Endemic ≠ Benign

 

“There is a widespread, rosy misconception that viruses evolve over time to become more benign. This is not the case: there is no predestined evolutionary outcome for a virus to become more benign, especially ones, such as SARS-CoV-2, in which most transmission happens before the virus causes severe disease…”

Aris Katzourakis
Professor of Evolution and Genomics
University of Oxford

 

I typically don’t like to post on a non-psychiatric topic immediately after posting one.  But the current level of misinformation on the pandemic necessitates this. That is obviously not because I am a big influencer with widespread readership – but I like responding to the sea of right wing misinformation on Twitter. And today it was all about how the response to the pandemic was an overreaction with far reaching effects. Nothing about how the virus has killed 1.1 million Americans, the impact of that mortality on families and businesses, the impact on the healthcare system and its workers, and the enduring disability of millions with long COVID.  The evidence is clear that the pandemic was mishandled early on as the Trump administration denied the degree of the problem and then falsely reassured the public that everything was under control. The only way the right wing can rewrite that history is to push a false narrative that there was a conspiracy theory to prevent any investigation of the lab leak theory, that face masks and public health measures don’t work, that school children are irrevocably damaged from online learning, and that all of these unnecessary measures were really an unnecessary infringement on freedom. Unfortunately, pandemic viruses don’t work that way. They do not really care about your political affiliation or what you read on Twitter.

One of the popular myths during the early to mid-pandemic was the idea of herd immunity and how by ignoring all of the public health suggestions up to and including the immunizations (or “jabs” as they are referred to by the right wing) the entire population would build up immunity and the pandemic would fade away. The way that argument was typically presented minimized any death or disability along the way.  Herd immunity would happen and it would happen quickly to resolve the problem.  It also implicitly assumed that writing off the elderly and the 10% of the population that is immunocompromised was morally acceptable.  Not much discussion of how herd immunity would happen without immunizations – since many of the proponents were ideologically sympathetic to the idea that public health measures and immunization were unnecessary.

An associated concept of endemic disease cropped up at one point. The popular usage was  to say: “This is no longer a pandemic, there are no more large outbreaks, therefore we can declare it is an endemic like the common cold viruses.”  Since this was also an ideological rather than scientific argument – it was also a rationale for stopping all of the suggested public health measures and getting things back to normal as soon as possible,

That brings me to a brief essay on endemics written by evolutionary virologist Aris Koutzourakis in Nature (1).  The title speaks for itself.  His definition of endemic is straightforward -  endemic infections mean that the infection rate is static – not rising or falling. The best intuitive example is common cold viruses – there are predictable seasonal fluctuations but the number of viruses and the composition of the pool of common respiratory viruses stays about the same and no one outcompetes the others. Nobody is too worried about common cold viruses because they are not too deadly and don’t commonly overwhelm the healthcare system.  Influenza viruses are somewhat different.  Whether and epidemic or pandemic occurs depends on an elaborate system of guessing the correct components for the influenza vaccine and measures taken to prevent zoonotic transmission of potentially more lethal influenzas viruses – like avian influenza. That backdrop of common cold versus influenza viruses seems like a way to understand endemicity.  It leaves out one important point and that is endemic pathogens can also be lethal and create disability.

Dr. Koutzourakis lists several examples of endemic, but lethal pathogens including malaria, polio, and tuberculosis.  They are all significant causes of mortality and morbidity.  He successfully predicted that unless the pandemic was stopped quickly subsequent evolving variants could be more transmissible and difficult to treat.  That occurred with the subsequent 4 SARS-CoV-2 variants. Viral evolution has also been observed with other pandemic viruses and the occurrence of more dangerous variants. He analyzes the current behavioral situation correctly in the United States.  Even if people are not using the word endemic – they are generally stating that the pandemic is over and that it is time for a return to normal.  Normal typically means no public health measures like masking, social distancing, or even deciding to stay home if you are ill.  The only place that those measures are acceptable is in a medical or dental facility and even then they are no longer universal. To compound the problem, the anti-public health ideologues are either bragging that they were correct all along or actively spreading misinformation about masks, vaccines, or the origin of the virus.

