If you’ve been watching recent claims of the anti-vaccine world, you may have noticed a belief that the flu vaccine and COVID-19 are related. This new trope is based on a recent article that is making the rounds with both COVID-19 and flu vaccine deniers (a special subset of anti-vaxxers).
Let’s see if this paper about an association between the flu vaccine and COVID-19 mortality has any merit. To save you some reading time, it has none, except to give me something to write about.
Flu vaccine and COVID-19 – the paper
In a paper by Christian Wehenkel, published in the open-access PeerJ, the author attempted to show a relationship between COVID-19 and the flu vaccine. Even though this study has made the rounds of the anti-vaccine and COVID-19 denier worlds, there are several reasons to dismiss both the quality of the data.
- Wehenkel is a professor of forest genetics, forest ecosystem analysis, forestry, biometrics, forest growth, and biodiversity. That is impressive if you’re studying a tropical forest, but that is not the background indicative of someone who is familiar with studying actual epidemiology. In fact, based on his methods, it is very clear that he lacks expertise or knowledge of epidemiology.
- This is an ecological study, which is a type of epidemiological study that geographic populations. Better epidemiological studies, like case-control and cohort, define the population so that it can be carefully controlled. Furthermore, the old adage that “correlation does not mean causation” is apt here – this study does not even try to perform a proper analysis of causality, which could have provided more evidence that the flu vaccine and COVID-19 are related. Anti-vaccine “researchers” utilize ecological studies because they are cheap and always have the appearance of good statistics. You see this research all the time when these “researchers” attempt to establish that the infant mortality rate is related to the number of vaccines given while ignoring all other factors.
- This study does not adjust for various confounders, such as diabetes, access to health care, and other factors, because that kind of ecological data is just available. A cohort study would adjust for diabetes by actually examining the risk of COVID-19 after a flu vaccine in patients that had diabetes.
- Even the journal put this warning on the article:
Given the public interest in articles which report on vaccination, the publisher reminds readers that correlation (which this article reports upon for a specific age group) does not necessarily equal causation.
What does that mean? By way of example, in some cities increased ice cream sales correlate with increased murder rates. But that doesn’t mean that if more ice creams are sold, then murder rates will increase. There is some other factor at play – the weather temperature.
Similarly, this article should not be taken to suggest that receiving the influenza vaccination results in an increased risk of death for an individual with COVID-19 as there may be many confounding factors at play (including, for example, socioeconomic factors).
Hey, I said that!
This is not a high-quality article, and it is absolutely not “evidence” that we should consider that the flu vaccine and COVID-19 mortality are related. On the other hand, is there evidence that contradicts this article?
Flu vaccine and COVID-19 mortality – more evidence
In a paper by Claudio Zenettini et al., which has not been published or peer-reviewed (see Note 1), the researchers examined the relationship between the flu vaccine and COVID-19 mortality in the USA. They concluded that:
Our results suggest that influenza vaccination coverage in the elderly population is negatively associated with mortality from COVID-19. This finding is robust to using different analysis periods, different thresholds for inclusion of counties, and a variety of methodologies for confounding adjustment. In conclusion, our results suggest a potential protective effect of the influenza vaccine on COVID-19 mortality in the elderly population.
In a paper by Daniela Marín-Hernández et al., published in the Journal of Medical Virology, the researchers examined whether there was an association between higher flu vaccine uptake in the elderly and lower COVID-19 mortality. Here’s what they concluded:
…where there were higher influenza vaccination rates, less deaths from COVID‐19 occurred.
In this case, the authors attempted to provide explanations on why they may have observed this correlation:
- The flu vaccine “could stimulate sufficient trained innate immune memory that when another respiratory pathogen like SARS‐CoV‐2 occurred, the local lung immune system would be primed for a rapid response, and that could impact the acquisition of SARS‐Cov‐2 or the COVID‐19 disease course.”
- The uptake of the flu vaccine might occur in higher economic groups who usually have better health and better access to healthcare.
- The relationship could just be random chance.
Similar to what I have advised about the flu vaccine and COVID-19, the authors similarly stated:
However, as vaccination against influenza is encouraged to help reduce hospitalization and to help in the differential diagnosis of viral‐mediated adult respiratory distress, there are already known benefits of influenza vaccination in regions experiencing SARS‐CoV‐2 infection.
Finally, in a systematic review (definitely at the top of the hierarchy of biomedical research, but it’s a preprint, so remember to read Note 1) posted by Marco Del Riccio et al., the researchers reviewed 12 articles that studied the association between the flu vaccine and COVID-19. They concluded:
We reviewed the association between seasonal influenza vaccination and the risk of SARS-CoV-2 infection or complicated illness or poor outcome (e.g. severe disease, need for hospitalization or ventilatory support, or death) among COVID-19 patients. None of the studies that were reviewed (n=12) found a significant increase in the risk of infection or in the illness severity or lethality, while some reported significantly inverse associations. Our findings support measures aimed at raising influenza vaccination coverage in the coming months.
Thus, if we do real science and look at all of the evidence, giving more weight to better designed and analyzed studies, we can come to a simple conclusion – the flu vaccine is not associated with increased COVID-19
- This is a preprint. There are nearly 10,000 articles on the major preprint server, Medrxiv, discussing COVID-19, SARS-CoV-2, and related topics, all awaiting publication. There are good reasons to post preprints during this coronavirus pandemic, but there are good reasons to be very skeptical of them. Mainly, peer-review is missing, an important aspect of vetting everything from the methodology to the statistical analysis. On the hierarchy of biomedical research, preprint research is near the bottom.
- Del Riccio M, Lorini C, Bonaccorsi G, Paget J, Caini S. The association between influenza vaccination and the risk of SARS-CoV-2 infection, severe illness, and death: a systematic review of the literature. medRxiv 2020.09.25.20201350; doi: 10.1101/2020.09.25.20201350
- Marín-Hernández D, Schwartz RE, Nixon DF. Epidemiological evidence for association between higher influenza vaccine uptake in the elderly and lower COVID-19 deaths in Italy. J Med Virol. 2020 Jun 4:10.1002/jmv.26120. doi: 10.1002/jmv.26120. Epub ahead of print. PMID: 32497290; PMCID: PMC7300995.
- Wehenkel C. Positive association between COVID-19 deaths and influenza vaccination rates in elderly people worldwide. PeerJ 2020 8:e10112 doi: 10.7717/peerj.10112
- Zanettini C, Omar M, Dinalankara W, Imada EL, Colantuoni E, Parmigiani G, Marchionni L. Influenza Vaccination and COVID19 Mortality in the USA. medRxiv [Preprint]. 2020 Jun 26:2020.06.24.20129817. doi: 10.1101/2020.06.24.20129817. PMID: 32607525; PMCID: PMC7325191.