#15,453
There is a good deal of uncertainty over what will happen this fall and winter when COVID-19, seasonal influenza, and the rest of our complement of winter respiratory viruses collide. The CDC, fearing that a simultaneous `twindemic' of COVID and flu could overwhelm hospitals this winter, has ordered in the largest quantity of flu shots in history.Our experience to date, however - at least in the Southern Hemisphere - has been that influenza has been a no-show (see WHO Graph below) since COVID emerged. The assumption is that social distancing, face covers, and hand hygiene against the pandemic has helped suppress influenza as well.
Whether this trend continues into this fall and winter . . . particularly now that schools are opening in the Northern Hemisphere, and a certain amount of `pandemic fatigue' has set in, resulting in less rigorous social distancing . . . remains to be seen.
And here, things start to get messy.
Long time readers will remember the flap over the `Canadian problem' early in the 2009 H1N1 pandemic, when news of several unpublished Canadian studies emerged suggesting prior seasonal flu vaccination made you more at risk of contracting the 2009 Pandemic virus.
At the time, delivery of the pandemic vaccine was still several months away - and plans were to roll out the seasonal vaccine first – to protect against non-pandemic flu strains. Helen Branswell, then science and medical reporter for the Canadian Press, was among the first to report on it (see Branswell On The Canadian Flu Shot Controversy).Suddenly, there was genuine concern that with a pandemic virus on the way, that rolling out the seasonal vaccine might be the wrong thing to do.
The CDC and the World Health Organization both scrambled to look at their available data, and stated that they could find no correlation between the seasonal vaccine and susceptibility to the pandemic flu . . . but that they would continue to look.
Meanwhile, with concerns rising, a number of Canadian Provinces halted or announced delays in their seasonal flu shot campaign, even though the study had yet to be published (see Ontario Adjusts Vaccination Plan).
October saw a number of new reports and studies that failed to corroborate the (still unpublished) findings, including a study published in the BMJ (British Medical Journal) that suggested exactly the opposite - that getting the seasonal flu vaccination may be slightly protective against the swine flu (see When Studies Collide).
By November, with no compelling corroboration of the `Canadian Problem’, Canada’s National Advisory Committee on Immunization (NACI) came out in favor of resuming seasonal flu jabs (see NACI: Canada Should Resume Seasonal Flu Vaccinations).
But the controversy did not go away. In April of 2010 the Canadian studies were finally published by PLoS Medicine. Writing for CIDRAP, Maryn McKenna detailed their findings.
New Canadian studies suggest seasonal flu shot increased H1N1 risk
Maryn McKennaBut other studies (see 2010 Eurosurveillance On `The Canadian Problem’ and 2012’s EID Journal: Revisiting The `Canadian Problem’) failed to find a correlation. In 2012, Dr. Danuta Skowronski, who was involved in the original Canadian studies, announced her team had recently duplicated the vaccine effect using ferrets in a double-blind study (see ICAAC: Ferreting Out The `Canadian Problem’).Contributing Writer
Apr 6, 2010 (CIDRAP News) – Despite a rapidly launched range of studies, investigators in Canada are still unable to say—or to rule out—whether receiving a seasonal flu vaccination in the 2008-09 season made it more likely that Canadians would become ill from 2009 pandemic H1N1 flu.
While this debate was ongoing, another hypothesis emerged (see 2010's Eurosurveillance: The Temporary Immunity Hypothesis) from Australian researchers that might explain the `Canadian Problem’.
Their research suggested that contracting seasonal flu (as opposed to being vaccinated against it) temporarily ramped up the body’s immune system against other viruses – and that this protective effect could last several months.
They suggested that those who eschewed the 2008-2009 flu shot in Canada were more likely to have contracted the flu over the winter, and therefore carried some `temporary immunity' against infection with the H1N1 pandemic virus the following spring.
While flu is the most obvious catalyst, there is some evidence that other respiratory viruses may have a similar effect. And in fact, during the 2009 H1N1 pandemic, some countries that reported rampant rhinovirus outbreaks in the fall of 2009 saw far less H1N1 activity than expected (see 2009 New Scientist article Common cold may hold off swine flu).
Whether you call it the temporary immune hypothesis, or `viral interference', this is an idea which has gained considerable ground over the past decade.
In 2017's PLoS Comp. Bio.: Spring & Early Summer Most Likely Time For A Pandemic, researchers used `viral interference' and/or temporary immunity to explain why historically pandemics almost always emerge in the spring or early summer; after the end of regular flu season.
With the caveat that there is a lot we still don't know about viral interactions, and the human immune response, we've a new on-point study today to ponder.
In additional to a clinical data analysis, these researchers simulated a`human airway' in vitro from human epithelial cells, and found that once they were exposed to a rhinovirus, they expressed interferon which - in the short term - prevented co-infection with influenza A.
Anchi Wu, BSE † Valia T Mihaylova, PhD † Prof Marie L Landry, MD Prof Ellen F Foxman, MDOpen Access Published:September 04, 2020 DOI: https://doi.org/10.1016/S2666-5247(20)30114-2
Findings
Between July 1, 2016, and June 30, 2019, examination of 8284 respiratory samples positive for either rhinovirus (n=3821) or IAV (n=4463) by any test method was used to establish Nov 1 to March 1 as the period of peak virus co-circulation. After filtering for samples within this time frame meeting the inclusion criteria (n=13 707), there were 989 (7·2%) rhinovirus and 922 (6·7%) IAV detections, with a significantly lower than expected odds of co-detection (odds ratio 0·16, 95% CI 0·09–0·28). Rhinovirus infection of cell cultures induced ISG expression and protected against IAV infection 3 days later, resulting in an approximate 50 000-fold decrease in IAV H1N1pdm09 viral RNA on day 5 post-rhinovirus inoculation. Blocking the interferon response restored IAV replication following rhinovirus infection.
Interpretation
These findings show that one respiratory virus can block infection with another through stimulation of antiviral defences in the airway mucosa, supporting the idea that interference from rhinovirus disrupted the 2009 IAV pandemic in Europe. These results indicate that viral interference can potentially affect the course of an epidemic, and this possibility should be considered when designing interventions for seasonal influenza epidemics and the ongoing COVID-19 pandemic.
Whether this same `blocking effect' would occur with our current coronavirus pandemic and other viral respiratory pathogens is unknown.
While only rarely reported, we have seen some reports of co-infection with Influenza A and COVID-19 (see Influenza and COVID‐19 coinfection: Report of six cases and review of the literature).
All of which leaves us with more questions than answers going into this fall's flu season.
- Will we see a `twindemic', or will influenza remain subdued this winter?
- Could contracting rhinovirus, influenza, or some other respiratory infection provide any short term immunity against COVID-19? If so, for how long?
- Is is possible that due to prolonged social distancing and wearing of face covers, our immune `shields are down', making us more susceptible to infection if we are exposed to flu or COVID-19?
- And if seasonal influenza remains subdued globally, will that make room for another novel flu (avian, swine, etc.) to emerge from the wild over the next year or so?
While inquiring minds may want to know, I have no clue. All of this remains admittedly highly speculative, and we are literally trudging into the unknown this winter.
Being part of a `vulnerable demographic', I still plan on getting the flu shot this month, and will continue to social distance, practice stringent hand hygiene, and wear a face cover in public.
While there are a lot of possible viral interactions and outcomes this winter, the only thing I'm truly expecting is to be surprised.
