2020


Influenza Deaths

Total Deaths:  24,000 - 62,000  2020 estimate based on above data and methodology

Death Rate/100,000:  7.3 - 18.9

First Case October 2019


The second consideration is that the COVID-19 pandemic is clearly not over. Different geographic areas in the US are at different points in the curve that depicts new cases.  The key point on that curve is the inflection point where the new cases per day go from a linear increase to an exponential one.  A panel of 20 experts in infectious disease modeling was referenced as the source for a recent White House estimate of 240,000 deaths by the end of 2020 (8).  If you look at that reference there is a wide confidence interval.  That is four times the CDC estimate of 2020 influenza deaths.  For comparison there were 675,000 deaths in the USA in the 1918 pandemic.

How does this information assist with the analysis of rhetoric?

1.  COVID-19 is no worse than seasonal flu: 

First off, influenza is a severe infection and can't be trivialized. Everyone who is able to should get an influenza vaccination. Based on the available data - is certainly seems that COVID-19 is as bad and much worse in the worst case scenario.  It is at least on par with modern CDC influenza death rates estimates over the past 20 years and based on the current number of deaths is likely to exceed the 2020 estimate for influenza deaths.  The outliers for the White House estimate in the survey are much higher - in some cases exceeding the mortality from the 1918 pandemic.  These estimates are also based on current rates and if the country is "opened" and stay-at-home orders, wearing masks and social distancing guidelines are abandoned it is very likely that there will be secondary spikes and prolonged exposure to the virus. Does anyone really want to take the chance of this virus killing more people than the 1918 pandemic?  

2.  COVID-19 rates are inflated based on inaccurate reporting:

This meme was reinforced by a physician appearing on a conservative talk show who stated that he only reports what he considers to be the underlying cause of death on death certificates.  The example given was that if the patient died of pneumonia - the cause of death was pneumonia and would not speculate on what caused the pneumonia.  The implication being that death certificates are highly accurate and the suggested reporting guidelines for COVID-19 will result in over-reporting the condition.  The information clearly shows that this is not the case. The actual numbers of deaths due to influenza as reported on death certificates are a fraction of the number estimated by the CDC.  The CDC plainly states that they have no idea how many people actually die from influenza and for decades they have estimated the number based on hospitalizations, hospital mortality, and other surveillance numbers.  COVID-19 death counts are made on the basis of death certificates.  Even though death certificates are not perfect, it is likely that many more people who die from COVID-19 are tested than people who die from influenza. It will be interesting to see if the CDC develops statistical models for COVID-19 to see if the current deaths are an underestimate like influenza. 

That is my brief look at these two arguments that are being used to suggest that the current environmental approach to virus containment are unnecessary.  I am also reminded of an old statistical concept called face validity.  Briefly stated that would mean the null hypothesis of no difference in death rates makes sense.  Given that COVID-19 has risen to the highest daily cause of death in the US, that hospital and ICU beds in many locations are overwhelmed, that there is a catastrophe in New York City at this point, and it has led to the only mass shortage of personal protective equipment, ventilators, and medical gear that I can recall in my 3 decade career - I don't think that it does make sense.

And this is exactly not the time to trivialize this pandemic.


George Dawson, MD, DFAPA


References:

1: CDC:  Frequently Asked Questions about Estimated Flu Burden.  Link

2: CDC:  Estimating Influenza-Related Deaths.  Link

3: National Center for Health Statistics. Guidance for certifying deaths due to COVID–19. Hyattsville, MD. 2020. Link

4: Reed C, Chaves SS, Daily Kirley P, Emerson R, Aragon D, Hancock EB, et al. Estimating influenza disease burden from population-based surveillance data in the United States. PLoS One. 2015;10(3):e0118369

5: Rolfes, MA, Foppa, IM, Garg, S, et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respi Viruses. 2018; 12: 132– 137. https://doi.org/10.1111/irv.12486

6: Centers for Disease Control and Prevention. Estimated influenza illnesses and hospitalizations averted by influenza vaccination – United States, 2012-13 influenza season. MMWR Morb Mortal Wkly Rep. 2013 Dec 13;62(49):997-1000.

7: Reed C, Kim IK, Singleton JA, Chaves SS, Flannery B, Finelli L, et al. Estimated influenza illnesses and hospitalizations averted by vaccination–United States, 2013-14 influenza season. MMWR Morb Mortal Wkly Rep. 2014 Dec 12;63(49):1151-4.

8:  Thomas McAndrew Spring March 25, 2020 COVID19-Expert ForecastSurvey6-20200325.pdf 


Graphics credit:

Lead graphic is from Our World in Data licensed under Creative Commons BY-SA and may be freely used for any purpose. 

All others are from the CDC under public domain.

Why “Reading” and “Doing Your Own Research” are not nearly enough….

 

 

Medical training is an exercise in repeatedly meeting people who know a lot more about the field than you do and hoping to learn something in the process.  It happens regularly – often several times a day.  It is a common occurrence to meet people with encyclopedic knowledge – not just of textbooks and papers but disease patterns and presentations as well as the best treatment approaches.  The knowledge can be obtained through straight didactics, informal seminars, bedside interactions, and direct observation.  It can be affiliative or adversarial. In other words, you might get the attending physician who asks you a series of questions until you run your knowledge base dry or you might get the attending who realizes that your life is difficult and details the pathophysiology while pointing you to the latest review to read.

All that dynamic learning happens in a certain time frame where everyone must focus on the problems of the day.  The recent COVID-19 epidemic is a striking case in point. During the years of my training and practice the pandemic of interest was the human immunodeficiency virus (HIV-1, HIV-2). I started to see those patients in residency training – typically for the neuropsychiatric manifestations. At the time there were full isolation precautions and we had to wear surgical gowns, caps, and masks to see the patients. There was also the concern about needlestick injuries and injuries sustained by during surgery on HIV positive patients – that was subsequently shown to be a rare occurrence.  

All primary care and specialty physicians need to have a knowledge of HIV/AIDS – because of the potential protean manifestations, the need to maintain medications, and for infection control purposes.  It is also useful to recall epidemiological and infectious disease concepts – the most relevant being that for a while the infectious agent of the disease was not known.  Early in the course it was characterized by epidemiological features. When the virus was eventually isolated – steady progress was made in the development of antivirals to the point where the virus can be suppressed and is no longer detectable.

Over the course of learning about the illness and its treatment – I observed a heavy toll on treatment providers. There were no effective treatments early on.  I had lunch every day with an infectious disease team who ran one of the early HIV/AIDS clinics. Providing care in that setting took an emotional toll on them.

Against that 40 year backdrop – Aaron Rodgers recent press conference stands in tragic contrast.  For a time, Rodgers assumed the role of inscrutable new age guru.  He refused to state his COVID vaccine status but talked in detail about the rejuvenative properties of ayahuasca.  But I want to focus on his 208-word commentary on HIV, COVID, and Dr. Fauci. The full video is linked above for viewing.  I will address his commentary on a subject-by-subject basis.

1:  There was a “game plan” in the 1980s to create a pandemic with a “virus that’s going wild.”

