Norovirus - Avoid It If You Can

 

Norovirus is an Increasing Problem

Norovirus is a non-enveloped single strand RNA virus.  One of the critical features of Norovirus is infectivity.  Infected individuals secrete the virus in feces, saliva, and oral mucus.  Virus can be detectable in the saliva for up to 2 weeks after infection even though most of the guidelines for food preparers suggests that they can go back to work 2-3 days after the acute illness has passed.  The infective dose for Norovirus is as little as 18 viral particles (1).  An infected person is excreting billions of these particles. For comparison, influenza virus requires a dose of about 1.95-3.0 x 10³ infectious particles, and most common respiratory viruses including SARS-CoV-2 are on par with Norovirus. 

The clinical syndrome develops rapidly after exposure resulting in abdominal cramping, vomiting and diarrhea.  It creates significant mortality and morbidity causing an estimated 213,000 deaths world-wide (2).  In the US 900 people die per year out of 21 million infections. Most of the fatalities occur in the elderly and immunocompromised. Rapid fluid loss and dehydration is most likely a causative factor especially in the case of pre-existing medical problems. There is a bias toward advising all people like they are healthy young adults and that this syndrome is a self-limited 2-3 day episode of stomach flu.

There is an asymptomatic carrier state with anywhere from 11.6-49.2% of measured populations carrying the virus. This also extends to 1-3.4% of food handlers.  Humans were previously the only known reservoir for this virus, but a recent review looked at modern data and concluded that it may be a reverse zoonosis with human to animal transmission in lab animals and the wild (3, 4). 

Outbreaks of the virus are getting more common especially in environments where there is close contact and contact with contaminated surfaces like schools, universities, elderly homes, and cruise ships.  In the US there are about 2,500 outbreaks per year and poor granularity in terms of geographic locations. In other words, unless a local news channel picks up the story of an outbreak – you probably will not know until you get there.  The distribution of outbreaks over the calendar year for the last 4 years is given at the top of this post.  Outbreaks tend to intensify in the winter months where there is more aggregation.   

The most common advice given to prevent Norovirus infection is hand washing and cleaning contaminated surfaces.  The virus remains physically stable in pH 3-7 condition and temperatures up to 60 degrees C (140 degrees Fahrenheit) but that conventional wisdom may not be enough.  The virus is aerosolized presumably by coughing, sneezing, and toilet flushing and has been detected in the air around hospitalized patients (8). The particles detected were in the droplet nuclei/aerosol range but that may be an artificial dichotomy (9).  The main point in this research is that the droplets detected contained sufficient virus to cause infection. Current CDC precautions for Norovirus do not include masking except where there is a risk of “splashes to the face during the care of patients, particularly among those who are vomiting.”  This is reminiscent of the reluctance to declare respiratory viruses including SARS-CoV-2 and influenza airborne. 

6.6% of the US population are immunosuppressed based on taking immunosuppressant drugs or having a health condition that affects immunity and that number is increasing (10).  Women are more likely to be affected than men. In addition to the immunocompromised - 39% of the population has at least one serious chronic illness any number of which can affect innate immunity (11).  In addition, many of these diseases or their management can end up compromised by severe acute gastroenteritis.  Common examples would be blood glucose management in diabetes mellitus and electrolyte and fluid management in hypertension, arrhythmias, and renal disease.  Since 42% of the population has 2 or more chronic conditions it is highly likely that recommended management of rehydration will need to be personalized to that patient.  

There are also nebulous recommendations about the quarantine necessary following an episode of this illness.  The CDC web site provides an example, in order:

“Most people with norovirus illness get better within 1 to 3 days; but they can still spread the virus for a few days after.”

“You can still spread norovirus for 2 weeks or more after you feel better.”

“Stay home when sick for 2 days (48 hours) after symptoms stop.”

Apparently, Norovirus has been detected in saliva for up to 2 weeks after infection – leading to this mixed recommendation. There is some additional information at a public health link – but not much more. This link has interesting information on clinical criteria without biological confirmation that a probable Norovirus outbreak is occurring. In a 2013 review, Norovirus was the second most common infection disease outbreak affecting psychiatric hospitals (13).  This review looks at infection control procedures that may be unique to psychiatry as well as those that address the difficult to destroy nature of the virus.  It is resistant to common hand sanitizers and the need for contact cleaning with hypochlorite while masked and gowned to prevent infection of staff.  The reference on the possible airborne nature of the virus also applies. A description of a psychiatric hospital with 4 previous Norovirus outbreaks and how that was stopped by a specific infection control program is also described (14).

That is currently the state-of-the-art on Norovirus. I have some additional information posted below.  The best defense at this point is to know that this is a highly infectious virus that is nothing to fool around with, especially if you are elderly, have chronic medical conditions, or are immunocompromised.  I don’t think it is my place to make specific rehydration recommendations because of the complexity I describe in the above paragraphs – but your personal physician certainly can.  No matter what you read – avoiding dehydration is the most important aspect.  Your physician can best describe how to do that given any other medical conditions. 

