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  Back in the days when I was working in an outdated building that had an HVAC system that was designed to contain heat rather than provide fresh air to dilute and remove airborne pathogens – I routinely observed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/),

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.

Acute-Care Psychiatry During the Pandemic

in the early days of this century, I spent a lot of time in Avian Influenza Task Force meetings. I was on two separate task forces and at the same time working on an acute care inpatient psychiatric unit. One of the meetings took up four hours in the afternoon and I would have to go back to my unit and make up those four hours. I made the mistake of that not saving all the documentation from those meetings. There were hundreds of pages. The main focus of one task force was on “surge suppression” or helping with crowd control to prevent emergency departments from being overwhelmed by people who did not really have the viral infection. The other meeting was more about the actual response to the viral infection. I was always skeptical of what I heard. We kept hearing that if there was an epicenter of infection, large pallets of Tamiflu would be on the way. We saw presentations with pictures of those pallets under plastic wrap. At the same time there was discussion about morgues and refrigerated trucks that have become part of the current crisis.

I was more concerned about what would happen to inpatient psychiatry units. I kept hearing that the medical and surgical beds would be overwhelmed. When I suggested that we increase the capacity of negative airflow rooms and rooms vented directly to outside air, I was told that was impossible. One expert gave the opinion that if there is an airborne virus in the hospital: “The minute you walk into the hospital you should be wearing an N95 mask”.

That was about 2005 and I had never heard of an N95 mask before that. I had certainly worn masks for painting, dust protection, and various chemical and biological experiments that I did in the course of education and research. I went out and bought a small package of N95 masks. I fitted them per the instructions and noticed a couple of things. The fit was extremely snug due to upper and lower elastic bands (that have a much smaller circumference than a human head or neck), the circular contour of the mask providing a suction fit to some extent, and a flexible metal band that bends over the bridge of the nose to effectively seal that area. When you are wearing an N95 mask your voice is muted and you are breathing against resistance. If you wear it long enough, it becomes soaked with exhaled droplets. I rapidly concluded that it would be nearly impossible to conduct a psychiatric interview wearing this mask.

I never really learned at the time whether there was a plan to shut down inpatient psychiatry and use all the beds for avian influenza patients. Thankfully it never got to that point. Flashing forward 15 years a real pandemic is upon us and the problems remain unsolved. Inpatient psychiatric units and residential drug and alcohol treatment units are considered necessary services in most states and they remain open. Very recent information from the authorities now suggest that SARS-CoV-2, the virus causing COVID-19 is airborne and that there are a significant number of asymptomatic carriers.

I have been using telepsychiatry at this point for two weeks and it seems to be going well. There are definite constraints compared with face-to-face interviews. I have noticed more constraints since my original post on this topic. I put a couple of questions out there on social media today to see how my colleagues who are still actively engaged in acute care are adapting to the changing parameters of this pandemic. Before putting those questions out, I had the thought that telepsychiatry could be used over the short distances in inpatient settings. As a resident I had the experience of observing psychotherapy firsthand and being observed from adjacent rooms that also had microphones for communication between those rooms. I was interested in seeing whether or not anyone had implemented those solutions.  I was pleased with the feedback that I have so far.

One of the first responses was that psychiatric staff were using surgical facemasks and face shields in some settings. In other settings, adjacent rooms and telepsychiatry both on-site and off-site were being used for acute-care units. The most unique solution I heard of was a consultation liaison team using iPads to interview medical and surgical patients remotely where possible. That reminded me that some people have joined my telepsychiatry sessions using smart phone apps. It was generally very suboptimal if the phone was not completely stabilized.  I also had the experience this week of getting a link sent to me from a colleague who worked for a large healthcare system. It was an invitation to open up a video session with him even though I am not registered in his clinic.  It was very similar to a Zoom session that I did for a podcast. All this information shows that there are technologies available right now that are effective and actively being used. They have also been very rapidly deployed or are in the process of being deployed. There is some potential that this sudden change in the delivery of psychiatric services may be a more permanent one.

I asked the question about whether or not the services were saving personal protective equipment (PPE). The response to that question was somewhat mixed. I am not clear on what it means but speculate that some of the staff still need to have direct patient contact at some point during the day. Most acute-care staff at this point have been assigned PPE. The PPE specifics seem to vary from place to place but it is clearly rationed. If I was designing a survey of acute-care psychiatric facilities I would like to see the specifics of how many people had N95 masks and other kinds of protective gear.