Multiple lines of evidence show that HIV resulted from cross species transmission of Simian Immunodeficiency Virus (SIV) existing in African primate species. The transmission occurred through infected blood or bodily fluid exposure from hunting (1).  The key concept is that many human pandemics originate from cross species transmission.  Further – there is ample evidence that the cross over to humans occurred decades before the first AIDS fatality occurred in the US in the 1980s.  The only "game plan" in place was evolution in nature - over millions of years.

2:  Dr. Fauci was given $350 million dollars to research this:

Dr. Fauci was appointed head of the National Institute of Allergy and Infectious Diseases (NIAID) in 1982. NIAID is one of 27 institutes and centers of the National Institute of Health (NIH).  The funding for AIDS research is available on several sites. In this paper Tables 4.2 and 4.3 give the research dollars as well as the distribution by institute. In 1982 for example – there was $3.6M in AIDS funding.  Looking at the 1990-1991 allocation NIAID got 53.1% of the research allocation. The detailed allocation of that grant money consists of intramural and extramural research funding as well as funding clinical centers of research with adequate patient numbers to advance the field. From that paper:

“The need for more—and more appropriate—facilities specifically for AIDS work was acutely apparent in early 1988 when NIH director James Wyngaarden and NIH AIDS coordinator Anthony Fauci testified before several congressional committees (U.S. Congress, 1988a:259, 1988c:331). Their concerns were echoed in the June 1988 report of the Presidential Commission on the HIV Epidemic. The commission noted that plans for AIDS office and lab space were seriously delayed, and recommended that intramural construction and instrumentation needs be assessed and made a high priority in future budget requests…”

When Dr. Fauci assumed control of NIAID, the total budget of that agency was $350M.  He described it as a relatively secondary institution, that he built up to a $6.3B agency over the next 38 years (3). 

3:  The only drug they came up with was AZT:

 Azidothymidine (AZT) was developed in 1964 by the National Cancer Institute (NCI) as a potential anti-cancer therapy.  It was ineffective but was included in screening as an HIV treatment where it stopped viral replication without damaging normal cells.  It was the first FDA approved drug to treat AIDS in 1987. Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) was founded at that time along with other networks though NIAID to conduct clinical trials in therapeutics for AIDS. Subsequent trials established more safe and effective doses as well as demonstrating a delayed onset of AIDS in HIV infected persons with AZT making it the first effective HIV treatment.

NIAID funded research for combination therapy, triple drug therapy and novel agents to the point where there are now 30 anti-retroviral drugs and new classes of therapeutic agents.  During Dr. Fauci’s tenure at NIAID, research has gone from antiretroviral treatment (ART) based remission to clinical trials looking at strategies for potential ART-free remission of HIV or cure (4).  That goal has not been realized but there is no question that the research work on HIV has been productive resulting in reduced transmission and mortality.

 4:  An “environment” was created where only one drug worked

The environment was a research environment looking for treatments at a time where there were so many AIDS related deaths that it led to public outcry and activism. AZT was discovered as effective in a standard screening protocol, but additional clinical trials were necessary to establish doses, safety, and efficacy for FDA approval.

5:  Just like HIV – only remdesivir worked for COVID until there was a vaccine

Just like HIV – additional therapies became available for COVID (SARS-CoV-2) including nirmatrelvir-ritonavir (Paxlovid), simnotrelvir-ritonavir, and high titer convalescent plasma.  A recent review of the issue of vaccine versus pills for COVID concludes that it is a false dilemma and that they may have complementary roles (5). There is active research continuing in SARS-CoV-2 antivirals and no reason to expect that there will not be many additional medications.

6:  Dr. Fauci had a conflict of interest because of a “stake in the Moderna vaccine.”

Dr. Fauci has no stock in Pharma companies. The “stake” in vaccines are royalty payments that researchers are obligated to take, the majority occurring before the COVID pandemic. That standard and the average payments have been documented in the medical literature where Dr. Fauci is on record as having donated payments to charity (6).  Without having a detailed list of royalty payments, what they were for, and the outcomes it is difficult to make any additional comments except to say that there was no violation of NIH policy – in fact not accepting the payments was a violation. Royalties are based on discoveries and not getting products to market, FDA approval, or sales.  My further speculation is that the royalties are a small fraction of actual sales and company profits and the original NIH policy was probably designed to retain talented researchers who would otherwise be lost to private industry. Major universities and research institutes generally allow their faculty to accept consulting and royalty fees. I have worked in several settings where those arrangements were spelled out in the initial employment contract, including intellectual property ownership.

7:  Pfizer is also “criminally corrupt” based on a fine that was paid.

Large fines against pharmaceutical companies are the rule rather than the exception.  In looking at this list of the largest settlements most of the fines are based on regulatory laws having to do with off label promotion of drugs beyond what is indicated in the FDA package insert. Practically all of the penalties have to do with marketing rather than research or production. It has been well known for decades that Pharma companies aggressively market their products to physicians, hospitals, clinics, and now direct-to-consumer advertising to potential patients. You could look at a list like this and decide against using a company’s product – but it might mean not taking a potentially safe and effective drug.  The same type of enforcement actions are taken against companies in other fields such as information technology.

8:  People who can “do their own research” and “read” are commonly vilified for that if they question authority

There is a basic difference between authority and expertise. The only vilification that I have noticed is of experts. Dr. Fauci is an extreme example but during COVID it extended to many local public health officials. It was a direct product of the minimization of COVID by President Trump and many of his officials as well as the MAGA movement.  Further it has led to political violence that includes threats of physical harm to Dr. Fauci and many other public health officials.  These threats are unprecedented and have been attributed to right wing political rhetoric.

9:  Why should science be trusted if it can’t be questioned.

Science is continuously questioned and this is probably the most significant public misunderstanding.  Science is a process where results are continuously challenged and updated. The politization of the COVID pandemic illustrates what happens when people who are not trained in the scientific method get involved. Suddenly each scientific modification means that somebody was wrong or lying. Scientists are treated like politicians and the politicians feel free to say anything that is not grounded in science. 

That is not how science works. It takes actual observations over time to test hypotheses.  As one example – I have collected about 200 hypotheses on the pathophysiology of depression over the past 40 years and to date – there are not sufficient observations to prove or disprove them and get to the level of a theory of depression. An equivalent scenario is the endless speculation of the lab leak hypotheses versus the cross-species transmission hypothesis of COVID origins.  Although the probability lies in the direction of cross species transmission – there are insufficient direct observations to prove one versus the other and ample discussions of the lab leak hypothesis by people with a complete lack of expertise.

Finally, with the errors in Rodger’s statement – I would be remiss if I did not mention Brandolini’s Law. Simply stated:

“The amount of energy needed to refute bullshit is an order of magnitude bigger than to produce it.”

This is true – especially when the false argument does not have to be based on facts, process, or rigorous standards. The politization of COVID and many other health issues by the extreme right wing should be a lesson that is not forgotten.  This video clip is a case in point.

 

George Dawson, MD, DFAPA

Supplementary 1:  The NIH policy on royalty payments to inventors can be viewed at this link.  The abbreviation IC stands for the Institutes and Centers of the NIH.  More detailed information can be found at this link.  The NIH also has conflict of interest policy (see conflict of interest in Appendix 1).