There are currently no vaccines or antiviral medications for Norovirus.  Vaccines are complicated by several factors discussed in this paper (15) that projected vaccine availability 5-10 years out from 2014.  Here we are 10 years out. Like the current SARS-CoV-2 vaccines early trials show a limited duration of immunity, but that can eliminate many cases in more vulnerable populations.

 

George Dawson, MD

 

Supplementary 1:

For 2025 – I decided to separate out my anecdotal experience from the published scientific data.   Readers of this blog know that my intent is generally to include it as additional relevant information and I have joked about trying to learn more about diseases by trying to get most of them.  That is no different with Norovirus.  The actual clinical syndrome I have seen many times dating back to my days as a Peace Corps volunteer travelling in East Africa.  It was referred to as “Traveler’s Diarrhea” and the theory was that it was caused by “enterotoxigenic E. Coli.”  Various remedies were suggested including Pepto Bismol (bismuth salicylate) or a prophylactic course of sulfamethoxazole/trimethoprim (SMX/TMP) – an antibiotic that I subsequently prescribed many times as an intern and resident.  

All Peace Corps volunteers were issued a medical kit and the two primary medications were a large bottle of Lomotil (diphenoxylate/atropine) and another large bottle of Benadryl (diphenhydramine).  So most acute diarrheal diseases were treated with Lomotil.  We also got IM cholera vaccines that interestingly were discontinued shortly after my Peace Corps tour because “they were more painful than protective.”  The only currently approved cholera vaccine is an oral vaccine.

My wife recently had a complicated course of appendicitis and there was concern about the possibility of an intraabdominal abscess.  As she recovered slowly from the surgery she had residual right upper quadrant pain and suddenly developed an acute illness again very similar to the appendicitis. I convinced her to go to free-standing emergency department where she was treated for nausea and rapidly given 1 liter of normal saline in less than 30 minutes. She was hypotensive and had a lot of vomiting and diarrhea in the hours before this assessment.  A CT scan of the abdomen was negative and a PCR test of a stool sample confirmed no C. difficile toxin and positive for Norovirus (see test panel below).

Returning home she recovered over the next two days – but I contracted it and am recovering on day 3.  I will post the symptom course in this note when I am fully recovered.  I will note that my wife has had 2 episodes of SARS-CoV-2 infections in the past 3 years and I did not get them from the airborne route but was masked and using a UV air cleaner at the time.  This time I was not masked – but I was using all of the CDC recommended contact precautions, the same UV air cleaner, and handwashing.       

Supplementary 2:

Sometimes it pays to be a hoarder. I found this book in my auxiliary library today.  It was sent to me by a friend who was attending Harvard Medical School when he heard I was definitely headed to Africa.  I regaled my Peace Corps colleagues with tales of possible infections in Africa. The most interesting section for this post is that it provides an anchor point for diarrheal disease classification in 1975. It lists invasive and enteropathogenic E. coli as the primary pathogens detectable by culture and bioassay or an assay set up to detect the toxin.  Epidemic viral gastroenteritis is attributed to Norwalk virus in the same book.  The name originated from immune electron microscopy of a viral particle identified as a causative agent in Norwalk, Ohio.  Episodic viral gastroenteritis at the time was attributed to rotavirus, duovirus, and orbivirus.

Supplementary 3:

I resumed working out on day #7 and have charted the symptoms using my invention of a malaise index.  Note that APAP here means acetaminophen that I take for symptoms that are generally caused by cytokines from the inflammatory response caused by viral and bacterial infections.  The index itself is included below the graphic of the course of the illness to explain what was rated.  For research purpose a Likert scale approach for every item would probably be used.  Even though the symptom descriptions are fairly basic - the underlying pathophysiology is not.  There are also some symptoms that I experienced that were not included like a sensory lack of taste for food. 

Supplementary 4: 

The Minnesota Department of Health came out with the following release on Norovirus today.  Apparently there have been 40 outbreaks in the state of Minnesota.  No specific locations are given and the general advice has the limitations I outlined in the above blog post.

All of the details can be found at this link.

Supplementary 5:

EPA Registered Products that will kill Norovirus:  Chlorox and Lysol products are the most recognizable names but there are many (386).  Note the necessary contact time in the table necessary to effectively eliminate the virus.

https://www.epa.gov/pesticide-registration/epas-registered-antimicrobial-products-effective-against-norovirus-feline

References:

1:  Winder N, Gohar S, Muthana M. Norovirus: An Overview of Virology and Preventative Measures. Viruses. 2022 Dec 16;14(12):2811. doi: 10.3390/v14122811. PMID: 36560815; PMCID: PMC9781483.