Preadmission screening remains a question mark.  There is general agreement that there is an asymptomatic carrier state for SARS-CoV-2 (1,2).  Carriers may have a lower viral load and be partially symptomatic. Most people admitted to inpatient psychiatric units these days require intensive nursing care for their own safety. If there were environments where patients with COVID-19 could be safely segregated and treated that would be ideal, but I doubt those kinds of environments exist on inpatient psychiatric units. Even then the asymptomatic carriers would require the same psychosocial interventions as non-carriers.  The general screening done is to ask about contact with known cases and daily temperatures. I am not aware of any screening procedures that involve trying to identify the virus and carrier state.

My overriding concern is that medical and psychiatric staff everywhere have adequate protection. We have known since my days on the avian influenza task forces that airborne viruses are difficult to contain. They can infect through surface contamination, droplet contamination, and traveling on air currents. Working to cancel all those routes of infection is a tall order especially on an inpatient psychiatric unit.

The only practical way to maintain the level of communication necessary and minimize risk of infection is through some type of electronic communication. Some of the early methods have been listed in this post. Having worked in these settings for a large part of my adult life I am very concerned about the staff with daily direct patient contact including nursing, nursing assistants, and occupational therapy.  Housekeeping staff also have a vital role and are directly exposed to most contaminated surfaces. I have seen large numbers of inpatient staff come down with seasonal respiratory viruses and I know that vulnerability is there. They all need PPE. We need additional innovation in these settings to protect all staff and patients.  

And we have needed that innovation for a long time.

George Dawson, MD, DFAPA




References:


1: Lai CC, Liu YH, Wang CY, Wang YH, Hsueh SC, Yen MY, Ko WC, Hsueh PR. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths. J Microbiol Immunol Infect. 2020 Mar 4. pii: S1684-1182(20)30040-2. doi: 10.1016/j.jmii.2020.02.012. [Epub ahead of print] Review. PubMed PMID: 32173241.

2: 1: Hu Z, Song C, Xu C, Jin G, Chen Y, Xu X, Ma H, Chen W, Lin Y, Zheng Y, Wang J,Hu Z, Yi Y, Shen H. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci. 2020 Mar 4. doi: 10.1007/s11427-020-1661-4. [Epub ahead of print] PubMed PMID: 32146694.

Supplementary 1:

I am very interested in what you are doing at your facility to contain this virus while continuing to go to work every day and treat patients.  I am also very interested in whether you have enough PPE.  I am interested in hearing from everybody staff psychiatrists, residents, social workers, occupational therapists, nurses, nursing assistants, and housekeeping staff.  Please post in the comments section below and feel free to remain anonymous. 


Graphic Credit:

Shutterstock per their standard agreement.

The First Case Report - Implications For Coronavirus Conspiracy Theories

At the time of this writing I have encountered at least three coronavirus conspiracy theories.  The American version goes something like this. The current pandemic resulted from a leak from a Chinese bioweapons laboratory. The supplementary information generally talks about how these particular bioweapons labs are not very secure and leaks are common. The Chinese version has a human twist and it involves a visit to China by 300 US military athletes. The suggestion is that these athletes intentionally introduced the virus or inadvertently passed the virus to the Chinese population. There is an Iranian version - suggesting that the virus is basically an American bioweapon.  There are various embellishments. Prominent politicians are involved in restating these conspiracy theories. I have been reading about bioterrorism for the past 20 years and would dismiss these theories as being implausible from a technical perspective. From a political perspective, it makes perfect sense to me that politicians will always try to look for a way to deflect any responsibility. One of the most common ways to do that is to blame an adversary - especially one that might be unpopular with the majority of citizens.

The report of the first case of coronavirus in the US is a rare opportunity to end all the conspiracy theories with real evidence. I do realize that conspiracy theories are not generally refutable by facts.  This post is directed at those who can incorporate factual information into their worldview. There has been a lot written lately about distinguishing opinion from fact, including the results of a standardized international test suggesting that American students may have some deficits in this area.