The graphic at the top of this page (click to enlarge) is taken from the CDC web site today.  Even though the area in the red rectangle looks fairly static going back to May of 2022 – the actual number of cases per week ranges from 170 to 900K.  That corresponds with weekly deaths 1,795 to 3,697.   Dr. Katzourakis suggests that there is the potential to see additional spikes of infection and suggests that the direction this pandemic will take at this point depends a lot on continued public health measures, immunizations, antiviral medication, and individual behavior.  One of the critical aspects of science as I explained in my previous post is that scientists look at data supporting or refuting hypotheses in terms of probabilities and also speculate with probability statements. Viral epidemiologists and evolutionary virologists know how viruses work and evolve. Their predictions are much more likely to be accurate than someone with no expertise and no data.  The next time you hear politicians or news personalities talking like this pandemic is over take it as an unfounded opinion. Do the same thing when your neighbor tells you that you don’t need to get any more vaccinations or wear a mask in crowded places.

Don’t let ideology blind you to science.

 

George Dawson, MD, DFAPA

 

References:

1:  Katzourakis A. COVID-19: endemic doesn't mean harmless. Nature. 2022 Jan;601(7894):485. doi: 10.1038/d41586-022-00155-x. PMID: 35075305.

2:  Centers for Disease Control and Prevention. COVID Data Tracker. Atlanta, GA: US Department of Health and Human Services, CDC; 2023, March 12. https://covid.cdc.gov/covid-data-tracker  accessed on 03/12/2023

3:  Callaway E. Beyond Omicron: what's next for COVID's viral evolution. Nature. 2021 Dec;600(7888):204-207. doi: 10.1038/d41586-021-03619-8. PMID: 34876665.

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.

 

Airborne Transmission - Once Again!

 

I thought I would take time for a rare celebration on this blog.  Most of my writing is about probabilities and uncertain outcomes. In many cases I am responding to the same tired arguments from people who don’t understand science, biology, medicine or psychiatry. Those positions generally result in some political attacks based on that lack of understanding or some specific political agenda. The position I am referring today is the airborne transmission of viruses. Although it seems like a straightforward scientific issue it has led to as much controversy as any psychiatric topic. Despite a significant amount of literature out there on airborne spread, there has been nothing but resistance to the concept.

Nowhere was the resistance more evident than the advent of the current SARS-CoV-2 pandemic. Initially the message was that the virus was spread by fomites or intermediate size droplets that fall within a few feet following a cough or a sneeze.  Accordingly, social distancing at more than a few feet, decontaminating hands and surfaces were recommended to counter this mechanism of transmission. Many experts claim that most respiratory viruses with very few exceptions are transmitted this way. Those same experts claim that airborne transmission of viruses in smaller droplets travelling much longer distances was controversial at best. All of those conflicting ideas led to recommendations for no masks in February of 2020 followed by recommendations for masks in the next two months.  The mask recommendations occurred in the context of widespread shortages of personal protective equipment (PPE) for health care workers.   

I posted my qualifications on the matter (2 Avian Influenza Task Forces earlier in this century, being subjected to multiple respiratory virus epidemics at work despite rigorous hand washing, and studying the available engineering and viral data, and lengthy discussions with HVAC experts) and began to write about it on this blog.  My perspective is clearly that respiratory viruses are airborne and therefore will not be stopped by handwashing alone, that there are clearly engineering approaches to stop respiratory viruses that will work much better than just handwashing, and that there should be a major research and development effort on environmental designs to minimize and even stop respiratory viruses in homes and public building. In fact, as I type this I have selected a UVC device to be installed in my home HVAC system and it will probably be installed in the next month or two.  Many of those posts on this blog can be found here or by using the search term “airborne” in the search box.

The victory lap today occurs with a press release from the CDC today that I consider a bombshell in terms of the airborne transmission concept.  The press release is a quick read but it highlights why surface contamination is unlikely to be a significant factor:

“Quantitative microbial risk assessment (QMRA) studies have been conducted to understand and characterize the relative risk of SARS-CoV-2 fomite transmission and evaluate the need for and effectiveness of prevention measures to reduce risk. Findings of these studies suggest that the risk of SARS-CoV-2 infection via the fomite transmission route is low, and generally less than 1 in 10,000, which means that each contact with a contaminated surface has less than a 1 in 10,000 chance of causing an infection.”

And further:

“The principal mode by which people are infected with SARS-CoV-2 is through exposure to respiratory droplets carrying infectious virus.”