 Supplementary 2:  A few relevant titles from my library - note dates. 

 

References:

1:  Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006841. doi: 10.1101/cshperspect.a006841. PMID: 22229120; PMCID: PMC3234451.

2:  Institute of Medicine (US) Committee to Study the AIDS Research Program of the National Institutes of Health. The AIDS Research Program of the National Institutes of Health. Washington (DC): National Academies Press (US); 1991. 4, Supporting the NIH AIDS Research Program. Available from: https://www.ncbi.nlm.nih.gov/books/NBK234085/

3:  Anthony Fauci: a scientific adviser's role from HIV to COVID-19. Bull World Health Organ. 2023 Jan 1;101(1):8-9. doi: 10.2471/BLT.23.030123. PMID: 36593776; PMCID: PMC9795384.

4:  Schou MD, Søgaard OS, Rasmussen TA. Clinical trials aimed at HIV cure or remission: new pathways and lessons learned. Expert Rev Anti Infect Ther. 2023 Jul-Dec;21(11):1227-1243. doi: 10.1080/14787210.2023.2273919. Epub 2023 Nov 8. PMID: 37856845.

5:  Papadakos SP, Mazonakis N, Papadakis M, Tsioutis C, Spernovasilis N. Pill versus vaccine for COVID-19: Is there a genuine dilemma? Ethics Med Public Health. 2022 Apr;21:100741. doi: 10.1016/j.jemep.2021.100741. Epub 2021 Nov 23. PMID: 34841029; PMCID: PMC8608621.

6:  Tanne JH. Royalty payments to staff researchers cause new NIH troubles. BMJ. 2005 Jan 22;330(7484):162. doi: 10.1136/bmj.330.7484.162-a. PMID: 15661767; PMCID: PMC545012.

7:  Mehellou Y, De Clercq E. Twenty-six years of anti-HIV drug discovery: where do we stand and where do we go? J Med Chem. 2010 Jan 28;53(2):521-38. doi: 10.1021/jm900492g. PMID: 19785437.

8:  Burke RV, Distler AS, McCall TC, Hunter E, Dhapodkar S, Chiari-Keith L, Alford AA. A qualitative analysis of public health officials' experience in California during COVID-19: priorities and recommendations. Front Public Health. 2023 Sep 13;11:1175661. doi: 10.3389/fpubh.2023.1175661. PMID: 37771831; PMCID: PMC10525347.

9:  Ward JA, Stone EM, Mui P, Resnick B. Pandemic-Related Workplace Violence and Its Impact on Public Health Officials, March 2020‒January 2021. Am J Public Health. 2022 May;112(5):736-746. doi: 10.2105/AJPH.2021.306649. Epub 2022 Mar 17. PMID: 35298237; PMCID: PMC9010912.

 10:  Royster J, Meyer JA, Cunningham MC, Hall K, Patel K, McCall TC, Alford AA. Local public health under threat: Harassment faced by local health department leaders during the COVID-19 pandemic. Public Health Pract (Oxf). 2024 Jan 24;7:100468. doi: 10.1016/j.puhip.2024.100468. PMID: 38328527; PMCID: PMC10847788.

 

Covid-19 Up Close and Personal

 On September 4, I started to feel typical symptoms of a flu-like illness. I have been a student of flu-like illnesses for at least the past 15 years. Some may say that I am obsessed with flu-like illnesses. By definition these illnesses start out as acute upper respiratory infections but also lead to systemic symptoms like malaise, weakness, and muscle pains or myalgias. In some cases, the symptoms can build to a disabling intensity. About five years ago I developed a flu-like illness after returning from Alaska that led to an exacerbation of asthma. I had not taken any asthma medications for 20 years but have been on those medications ever since. Researching that area suggested that flu-like illness was probably a rhinovirus. Some researchers think that rhinovirus is one of the main precipitants of asthma. Rhinovirus also happens to be a common circulating respiratory virus along with about 20 others that cause respiratory infections every year.  There are several non-COVID-19 coronaviruses in this group.

There were definite early signs even before the first respiratory symptoms. I have a fairly set exercise routine that I do every week and I noticed that my baseline heart rate (54 bpm) and blood pressure (105-110 mm Hg systolic) were increased and my exercise capacity was decreased by about 40%. That occurred about 48 hours before the onset of symptoms. As the symptoms increased my first thought was that I needed to get tested for coronavirus. That took an additional four days. It wasn’t from a lack of trying, but more a lack of resources going into the weekend. That delay highlights a significant weakness in the American healthcare system. I self-quarantined during that time but there are a lot of people who would need to see the test result before they could.  I did get positive test on day seven, I canceled the rest of the day at work and have been home recovering ever since.

The overall course of the illness has been very similar to a moderate case of influenza with the exception that I did not get a fever. It measured every day in the normal range. I also did not get shortness of breath.  Having the risk factors of asthma and old age, I was fairly anxious about any shortness of breath as a symptom. My symptoms are basically as graphed with a few exceptions of what I would refer to as atypical symptoms. The first one would be feeling flushed or like the skin temperature is elevated. That has been a fairly consistent feature that I have not seen mentioned anywhere. My skin was always cool to the touch and not moist. Another atypical symptom is laryngitis.  I have observed that in several COVID-19 patients in the media.  It can be fairly limiting if you have to talk all day at work like I do. The third atypical symptom was viscous mucus in the nose and throat. It was not abundant but difficult to clear and never reached the volumes typically seen in bronchitis.

One of the questions that I have been asked is: “How does a guy as careful as you end up catching COVID-19?”  It turns out that is an excellent question. As noted elsewhere on this blog I have essentially self-quarantined at home since the end of March or the start of the pandemic. I have had limited contact with people. I do not go into stores, supermarkets, coffee shops, or any public space. I pick up groceries ordered online and then collect them from a site where a masked attendant loads them into the back of my SUV.  All of my clinical work, continuing education, and professional meetings are done online.  I prepared a timeline of all contacts in or around my home for the previous 19 days (click to enlarge).  

From the summary, of the 18 total contacts I had direct contact with 6, only 4 of them about 6 days prior to the onset of symptoms.  All 4 of those contacts were wearing masks and none have tested positive for COVID-19.  My wife had contact with the other 12 and 9 of them were socially distanced or masked.  Only the electrician and three of the appliance repair/installers were not but they were socially distanced.  In addition, we made an effort to air out the house when they were there and after the left.  There was a total of 5 tradesmen in the house. They were all there for an average of about 1 hour.  I greeted one of them at a distance of about 12 feet and he was not wearing a mask. According to a recent hierarchy of transmission risk, I had no high-risk contacts for transmission (3).

My wife on the other hand was in a couple of higher risk scenarios (but not much higher).  As an extrovert, she was also out talking with people every day and exercising with several of her health club friends at their homes. She did however test negative for COVID-19 on the exact same test that I took. There are various estimates that 20-40% of COVID-19 infections result in asymptomatic carriers. It may be possible that she was a carrier and subsequently cleared the virus so that no viral RNA was detected on the nasal swab.  We are both currently trying to get antibody testing to COVID-19. It will confirm that I have short term immunity and possibly that my wife was an asymptomatic carrier.