2:  Pires SM, Fischer-Walker CL, Lanata CF, Devleesschauwer B, Hall AJ, Kirk MD, Duarte AS, Black RE, Angulo FJ. Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food. PLoS One. 2015 Dec 3;10(12):e0142927. doi: 10.1371/journal.pone.0142927. PMID: 26632843; PMCID: PMC4668836.

3:  Robilotti E, Deresinski S, Pinsky BA. Norovirus. Clin Microbiol Rev. 2015 Jan;28(1):134-64. doi: 10.1128/CMR.00075-14. PMID: 25567225; PMCID: PMC4284304.

4: Villabruna N, Koopmans MPG, de Graaf M. Animals as Reservoir for Human Norovirus. Viruses. 2019 May 25;11(5):478. doi: 10.3390/v11050478. PMID: 31130647; PMCID: PMC6563253.

5:  Karimzadeh S, Bhopal R, Nguyen Tien H. Review of infective dose, routes of transmission and outcome of COVID-19 caused by the SARS-COV-2: comparison with other respiratory viruses. Epidemiol Infect. 2021 Apr 14;149:e96. doi: 10.1017/S0950268821000790. Erratum in: Epidemiol Infect. 2021 May 14;149:e116. doi: 10.1017/S0950268821001084. PMID: 33849679; PMCID: PMC8082124.

6: CDC.  Norovirus Facts and Stats.  (accessed on 12/15/2024): https://www.cdc.gov/norovirus/data-research/index.html

8:  Alsved M, Fraenkel CJ, Bohgard M, Widell A, Söderlund-Strand A, Lanbeck P, Holmdahl T, Isaxon C, Gudmundsson A, Medstrand P, Böttiger B, Löndahl J. Sources of Airborne Norovirus in Hospital Outbreaks. Clin Infect Dis. 2020 May 6;70(10):2023-2028. doi: 10.1093/cid/ciz584. PMID: 31257413; PMCID: PMC7201413.

9:  Drossinos Y, Weber TP, Stilianakis NI. Droplets and aerosols: An artificial dichotomy in respiratory virus transmission. Health Sci Rep. 2021 May 7;4(2):e275. doi: 10.1002/hsr2.275. PMID: 33977157; PMCID: PMC8103093.

10:  Martinson ML, Lapham J. Prevalence of Immunosuppression Among US Adults. JAMA. 2024 Mar 12;331(10):880-882. doi: 10.1001/jama.2023.28019. PMID: 38358771; PMCID: PMC10870224.

11:  Benavidez GA, Zahnd WE, Hung P, Eberth JM. Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area. Prev Chronic Dis 2024;21:230267. DOI: http://dx.doi.org/10.5888/pcd21.230267

12:  Fukuta Y, Muder RR. Infections in psychiatric facilities, with an emphasis on outbreaks. Infect Control Hosp Epidemiol. 2013 Jan;34(1):80-8. doi: 10.1086/668774. Epub 2012 Nov 27. PMID: 23221197.

13: Tseng CY, Chen CH, Su SC, Wu FT, Chen CC, Hsieh GY, Hung CH, Fung CP. Characteristics of norovirus gastroenteritis outbreaks in a psychiatric centre. Epidemiol Infect. 2011 Feb;139(2):275-85. doi: 10.1017/S0950268810000634. Epub 2010 Mar 25. PMID: 20334730.

14:  Tseng CY, Chen CH, Su SC, Wu FT, Chen CC, Hsieh GY, Hung CH, Fung CP. Characteristics of norovirus gastroenteritis outbreaks in a psychiatric centre. Epidemiol Infect. 2011 Feb;139(2):275-85. doi: 10.1017/S0950268810000634. Epub 2010 Mar 25. PMID: 20334730.

15:  Gupta SS, Bharati K, Sur D, Khera A, Ganguly NK, Nair GB. Why is the oral cholera vaccine not considered an option for prevention of cholera in India? Analysis of possible reasons. Indian J Med Res. 2016 May;143(5):545-51. doi: 10.4103/0971-5916.187102. PMID: 27487997; PMCID: PMC4989827.

16:  Benenson AS (ed).  Control of communicable diseases in man – 12^th Edition. American Public Health Association. Washington, DC.  1975:  96-101, 125-129.

17:  CDC.  Confirmed norovirus outbreaks submitted by state.  Good source of data from CaliciNet updated every months.  Gives number of outbreaks per state in the past year and rough data on virus genotype.  https://www.cdc.gov/norovirus/php/reporting/calicinet-data.html

 

Stay Indoors - But Is That Enough?

 

Any casual reader of this blog might know that I was interested in indoor air quality including airborne viruses – long before it became fashionable. That had various origins including an undergrad focus on ecology, being raised by two heavy smokers, having to manage a coal fired stoker as a kid, working in a HEPA filtered clean room as a research assistant, and routinely getting viral respiratory infections in a hospital staff setting where we were all advised that hand washing was supposed to stop the mini-epidemics. And having asthma through all of that.