This information has been slowly presented over the course of the past several months.  For example, Dr. Fauci mentioned on several news outlets that cleaning all of the mail and groceries was not necessary because it was not considered a main route of transmission. A logical inference from that statement is why there is a concern about any surfaces at all unless there is a person with a known infection close by.  And by extension, if surface contamination is not that much of a problem why the concern about accidentally touching your face?  As Dr. Fauci typically states we now have the science behind the transmission and the recommendations can be adapted to the new findings.

The CDC press release does not come right out and say airborne transmission.  They continue to say respiratory droplets are the predominate mode of spread and the old document on respiratory droplets says nothing about differentiating between moderate sized droplets that typically fall to the ground within a 6-foot radius of where they are generated or airborne droplets that are lighter, spread past 6 feet from the generation site and remain suspended for longer periods of time.

Some of the comments on the press release have been much more definitive. The only reference to this post has a good timeline on the airborne controversy and this quote from atmospheric chemist Jose-Luis Jimenez: “If we took half the effort that’s being given to disinfection, and we put it on ventilation, that will be huge.”  In the same reference Germany has invested a half billion dollars in improving ventilation and indoor air quality.

Overall, it appears that the CDC is slowly coming around to the idea that respiratory viruses are transmitted via airborne routes, but some resistance is still evident in the press release they link to an earlier non-descript respiratory droplet transmission document.  There are many potential advantages to fully backing the airborne transmission concept (in addition to the available science).  Research and development is at the top of the list. In an early blogpost, I pointed out that UV decontamination was routine in buildings when I was a kid in a small town in northern Wisconsin.  The currently available UVC is much safer and very effective for killing airborne biological particles. From a clinical trials perspective, deployment of these systems on a large scale and following the number of respiratory infections in facilities with and without the technology seems like a fairly basic experiment.

It is also interesting to consider the resistance. There is undoubtedly politics in science and that can be a factor. There may be a medical intervention bias. In other words, we need some magical intervention like a vaccine, antiviral medication, or general polypharmaceutical modality that can either cure or prevent the excessive morbidity and mortality from respiratory viruses.  The track record there is some wins and many losses.  Every year various populations around the world are subjected to significant effects from flu-like illness that are nowhere as lethal as SARS-CoV-2.  Remarkably – everyone accepts this state of affairs until a more lethal virus comes around and affects a larger group of people.  There is politics as usual leading to irrational attitudes about viruses and physical interventions.  The appropriate environmental interventions may make mask refusers irrelevant at some point in the future.

The bottom line of today’s release is good news for all of the airborne virus crowd and I definitely consider myself in that crowd. I would still like to see the CDC modify their position on transmission in respiratory droplets and I think that is coming.  But most of all, I would like to see us get serious about using environmental measures to limit the exposure and spread of all respiratory viruses including the current one that has killed far more Americans than any influenza epidemic since 1918.

 

George Dawson, MD, DFAPA

 

References:

1:  Lewis D. Why indoor spaces are still prime COVID hotspots. Nature. 2021 Apr;592(7852):22-25. doi: 10.1038/d41586-021-00810-9. PMID: 33785914.

2: Dietrich WL, Bennett JS, Jones BW, Hosni MH. Laboratory Modeling of SARS-CoV-2 Exposure Reduction Through Physically Distanced Seating in Aircraft Cabins Using Bacteriophage Aerosol — November 2020. MMWR Morb Mortal Wkly Rep. ePub: 14 April 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7016e1

3: Greenhalgh T, Jimenez JL, Prather KA, Tufekci Z, Fisman D, Schooley R. Ten scientific reasons in support of airborne transmission of SARS-CoV-2.  The Lancet (online).  Published 4/15/2021. https://doi.org/10.1016/S0140-6736(21)00869-2  Current link

4: Tang JW, Bahnfleth WP, Bluyssen PM, Buonanno G, Jimenez JL, Kurnitski J, Li Y, Miller S, Sekhar C, Morawska L, Marr LC, Melikov AK, Nazaroff WW, Nielsen PV, Tellier R, Wargocki P, Dancer SJ. Dismantling myths on the airborne transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Hosp Infect. 2021 Apr;110:89-96. doi: 10.1016/j.jhin.2020.12.022.  Current Link

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.

       

Airborne Transmission Denial Dies Hard ........