When I did find out that I tested positive, I self-quarantined in the house pending my wife’s test and have been quarantined ever since.  The health plan recommendation is to wait for day 14 and if asymptomatic at that point, the self-quarantine can end. My wife is using the same date to end her quarantine and remained asymptomatic.  We have the luxury of having a large enough house where we can occupy separate areas and have separate bathrooms that are exhausted to the outside of the house.  I also kept an electronic air filter with a UVC germicidal light at the entrance to my office and between us in any public areas.  Several questions arise from this experience including:

1.  Why were my symptoms so mild (relatively speaking)?

Considering the actual statistics of the pandemic in the United States – my outcome is not that surprising.  About 1 in 34 cases have died and that number increases to 1 in 13 in my age range and 1 in 5 in the next highest age decile.  At the time of this posting there have been 197,000 deaths and 6.7 million cases.  There is a lot of comparison with influenza, but at this time there should be no mistake that while influenza typically generates more cases and more hospitalizations – there has only been one year where influenza mortality exceeded current SARS-CoV-2 mortality and that was the pandemic of 1918. 

The second consideration are the physical parameters of the environment. Assuming that my wife is not an asymptomatic carrier, the only time I was at a distance of less than 4 meters I was wearing a mask and so were the people I was in proximity to.  The contact lasted less than 10 minutes. And not a lot was said. We know that masks, distancing, and dilution in outdoor air probably works be reducing the concentration of airborne viral particles.  With that reduced concentration, any inhaled inoculum will be less resulting in a less severe infection. The estimated number of viral particles necessary to precipitate a case of COVID-19 is about 280 particles. That is 2-3 orders of magnitude higher than more virulent and lethal viruses like smallpox.

A few other lifestyle considerations. I eat a high-protein, high fiber, high whole grain, and low fat/low sugar diet.  I try to maintain a healthy weight.  I drink a lot of fluids every day.  I have been doing that for at least 30 years on the advice of a rheumatologist in order to maximize uric acid secretion and decrease the risk of gout attacks (I am an undersecretor of uric acid and had my first gout attack in medical school). Anyone reading this should drink a lot of fluid only based on their physician’s advice.  The only relevant factor in this paragraph in surviving the virus is probably maintaining a healthy weight and a good diet.  I was able to maintain my usual fluid intake during the course of this illness.

I take Vitamin D every day because my levels are typically marginal.  I take famotidine daily to prevent anaphylactic reactions. I only take it because the original H-2 antagonist recommended by my allergist (ranitidine) was taken off the market because of contamination in the manufacturing process. There has been some suggestion that famotidine is useful in the prevention or treatment of COVID-19 and for a while it nearly disappeared off the generic market.  I am not aware of any randomized clinical trial (RCT) results of famotidine and it has been demonstrated to not have any direct antiviral effect in vitro.  There is current speculation that in combination with H-1 antagonists that it may reduce histamine associated cytokine effects (13). At this point I would not consider it to be too relevant.

Exercise is a big part of my life and has been for the past 30 years. I typically exercise vigorously for 90 to 120 minutes per day.  Recent research (11,12) suggests that people who exercise vigorously into old age have better acute adaptive immunity (T-cell response) due to a better thymic environment.  One of the purported mechanisms is IL-7 production by skeletal muscle.  IL-15 is also an exercise responsive interleukin that enhances T-cell survival.  The net effect of these changes in the older person who exercises vigorously has a greater input of thymocyte progenitor cells and an enhanced output of CD4 and CD8 cells that are recent thymic emigrants (RTE). Both of these cells populations are critical for the acute adaptive response to novel viruses.  If I had to speculate about the lifestyle factors that are important it would probably be the effects of exercise, diet, not smoking and no alcohol intake on immunity and pulmonary function.

 2.  Why is there such heterogeneity in responses?

The host determinants of response are not well characterized at this point- other than the suggestion that previous exposure to common circulating coronaviruses could possibly lead to an enhanced antibody effect and either apparent asymptomatic carrier status or a less severe case as an adult.  Is it possible that the severe respiratory infection that I got in January was a coronavirus that was not SARS-CoV-2 and that it conferred some immunity?  This is one of the theories about why children are less affected by COVID-19 than adults – they tend to get more respiratory virus infections per year. Human coronaviruses and rhinoviruses are generally considered to cause up to 50% of common cold infections per year (10).  The Minnesota Influenza Incidence Surveillance Project, (MIISP) 3 of the 4 normally circulating human Coronaviruses – NL63, HKU1, and 229E (not OC43) since last September. Although these coronaviruses are now considered all part of the collection of common cold viruses they have been fairly recent discoveries with NL63 discovered in 2004 (7) and HKU1 discovered in 2005 (8).  The common coronaviruses have considerable RNA sequence homology with SARS-CoV-2 suggesting cross immunity can exist (9).  For example, pre-existing T-cell immunity in blood donors to SARS-CoV-2 is documented and is thought to be due to exposure to beta-coronaviruses that are in circulation (4).  But there is also evidence suggesting that pre-existing coronavirus immunity is not effective with SARS-CoV-2 (15).

One the genetic side, there are essentially no data at this point about genetic factors that favor successful recovery from the pandemic virus (click to enlarge).

 

3.  Given the exposures – is it possible that some other exposure (packaging, mail, aerosols from washing packing or mail) is more important than suggested by conventional wisdom?

Even though handwashing and washing of frequently touched surfaces is a top recommendation the current opinion is that transmission is unlikely from either groceries or mail based on studies that look at virus survival on different materials over time.  To me that is somewhat inconsistent with the hand washing advice.  The original theory was that a person could touch a contaminated surface, touch their face, and then end up with the infection through mucus membranes.  Groceries and the mail seem to be designated as infrequently touched surfaces relatively free from contamination.  An additional question for consideration is whether aerosols generated in washing the surfaces of groceries can transmit. SARS-CoV-2.  I use a UV sanitizer for mail and any objects the size of a large book or smaller. That method has limitations in terms of how accessible the surfaces of any contaminated object are.

One final critical consideration is the person you are in quarantine with. Do they share your goals and risk tolerance or not?  In my particular case, I am not risk tolerant at all if the risk is contracting a virus that has a 1 in 13 chance of killing me.  The prior probability of an adverse outcome is higher due to me having asthma, but the exact numbers are probably not known at this time. I would happily remain at home, not get a haircut (I have not), and just go out for groceries and necessary medical care.  My wife on the other hand is very social, and has maintained an active schedule with her friends and associates over the entire pandemic.  She spends her days exercising, socializing, and attending limited activities with friends.  She is distanced and wears a mask when necessary. Despite our ability to pick up groceries without having to enter a store she will spontaneously stop at these stores, put a mask on, and pick up a few items. This difference in approaches to the pandemic does create some tension.

Whether our different approaches produced predictable outcomes or not is up in the air at this point.  She was just approved for antibody testing and I still have to get approval at an appointment next week. All we know is that I was positive for SARS-CoV-2 on a PCR test and she was not. That leaves either airborne transmission, contaminated surfaces, or aerosols from washing contaminated services.

Getting through this does provide a sense of relief.  Even though immunity to this virus does not seem to be permanent at this point I am very grateful to have made it through these two weeks.  My boss sent me an email and asked what that sense of relief was like and I told him:

“It feels like I dodged a bullet.”