The indoor air quality issue has become complicated as our outdoor environment deteriorates. As an undergrad 50 years ago, we studied air pollution scenarios that affected large cities.  That included the concept of how smog was created by photochemical reactions but a lot of the specifics were not known.  More recently the entire Midwest and Northeastern US has been blanketed by wildfire smoke from Canada. Wildfire smoke is chemically complex.  In a lot of areas there are air quality alerts on one day due to wildfire smoke and ozone the next day. Those alerts are graduated to advise people with health conditions like asthma, emphysema, and heart disease on the lower end to limit outdoor activities or stay inside.  At high levels everyone gets the same advice.

The advice to stay inside assumes that your indoor air quality is better than the outdoor air quality that you are being warned about.  But is that a valid assumption?  How do you get measurements on everything and know the critical differences?  A good place to start is the outdoor air quality. The EPA has developed a nationwide network of sensors that detects particulates and ozone in the air and calculates the air quality index.  The AirNow app is available for your smart phone.  It gives you the outdoor reading, particulates, and ozone, as well as the break points from Good (0-50) to Hazardous (301-500). It will give you conservative advice about what to do about health and activity for those break points.

The CDC has a publication on indoor air quality in airports (1) where smoking was allowed. It provides some more intuitive markers of indoor quality. They found that the PM 2.5 (<2.5 micron particles per cubic meter) were 300+ in the smoking areas and 50+ in the areas adjacent to the smoking areas.  300+ levels are considered “very unhealthy”.  Anyone who has ever been in a smoke-filled room can probably sense that the atmosphere is not very good for your health either immediately of after leaving.  In Minnesota when the AQI was greater than 300 due to wildfire smoke – you could smell the wood fired smoke.

With an accurate assessment of the outdoor air – what about your indoor air quality?  I was fortunate enough to have purchased an air cleaner for my office with a PM 2.5 measure built into the machine. It usually reads in the 1-5 range but when the wildfire smoke arrived it was suddenly reading 40+ indoors. I had to figure out why that number was so high.  I had just replaced my furnace and it has a MERV13 filter that should provide some filtering efficiency.  The question mark was how my air exchanger fit into the mix.

My house is about 15 years old and like most modern houses it is considered airtight.  The concern by builders and contractors with modern homes is that they are so airtight that it leads to indoor air pollution from a number of sources including any combustion processes in the home and volatile compounds in the air from various sources like cleaning products.  As a result, air exchangers are installed to vent the indoor air and bring in fresh outdoor air.  These air exchangers are designed to reduce heat exchange and most do not have HEPA ( High Efficiency Particulate Air [filter])  filters.  They have a relatively primitive filtration system to remove mainly insects and very large particles. They can easily bring in outdoor smoke so it is a good idea to have it shut off on days where there is very high particulate matter.

The problem with my new system is that I was not sure that the air exchanger was off.  When my new furnace was installed the air exchanger was integrated into a touch panel with 30 different options and several ventilation settings.  I talked with 5 technicians (3 from the HVAC contractor, 1 from the air exchanger manufacturer, 1 from the smart thermostat manufacturer).  They all agreed shut off the air exchanger was a good idea but they gave me widely varying advice.  I decided to experiment myself over a period of 12 hours and generated the following graph (click to enlarge).

The first section shows the AQI outdoors versus indoors running the MERV 13 filter through the furnace.  There is no difference over that time period.  The next period I shut off the furnace filter and used a free-standing Space Gaard air cleaner with a MERV 8 (MERV = Minimum Efficiency Reporting Values) filter. Notice that during this time period the wind picked up outdoors, blew off some smoke and the PM 2.5 dropped from 160 to about 90.  At that time I talked with a 6^th technician and he gave me clear advice on how to shut off the air exchanger.  The last section is with the air exchanger off and all air circulating through the furnace filter MERV 13.  At that point the indoor AQ drops consistently despite a blip upwards in the outdoor PM 2.5 and continued to drop to 10.  To me that illustrates the importance of making sure the air exchanger if off when the outdoor AQ is poor and actively managing it to turn it one when the outdoor AQ is acceptable.

A related indoor AQ related to viral transmission is the carbon dioxide CO₂ levels.  Lower levels correlate with less people rebreathing air in the room and that decreases the risk of infection from airborne viruses. Outdoor CO₂ is roughly 400-420 ppm. My indoor measure is currently 570 without the air exchanger on.

There are currently PM 2.5 and CO₂ monitors available in most home stores and large online retailers.  What we really need is a more comprehensive single device that measures and records all of the parameters. I would suggest PM 2.5, PM 10, CO₂, Ozone, and Volatile Organic Compounds (VOC).  The closest I could come to that device was a gadget that required that I purchase a separate weather station and even then the bandwidth to multiple devices was limited.

