The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is the cause of COVID-19 is still a bit of a mystery. Even how it travels in the air is unclear, as the debate on the subject shows. The public fear and panic of living under a viral cloud has led to new levels of paranoia. Gradually, however, the experts are teasing out the secrets of the inscrutable virus.

Thomas Yuill is one of the disease moderators of Program for Monitoring Emerging Diseases (ProMED-mail), a project of the International Society for Infectious Diseases. It’s an electronic surveillance and reporting system for outbreaks. It reports on diseases of infectious or toxic origin that affect people, plants and animals, including zoonoses. Each report is checked for accuracy—disease moderators provide context by commentary and reference—and then posted to its website and sent to its subscribers. On a global scale, it helps the flow of communication among the infectious disease community.

Yuill is a professor emeritus in pathobiological science, forest and wildlife ecology at UW-Madison University, Wisconsin, USA.

His interest was kindled in his undergraduate training in wildlife ecology, working on parasites of geese and deer. It became more focused on viruses and virus disease in graduate school with joint majors in wildlife ecology and virology with field studies on arboviruses in Alberta, Canada. Initial exploration of parasites made him aware that there are pathogenic organisms in populations of wild animals. That exploration grew in graduate school under the influence of his advisor, Professor Robert Hanson.

After his Ph.D, he was in the US army, posted as a virologist at the Walter Reed Army Institute of Research with field and laboratory work on eastern equine encephalitis and other arboviruses. That was followed (after the army) by two years of arbovirus field research (Japanese encephalitis and dengue) in the Virus Diseases Department SEATO Medical Research Laboratory.

Later, he was invited to join the departments of Veterinary Science and Wildlife Ecology at the University of Wisconsin-Madison (UW) as an assistant professor. His initial task was to organize a field training and research program in collaboration with the Veterinary School of the University of Antioquia (U de A) in Medellin, Colombia. He lived in Colombia for two years and then commuted there frequently for over 15 years. There he worked on several arboviruses that caused periodic outbreaks in humans and in animals.

He and his graduate students were part of the team that discovered the maintenance and transmission cycles of the La Crosse virus, a significant public health problem. Although retired, he continues to teach at UW and at the Autlan campus of the University of Guadalajara in Mexico and give occasional lectures in at the U de A in Colombia.   

His work has provided solutions. For Venezuelan equine encephalitis, a vaccine was developed to make horses immune, and without epidemics in horses there were no epidemic involving people. By discovering which mosquito was the vector of La Cross virus, it became possible to get towns and rural people to eliminate many breeding sites of the mosquito thus reducing cases of encephalitis in children to very low levels. Although not involved personally, he was watching the development of dengue vaccines with considerable interest. He thinks there will be one effective against all four serotypes of that virus available in a year. He also has hope for the successful development of a vaccine fo SARS CoV-2 within a year.

Yuill has been with ProMed since 2007. “I value my ProMED work because it keeps me up-to-date in the fascinating field of virus diseases.”

In a conversation with Fountain Ink, Yuill talks about things that are known and still to be known about SARS-CoV-2.

ProMED was the first to get off the blocks on the new Coronavirus with the first report on undiagnosed pneumonia in China on December 30, 2019. How was it like to know about something new?

ProMED moderator Dr. Marjorie Pollack was the first to post the report of undiagnosed pneumonia in Wuhan, China, in late December 2019.  That sounded the alarm for all of us ProMED virus diseases moderators because of the suspicion that SARS coronavirus might have reappeared. At first, we did not know if we were dealing with the previous SARS virus or something new but by January 8 a new coronavirus was identified.

Although Dr. Pollack was the moderator handling the expanding epidemic, I was her backup and posted a few reports when she was unavailable. My reaction was a serious concern because there were so many unanswered questions. It soon became apparent that the virus was spreading rapidly person-to-person and expanding geographically in China and was likely to spread to other countries. It did and quickly.

My concern, and that of my ProMED colleagues, grew and continues to the present time. We have experienced some frustration with the emergence of information that is not true that complicates the understanding of what is really going on by the public, media and some politicians and interferes with sound decision-making and needed action and public compliance.

Could you tell us how ProMED keeps tabs on incidents of viruses entering communities. What are the mechanisms involved?

ProMED receives daily reports from all over the world. These reports come from a variety of sources: the WHO, national and local health departments, individuals who submit information and the media. The media are usually print-source articles that mainly come to us from HealthMap and Google search engines and those that we may find ourselves. We assess their accuracy and usually make comments about the content.

How would disease trackers think through these things? Obviously, nothing much was known about the new virus then.

It is normal to draw on experience and knowledge of past epidemics. However, every epidemic is different so extrapolations must be made with caution. It becomes a matter of making comparisons constantly and, as new information on the current epidemic becomes available, making modifications of the current situation and possible future scenarios.

I and my colleagues were seriously concerned about the appearance of the new virus. Because it was genetically similar to SARS coronavirus, we thought it could be equally transmissible and pathogenic for humans. As the epidemic progressed, it became apparent that it was more transmissible between people and caused more cases of significant disease and death.

Although SARS and MERS inflict severe illness and death, the six members of the coronavirus family haven’t caused a pandemic. Why has SARS-CoV-2 become a pandemic?