And it does…..

 

George Dawson, MD, DFAPA

 

References:

1:  Stephens DS, McElrath MJ. COVID-19 and the Path to Immunity. JAMA. Published online September 11, 2020. doi:10.1001/jama.2020.16656

2:  Gandhi M, Beyrer C, Goosby E. Masks Do More Than Protect Others During COVID-19: Reducing the Inoculum of SARS-CoV-2 to Protect the Wearer [published online ahead of print, 2020 Jul 31]. J Gen Intern Med. 2020;1-4. doi:10.1007/s11606-020-06067-8

3:  Jones Nicholas R, Qureshi Zeshan U, Temple Robert J, Larwood Jessica P J, Greenhalgh Trisha, Bourouiba Lydia et al. Two metres or one: what is the evidence for physical distancing in COVID-19? BMJ 2020; 370 :m3223 Link

4:  Stephens DS, McElrath MJ. COVID-19 and the Path to Immunity. JAMA. Published online September 11, 2020. doi:10.1001/jama.2020.16656 Link

5:  Fischer EP, Fischer MC, Grass D, Henrion I, Warren WS, Westman E. Low-cost measurement of face mask efficacy for filtering expelled droplets during speech. Sci Adv. 2020;6(36):eabd3083. Published 2020 Sep 2. doi:10.1126/sciadv.abd3083 Link

6:  Bar-On YM, Flamholz A, Phillips R, Milo R. SARS-CoV-2 (COVID-19) by the numbers. Elife. 2020 Apr 2;9:e57309. doi: 10.7554/eLife.57309. PMID: 32228860.

7:  Fouchier RA, Hartwig NG, Bestebroer TM, Niemeyer B, de Jong JC, Simon JH, Osterhaus AD. A previously undescribed coronavirus associated with respiratory disease in humans. Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6212-6. doi: 10.1073/pnas.0400762101. Epub 2004 Apr 8. PMID: 15073334; PMCID: PMC395948.

8:  Woo PC, Lau SK, Chu CM, Chan KH, Tsoi HW, Huang Y, Wong BH, Poon RW, Cai JJ, Luk WK, Poon LL, Wong SS, Guan Y, Peiris JS, Yuen KY. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J Virol. 2005 Jan;79(2):884-95. doi: 10.1128/JVI.79.2.884-895.2005. PMID: 15613317; PMCID: PMC538593.

9:  Yaqinuddin A. Cross-immunity between respiratory coronaviruses may limit COVID-19 fatalities. Med Hypotheses. 2020 Jun 30;144:110049. doi: 10.1016/j.mehy.2020.110049. Epub ahead of print. PMID: 32758887; PMCID: PMC7326438.

10:  Greenberg SB. Update on Human Rhinovirus and Coronavirus Infections. Semin Respir Crit Care Med. 2016 Aug;37(4):555-71. doi: 10.1055/s-0036-1584797. Epub 2016 Aug 3. PMID: 27486736; PMCID: PMC7171723.

11:  Duggal NA, Pollock RD, Lazarus NR, Harridge S, Lord JM. Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood. Aging Cell. 2018;17(2):e12750. doi:10.1111/acel.12750

12:  Lazarus NR, Lord JM, Harridge SDR. The relationships and interactions between age, exercise and physiological function. J Physiol. 2019;597(5):1299-1309. doi:10.1113/JP277071

13:  Hogan Ii RB, Hogan Iii RB, Cannon T, et al. Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients [published online ahead of print, 2020 Aug 29]. Pulm Pharmacol Ther. 2020;63:101942. doi:10.1016/j.pupt.2020.101942.

14:  Minnesota Influenza Incidence Surveillance Project,  (MIISP). Minnesota Department of Health.  Correspondence on circulating common coronaviruses in Minnesota.  Received on 9/19/2020. 

15:  Loos C, Atyeo C, Fischinger S, Burke J, Slein MD, Streeck H, Lauffenburger D, Ryan ET, Charles RC, Alter G. Evolution of Early SARS-CoV-2 and Cross-Coronavirus Immunity. mSphere. 2020 Sep 2;5(5):e00622-20. doi: 10.1128/mSphere.00622-20. PMID: 32878931; PMCID: PMC7471005. 

Supplementary 1:

My wife tested negative for SARS-CoV-2 IgG antibodies today (9/22/2020) in addition to the negative nasal swab PCR tests - making her an unlikely source of infection.

Supplementary 2:

COVID-19 follow-up: 

Saw my internist yesterday (9/25/2020). 

My course of the illness was "average" for all of the patients he has seen. He agreed that PCR false positives are not likely but false neg are. He declined Ab testing. I applied to the Red Cross convalescent plasma program.

       

The Many Excuses for Ignoring Science – Where Did SARS-CoV-2 Originate?

 

The COVID origins story started off with a bang last weekend.  Woody Harrelson gave the monologue on Saturday Night Live comparing pharmaceutical companies to drug cartels and COVID vaccinations to illicit drugs. He was conveniently able to ignore the fact that these vaccinations have saved an estimated 20 million lives and could have saved more if vaccination goals were met. By way of contrast there are about 30,000 drug related homicides in Mexico every year, several thousand per year in the US, and tens of thousands dead from overdosing on illicit drugs. A stark contrast to the way this monologue was presented. There was plenty of commentary on the monologue – mostly focused on Harrelson’s antivaxx stance in the past including a post that he had to remove at one point. Elon Musk enthusiastically supported the monologue – but didn’t say if it was for the comedic or scientific genius. Harvey Levin praised producer Lorne Michaels for not censoring Harrelson, but didn't comment on editing for comedic content. Nobody recited the simple facts listed above.

The monologue was followed Sunday by a more detailed story without much more scientific credibility in the Wall Street Journal (1).  The authors of that story discuss a 5-page report by the Department of Energy stating the opinion that a lab leak was the likely cause of the pandemic but that theory was given a ‘low confidence’ rating.  They describe the DOE as having many relevant scientists.  Other than controversial headings and fueling partisan debate – what good is a low confidence theory?  The FBI has the same theory with “moderate confidence.” They explain that the US has an 18 agency intelligence community implying that there is adequate expertise there for these low to moderate confidence lab-leak theories. Is this the same intelligence community that was confident that there were weapons of mass destruction in Iraq and who seemed vaguely aware of Chinese balloons invading US air space?  They might have better things to do than speculate about pandemic virus origins and rate those speculations.  Protecting US infrastructure against cyberattacks and criminal activity would seem to be at the top of that list.

I would like to see that 5 page report at this point – to see if there is any reference to a recent consensus statement from the virology community on the origins of SARS-CoV-2 (2).  The full text of that report is available online.  If you read that report a few points jump out at you.  First – these are the professionals with the most expertise in viral genetics and evolution. It is their full-time job and they do active research in the area.  Second – beyond claiming expertise virologists have been very successful at reducing the disease burden through their efforts.  They get results. Third – while emphasizing neutrality they point out that the zoonosis hypothesis (wild origin) has the most supporting data and that there is “no compelling data” to support either a lab leak or intentional contamination hypothesis. Fourth they point out that “gain-of-function” is an inexact term but within the field it also means modification for therapeutic purposes.  The term has been used by some politicians to suggest “nefarious” activity. Fifth – they review the extensive oversight of their research.  They conclude that millions of people are alive today because of their research and that there is adequate oversight. All of that clearly stated before the start of Congressional hearings on these issues.