Detailed case report in the New England Journal of Medicine is interesting from a number of perspectives.  The patient is a 35-year-old man walked into an urgent care in Snohomish County, Washington on January 19, 2020 the four-day history of cough and “objective fever”. He had returned from visiting relatives in Wuhan, China. His health history was basically unremarkable. Initial vital signs showed a temp of 37.2°C, BP of 134/87, and pulse was 110 bpm. Restaurant rate was 16 breaths per minute and O2 sat was 96% on room air.  Initial viral screen for influenza a and B, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, and for common coronaviruses was negative. The CDC was contacted and samples were collected for 2019-nCoV. The virus was confirmed one day later.

The patient had been discharged home but after 2019-nCoV was confirmed he was admitted to an airborne isolation unit for observation. The clinical course is described in the figure below that is taken from the original paper (with permission). The symptom course before the admission date of January 20 is estimated on the diagram. I think it is instructive to note that cough preceded the development of a low-grade fever on day five of 37.9°C or 100.2°F. The patient also had fatigue nausea and vomiting before the development of fever.

Laboratory findings over the course of the illness are presented in the original article and six blood samples did not show any marked abnormalities. He had mild elevations of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Blood tests were done due to fevers and they showed no growth.  Chest x-ray on day 9 of the illness showed left lower lobe pneumonia that correlated with decreased O2 sat down to 90%. At that time he was put on supplemental oxygen. It is also treated with vancomycin and cefepime for presumed hospital acquired pneumonia. On day 10, based on his chest x-ray, the need for supplemental oxygen, and reports of the development of severe pneumonia is physicians decided to treat him with an investigational drug - remdesivir. By day 12 he was clinically improved and no longer needed supplemental oxygen. His oxygen saturations were normal on room air. As seen in the diagram, is always symptoms at the time were a cough and rhinorrhea.

Contrary to the conspiracy theories, this paper points out that the Chinese researchers shared the full genetic sequence of the 2019-nCoV in the National Institutes of Health GenBank Database and the Global Initiative on Sharing All Influenza Data (GISAID) database. 

The authors emphasize at the time of this writing that the full spectrum of clinical disease is undetermined. Transmission dynamics are also undetermined because the patient had not visited the seafood market in Wuhan or had any contacts with known cases in China. They list several complications noted in the Chinese population including acute respiratory distress syndrome, severe pneumonia, respiratory failure, and cardiac injury. There are several radiographs on Twitter suggestive of significant lung injury and at least one report of myocarditis in a significant subset of patients. The authors also point out that the patient had nonspecific symptoms prior to the onset of pneumonia that were consistent with a number of common respiratory viruses. In differentiating this illness travel history, the decision by the patient to seek treatment, and a coordinated effort among public health officials led to the timely identification of the virus. I would add that this case report also shows the clear need for clinical expertise as the illness transforms from what appears to be a typical respiratory virus to pneumonia. The question that needs to be asked is whether that level of expertise is available everywhere in the country.

Addressing the threat of emerging infectious diseases requires a public health infrastructure and cooperation across many countries with their own political interests. Many those countries may have public health officials that are cooperating with one another, but politicians who may decide to use a pandemic for their own interests. With most countries engaged in significant quarantine efforts at this time, clear cooperation among world leaders in stopping this pandemic is urgently needed.

George Dawson, MD, DFAPA

References:

1: Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, Diaz G, Cohn A, Fox L, Patel A, Gerber SI, Kim L, Tong S, Lu X, Lindstrom S, Pallansch MA, Weldon WC, Biggs HM, Uyeki TM, Pillai SK; Washington State 2019-nCoV Case Investigation Team. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Mar 5;382(10):929-936. doi: 10.1056/NEJMoa2001191. Epub 2020 Jan 31. PubMed PMID: 32004427.



Permission:

Figure 2 above is from the original article in reference 1 - with permission from the Massachusetts Medical Society.  License date is March 16, 2020 - license number is 4791120888948 for 12 months from the date of the license. 

New Twist On An Old Method To Kill The Flu Virus

Right after posting the previous article on the latest confirmation that influenza virus is airborne, I came across and article in Nature that had me thinking back to my childhood.  I remember walking into an insurance office on Main Street in our small town.  There was something strange about the environment.  Up next to the ceiling were ultraviolet lights.  The lights were shielded so that they only reflected up toward the ceiling.  I asked my parents what they were and got the answer: "They are there to kill germs."  My head was spinning from that answer: "There are germs in the air? They are up next to the ceiling? What kills the germs that are down here next to me?" Yes - I was a neurotic little kid.