Home HVAC system design could also use some innovation. Just based on my experience durability is a problem. Should an HVAC system last longer than 14 years?  Probably.  But the design itself does not seem very efficient.  I am not a certified HVAC tech by any means but it appears to me that the air exchanger introduces outdoor air into the system after the air filter so that any particulate matter in the outdoor air does not get at least one pass through the highest efficiency filter.

Outdoor air quality is a little discussed casualty of climate change. As the environment deteriorates, I expect that there will be increasing amounts of wildfire smoke and it will be chemically more complex. I currently wear an N95 mask outdoors during the alerts, but I can envision a time in the not-too-distant future where respirators that can also remove ozone and organic chemicals will also be necessary. Geography is no longer helpful in separating clean air from polluted air. Monitoring your personal indoor air quality and figuring out how to manage it will become the most critical part of home management. I have posted a few things that you can do right now and I am always interested in other ideas about how to address this problem.  Please post any of those ideas in the comments section.

 

George Dawson, MD, DFAPA

 

 

References:

1:  Centers for Disease Control and Prevention (CDC). Indoor air quality at nine large-hub airports with and without designated smoking areas--United States, October-November 2012. MMWR Morb Mortal Wkly Rep. 2012 Nov 23;61(46):948-51. PMID: 23169316.

2:  CDC Health Alert Advisory.   Wildfire Smoke Exposure Poses Threat to At-Risk Populations.  Link

Update 07/06/2023: 

One week after turning off my air exchanger - the PM 2.5 in my house is down to 6 or essentially normal.  I talked with my air conditioning tech who also services the air exchanger and he agreed with the approach.

Image Credit:

Canadian Wildfire Smoke in Minneapolis

Chad Davis from Minneapolis, United States, CC BY 2.0 <https://creativecommons.org/licenses/by/2.0>, via Wikimedia Commons

file URL:  https://upload.wikimedia.org/wikipedia/commons/c/c0/Canadian_Wildfire_Smoke_in_Minneapolis_%2852907984452%29.jpg

page URL:

https://commons.wikimedia.org/wiki/File:Canadian_Wildfire_Smoke_in_Minneapolis_(52907984452).jpg

The Tomorrow River

 

The Tomorrow River is a small Wisconsin stream that crosses US Highway 10 three or four times between Fremont and Waupaca.  It eventually runs into a creek and becomes the Waupaca River.  I crossed all those tributaries twice on a trip last weekend. It gave me the usual opportunity to free associate to my past life. Two memories came immediately to mind – both from about 1977.  I was freshly out of the Peace Corps and trying to establish myself in a job as a research assistant cloning trees at an Institute in the area. That involved a lot of travel down Highway 51 to Highway 10 and I did not have a car.

One day I was travelling on a Greyhound bus heading to my apartment.  That was the first time I caught the Tomorrow River sign, as I looked up from a letter I was writing to my friend Glenn. I had a good experience in the Peace Corps entirely due to the Americans I met in my group.  They were bright, excitable, and energetic. We had gatherings where we listened to music, ate pizza, and played basketball.  We had long discussions into the night about what was important, what art meant, literature, music, math, science, and the meaning our work as high school teachers in the Peace Corps. We read the hipster literature of our time – Kerouac, Pirsig, Kesey, Brautigan, Wolfe, and others.  There were animated discussions and arguments.  All of that probably influenced the letter I was writing and then I saw the sign. The letter took on a surrealistic quality that Glenn appreciated in a letter he sent back to me.  As I visualized that decades old experience – it was a good feeling. I still feel a connection to my Peace Corps friends even though it has been decades and we rarely see one another or communicate.  I know that when I do – we will pick things up the way they have always been.

Between the second or third Tomorrow River sign there is an uphill curve in the road that bends to the left when you are traveling east. It is a long half mile bend. Later that same year just after Thanksgiving – I was getting a ride to my apartment from my friend Walt.  We went to the same high school and college. He was two years younger than me. Walt’s personality was completely the opposite of me. He was spontaneous, outgoing, and engaging. He could joke about anything.  I was the lab assistant in his organic chemistry section and one day his condenser hose broke loose and started spraying water just over the top of a freshly cut pile of sodium metal. I was able to grab the hose and redirect it.  Luckily there was no contact with the sodium, but after that point he started referring to himself and his lab partner as Captain Sodium.  On that day he was dropping me off and heading to his graduate program in endocrinology in Chicago.  The weather was not cooperating.  On that bend – the traffic that was usually travelling at 65-70 mph was at a dead stop in an ice storm and backed up for miles.  We both got out for a better view and realized it was impossible to stand on the road. Even  maintaining your balance, you eventually slid from the highest to the lowest part of the road and were forced to crawl back across the lane of oncoming traffic. We got back in the car and spent a long time joking about his bright reddish orange Dodge sports car and all of the trash talk he got from people in our home town about that car.  When he walked into a local bar he would hear: "Here comes the Fire Chief!"  We eventually completed the trip and I would see him from time to time over the next decades as he completed his PhD, then medical school, then residency in anesthesiology.  He became one of the top anesthesiologists in the country. And then several years ago, I got the news that he had died suddenly after a brief illness.  He was at the top of his game at the time – a department head and national expert in neurosurgical anesthesia.  I felt badly about not seeing him and not congratulating him on all of his success. I always feel badly when people don’t make it to retirement and a lot worse if I know them.  