 There is pre-existing research on viral origins from other groups and wild origin is the most likely scenario (3, 11, 12).

In an interesting twist of events the celebrity gossip show TMZ (10:34 to 18 minute mark) ran with the story.  They started out with the Harrelson monologue followed by Harvey Levin’s characterization that the lab leak theory “blossomed” with the Wall Street journal article.  To their credit they brought on Michael Worobey an evolutionary virologist with a previous description of the wild origins of SARS-CoV-2 in Science (4).  Dr. Worobey pointed out that he wrote a letter in 2021 that the ‘lab leak’ hypothesis had to be taken seriously, but since then then there has been “really strong scientific evidence” of a wild origin of the virus and no real scientific evidence of a lab leak.  Just from a probability standpoint he pointed out that all of the cases were in the area of the Wuhan market, there were animals present that carried coronaviruses, and there is really no other explanation for that degree of localization in a city of 12 million people. He also pointed out the severe social media backlash that he received as a result of following the evidence but encouraged a systematic approach to the research.  He suggested taking the DOE report with a “grain of salt”.

A final comment on the DOE report was made on the public radio show All Things Considered.  Michael Osterholm from CIDRAP was interviewed (5).  He describes himself as being agnostic towards the lab leak versus zoonoses but clearly sees the preponderance of data supporting the wild origin.  He goes on to suggest that people want certainty when a high degree of certainty is not possible and that has led to definitive headlines (about lab leak for example) when hard evidence is lacking. He adds the following characterization and challenges the DOE to present their data:

“…. again, there is a very different type of theater being played out here. It's not one that's based on science.”

He also describes a very plausible scenario of a new virus occurring in the Caribbean and how that could be spun into a ‘lab leak’ from the CDC in Atlanta.

Expect a lot of political demagoguery on the issue with Congressional hearings in the months to follow. Unless there is any data as good as the references I have posted - keep an open mind.  In a postmodern world – people with no or vague expertise make unfounded claims about scientific evidence.  The strongest evidence by far is with the experts and scientists listed in this essay. And that is a wild origin of the virus – just like previous coronaviruses. Anyone suggesting otherwise needs to show up with some data and not excuse making or political theater.

 

George Dawson, MD, DFAPA

 

References:

1:  Gordon MR, Strobel WP. DOE Says Lab Leak Is Likely Origin of Covid-19 ---New intelligence about China outbreak spurs assessment; finding is given 'low confidence'.  Wall Street Journal.  Wall Street Journal.  February 27, 2023.

2:  Goodrum F, Lowen AC, Lakdawala S, Alwine J, Casadevall A, Imperiale MJ, Atwood W, Avgousti D, Baines J, Banfield B, Banks L, Bhaduri-McIntosh S, Bhattacharya D, Blanco-Melo D, Bloom D, Boon A, Boulant S, Brandt C, Broadbent A, Brooke C, Cameron C, Campos S, Caposio P, Chan G, Cliffe A, Coffin J, Collins K, Damania B, Daugherty M, Debbink K, DeCaprio J, Dermody T, Dikeakos J, DiMaio D, Dinglasan R, Duprex WP, Dutch R, Elde N, Emerman M, Enquist L, Fane B, Fernandez-Sesma A, Flenniken M, Frappier L, Frieman M, Frueh K, Gack M, Gaglia M, Gallagher T, Galloway D, García-Sastre A, Geballe A, Glaunsinger B, Goff S, Greninger A, Hancock M, Harris E, Heaton N, Heise M, Heldwein E, Hogue B, Horner S, Hutchinson E, Hyser J, Jackson W, Kalejta R, Kamil J, Karst S, Kirchhoff F, Knipe D, Kowalik T, Lagunoff M, Laimins L, Langlois R, Lauring A, Lee B, Leib D, Liu SL, Longnecker R, Lopez C, Luftig M, Lund J, Manicassamy B, McFadden G, McIntosh M, Mehle A, Miller WA, Mohr I, Moody C, Moorman N, Moscona A, Mounce B, Munger J, Münger K, Murphy E, Naghavi M, Nelson J, Neufeldt C, Nikolich J, O'Connor C, Ono A, Orenstein W, Ornelles D, Ou JH, Parker J, Parrish C, Pekosz A, Pellett P, Pfeiffer J, Plemper R, Polyak S, Purdy J, Pyeon D, Quinones-Mateu M, Renne R, Rice C, Schoggins J, Roller R, Russell C, Sandri-Goldin R, Sapp M, Schang L, Schmid S, Schultz-Cherry S, Semler B, Shenk T, Silvestri G, Simon V, Smith G, Smith J, Spindler K, Stanifer M, Subbarao K, Sundquist W, Suthar M, Sutton T, Tai A, Tarakanova V, tenOever B, Tibbetts S, Tompkins S, Toth Z, van Doorslaer K, Vignuzzi M, Wallace N, Walsh D, Weekes M, Weinberg J, Weitzman M, Weller S, Whelan S, White E, Williams B, Wobus C, Wong S, Yurochko A. Virology under the Microscope-a Call for Rational Discourse. mSphere. 2023 Jan 26:e0003423. doi: 10.1128/msphere.00034-23. Epub ahead of print. PMID: 36700653.

3:  Garry RF. The evidence remains clear: SARS-CoV-2 emerged via the wildlife trade. Proc Natl Acad Sci U S A. 2022 Nov 22;119(47):e2214427119. doi: 10.1073/pnas.2214427119. Epub 2022 Nov 10. PMID: 36355862; PMCID: PMC9704731.

4:  Worobey M. Dissecting the early COVID-19 cases in Wuhan. Science. 2021 Dec 3;374(6572):1202-1204. doi: 10.1126/science.abm4454. Epub 2021 Nov 18. PMID: 34793199. (see also the map of SARS-CoV-2 origins)

5:  Contreras G, Brown A, Shapiro A, How an infectious disease expert interprets conflicting reports on COVID-19's origins.  All Things Considered.  February 27, 2023.

https://www.npr.org/2023/02/27/1159821909/how-an-infectious-disease-expert-assessed-how-covid-19-started

6:  Worobey M, Levy JI, Malpica Serrano L, Crits-Christoph A, Pekar JE, Goldstein SA, Rasmussen AL, Kraemer MUG, Newman C, Koopmans MPG, Suchard MA, Wertheim JO, Lemey P, Robertson DL, Garry RF, Holmes EC, Rambaut A, Andersen KG. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science. 2022 Aug 26;377(6609):951-959. doi: 10.1126/science.abp8715. Epub 2022 Jul 26. PMID: 35881010; PMCID: PMC9348750.