Over time I learned a little about the nature of ultraviolet light, especially that it could cause eye damage if you looked right at it. As I got into the 1970s, the hippie era, and psychedelia that because less important.  There were UV lights everywhere - blacklight posters and the detergent residues in clothing phosphorescing white light after it has been activated by UV light.  In some environments everyone was bathed in UV light.

Today most Americans are aware of UV light because of sunscreen and eyeglass applications.  Long and medium wavelength (UVA and UVB) and not absorbed by the ozone layer.  It is recommended that glasses block 100% of the UVA and UVB for maximum eye protection.  That can also be designated as UV400 because they block all UV light from 280-400 nm.  The part of the UV spectrum is also important in sunscreens.  UVA penetrates the skin to a deeper level and is responsible for damaging keratinocytes, cataracts and causing premature aging.  UVB is responsible for burning and carcinogenesis.  UVA and UVB are considered both carcinogenic and carcinogenic.  Even those UV light has been known to be germicidal for over 80 years that human toxicity has limited the application.

UVC (100-280 nm) is blocked by the ozone layer and therefore is not a consideration in either eye or skin protection.  It is considered to be the part of the spectrum that is potentially germicidal and that is where the latest application begins.  In this report the authors used filtered 222-nm light sources in an experiment to see if they could inactivate aerosolized H1N1 influenza virus.  They were able to accurately measure the light dose and estimate virus inactivation using an epithelial cell model that measured infected cells by fluorescence.  The authors aerosolized the virus into a UV irradiation chamber.  The chamber had a total volume of 4.2 liters and had a characteristic particle distribution of 87% < 0.3 - 0.5 μm, 11% 0.5 - 0.7 μm, and 2% > 0.7 μm.  Those are characteristic particle distributions of airborne droplets that occur with breathing, talking, and coughing.

An air flow of 12.5 L/min through the chamber was noted and they calculated that this meant a single droplet passed through the chamber in about 20 seconds.  I think that is significant because it in unlikely in a typical building that a person would be standing in an air current moving that quickly. In other words, if the aerosolized virus can be inactivated in an airstream moving that quickly - it might have practical applications in most environments.  The authors were able to construct a dose response curve showing that at a dose of 2 mJ/cm² viral survival is negligible.

I found this to be extremely impressive work because it clearly shows that airborne influenza virus can be inactivated using a far-UV source that is much safer to humans than previous germicidal UV sources.  Furthermore the sampling and intervention characteristics seem to be very realistic in terms of what might be encountered in public facilities.  The real question seem to be whether any commercially available air cleaner/purifiers come close to matching the characteristic of this experiment.  A preliminary search of these devices shows that the airflow characteristics are typically not listed, very few use far-UVC light sources (most use germicidal 254-nm sources shielded in the device), and none are certified in terms of how much virus they kill. They typically suggest that germicidal UV light is all that is needed for air purification.  There is also the question of whether using a device in your office at work confers any degree of protection once you leave that office and start walking down the hallways.  My speculation is that it would not, but the amount of virus generated in your office may be a significant variable.

The authors themselves suggest that if their results are confirmed far-UVC represent a significant opportunity to limit the transmission of airborne disease and that it could be widely used in medical offices and buildings as well as public areas where disease transmission is common like airports and airplanes.

I am hoping that this areas of research yields rapid results and broad implementation.

George Dawson, MD, DFAPA 


Reference:

1:  David Welch, Manuela Buonanno, Veljko Grilj, Igor Shuryak, Connor Crickmore, Alan W. Bigelow, Gerhard Randers-Pehrson, Gary W. Johnson, David J. Brenner.  Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases.  Scientific Reportsvolume 8, Article number: 2752(2018).  doi:10.1038/s41598-018-21058-w

Graphics Credit:

Table 1, Figure 1, and Figure 2 are all used from reference 1 per the Creative Commons Attribution 4.0 International License.

Viruses Are In The Air - Protection From Airborne Viruses

Today was a good day.  I got up this morning and there on the morning news was a headline that I had been waiting to hear for at least 20 years.  There on CBS This Morning, Gail King was saying: "The flu can spread just by breathing so that is kind of scary."  That is kind of scary.  It is even scarier if you know that fact and listen to 20 years of how hand washing will prevent the flu. Hand washing is good only for surface contamination.  It does nothing for airborne viruses.  There is no known protection from airborne viruses other than biohazard environments.

