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.

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/),

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.

SARS-CoV-2 is an Airborne Virus?

I thought I would say something more about airborne viruses. They have been a hobby of mine for some time.  The first time I heard about how easily the current coronavirus was spreading I thought “this is an airborne virus”. But then there were the usual protests. Some scientists came out and said that coronavirus requires “droplet” precautions rather than “airborne” precautions. The common definition is that droplets are large enough settle out quickly. They may touch you directly if you are close enough but a lot of what droplets do is settle on surfaces. That leads to surface contamination and spread of the virus.  Airborne viruses can travel longer distances within smaller droplets. An even more unique characteristic is that airborne viruses are released with normal expiration. No coughing, sneezing, or shouting is necessary. Just normal breathing can release airborne respiratory viruses into the air in the smallest droplet fraction.

An easy way to conceptualize airborne viral spread is to look at the distribution of particles occurring with every breath. They can range in size from 200 µm on the large end to less than 5 µm on the lower end. Experiments can be done to show how aerosols of these particle sizes spread through a room. Naturalistic experiments can also look at how these are all spread through hospitals, airplanes, and other natural settings. By looking at those patterns and the distance involved as well as any other paths that could lead to transmission – a determination can be made about whether or not a viruses “airborne” or not.

The second issue is whether or not live infectious virus is spread by these droplets. In many cases that has been limitation in the experiments. Direct evidence of viral spread at a distance requires culture of the virus or a bioassay that shows the samples have a cytopathic (killing) effect on live cells. Indirect evidence is typically by PCR where the available nucleic acid is amplified and assayed.  In researching this topic, I found early literature that documented numerous respiratory viruses in ventilation systems of buildings. That research was possible because nobody knew how to capture and culture the virus samples until that time. The other technical issue is air sampling. Certain air sampling devices do not allow for adequate virus detection. There is a technical report recently that showed of a total of four commonly used air sampling devices only one allowed virus to be identified or cultured. These technical constraints have led to a lot of confusion about whether a particular virus is airborne or not.

A practical definition of an airborne virus is one that is exhaled during normal breathing can travel a distance in small droplets (less than 5 µm) and create infection by landing on mucosal surfaces, facial services, or the lining of the nasopharynx, oropharynx, or lungs.  In that case you don’t have to be in the presence of anyone coughing or sneezing. You don’t have to touch any contaminated surfaces. You don’t have to touch your face. You just have to breathe contaminated air. It is entirely possible that you can walk through a cloud of airborne virus and not be aware of how it got there. A common example is walking down the hallway after a crowd of people have walked through some of them carrying the virus. Once you know about airborne viruses it gives you an entirely different perspective on social distancing.  Airborne particles can easily transverse the longest dimension of typical rooms. The distance of 6 feet suggested in typical social distancing guidelines is not nearly far enough.

In a previous post I highlighted an experiment by Donald K. Milton where he designed a machine to sample flu viruses in a natural setting. Research subjects breathed normally and their expired air was sampled for influenza virus. Influenza virus was recovered from 89% of the nasopharyngeal swabs and 39% of the fine aerosol sample defined as droplets less than or equal to 5 µm and greater than 0.05 µm. There was no coughing or sneezing during the collection.. That is proof that influenza virus is airborne.

A recent experiment carried out at the University of Nebraska Medical Center (3) in their bio containment and quarantine units showed that in addition to abundant surface contamination by SARS-CoV-2 the virus was also present in hallway air samples, in areas where only aerosol deposits could reach, and personal air samplers carried by staff.  The virus was detected by PCR analysis as well as culture in some cases. The authors concluded that this was definite evidence of an airborne virus and that facilities treating patients with SARS-CoV-2 should use airborne precautions. This paper is currently undergoing peer review and is on a preprint server.

The technical aspects of aerosol fractionation and dispersion is a subject best addressed in the engineering literature. The best paper I could find on the subject (4) had a goal of studying the dispersion characteristics of exhaled droplets in a ventilated room. The engineering goals are to find out what physical parameters affect the dispersion rate and hopefully lead to better indoor environments. The experimental paradigm looked at a room that was 5 x 4 x 3 m (L x W x H) and ventilated by a downward airflow from the ceiling. Aerosols were injected into this room and the following distance and trajectory along with trajectory time was calculated for the fractional droplets. As expected droplets with larger diameters (110-115 µm) fell at a faster rate and traveled a much shorter distance than the smaller diameter fraction. Droplet dispersion was studied under a number of physical conditions including different airflow, different temperatures, different relative humidity, and the original exhaled initial velocity.

