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):