Those troublesome asymptomatic infections

When I wrote my scientific review of the seasonality of respiratory illness in Medical Hypotheses (2016) I devoted several paragraphs to trying to show that respiratory viruses could become dormant, lurking unseen in their human hosts without producing symptoms, and that they could be reactivated, often after changes in ambient temperature.  I did this because at that time many scientists wouldn’t accept that the common  respiratory viruses could possibly become dormant.  In fact I was spurred on to write the article by a conversation that I had with a famous UK virologist; she told me that flu (as an example) was spread by an “endless chain of symptomatic individuals”.  If I were to write that article now, I would cut out most of that section and just cite a paper that came out last year, describing the work done by scientists at Columbia University [1].  They tested residents of New York City for the presence of respiratory viruses throughout the year, whether or not they showed symptoms of a cold or flu.  The results were remarkable.  First, they found that roughly 60% of people carrying respiratory viruses were asymptomatic.  Second, they found that people carried these viruses year-round: as many tested positive in summer as in winter.

Aymptomatic Shaman

This new information makes it difficult to interpret some other recent publications.  For example, researchers the Royal Infirmary in Edinburgh also published a paper last year, where they analyzed the seasonality of a similar group of common respiratory viruses [2].  This paper has been very influential in discussions of the likely seasonality of Covid-19, and it’s regularly mentioned in Twitter.  People say that it shows that various viruses have different seasonality, with, for example, non-enveloped viruses (meaning rhinoviruses and adenoviruses) causing infection throughout the year.  The problem is, we don’t know in how often the virus was actually causing illness- many of the infections detected could have been asymptomatic.  (To make better sense of the results we’d also like to know how many tests were done each day.)  In order to find out what’s really going on, more studies like the Columbia one will be needed.

We’d like to make predictions of the likely course of epidemics such as Covid-19, so we’d like to understand the seasonality of the well-established human viruses.  Do we want to know the seasonality of positive tests results, i.e. the seasonality of the presence of the virus?  Or do we want to know the seasonality of the illnesses caused?  The answer is we need both.  We’re going to want models, but they need to be more complicated, with a visible component – representing the people who are sick – and also a hidden component representing the asymptomatic cases where the virus is lurking undetected.  And we need a lot more data of the kind generated by the Columbia group to make the models meaningful.

Patrick Shaw Stewart, 9 May 2020

Note added 14 May 2020.  We will need to rethink our picture of respiratory illnesses in the light of the Columbia University studies.  We can now see that respiratory infections are very largely asymptomatic and that respiratory viruses are, to a great extent, symbiotic.  The body seems to get rid of them periodically, presumably when they get a little out of hand – often after personal chilling or cold weather.  In any case, viruses were detected in only 17% of samples collected, suggesting that these infections come and go.  Maybe the function of a cold is to have a clear-out of respiratory viruses and prevent more serious illnesses that might arise the the virus were to mutate and become virulent (it might, for example, lose its temperature-sensitivity).  We don’t yet know whether  symptomatic infections are normally required to pass the virus on to other individuals.  We do know, however, that symptomatic infections are more common during the colder months, so the observation that respiratory viruses are present as often in summer as winter suggests that these asymptomatic infections can be contagious, sometimes giving rise to new asymptomatic infections directly.   If this turns out to be the case, there might be more transmission events than we’ve been aware of, giving extra opportunities for natural selection to act and for respiratory viruses to fine-tune their behavior.  Once again, experiments are called for.

For more thoughts on the Columbia University study and its implications for the mechanisms that underlie the seasonal appearance of respiratory illnesses  click here.

[1] Galanti, M., et al. “Rates of asymptomatic respiratory virus infection across age groups.” Epidemiology & Infection 147 (2019).

[2] Price, Rory Henry Macgregor, Catriona Graham, and Sandeep Ramalingam. “Association between viral seasonality and meteorological factors.” Scientific reports 9.1 (2019): 1-11.

Other papers on the NYC study:

Birger, Ruthie, et al. “Asymptomatic shedding of respiratory virus among an ambulatory population across seasons.” mSphere 3.4 (2018): e00249-18.

Galanti, Marta, et al. “Longitudinal active sampling for respiratory viral infections across age groups.” Influenza and Other Respiratory Viruses 13.3 (2019): 226-232.

_____________________

The TDVT Hypothesis, as explained by my friend Brian.

For a general discussion of the seasonality of respiratory viruses, written for the layperson, please see  Every winter, colds and flu increase.

Author: PatrickSStewart

I’ve been helping structural biologists for 30 years to crystallize their proteins and I’m one of the two founders and Directors of Douglas Instruments Ltd, a small UK company that manufactures automatic systems for protein crystallization. I worked with Professor David Blow in the 1990s, and have published 15 papers about protein crystallization that have together been cited over 950 times. A few years ago I began to think about respiratory viruses when a friend bet me that I couldn’t find biochemical evidence that chilling could trigger vARIs. I started to write a short note, but everything fell into place so neatly that I ended up writing an article in Medical Hypotheses, and writing this blog.

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