I started this post as I left a staff meeting today on containing the coronoavirus. We had a similar meeting 2 months ago and at that point I added that there was airborne transmission of the virus.  The only comment I got was a condescending remark about how we don't know much about airborne transmission and we need to wait and see and blah, bah, blah. It was "as if" I did not know what I was talking about or any of the surrounding controversy.  To my surprise the same people today were sold on airborne transmission. They were even interested in HVAC issues and negative pressure rooms – all of the stuff I have been studying for 20 years.  Nobody mentioned UVC or air filtration.  I decided just to keep my mouth shut. Just like I usually do when politics seems to be the priority rather than science.  But the good news was undeniable.  Airborne transmission has much greater acceptance than it did prior to the current pandemic and there are clear reasons for it.

That staff meeting is a small part of a larger landscape of what airborne transmission advocates like me have been talking about for decades or longer.  Back in the days when I was working in an outdated building that had an HVAC system that was designed to contain heat rather than provide fresh air to dilute and remove airborne pathogens – I routinely observed the effects of this approach on myself and my coworkers.  Upper respiratory infections were endemic.  If one person came into that building with a severe form of a respiratory virus – most people got it. I can recall coming down with an acute flu-like illness one morning at work and getting ill so quickly and severely that I was barely able to make it home due to the cognitive effects.  I was close to delirium.

When you are in medical facilities, the party line is always “wash your hands”. I got the respiratory infections if I washed my hands 20 times a day or a hundred times a day.  The pandemic equivalent of that advice has been “don’t touch your face”.  But it is apparently safe to eat food that has been contaminated with SARS-CoV-2 because the virus is not infectious via gastrointestinal pathways.  The expert opinion is really based on the lack of evidence that eating food or touching food packaging is associated with SARS-CoV-2 infections.  We hear about the virus being infectious through the eyes and nose. It could be rubbed into the eyes from the face or into the nose by nose picking – but how common is that?  Certainly, washing your hands and not touching your face along with physical distancing at 6 feet seem like common sense rules.  But is that going to protect you?

I have never felt like any of those measures was enough and this week a letter came out pointing out the evidence for airborne transmission of respiratory viruses in general and for SARS-CoV-2 in particular.  I was pleased to see Dr. Milton as a co-author of this statement.  I have been reading his work for 20 years on airborne viruses in buildings of different design including the viruses that have been detected both in the air and the occupants of the building. This paper is a brief commentary specific to SARS-CoV-2 with a couple of generalities about airborne viruses and it is signed by 239 scientists who support it. 

   

The commentary starts out as an appeal to the medical community to recognize the potential for airborne spread of COVID-19.  Airborne transmission is defined as the release of droplets containing viral particles during breathing, coughing, sneezing, and any type of vocalization.  There is no doubt this happens. A distribution of droplet particle sizes occurs.  The larger droplets at a typical velocity settle out of the air in shorter distances typically in about 2 meters or 6 feet. The smaller droplets can travel much longer distances.  The authors cite an example of a 5 µm droplet at an original height of 1.5 meters and expelled at a typical indoor velocity travelling for “tens of meters” before it falls to the floor. This is typical airborne transmission and it will obviously not be contained by hand washing or physical distancing.

The authors on to describe some of the well-known scenarios where COVID-19 was transmitted despite no observed direct or indirect contact among the parties where the transmission occurred by video recordings.  They go on to cite other experiments demonstrating that several viruses (influenza, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and respiratory syncytial virus (RSV) can all be spread by airborne routes. Although they don’t go into a lot of technical detail in the commentary, respiratory viruses are exhaled in normal tidal breathing.  The distribution and velocity of exhaled droplets will vary based on the way they are generated.  Infective viral RNA in small (5 µm) droplets from COVID-19 has been detected.

The critical sentence from this document follows:

“Hand washing and social distancing are appropriate, but in our view, insufficient to provide protection from virus carrying respiratory microdroplets released into the air by infected people.”

The is really a landmark statement from this group of experts. In my opinion it revolutionizes the approach not only to this virus but all respiratory viruses.  They all have access to the same type of spread and many have already been shown to have permeated heating and ventilation systems.  One of the main differences is virulence of the virus.  For example, smallpox or variola virus can cause an infection from the inhalation of a single viral particle (6).  Adenovirus, a much more common respiratory virus can cause an infection by the inhalation of as little as 6 viral particles (3).  Although adenovirus is potentially a flu-like respiratory virus, the main initiative at preventing the associated morbidity and mortality occurs in the military where a vaccination is used. The SARS-CoV-2 infections dose has been estimated to be about 280 particles – but the authors of one study suggest it is in the same ballpark of influenza virus and in that paper suggest that the amount of virus leading to infection in volunteers may be twice the amount of the aerosolized virus (5).

