After three years of studiously ignoring obvious patterns, The Science inches closer to acknowledging that viral interference is a thing

A news article at Science throws water on the prospect of an impending SARS-2, RSV and influenza “tripledemic”, pointing to “a growing body of epidemiological and laboratory evidence” which suggests that “SARS-CoV-2 and other respiratory viruses often ‘interfere’ with each other.” There is therefore little chance that all three viruses “will peak together and collectively crash hospital systems.”

Sporadic epidemiologic reports have documented how waves of influenza seemed to crowd out RSV, parainfluenza, and other respiratory viruses. …

The influenza pandemic in 2009, driven by a novel flu virus dubbed pH1N1 that had recently emerged in pigs, put the study of viral interference on more solid footing. When populations have scant immunity to a novel flu strain, it can circulate widely outside of the winter season, as happened with pH1N1 worldwide. But groups from Sweden and France, who used the highly sensitive polymerase chain reaction (PCR) assays to detect viral genetic sequences, showed that in those countries, spikes of rhinovirus infections in late summer delayed the peaks of influenza until late fall, the normal start of flu season.

Emphasis mine. Rhinoviruses appear to have an array of antagonistic reactions with other common respiratory viruses. They are typically active not in the dead of Winter, but in the Fall and Spring, and the decline in rhinovirus cases every Fall tends to mark the beginning of the Winter virus season.

More recently, in one of the largest, longest, and most comprehensive studies of respiratory virus infections in humans, Murcia and colleagues used a PCR assay that can identify members of 11 viral families to probe nasal and throat samples from more than 36,000 individuals who sought care from the National Health Service in Glasgow over 9 years. Among other examples of viral interference, their data clearly showed rhinovirus and influenza A peaked at different times … demonstrating a “negative interaction” between the two viruses, the group concluded in the 26 December 2019 issue of the Proceedings of the National Academy of Sciences.

Here’s what that looks like:

The next year, Foxman and colleagues reported finding interference after PCR testing for 10 different viruses in 13,000 respiratory samples from adults who sought care at the Yale New Haven hospital system. Between 2016 and 2019, about 7% of people tested positive for rhinovirus or influenza A virus, but of these 1911 samples, only 12 had both viruses, significantly fewer than expected, they reported in The Lancet Microbe …

The claimed interference mechanism, as always, is interferon. This is an antiviral protein released in response to virus infection, which limits the capacity of other infecting viruses to replicate for a refractory period that may last as long as a month.

I’m sure that interferon plays an important role, but it’s probably only one of multiple factors at work here. To begin with, there’s one of my favourite hardly acknowledged virus facts, namely that “the overall prevalence of any viral respiratory infection among patients with respiratory illness is relatively stable over time, despite strongly varying prevalences of individual viruses.” Relatedly, we know from fever gauge data that overall rates of respiratory illness appear to be capped at around 10% of the whole population, and that rates of infection tend to collapse directly after reaching this ceiling.

To this comes the strange evidence of challenge studies like this one, where researchers could only infect 18 of 36 unvaccinated, previously uninfected study participants by squirting a SARS-2 solution directly up their noses. Influenza challenge studies have had even less success. For whatever reason, at any given moment, most people just aren’t susceptible to respiratory infection, and it looks like even novel viruses at the most favourable of times must compete for a small minority of human lungs.

While the rate of virus infections remains relatively constant, the mix of viruses is always changing. In the PNAS paper linked above, we find this graphic, which illustrates the relative prevalence of major respiratory viruses in their subject samples:

In 2009, we see that the overhyped Swine flu (orange) beat back rhinovirus (red) substantially, and that RSV and ordinary coronaviruses (dark and light green respectively) hardly appeared at all that year. For most people, Swine flu was an unusually mild influenza infection, but despite that it pushed out several of its major competitors, with the result that respiratory disease burden of the 2009/10 season struck many as lower than normal.

This is not just a minor curiosity. It’s a powerful reason to avoid interference with the broader viral ecosystem via insane policies like mass containment. Rhinoviruses, for example, seem to have proven at least somewhat robust to the pervasive use of hand sanitiser, although they depend heavily on surfaces for transmission. We should be grateful for that, because they cause extremely mild infections, and they also seem to play an important role in regulating the seasonality of other, more serious pathogens, like influenza. And while our lockdowns didn’t seem to affect rhinovirus very much, it’s plausible that they did take out some of Corona’s less contagious competitors. This is probably one of the reasons that containment policy and virus mortality often seem to be so closely correlated. Care homes, for example, were subject to some of the most zealous containment measures of all, and they were repeatedly ravaged by high-mortality SARS-2 outbreaks.

Viral interference is one of the first themes I ever wrote about here at the plague chronicle, and I’ve returned to it repeatedly since then. I’m very pleased to watch yet another conspiracy completing its transformation into generally accepted (if awkward) truth. This is one of the primary reasons that we should think less about viruses. We find faeces deeply revolting, and this is an evolutionary adaptation, because faecal matter is full of dangerous bacteria. We have similar disgust reactions to vermin and insects, which are likewise notorious vectors of disease. In contrast, we generally don’t find coughing or sneezing to be an inherently disturbing activity, and the reason is very likely that there’s no upside in trying to avoid seasonal respiratory infections.