SARS-CoV-2 became pandemic because it was rapidly transmissible between people. Through the course of the epidemic so far, a single infected person spreads the virus and infects 2.4 additional people, making the increase exponential. The movement of infected people rapidly spread the virus first within China and then to other countries.

Could you explain, so far is known, the biology of the virus? And, why it behaves the way it does.

Transmission mainly is through aerosolized droplets produced when coughing, sneezing or just talking. Virus in these droplets is viable for three hours. The virus can persist on hard surfaces such as plastic and stainless steel for 2-3 days. The virus is enclosed in a covering (capsid) that protects it from adverse environmental conditions.

From the point of view of the virus, there will be genetic selection of viruses that are optimally transmitted from person-to-person. From the point of view of susceptibility of humans, genetic studies are underway.

Could you talk about the molecular genetics and biochemistry involved in the pathogenesis of the virus?

Coronaviruses are spherical and have spikes protruding from the capsid covering. The glycoprotein structure at the end of the spike determines which species it can infect. If cells have protein receptors (protein angiotensin-converting enzyme 2 (ACE2)), that match the structure on the spike, it can attach to the cell, be incorporated into the cell and carry out replication. Cells in the human mucosal lining of the nose, pharynx, respiratory tract and gastrointestinal tract have cells with the receptors for SARS-CoV-2 virus. The spike structure is important not only to understand the virus-cell relationship, but for future vaccine development.

It latches onto the upper respiratory tract and then eases into the lower respiratory tract. Is it because it sticks in the upper respiratory tract that it is rampant? Are there other viruses that do the same?

Where the virus initiates replication depends on where it encounters susceptible cells. Very small droplets can penetrate deeply into the respiratory tract; larger droplets higher up. Once replication is initiated, large numbers of virus are released, can infect neighbouring cells and are carried in mucosal secretions throughout the tract. There is some evidence that a viremia can result that would carry viruses throughout the body.

What about virulence?

From the point of view of the virus, there will be genetic selection of viruses that are optimally transmitted from person-to-person. From the point of view of susceptibility of humans, genetic studies are underway.

Could you tell us about viremia (presence of virus in blood) and contagion and the severity of the illness. Any correlations you have come across in Italy and Spain and even the US. Can we understand the virus better when seeing what is happening in Italy, Spain, and the US...What is going to happen to India? 

Viremia does not seem to be the critical factor in contagion and it remains to be seen how important it is in severity of illness. The high case fatality rate in Italy appears to be due to the hospitals (and especially intensive care units) being overwhelmed by a flood of patients so that optimal or even adequate care could not be provided and more patients died.  This is what needs to be evaluated in India before the epidemic curve increases rapidly. 

I hope that is going on there now. Time is of the essence. The situation needs to be evaluated holistically. A testing strategy has to be formulated in advance in order to be widespread in application and in the right places to find out where the virus is currently and where it is likely to go. That means that there has to be an adequate number of test kits, personnel and materials to take samples and laboratory support to test the samples.

Information flow is essential: test results go to the individual tested, the attending physicians and the epidemiology unit that complies and evaluates test results and determines their significance. There must be a central information unit that provides timely, reliable information to the public and to policy decision makers. If this is not done, false information and rumors will fill the void. Policy must be based on scientifically sound information and action must be based on cooperation by an informed public. Changes in usual behaviour are not easily affected, especially in a country like India with a wide variety of cultures and economic strata.

What about the generation time and reproduction number of the virus? What is known and what needs to be known.

Generation time is based on R sub naught (R0), which is the number of individuals that a currently infected individual will, in turn, infect. Currently it is 2.4, or an infected person will infect an additional 2.4 people. When it is 1, the curve is flat and when it is less than 1 the curve goes down.

What is the incubation period and how long does it take for symptoms to appear? Are asymptomatic people shedding the virus and infecting, and on what scale?

The incubation period is the time from when the infection is first acquired until the first symptoms occur. Fourteen days is the incubation period for the virus. There is some evidence that virus shedding can occur before symptoms appear with this virus.

Subclinical is infection with no symptoms. Pre-symptomatic is the period before symptoms appear, and asymptomatic is infection without symptoms. These terms are often used interchangeably

Pre-symptomatic people shed the virus before symptoms appear. Some individuals who are infected but asymptomatic and never develop symptoms are reported to shed as well. I have not seen an extensive study that demonstrates how long they shed and if they shed high quantities of virus, enough to transmit effectively to other people. 

It is unfortunate if no surveillance for community transmission is taking place in India. The outbreak is likely to get out of hand.  

The virus has not yet hit India that hard. What are the chances of India going the Italy or Spain or US way...How much time do we have?

I am not in a position to know how hard India will be hit, nor when. This is something that you can evaluate, based on the criteria mentioned  above. I fear for the potential of a more serious epidemic should the virus get into the slums of large cities like Kolkata.

What are likely scenarios how this would end in the world and in India?

The epidemic will end when the R sub naught gets to zero.  But it may not do that and smoulder on at low levels like influenza does, with repeated outbreaks seasonally. The vaccine could end it forever if it is inexpensive and applied comprehensively around the world. I am quite sure that an effective vaccine will be available in a year or so.

Is it going to be endemic?

Probably.