The Unexpected Case of the Disappearing Flu

Some endemic respiratory viruses on hiatus during the 2020–21 season

H1N1 influenza virus (https://commons.wikimedia.org/wiki/File:H1N1_influenza_virus.jpg)

During the months preceding the surge of SARS-CoV-2 infections this fall and winter, many public health officials expressed concern about the potential for a “double-barreled” respiratory virus season. In this scenario, healthcare facilities would be totally overwhelmed by: 1) patients afflicted by infections caused by endemic respiratory viruses (such as influenza) that occur during any normal year, and 2) a massive influx of coronavirus patients. Fortunately, such a catastrophe did not come to pass. The reason for this is an unprecedented reduction in flu prevalence for the 2020–21 season.

Before proceeding, it should be noted that not all acute respiratory infections during the so-called “flu season” actually result from influenza viruses. In fact, influenza viruses account for only a minority of such infections in many cases, with the causative pathogen commonly going unidentified. Other viruses causing the same general suite of symptoms include: rhinoviruses, coronaviruses, adenoviruses, respiratory syncytial viruses, among others.

Many public health experts have made statements regarding the reduction in influenza cases this season. These experts have attributed the phenomenon to such things as flu vaccinations, hand-washing, mask-wearing, and social distancing. However, these explanations are largely implausible for the following reasons:

1. As previously discussed, a large number of acute respiratory infections are not caused by influenza viruses, so vaccination against influenza cannot explain the overall low rate of hospital visits for influenza like illnesses (ILI) this season. Moreover, given that the benefits of flu vaccination have been largely overstated, it is unlikely that this year’s flu vaccine has reached an unprecedented level of efficacy. For example, a recent Cochrane Review found that “influenza vaccines probably have a small protective effect against influenza and ILI, as 71 people would need to be vaccinated to avoid one influenza case”.
2. As with SARS-CoV-2, the spread of influenza virus via fomites is not thought to be a significant route of transmission. As such, hand-washing likely plays a minimal role in mitigating the spread of many respiratory viruses.
3. The reduction (or more accurately disappearance) in influenza cases has occurred in all geographic regions, regardless of the nonpharmaceutical interventions (NPIs) that have been employed. This disappearance coincides with the arrival of SARS-CoV-2, and is consistent worldwide:

4. If the wearing of masks was capable of almost entirely removing influenza from circulation, as has been observed, then this approach would also eliminate SARS-CoV-2. Indeed, SARS-CoV-2 virions, which range from ~50 to 200 nm, are similar in size to those of influenza (~80 to 120 nm), adenoviruses (~90 to 100 nm), and other endemic betacoronaviruses, such as HCoV-OC43 and HCoV-HKU1 (~118 to 140 nm), which share the same genus as the novel virus. Since SARS-CoV-2, influenza, and various other respiratory viruses are largely spread by fine-particle aerosols in indoor settings, an intervention that works for one should logically work for the other. But in spite of the stringency of interventions, SARS-CoV-2 cases have skyrocketed. At the same time, infections of endemic betacoronaviruses, which should respond to NPIs in the same manner as SARS-CoV-2, have also largely disappeared:

However, the presence of adenoviruses, which are also spread via aerosolized particles, have been consistently detected throughout the coronavirus pandemic. If mask usage were almost entirely removing influenza and coronaviruses from circulation, why not SARS-CoV-2 and adenoviruses, which share similar virion sizes and modes of transmission?

Human Coronavirus OC43 — Likely culprit of the 1889–90 “Russian Flu” (https://commons.wikimedia.org/wiki/File:TEM_of_coronavirus_OC43.jpg)

It is clear that attributing the current disappearance of multiple influenza and coronavirus types to NPIs is not logical, but what plausible explanations exist for this phenomenon? Is some previously unknown biological dynamic at play? Not exactly.

In his seminal work “The Transmission of Epidemic Influenza”, Edgar Hope Simpson provides some discussion regarding such disappearances, which have been observed throughout history. Coined “The Vanishing Trick”, he writes:

So perhaps a biological process, whereby viruses engage in some form of competition, or interactions, can better explain disappearances such as those currently being observed.

Subsequent research has borne out real world examples related to the phenomenon described by Simpson. According to a group of researchers at Yale, it is likely that a 2009 autumn rhinovirus epidemic interrupted the spread of influenza. The authors of that study write: “one respiratory virus can block infection with another through stimulation of antiviral defenses in the airway mucosa”. Results from another study, conducted in mice, support those findings. Mice were infected with either a rhinovirus or a murine coronavirus, and it was found that both attenuated influenza disease. Moreover, it was observed that the murine coronavirus infection reduced early replication of the influenza virus. In another study, negative interactions between noninfluenza and influenza viruses were suggested. According to the authors: “when multiple pathogens cocirculate this can lead to competitive or cooperative forms of pathogen–pathogen interactions. It is believed that such interactions occur among cold and flu viruses”. A recently published study examining the effects of interactions between an adenovirus and influenza in mice suggested that certain respiratory infections could impede “other viruses’ activities within the respiratory tract without attacking unrelated viruses directly”. Finally, in a paper entitled “A systematic approach to virus–virus interactions”, the authors state: “increasing evidence suggests that virus–virus interactions are common and may be critical to understanding viral pathogenesis”.

Since the current disappearance of various endemic influenza and coronaviruses cannot logically be attributed to NPIs (for the reasons previously discussed), biological phenomena (interactions between viruses), which are currently not well understood, present a far more plausible explanation.

Citations

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