The 0.1, 1.0, and 10 µm droplets covered horizontal distance of 5 m or the entire length of the room. Droplets in the range of 50 to 200 µm cover distances ranging from 0.5 to 4 m.  This study has numerous excellent graphs about varying conditions and how droplets in different fractions are dispersed. The reader is referred to the original reference to review all those conditions. The bottom line for me was it is clear that airborne droplets in the 0.1 to 10 µm range are commonly seen in exhaled air and easily covered distance in this experiment of 5 m or (for Americans) 16.4 feet. That is well beyond social distancing recommendations it explains why this virus continues to spread. Within the past week I have seen clips of New Yorkers in congested subway cars.  Any asymptomatic SARS-CoV-2 carriers in those cars are expelling virus into the air just by tidal volume breathing.  Coughing and sneezing is not required. It would be very good if you covered your cough or sneeze but when your mouth is not covered and you are a symptomatic or asymptomatic carrier you are exhaling viral particles.

The relevance of this virus being airborne cannot be underestimated. It is a substantial part of the reason behind social distancing and stay-at-home orders. It is the reason for the new recommendation to wear masks in public and the various explanations being given for those masks. The absolute best approach is to not have any close social contact until this pandemic is over. I am very concerned about my colleagues and fellow healthcare workers who have inadequate personal protective equipment (PPE). The expectation is that they will continue to take care of the very ill patients with COVID-19. Every effort must be made to make sure they have adequate protection. 

In my particular specialty, all psychiatrists should have access to electronic interviewing at this point. As I pointed out in my earlier posts, I am used to talking people for 30 to 60 minutes at time. Some of those evaluations are 90 minutes in duration. During that time the patient may be coughing or sneezing but for the most part they are breathing and engaged in normal interview conversation. My office is smaller than the room described in the droplet dispersion experiment. By the end of one interview, the smallest fraction of exhaled droplets is dispersed throughout the room. Any viral particles in that fraction can lead to infection.

All health care workers in these environments need immediate protection by the implementation of airborne precautions. I am hopeful that as more people become aware of the airborne route of transmission that it will lead to more caution on the part of the public and the social distancing and staying at home and away from this kind of transmission will make more sense. In the future we need to design indoor environments that can minimize this type of transmission. There is too little innovation in the role of the physical environment in airborne transmission of infectious illness.

I hope the added cost will be looked at in terms of the total cost of illnesses caused by respiratory viruses every year with the recognition that they can still cause devastating pandemics.

George Dawson, MD, DFAPA


References:


1: Lei H, Li Y, Xiao S, Lin CH, Norris SL, Wei D, Hu Z, Ji S. Routes of transmission of influenza A H1N1, SARS CoV, and norovirus in air cabin: Comparative analyses. Indoor Air. 2018 May;28(3):394-403. doi: 10.1111/ina.12445. Epub 2018 Jan 6. PubMed PMID: 29244221. 

2: Yu IT, Li Y, Wong TW, Tam W, Chan AT, Lee JH, Leung DY, Ho T. Evidence of airborne transmission of the severe acute respiratory syndrome virus. N Engl J Med. 2004 Apr 22;350(17):1731-9. PubMed PMID: 15102999.

3: Santarpia et al. (2020) Transmission potential of SARS-CoV-2 in viral shedding observed at the University of Nebraska Medical Center. Retrieved from https://www.medrxiv.org/content/10.1101/2020.03.23.20039446v2.

4: Chen C, Zhao B. Some questions on dispersion of human exhaled droplets in ventilation room: answers from numerical investigation. Indoor Air. 2010 Apr;20(2):95-111. doi: 10.1111/j.1600-0668.2009.00626.x. Epub 2009 Sep 24. PubMed PMID: 20002792.

5: Li, Y., Huang, X., Yu, I.T.S., Wong, T.W. and Qian, H. (2005), Role of air distribution in SARS transmission during the largest nosocomial outbreak in Hong Kong. Indoor Air, 15: 83-95. doi:10.1111/j.1600-0668.2004.00317.x

6: Carl Heneghan, Jon Brassey, Tom Jefferson. SARS-CoV-2 viral load and the severity of COVID-19.  March 26, 2020.  Link

7:  National Research Council 2020. Rapid Expert Consultation on the Possibility of Bioaerosol Spread of SARS-CoV-2 for the COVID-19 Pandemic (April 1, 2020). Washington, DC: The National Academies Press. https://doi.org/10.17226/25769.

"While the current SARS-CoV-2 specific research is limited, the results of available studies are consistent with aerosolization of virus from normal breathing."

8: Pan M, Bonny TS, Loeb J, Jiang X, Lednicky JA, Eiguren-Fernandez A, Hering S, Fan ZH, Wu CY. Collection of Viable Aerosolized Influenza Virus and Other Respiratory Viruses in a Student Health Care Center through Water-Based Condensation Growth. mSphere. 2017 Oct 11;2(5). pii: e00251-17. doi: 10.1128/mSphere.00251-17. eCollection 2017 Sep-Oct. PubMed PMID: 29034325.

9: Lu J, Gu J, Li K, Xu C, Su W, Lai Z, et al. COVID-19 outbreak associated with air conditioning in restaurant, Guangzhou, China, 2020. Emerg Infect Dis. 2020 Jul [date cited]. https://doi.org/10.3201/eid2607.200764

Graphics Credit:

Graphic is from Shutterstock per their standard agreement.