Even before I went into the Peace Corps, I spent a lot of time navigating these roads with my friend Al.  We did that mostly in a 20-year-old Volkswagen beetle with a defective gasoline heater. When you tried to turn the heater on it might blow the hood open. Al was a mathematical genius and had accumulated almost enough math credits for a major when he was in high school - all self-taught by reading the texts. He decided to go to medical school and that led him to spend an additional 2 years as an undergrad taking the prerequisite courses.  Somewhere along the line driven by my insomnia and his sense of adventure, we ended up driving long distances to other towns at night to see movies or bands that we knew would never come farther north to our college town.  When you drive on roads in Wisconsin, Minnesota, and Michigan unusual things can happen.  When the pitch-black night is underlit by the snow cover – anything can happen. One night at about 2 AM we were on a road running parallel to Hwy 51 north when suddenly – an old model Chevrolet was airborne about 50 feet in front of us.  By airborne I mean it crashed over the top of a 5- or 6-foot snowbank at a high rate of speed and crossed our highway in a perpendicular path.   It landed on the other side of the road clipping the top of that snowbank first.  Turning around it was obvious that this was a planned attempt to launch the car from a parking lot outside of a bar to the other side of the road.  A few seconds later would have resulted in our Volkswagen being T-boned. That night we were able to turn up the radio and keep going.

These are the kinds of associations I have when I am driving these roads.  The paragraphs seem flat compared to the images in my head. I can envision my friends, our youth, images of what happened, the associated emotions, and the thoughts I have stacked on these events over the past 40-50 years. People I knew then often in a casual way.  People who I wanted to know better. People who – if I had interacted with them differently – would have drastically altered the course of my life and the people who did alter the course of my life. People who I wish would call me or send me an email.  People who I regularly think about and dream about.  But then I tell myself – “This is your own weird perspective on life – most people don’t think like this.”  Generally, that is good to know but at the same time – people do reach out from the past. They seem to realize that we are not the same people we used to be – but the common experience means something.  In many cases, it means a lot.  At my 50^th high school reunion, I was sitting outside of the main room when a classmate approached me and asked if she could sit down. I have known her for over 50 years and yet, that conversation was the longest I had ever spoken with her. It was longer than all of the conversations I ever had with her combined.  It was probably the best experience of the reunion.

I should probably clarify that I have no regrets and consider myself to be very fortunate.  All of these thoughts about the past don't cause regret - but there is often that feeling that you get when you go back to your home town for the first time. You see things in a different light.  You realize that you can't go back to the way things used to be. These thoughts have continuity with the present and the future.

At some point in the drive, I do a memory check.  I use the autobiographical memory test format and think of famous movie stars, visualize their image, and try to match names.  So far – so good.

I fantasize - primarily generative fantasies. I first encountered that term in the writings of the late Ethel Persons, MD.  She was an American psychoanalyst I found when I started to research fantasies in the 1990s.  She seemed to be one of the few psychiatrists writing about it. Generative fantasies are primarily problem solving fantasies that are more stimulating than coming up with lists in your head or your software. As I type that I am reminded of another road trip (east of Duluth on Hwy 2) when my wife asked me: "Do you ever have fantasies?' I told her I was fantasizing right at that time and she was very interested in the content. "I was thinking about what it would be like to win the men's 500M in the Olympics." She knew immediately that I was thinking about speedskating. I took up speedskating during residency and got quite good at it in my 40s. I was never an elite speedskater by any means, but I had the movements down, could endure the pain, and skated a lot of laps.  Part of learning the movement had to do with fantasies and thinking about the skaters I was seeing in the Olympics and racing against and remembering any advice I had received. I always have plenty of these thought patterns that seem focused on a hypothetical future.

 As a student of consciousness, I always wonder about how all of these thoughts are generated and (as a psychiatrist) what they might mean. Twenty years ago, I did a presentation on what I called the bus theory of the human brain. In computers, a bus is any system that connects components and allows data transfer between those components.  I decided that there was not enough emphasis on white matter and studied those tracts, their fiber content, and tried to calculate the bandwidth of those fiber tracts. At about the same time, I was wrapping up a course that I taught for many years on dementia diagnosis and cortical localization that was more of a behavioral neurology approach to the problem.  I tried to think of all of the recent papers I had pulled on hippocampal connectivity and recent papers on the neurochemistry of the hippocampus.  I thought about a paper I recently read on entropy and consciousness and whether thermodynamics could be a granular explanation for conscious states.  I am still a skeptic.

