#16,235
Although no one can predict with any confidence when seasonal influenza will return after its (now) 18 month hiatus - or how bad it will be - there are concerns that with reduced face mask wearing and increased social interaction, and recent spikes in RSV around the world, it could happen sooner rather than later (see UK Academy Of Medical Sciences: Looking Ahead To COVID-19 Over Winter 2021/22 & Beyond).
Whether it happens this fall or winter, or next year, at some point we expect to see the co-circulation of COVID and influenza. This would not only `muddy the waters' when it comes to testing for COVID, and potentially overwhelm hospitals, it could lead to a significant number of COVID-Flu coinfections as well.
Influenza was basically a no-show last year, but in the spring of 2020 we did see a brief period of viral overlap, and while the number of co-infections that were confirmed were small, early reports suggested an increased severity of illness (see IDCases: Co-infection With SARS-CoV-2).
A year ago, in PHE Study: Co-Infection With COVID-19 & Seasonal Influenza, we looked at a Public Health England study that warned that being co-infected with influenza and COVID more than doubled the risk of death over having COVID alone.
While being infected with Influenza lowered the risk of contracting SARS-CoV-2 (likely due to `viral interference'), among those who did contract both, they determined:Authors: J STOWE, PhD 1* , E TESSIER, MsC 1* , H ZHAO, PhD 1 , R GUY, BSc 2 , B MULLER-PEBODY, PhD 2 , M ZAMBON, PhD 3 , N ANDREWS, PhD 4 , M RAMSAY, MBBS, 1 , J LOPEZ BERNAL, PhD 1
`. . . the risk of death was nearly six times greater among individuals with a SARS-CoV-2 and influenza coinfection than those with neither influenza nor SARS-CoV-2 and that this effect is significantly higher than the risk associated with SARS-CoV-2 infection alone.'
With there have been relatively few human cases to study, in October of 2020, in PrePrint: Sequential Infection with Influenza A virus Followed by SARS-CoV-2 (In a Mouse Model) - we looked at a study found that mice co-infected with influenza A & SARS-CoV-2 fared significantly worse than those infected with either Influenza A or SARS-CoV-2.
Granted, there is an old research adage that `Mice lie and monkeys exaggerate', but these human proxies can often be an effective tool for biomedical research.
With that caveat in mind, we have another mouse study, published yesterday in the journal Nature, that suggests flu vaccination might provide an additional layer of protection against the development of severe illness among coinfected individuals.
This is a lengthy, and at times, technical, report which many will want to read in its entirety. I've only excerpted the less technical Abstract and Introduction. I'll have a brief postscript after the break.
Nature Communications volume 12, Article number: 5819 (2021) Cite this article
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The continued spread of SARS-CoV-2 increases the probability of influenza/SARS-CoV-2 coinfection, which may result in severe disease. In this study, we examine the disease outcome of influenza A virus (IAV) and SARS-CoV-2 coinfection in K18-hACE2 mice. Our data indicate enhance susceptibility of IAV-infected mice to developing severe disease upon coinfection with SARS-CoV-2 two days later.
In contrast to nonfatal influenza and lower mortality rates due to SARS-CoV-2 alone, this coinfection results in severe morbidity and nearly complete mortality. Coinfection is associated with elevated influenza viral loads in respiratory organs. Remarkably, prior immunity to influenza, but not to SARS-CoV-2, prevents severe disease and mortality. This protection is antibody-dependent. These data experimentally support the necessity of seasonal influenza vaccination for reducing the risk of severe influenza/COVID-19 comorbidity during the COVID-19 pandemic.
Introduction
The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed serious threats to global health and economy. The COVID-19 pandemic presents a broad spectrum of severities, ranging from asymptomatic presentation to severe pneumonia. Most of the mildly to critically affected patients show respiratory complications, including moderate to severe pneumonia, which can further progress to acute respiratory distress syndrome, sepsis, and multiple organ dysfunction in severely ill patients1.
Most of these clinical symptoms are associated with the respiratory system, specifically the lungs, resulting in the depleted lung functionality2. Several risk factors for severe COVID-19 disease, such as the age, sex, and obesity have been identified3. However, more research is needed to better understand the involvement of these and other risk factors in severe illness or complications.
Whether coinfection with other pathogens may impact disease severity is yet to be elucidated. Previous studies have reported coinfections between SARS-CoV-2 and common respiratory viruses, including rhinovirus, influenza virus, metapneumovirus, parainfluenza virus, and respiratory syncytial virus4.
A meta-analysis of 30 studies including 3834 patients with COVID-19 revealed that overall, 7% of hospitalized patients with COVID-19 had a bacterial coinfection, while the pooled proportion of viral coinfections was 3%, with respiratory syncytial virus and influenza A virus (IAV) being the most common5. However, the prevalence and disease outcomes of viral coinfections in the SARS-CoV-2-positive population remain controversial6,7,8,9.
IAV is a leading cause of respiratory infection, resulting in respiratory disease10. Complications involving secondary infections with other pathogens, mostly bacteria, significantly exacerbate the risk of severe disease due to IAV and other viral respiratory pathogens11,12,13,14.
However, whether coinfection with IAV and SARS-CoV-2 presents more severe disease than a single infection is not clear.
In this study, we delineate the interplay between IAV and SARS-CoV-2 infections. For this purpose, we employ transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under control of the human cytokeratin 18 promoter (K18-hACE2 mice) to establish a SARS-CoV-2-susceptible murine model15.
We show that IAV-infected mice have enhanced susceptibility to developing severe disease upon coinfection with SARS-CoV-2 two days post influenza infection (dpIi). In contrast to nonfatal influenza disease and lower rates of mortality due to SARS-CoV-2 alone, this coinfection is associated with elevated influenza viral loads in respiratory organs, while SARS-CoV-2 viral load was reduced following coinfection. Remarkably, prior immunity to influenza, but not to SARS-CoV-2, prevents severe disease and mortality. Finally, we show that this protection is antibody dependent.
While we still don't have a lot of human data on COVID-flu coinfection, or the impact of influenza vaccination on their outcomes, what we have seen continues to support some potential beneficial impact against COVID fby the flu vaccine. A rew examples:
PLoS One: Potential Benefits of the Influenza Vaccine Against SARS-CoV-2 (Retrospective Cohort Analysis
AJIC: Impact of the Influenza Vaccine on COVID-19 Infection Rates and Severity
Beyond this potential COVID protection, we've numerous studies showing that getting the seasonal flu vaccine can reduce your odds of having a heart attack or stroke. Some recent examples include:
Flu Vaccine May Lower Stroke Risk in Elderly ICU Patients
While the current flu vaccine technology is far from perfect, and can’t promise 100% protection, it – along with practicing good flu hygiene (washing hands, covering coughs, & staying home if sick) – remains your best strategy for avoiding the flu and staying healthy this winter.
And with our concurrent COVID pandemic, anything that can help keep you out of the hospital this fall and winter is seriously worth considering.