The main implication of airborne spread is that sustained inhalation of COVID-19 in poorly ventilated spaces of just being indoors increases risk of transmission. People who are coughing, sneezing, singing or engaged in any activity that results in forceful exhalation will expel small droplets at higher rates of speed and they will remain airborne for a longer period of time and travel much greater distances than the current suggested social distancing of 6 feet. 

To reduce the airborne transmission risk they have straightforward recommendations to avoid overcrowding (every additional person in the room is generating airborne droplets), have adequate ventilation, and supplement these measure with additions like HEPA filtration, germicidal UVC light, and exhausting room air rather than recirculating it. I can recall getting into an argument at one of my Avian Influenza Task Force meetings about a fast way to change the hospital ventilation system in the event of an influx of avian influenza patients.  Recall that the hospital was designed to retain heat by recirculating room air rather than exhausting it – like modern hospital rooms.  At the time, the counterargument was that it was just too expensive to build negative airflow rooms to prevent the flu virus from leaving the room with medical staff caring for the patients.  Most hospital rooms, even the ones I worked in that were built in the 1960s, had windows to the outside.  How difficult would it be to fit these windows with exhaust fans to the exterior of the hospital? 

This consideration is important now that there are political initiatives to reopen schools and other public places.  The ventilation systems of all of these places should be looked at and that assessment incorporated into the overall decision about how safe they are to open.  Further, there should be a systematic approach to how safe buildings are in general from the perspective of transmission of respiratory viruses.  A prospective approach that looks at how buildings in temperate climates need to be designed to minimize the spread of respiratory viruses needs to be a long term goal.  

It took a virus with heightened mortality and morbidity to raise awareness that physical measures rather than any available medication may be the best way to contain respiratory viruses.  Airborne transmission of respiratory virus denial dies hard - but hopefully it is being put to rest once and for all.  That should be a continued priority for everyone and momentum we cannot afford to lose.

George Dawson, MD, DFAPA

References:

1:  Lidia Morawska, Donald K Milton, It is Time to Address Airborne Transmission of COVID-19, Clinical Infectious Diseases, , ciaa939, https://doi.org/10.1093/cid/ciaa939

2:  Erin Bromage.  The Risks - Know Them - Avoid Them.  Erin Bromage COVID-19 Musings.  May 16, 2020.  Link

3:  Yezli S, Otter JA. Minimum Infective Dose of the Major Human Respiratory and Enteric Viruses Transmitted Through Food and the Environment. Food Environ Virol. 2011;3(1):1–30. doi: 10.1007/s12560-011-9056-7. Epub 2011 Mar 16. PMCID: PMC7090536.

4:    Nicas, M., Hubbard, A. E., Jones, R. M., & Reingold, A. L. (2004). The Infectious Dose of Variola (Smallpox) Virus. Applied Biosafety, 9(3), 118–127. https://doi.org/10.1177/153567600400900302

5:  Schröder I. COVID-19: A Risk Assessment Perspective. J Chem Health Saf. 2020;acs.chas.0c00035. Published 2020 May 11. doi:10.1021/acs.chas.0c00035

Previous Airborne Transmission Posts from this Blog:

SARS-CoV-2 Is An Airborne Virus?

Viruses Are In The Air - Protection From Airborne Viruses

Hand Washing

New Twist On An Old Method To Kill The Flu Virus

Is It Time To Quarantine Air Travelers?


Supplementary:

This statement from a recent Nature article:

"But this conclusion is not popular with some experts because it goes against decades of thinking about respiratory infections. Since the 1930s, public-health researchers and officials have generally discounted the importance of aerosols — droplets less than 5 micrometres in diameter — in respiratory diseases such as influenza."

from:  Dyani Lewis.  Mounting evidence suggests coronavirus is airborne — but health advice has not caught up.  Link.



Graphics Credit:

Graphic at the top is from Reference 1 based on the following CC License.  This is an Open Access article distributed under the terms of the Creative Commons Attribution- NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/),