My wife wakes up.  We are driving home from her high school class reunion. There is a significant celebrity in her class and he sent a video when he could not make the reunion. The audio-visual equipment did not work, but we could see his projected image. We start to talk about the events of the night and what some of them might mean.  We talk about the A-V problems and the celebrity who clearly has become a projective test for everyone in her class. We talk about how good it will be to get back home and what we will need to do to reestablish the routine.

Thinking is a big part of life for me and life is very good…..

 

George Dawson, MD, DFAPA  

 

Photo credit for this one goes to my wife.  That is a Tomorrow River sign shot alongside Highway 10 last weekend.

References:

1:  Osanai H, Nair IR, Kitamura T. Dissecting cell-type-specific pathways in medial entorhinal cortical-hippocampal network for episodic memory. J Neurochem. 2023 May 30. doi: 10.1111/jnc.15850. Epub ahead of print. PMID: 37248771.

This Is How Civilization Ends...

I had that thought immediately after seeing the above graph on the CDC web site. Over a million new cases.  An all-time high by far.  At that point, the news had been heavy with discussions about the Omicron virus for about 3 weeks. The trail though Africa and Europe was described.  In the United States we had plenty of warning and plenty of time to adjust.  It wasn’t like that first peak in the fall and winter of 2020-2021.  Back then there were no vaccinations.  My wife an I finally got vaccinated in March of 2021 and then only by an extraordinary stroke of luck.  Before Omicron we were flush with vaccinations.  Two different retail pharmacy chains were scheduling appointments and they were free. When the booster came out that was also free and much easier to get. The overwhelming scientific evidence was that the immunizations were safe and effective.

The public health measures seemed less effective. That could be confirmed by a walk around Target or Walmart. At the absolute peak of mask wearing in Minnesota, my estimates were up to 30% of shoppers were masked. Half of those masks were loose fitting cloth masks and probably not very effective. Today, at the height of the Omicron spike 10% of the people in my coffee shop were masked and I was the only guy wearing an N95.  Despite an increasingly vocal group of aerosol scientists most people remain shockingly ignorant or willfully ignoring the airborne route of transmission. The most easily observed scenario is restaurant dining where the customers wear a mask to the table and then take it off to eat and talk for the next two hours. There is no magical protection from airborne virus in that scenario. Forget about the 6 feet safe distance rule at the start of the pandemic. Looking for restaurants that have improved their HVAC systems to improve airflow and air exchanges over time was also disappointing. So far in the Twin Cities Metro area I have found 1 restaurant. No restaurant or business as far as I know is posting their air exchanges per hour or carbon dioxide measurements to describe the potential risk of their environment. They are posting that they adhere to social distancing and all of the surfaces are wiped clean between diners.

Despite all of that inertia, the restaurants are packed.  Typically, shutdown occurs when a significant number of staff are ill with coronavirus and they cannot stay open. I dodged a bullet at Christmas just as infections were increasing. My wife and I were supposed to meet another couple at a restaurant. My suggestion to get take out and eat it at either of our homes was met with resistance. I was saved by a call from that restaurant that significant numbers of their staff were ill and they would be closing until things improved.   

The general cultural landscape has been even more grim. I follow all of the experts in the media on a regular basis – Drs. Fauci, Hotez, Jha, and Walensky.  On an average day they are awash in a sea of misinformation.  That sea contains the entrepreneurs who see the pandemic as a money-making scheme as well as the purely irrational who find that conspiracy theories about the virus, vaccine, and public health measures are easier to understand and believe than the science. Political opportunists are in the mix and as recently as today were suggesting that “white people” were being discriminated against and were less likely to get the vaccine as a result. The Florida Governor made this statement:

“We reject the biomedical security state that curtails liberty, ruins livelihoods and divides society.”

Biomedical security state? The politicization of this pandemic knows no bounds. It obscures both the science and goodwill toward the scientific and medical communities.  But it doesn’t stop there.  In some large health care organizations 10% of the workforce has been fired for not complying with workplace mandates on COVID-19 immunizations.  Some of these workers are physicians who should have been taught basic epidemiological concepts – the most basic being that vaccinations are a rare medical miracle that have saved the lives of tens of millions of people.  Disease have been eradicated, prevented, and the course of infectious diseases has been altered.  And even if you are not a physician, everyone has the experience of taking all of the mandatory vaccinations required to attend school.  Most of these vaccinations had a significantly worse side effect profile than the currently available COVID-19 vaccinations.