7:  Pekar JE, Magee A, Parker E, Moshiri N, Izhikevich K, Havens JL, Gangavarapu K, Malpica Serrano LM, Crits-Christoph A, Matteson NL, Zeller M, Levy JI, Wang JC, Hughes S, Lee J, Park H, Park MS, Ching Zi Yan K, Lin RTP, Mat Isa MN, Noor YM, Vasylyeva TI, Garry RF, Holmes EC, Rambaut A, Suchard MA, Andersen KG, Worobey M, Wertheim JO. The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. Science. 2022 Aug 26;377(6609):960-966. doi: 10.1126/science.abp8337. Epub 2022 Jul 26. PMID: 35881005; PMCID: PMC9348752.

8:  Bloom JD, Chan YA, Baric RS, Bjorkman PJ, Cobey S, Deverman BE, Fisman DN, Gupta R, Iwasaki A, Lipsitch M, Medzhitov R, Neher RA, Nielsen R, Patterson N, Stearns T, van Nimwegen E, Worobey M, Relman DA. Investigate the origins of COVID-19. Science. 2021 May 14;372(6543):694. doi: 10.1126/science.abj0016. PMID: 33986172; PMCID: PMC9520851.

This is an important reference form May of 2021 signed by Dr. Worobey suggesting that a more thorough investigation of the origins of the SARS-CoV-2 virus needs to be done.  Per the above assay and several references - he has concluded that the virus originated in the wild rather than lab leak since this letter. I think this letter also addresses the censorship comments.  Clearly the suggestion by this group that the lab leak had to be reinvestigated illustrates there was no censorship on the science side. 

9:  Chait J.  The Surprisingly Contrarian Case Against Lying About Science.  The Intelligencer.  February 28, 2023  https://nymag.com/intelligencer/2023/02/lab-leak-hypothesis-lying-about-science-is-bad-for-liberals.html 

10: Garry RF. SARS-CoV-2 furin cleavage site was not engineered. Proc Natl Acad Sci U S A. 2022 Oct 4;119(40):e2211107119. doi: 10.1073/pnas.2211107119. Epub 2022 Sep 29. PMID: 36173950; PMCID: PMC9546612. 

11:  Pekar JE, Magee A, Parker E, Moshiri N, Izhikevich K, Havens JL, Gangavarapu K, Malpica Serrano LM, Crits-Christoph A, Matteson NL, Zeller M, Levy JI, Wang JC, Hughes S, Lee J, Park H, Park MS, Ching Zi Yan K, Lin RTP, Mat Isa MN, Noor YM, Vasylyeva TI, Garry RF, Holmes EC, Rambaut A, Suchard MA, Andersen KG, Worobey M, Wertheim JO. The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. Science. 2022 Aug 26;377(6609):960-966. doi: 10.1126/science.abp8337. Epub 2022 Jul 26. PMID: 35881005; PMCID: PMC9348752.

12:  Worobey M, Levy JI, Malpica Serrano L, Crits-Christoph A, Pekar JE, Goldstein SA, Rasmussen AL, Kraemer MUG, Newman C, Koopmans MPG, Suchard MA, Wertheim JO, Lemey P, Robertson DL, Garry RF, Holmes EC, Rambaut A, Andersen KG. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science. 2022 Aug 26;377(6609):951-959. doi: 10.1126/science.abp8715. Epub 2022 Jul 26. PMID: 35881010; PMCID: PMC9348750.

13:  Wu Y, Zhao S. Furin cleavage sites naturally occur in coronaviruses. Stem Cell Res. 2020 Dec 9;50:102115. doi: 10.1016/j.scr.2020.102115. Epub ahead of print. PMID: 33340798; PMCID: PMC7836551.

14:  Xiao, X., Newman, C., Buesching, C.D. et al. Animal sales from Wuhan wet markets immediately prior to the COVID-19 pandemic. Sci Rep 11, 11898 (2021). https://doi.org/10.1038/s41598-021-91470-2

15:  Lenharo M, Wolf L. US COVID origins hearing renews debate over lab-leak hypothesis. Nature. 2023 Mar 9. doi: 10.1038/d41586-023-00701-1. Epub ahead of print. PMID: 36890328.

"Michael Worobey, an evolutionary biologist at the University of Arizona, Tucson, who has studied genetic evidence from the early days of the pandemic, told Nature that he found the proceedings “shockingly unscientific” and that they do not bode well for the overall investigation. “Not one of those witnesses had any scientific record of investigating and publishing peer-reviewed research on the origins of this virus in quality journals,” he said."

16:  Cohen J.  Science takes a backset to politics in first House hearing on origin of COVID-19 pandemic.  Science.  March 8, 2023.  doi: 10.1126/science.adh5155

Very useful essay that points out little science is occurring and the intelligence is very sketchy.

17:  Rutledge PE. Trump, COVID-19, and the War on Expertise. The American Review of Public Administration. 2020 Aug;50(6-7):505-11.

This is a good reference to keep in mind because it points out that President Trump and his administration actively promoted the lab leak theory of the pandemic dating back as far as May 2020.  All of the pundits decrying censorship of the lab leak hypothesis should ask themselves how censorship is possible when the theory is being actively promoted by the Executive Branch. 

18:  Maxmen A. Wuhan market was epicentre of pandemic's start, studies suggest. Nature. 2022 Mar;603(7899):15-16. doi: 10.1038/d41586-022-00584-8. PMID: 35228730.

This study links to three preprints describing the origin of the virus in the wild with spillover to humans.  As far as I can tell these preprints became the 2 papers listed below as well as reference 12 above:

19:  Pekar JE, Magee A, Parker E, Moshiri N, Izhikevich K, Havens JL, Gangavarapu K, Malpica Serrano LM, Crits-Christoph A, Matteson NL, Zeller M, Levy JI, Wang JC, Hughes S, Lee J, Park H, Park MS, Ching Zi Yan K, Lin RTP, Mat Isa MN, Noor YM, Vasylyeva TI, Garry RF, Holmes EC, Rambaut A, Suchard MA, Andersen KG, Worobey M, Wertheim JO. The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. Science. 2022 Aug 26;377(6609):960-966. doi: 10.1126/science.abp8337. Epub 2022 Jul 26. PMID: 35881005; PMCID: PMC9348752.

20:  Mueller B.  W.H.O. Accuses China of Withholding Data on Pandemic’s Origins.  New York Times March 17, 2023.

21:  Cohen J. Anywhere but here. Science. 2022 Aug 19;377(6608):805-809. doi: 10.1126/science.ade4235. Epub 2022 Aug 18. PMID: 35981032.

22:  Cohen J.  Chinese researchers release genomic data that could help clarify origin of COVID-19 pandemic.  Science 2023 March 29; doi:10.1126/science.adi0330.

Supplementary 1:

The director of the FBI came out in the media today (02/28/2023) and reiterated that the FBI has concluded the virus most likely originated as a lab leak but provided no additional data. As far as I know at this point the FBI and DOE data has not been released to the public.

Supplementary 2:

How is science ignored?  I realize after reading the post it contains historical information but nothing explicit about how science is ignored.  Here is the short list:

1:  Science is a process of serial approximations to reality or more to the point - an empirically acceptable model of reality.  Politics, journalism, and entertainment clearly are not. As a result the scientifically informed realize this is often series of hypothetical steps and missteps until a widely agreed upon model is accepted in the scientific community.  That contrasts sharply with a long series of provocative headlines and opinion pieces.  