I did not come by the knowledge easily.  Before medical school, I was a research assistance in a plant tissue culture lab.  Our job was to try to clone Loblolly Pine (Pinus taeda) and Douglas Fir (Pseudotsuga menziesii) trees from elite seed.  That required a sterile environment for tissue and media manipulations.  I spent much of the day working in a laminar flow hood bathed in sterile air.  We were not concerned at all about viruses at the time, but there were always experiments lost due to yeast and fungal contamination of the culture medium.  From there it was off to medical school and observations about just how contagious airborne viruses could be.  On some rotations the entire team was ill with respiratory infections.  I notice there is some movement today on telling physicians to stay home if they are sick.  If all of the people who were sick on one of these teams stayed home - there would be nobody there to take care of patients.  I did work with one attending physician who wore a surgical mask in a medicine clinic as a barrier to viruses.  Today we know that these masks are ineffective in blocking viruses.

The real eye opener came in practice.  For over 20 years I worked in an inpatient environment that was designed in the 1960s.  According to the HVAC experts I have consulted with, the environments in those days were designed to preserve heat.  They were not designed to provide fresh air in a manner that would minimize the risk of airborne virus infections.  All of the rooms in that environment had individual radiators equipped with fans.  The room air was recirculated.  At the top of each room was a 12" x 12" square vent that moved the air down  the length of the building to a few air shafts that traveled up and down between floors.  I was reassured that there was adequate air flow and that it was measured.  I was provided with some diagrams that did not really show any solid data.

In that environment, airborne viral infections ran rampant.  They were acute care psychiatric units - so many of the patients directly admitted had influenza.  It was just a matter of time before it was picked up by the staff and then transmitted from person to person.  Getting one or more of these infections predictably was quite depressing.  As anyone knows - a severe case of the flu disrupts your entire life.  The polypharmacy that the staff was subjected to was also impressive.  Long complicated courses of antibiotics for secondary infections after the flu had passed.  Exposure to prednisone and methylprednisolone for post-viral bronchitis and asthma exacerbations.  All of the infected staff were schooled in proper handwashing techniques by Infection Control.  During flu season we were basically adrift in tight confines - breathing contaminated air.  It is well documented by studies in hospital and other building environments that there are a significant amount of viral and other pathogens in the air that can be collected by a number of means (2).

The other enlightening experience involved my participation in two Avian Influenza task forces.  Practically all of the work that I saw being done seemed to ignore the issue of airborne spread.  That was probably at least in part due to the fact that the hospital capacity of negative air pressure rooms would be immediately overwhelmed.  At that point, I heard one expert say: "You need to have an N95 respirator mask on as soon as you walk through the door of the hospital."  The efficacy of those masks in preventing flu transmission is limited but probably offers some moral support when you are walking into an environment that is full of highly lethal influenza virus. Most of the planning done on the task forces seemed to be designed to prevent a large surge of patients going to the emergency department, providing psychological support to the overwhelmed, and hoping the military really did have that palette full of Tamiflu that they keep showing us in the PowerPoint presentations.

One of the questions I frequently get is - what about the vaccine?  Designing an effective flu vaccine is part science and part speculation.  It involves anticipating the viral strains of the next epidemic and that is difficult to know with certainty.  This is the first year that I can recall public health officials coming out with the actual numbers.  Most Americans have heard that this years vaccine is about 30% effective and that the most effective vaccines are 50-60% effective.  The argument is that the vaccine improves herd immunity and decreases the spread of the virus.  Exactly how much of that is cancelled out by broad exposure to an airborne virus is unknown, but I do think that is sufficient reason to always get the vaccination.  I was my own experiment for about 30 years.  I reacted to an anti-rabies duck embryo vaccine in my 20s and did not get the vaccine for the subsequent years.  I finally saw an allergist/immunologist about 7 years ago and have been getting the vaccine since.  Since then there has been no detectable change in the number or intensity of flu-like illnesses that I have developed.  During the time unvaccinated, I had the experience of developing an acute fever after being exposed to a colleague with the flu, taking Tamiflu (oseltamivir) and having the symptoms resolve within 24 hours.  There is a chance that a universal flu vaccine can be designed and I hope that is true.  In the meantime we are left dealing a number of airborne viruses and altering the environment seems like the best approach.   