Apart from reducing rates of infection, hospitalization, and death these modern vaccinations also reduce the risk of chronicity. Chronic or “long COVID” symptoms might occur in as many as 70% of patients after the infection. Remission rates and rates of disability are still being determined at this time.  Given the risk/benefit considerations of the vaccinations it is difficult to see how any rational person would refuse it.  It is even more difficult to understand how a rational person would not take basic measures to protect themselves and their families from airborne virus or justify ignoring the pandemic on the basis of a completely implausible conspiracy theory. In some cases, the motivations are very clear.  Politicians would rather use various forms of rhetoric to attack the idea of a pandemic and what it takes to resolve it for political gain rather than taking positive steps recommended by experts. It is a standard political tactic.  That rhetoric has been advanced to extreme levels and to the point where scientists and their families are being threatened.  Today the suggestion that “white people” were being discriminated against struck me as white nationalist rhetoric.  It was viewed just as another “falsehood” in the media.  Certainly, blind partisan acceptance of these statements is not very likely to exhibit flexibility in thinking about the pandemic, the virus, or possible solutions.

The press has stepped in and commented on the process as a “mass delusion” or “mass psychosis” as if the use of psychiatric jargon by a journalist would add credibility to the criticism of many people thinking and acting irrationally. Many of them are agitated, visibly angry, and can become aggressive typically when confronted about pandemic precautions in schools and businesses.  Hardly a day goes by without seeing an airline passenger or town hall meeting participant screaming until they are red in the face and carted away by security. None of these people has a psychiatric disorder.  They can cool off somewhere, suppress their irrational thoughts and the associated anger, and get up and go to work the next morning.  During the run up to the 2020 Presidential election there was heated commentary about President Trump’s mental health and fitness for office. There was some debate in the psychiatric community if it was appropriate to discuss that issue based on Trump’s observed behavior rather than a psychiatric assessment. This essay looks at the other side of that debate. Why do so many people follow leaders who make repeatedly false statements that in some cases are viewed as potentially inciting people to do the wrong thing? And conversely – how do so many people accept the more obvious rational path and reject all of the paranoia and conspiracy theories?

There are of course numerous theories about how this comes about.  The theories generally depend on the same theories that have been used to describe normal development, psychopathology, and normal learning processes.  In some cases the theories have a philosophical basis – that seem to be fashionable these days. And despite many of these theorists incorporating a neurobiological model – very little explanation about how that is relevant.

The relevance is obvious to me starting with the relationship between emotion and cognition specifically decision making. In order for it to be obvious, the relationship between emotions and normal decision making needs a brief exploration. Human decision making typically occurs as an integrated process in the frontal cortex. I won’t digress into any subdivisions or tracks in this post. The key word here is integrated. That means the frontal cortex takes a large number of inputs and uses them to varying degrees in the ultimate decision. That includes a lot of memory input, specific types or learning, emotional input, and real time sensory and perceptual data.  The amount of input is large and much of it occurs at an unconscious level. How it occurs is largely unknown at this point but with our limiting inputs have been determined.  One of those inputs is emotion. We know for example from lesion studies that emotional input is absolutely critical for normal day to day decision making. Of the vast number of potential decisions we all have a subset that are associated with emotional valences that can affect our preferences. Without access to those valences decision making slows and grinds to a halt.

Restricting our consideration of the decision space to all of the possible decisions about the pandemic and how to proceed – all of the medical, scientific, personal, political, manipulative, and conspiracy theories the possibilities are very large. If we have 300 million decision makers and they all have unique conscious states and personal capacities for decision making the potential outcomes are large. It is also a more complex scenario than all of the typical explanations for pandemic denial.  Each one of our 300 million decision makers has unique experience affecting the emotional valences of their decisions. The overt decisions may seem to coalesce at some points but for many different reasons. For example, believing what a politician says despite the clear documentation that they are lying can occur as the result of identification with similar people in the past, identification with a general class attitude or ethos that it represents, or it simply could be activated by the angry emotion that politician effects. Those are just a few possibilities.

The pandemic vaccination vs. anti-pandemic antivaxx is by definition a binary polarized debate – the reality based on what we know about how the brain works it is far from that simple.  Even on what appears to be the rational side there is no Spock-like analysis.  The public health experts are all accessing emotion when making their decisions. Rational thought is reward-based learning and associated to one degree or another with a “Eureka” moment.    

The key question going forward is what can be done to address the degrees of freedom associated with the possible decisions of this brain process.  What can be done to improve the process and by improve, I mean assure that civilization survives the current and potentially more lethal pandemics. To that end, there are numerous cinematic depictions of apocalyptic pandemics. Based on the depictions prior to this pandemic they are probably fairly accurate. Once a lethal pandemic takes hold, the decision space for survival collapses as fewer and fewer decisions are possible. An intuitive writer or film maker knows that at some level.  Time to make it general knowledge.

 

George Dawson, MD, DFAPA

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

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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.