2:  Science deals with probability statements - politics, journalism, and entertainment exists largely on the plane of dichotomous thinking.

3:  The probabilities on the probability statements can be adjusted in either direction.  As is the case in the Dr. Worobey references above - his probability of a "lab leak or nefarious activity" hypothesis was adjusted drastically downward over time as the probability of a wild origin was adjusted upward to the point where it became most likely.  This adjustment of probabilities is often seen as a "mistake" or "lie" by the nonscientific community. Within the scientific community it can be difficult to change your mind.  Neither of those considerations invalidates the process. 

4:  There are still scientific standards that acknowledge expertise and peer review. Although peer review is criticized by authors it has resulted in conventions that probably limit grand pronouncements like a newspaper headline.  The evidence should be in the 'limitations' section of any scientific paper.  In the postmodern world expertise is seen as relative by those in many nonscientific endeavors - to the point that anyone who can Google is considered an expert. This is also the predominate social media method of operation. 

5:  The legal/political model of ascertaining the truth or reality is highly flawed - and the evidence is obvious in studies of racial profiling, unjustified violent encounters with law enforcement, wrongful convictions, unequal treatment based on economic considerations, fallible eyewitness testimony, and highly flawed interrogations. Focusing only on coronavirus - the interrogations of Dr. Fauci by Sen. Paul is an additional example. And yet - this is the process that is going to be used by the government to decide on the origins of the virus.  Unless the DOE or the FBI have concrete scientific proof - it will be an exercise in rhetoric.

6:  If not science what? Typical analyses presented in the media can occur at several levels that cut science out of the mix. Anytime you hear an analysis by a group of journalists, politicians, regulators, administrators or consultants who lack the requisite expertise to analyze the problem take a close look at that final product. Ask yourself if there is anyone with scientific expertise who should have looked at it.  Be very skeptical of analyses that are not disclosed because they are proprietary or classified.

Supplementary 3 (Updates):

Update 03/02/2023:  As expected the COVID origins appearance of controversy was still whipping up the media today.  TMZ continued with their fractured analysis – continuing to focus on the FBI and DOE reports as a game changer and not mentioning at all what the evolutionary virologist Michael Worobey told them yesterday.  They played a brief John Stewart tape and suggest that he was now “vindicated” for suggesting early in the pandemic that this was probably a lab leak. Harvey Levin pointed out that Stewart was not crowing about being correct in the brief clip that they played and how could he? How can a guy who knows nothing about epidemiology or pandemic viruses and has no information about what transpired in Wuhan suggest there was a lab leak?  The excerpt that I saw had Stewart talking about the need to have both sides represented.  TMZ did touch on the most important aspect of this debate and that was rhetoric and how President Trump’s racist polarizing rhetoric led to conflation of the viral origin hypothesis with racism and that created significant backlash from the left. But we are still dealing with a non-scientific argument and ignoring Dr. Worobey. Harvey Levin seems stuck on these events as primarily a free speech issue.  To me that is obviously not a problem given the degree of bullshit and demagoguery that occurred around this issue.  There was probably no more “free speech” exercised at any other time in the history of the country. Watching TMZ the last two days just illustrates that they can avoid science as rigorously as anyone else – even after talking to a top scientist in the field. As some level the free speech argument just becomes a rationalization.

New York Times political columnist Jonathan Chait wrote a piece in the Intelligencer entitled “The Surprisingly Contrarian Case Against Lying About Science”.  He claims the DOE analysis has weight because there is a division there that is supposed to assess bioweapons threats. To me that just deepens the nonscience of it all. From a rhetorical standpoint we have gone from an appeal to emotion to an appeal to authority.  He goes on to analyze the rhetoric starting with the need to shift blame away from the Trump administration and their “mishandling of the epidemic.”  He is the first journalist I have seen who writes about how China unleashing the virus on their own people (one suggestion) is absurd.  I would add even considering the coronavirus as a bioweapon is equally absurd. In his analysis of Peter Hotez Tweets he gets it wrong.  Dr. Hotez characterizes the antiscience aggression of certain elements of the media and Congress as: “The best defense is a good offense”.  Chait’s response is:

 “I’m neither a professor, a doctor, nor a Ph.D., but I know enough to state confidently that the ethos of the scientific method is not “the best defense is a good offense.”

What about the ethos of journalism and politics? I am confident that is what Hotez is referring to.  He ultimately makes the argument that the left is not skilled enough to parse the anti-science rhetoric of the right and as a result lump legitimate scientific discussion with anti-science crankery and this is not a good thing. He concludes that ideology cannot be used to settle scientific debate. Some good points and some bad points. I will add it is pretty obvious to anyone who knows a thing about science that real scientific debates cannot be settled in the media and every scientist I know has had bad experiences with the media because they are trying to tell the story they want to tell.  My classic example was television interviews that I was asked to give around the Christmas holiday when I was a young psychiatrist. I knew the reporter was trying to sell the story that there were more suicides at Christmas and no matter what I said there would be that suggestion. I finally just told them – no more interviews. After all – in this case what is the more provocative headline ‘COVID is a bioweapon leaked or intentionally released’ or ‘COVID is a coronavirus that jumped from animal populations to humans like all human coronaviruses before it – including the 4 normally circulating coronaviruses that are considered common cold viruses.”  Rhetoric is a very strong component here and if the press wanted to really be useful, they might point out that on a timeline basis.  The arguments are largely rhetorical rather than scientific and factual.  All the press would have to say about the science is that it is not settled and digress a little into how scientific decisions are made. But I have never seen that happen.     

Update 03/03/2023:  The following document reviews some of the history of the controversy and points out that there really is no definitive proof of the viral origins at this point.  In the last few paragraphs the scientists who see zoonoses/spillover as the most plausible scenario are looking for falsifying data but have not found it.

Robertson L.  Still No Determination on COVID-19 Origin.  FactCheck.org 03/02/2023: https://www.factcheck.org/2023/03/scicheck-still-no-determination-on-covid-19-origin/

Update 03/06/2023:  TMZ was at it again today.  They put up a weekend poll on the origins of COVID and posted 2 possibilities -  wet market or lab leak.  The vote went like this:

wet market - 12%

lab leak - 88%

Harvey Levin's analysis was that this showed censoring the lab leak hypothesis at the outset was the problem.  This analysis is incorrect at two levels. First, there are endless headlines from 2021 where Republicans like Senator Rand Paul accused Dr. Fauci of lying about gain-of-function and labs leaks.  The demonized Dr. Fauci about this to the point that he started getting threats and needed protection for himself and his family. The same sequence of events happened to many public health officials who became objects of right wing scorn.  Secondly - I don't know what you expect when you are hyping unscientific proclamations about lab leak for the past week. Let's not pretend the media is a disinterested party here. TMZ chose the story about "censorship" when there was none and chose to suggest that was a better explanation for why two government agencies were suggesting a lab leak over the expert they interviewed last week. Just another clear example of the title of this post. 

Supplementary 4:

House Committee on Oversight - COVID origins:

Here is the web site - not the current references to Fox News and the New York Post - both obviously the farthest information from science:

https://oversight.house.gov/landing/covid-origins/

Graphics Credit:

Eduardo Colon, MD photo is much appreciated.