Flashing forward to this morning.  Part of the story focused on Donald K. Milton and the work he did in designing a machine to sample flu viruses in a natural setting.  Other sampling techniques have typically involved subjects breathing according to protocol into a device.  The large reverse megaphone type of device that this group is using allows air flow past the face at a regular rate.  It allows research subjects to breath normally and sample their expired air for influenza virus.  The sample in this case was a group of healthy 19-21 year old college students with a high asthma prevalence (21%) and a low influenza vaccination rate.  Nasopharyngeal (NP) sampling and RNA detection was used to diagnose influenza and RNA copies.

The subjects were asked to breathe, talk, cough, and sneeze into the sampling device with no constraints on that activity.  They were asked to recite the alphabet at 5, 15, and 25 minutes.  Coarse droplets (> 5 μm ) and fine droplets (≤ 5 μm and >0.05 μm) were collected separately. Influenza virus was recovered from 89% (N=150) of the NP swabs and 39% (N=52) of the fine aerosol sample. This is positive proof that just breathing (tidal volume breathing) results in dispersing infectious viral particles into the air.  The influenza cases did not sneeze during the collection period. Viral shedding was greater for men.  Women coughed more frequently but shed significantly less virus per cough.  Increased BMI produced increased viral shedding in the fine aerosol and the speculation was that increased BMI causes a tendency for small airway collapse and that may lead to increased shear forces that produce the fine aerosol.  Since sneezing was not observed - it was not considered necessary to produce the fine or coarse aerosol.  Coughing was present and was a significant predictor of both coarse and fine aerosols.

 
This is a critical paper that I hope that all public health officials, administrators and architects will take note of.  It takes more than handwashing and coughing into your sleeve to protect people against influenza virus.  It takes recognition that this is an airborne virus and it is aerosolized by breathing.  Physicians are on the front lines when it comes to virus exposure and we need better barrier methods to prevent exposure.  During flu season I sit in a 8 x 10 foot office and talk with people who sit about 4-5 feet away from me.  I talk with most of them for 20-30 minutes or about the length of time of the experiment.  The symptoms listed in the severity scale below are incorporated into my review of systems and there are some days when 100% of the people I see have a respiratory infection.  If they all have influenza, 30% will leave aerosolized virus in my office just from talking with me.  Is there a better way to do things to minimize exposure?

I think it starts with building design.  Rooms that are all individually vented to the outdoors on both the intake and exhaust side.  Heat exchangers exist today and can be used for this purpose.  Starting with influenza as the model and optimizing air flow and humidity to decrease infection rates is a start.  Interviewing people across barriers or using television cameras is another possibility especially if vulnerable populations need to be protected from consultants who may be carriers. The tremendous lack of psychiatric infrastructure compounds the problem.  Although the building that I refer to was ultimately replaced and torn down - psychiatric services are typically housed in the oldest and most run down buildings.  Today jails have replaced psychiatric hospitals and the jail infrastructure is no better.  It is common to see patients who are acutely ill with influenza in these settings.  Psychiatric beds need to be in an environment that reduces the transmission of infectious diseases including airborne viruses.   

The work does not stop at that level.  The ways hospitals and buildings are cleaned needs to be thoroughly investigated.  Carpet and floor cleaning equipment clearly leads to the dispersion of particles in the carpeting or on the floor.  I am not aware of any initiative to make sure that cleaning the surfaces in buildings does not leave the air contaminated.

My advice is to spread the word and this reference to anyone who is unsure about airborne viruses. I am hopeful that at some point over the next 10-20 years the environmental aspects of the problem will be addressed.  That will change the nature of influenza transmission as well as a host of other viruses that get sampled in the HVAC systems of old buildings - probably long after the occupants have been infected by them.



George Dawson, MD, DFAPA


References:


1:  Yan J, Grantham M, Pantelic J, Bueno de Mesquita PJ, Albert B, Liu F, Ehrman S, Milton DK; EMIT Consortium. Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community. Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):1081-1086. doi: 10.1073/pnas.1716561115. Epub 2018 Jan 18. PubMed PMID: 29348203; PubMed Central PMCID: PMC5798362

2:  Airborne Virus Monitoring: unedited search



Supplementary:

Image at the top uses a crowd infographic from Shutterstock per their licensing agreement.

Supplementary 2:

This is the approach the authors used to scoring the flu symptoms severity in their paper (my interpretation) (click to enlarge):

Current Treatment of Respiratory Viruses - More Homilies

With Permission: SIB Swiss Institute of Bioinformatics,
Philippe Le Mercier, ViralZone.

My Facebook feed got me going today.  I get the Mayo Clinic feed since I consider their clinical care and some of their research to be the best in the world.  Of course social media is much less rigorous and sometimes it comes down to just advertising and promotion.  That was my assessment of the link to this document this morning.  It is a business document that purports to give advice on how to decrease your chances of a respiratory infection this winter.  Some of that advice is given by a Mayo Clinic Infectious Disease specialist and a Cleveland Clinic family physician.  There was one number I had not seen before and that is the Number Needed to Treat (NNT) for the flu vaccine is 40.  Forty people need to be vaccinated to prevent one case.  The advice is the usual set of homilies about respiratory infections including get the flu vaccination, wash your hands, sneeze into your sleeve, take care of yourself and stay home of you are sick.  In other words, there is no way in hell that you are not going to get sick at least once this winter.

Our continued 1950's approach to viral infections remains a mystery to me.  Certainly there are technical problems with trying to design vaccines for over 200 viruses that can cause the common cold.  But the reality is, vaccine design for influenza virus - easily the most lethal of these viruses is obviously not so hot.  As far as I know, vaccines for the most common of the cold viruses - Rhinovirus - is non-existent.  Anti-viral medications for respiratory viruses are more controversial.  Looking at the most popular one Tamiflu or oseltamivir.  The NNT to prevent one death may be 1,800 - 3,200.  The NNT to prevent one hospitalization may be 97 to 142 depending on criteria.  The NNT group suggests somewhat better NNTs of 36 and 83 for preventing a culture positive case of influenza and preventing pneumonia respectively.    Contrast that with the NNT for antidepressants of 5-10 as determined by Leucht, et al (2) in their comparison to other medications for various medical conditions.  And you thought antidepressants were ineffective?

Infectious disease respiratory virus research is a goldmine for all of the Luddites out there.  There are a number of web sites that provide free access to just about everything you ever wanted to know about every virus known to man.  The viral particle shown at the top of this page is the order that contains Rhinoviruses one of many common cold viruses and one of the viruses that may be responsible for the expression of asthma in predisposed individuals or exacerbations of asthma in asthmatics who are asymptomatic.   This illustration is from the ViralZone, one of many free online databases with detailed information about the molecular biology and genetics of viruses.  If I was an aspiring Luddite wanting to be provocative about the field of medicine being stuck in the 1950s despite the availability of all of this advanced information - this would be a logical place to start.

In previous posts here I have also critiqued the lack of attention given to environmental approaches to respiratory viruses and the fact that the airborne nature of some of these viruses is not acknowledged - possible because airborne viruses are not contained by hand washing and other direct contact techniques.  It s well know that viruses can be collected in the heating and air conditioning systems of public buildings and that altering the humidity and air flow characteristics in those buildings can change the viral concentrations in the air.  Whenever I have mentioned this to the administrators of buildings where repeated respiratory epidemics swept through the staff - I got the same response that I received from an airline after I reported a severe respiratory infection after one of their flights: "We are really sorry that you had flu-like symptoms after your flight and look forward to your future comments to help us improve our service."

What?!

 Time to get serious about respiratory infections and come up with some effective interventions.  Effective medication to prevent viral replication and spread in the infected and to create barriers to infection would be ideal and so would environmental methods to reduce the infection rate.  Considering the strong incentives in America to work while sick and considering that the average worker is going to get 2 to 3 respiratory infections per year that can last up to 3 weeks in duration means that very few of us and the patients that we treat are not going to be exposed and infected.  With the current advanced knowledge of the pathogens and modern heating and air conditioning systems it seems like a lot more could be done right now.


George Dawson, MD, DFAPA


References:

1:  Postma MJ.  Re: Tamiflu: NNT to prevent a pandemic flu death may be a million.  BMJ 2005; 331:1203.

2:  Leucht S, Hierl S, Kissling W, Dold M, Davis JM. Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses. Br J Psychiatry. 2012 Feb;200(2):97-106. doi: 10.1192/bjp.bp.111.096594. Review. PubMed PMID: 22297588.


Attributions:

Graphic at the top of this post is courtesy of: SIB Swiss Institute of Bioinformatics, Philippe Le Mercier, ViralZone.  http://viralzone.expasy.org/  licensed via Creative Commons Attribution- NonCommercial 4.0 International License.