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Flu Vaccine May Protect Against COVID-19 Infection


A recent study found that patients immunized against influenza were less likely to test positive for or have serious complication related to coronavirus disease 2019 (COVID-19).

Patients who have received an influenza vaccine were found to have 24% lower odds of testing positive for coronavirus disease 2019 (COVID-19), according to a recent study published in the American Journal of Infection Control.

Additionally, patients who were vaccinated against influenza and tested positive for COVID-19 were more likely to have better clinical outcomes than those who were not vaccinated.

The investigators said their study is the first to explore whether there is an association between standard influenza vaccines and COVID-19.

As of February 24, 2021, there have been 112 million confirmed cases of COVID-19 and 2.5 million deaths worldwide. Although the FDA has approved 2 COVID-19 vaccines and soon may approve Johnson & Johnson’s 1-dose formulation, not everyone is eligible yet to receive one, “making it imperative to explore the effects of currently available medical interventions that may lessen the susceptibility to and burden of disease,” noted the investigators.

The retrospective cohort study included data from the Michigan Medicine health care system. Testing information was processed from February 27, 2020, to July 15, 2020, and vaccination records from August 1, 2019, to July 15, 2020 were included to account for the entire 2019 flu season.

During the study period, 27,201 patients received a COVID-19 test: 1218 (4.5%) tested positive and 25,983 (95.5%) tested negative. Of these patients, 12,997 (47.8%) received an influenza vaccine during the prior flu season and 14,204 (55.2%) did not.

Patients who got a flu vaccine tended to have more comorbidities and be older (48.4 vs 46.1 years; P < .001), female (61.0% vs 50.9%; P < .001), and White (80.1% vs 74.6%; P < .001) vs those who were unvaccinated. These patients also were significantly less likely to get a positive COVID-19 test result compared with those who were not vaccinated (odds ratio [OR], 0.82; 95% CI, 0.73-0.92; P < .001).

Of the patients who were vaccinated, 4% tested positive for COVID-19 compared with 4.9% of nonvaccinated individuals. This association remained significant after the investigators controlled for baseline covariates (OR, 0.76; 95% CI, 0.68-0.86; P < .001).

Additionally, the investigators found that vaccinated patients had lower odds of requiring hospitalization (OR, 0.58; 95% CI, 0.46-0.73; P < .001) and mechanical ventilation after hospitalization (OR, 0.45; 95% CI, 0.27-0.78; P = .004). They were also more likely to have a shorter hospital stay (risk ratio [RR], 0.76; 95% CI, 0.65-0.89; P < .001).

There were no significant differences observed for mortality or use of intensive care units. However, this may have been due to the small sample size and low number of deaths during the study period.

The investigators noted that the observed protective association between the influenza vaccine and COVID-19 may be impacted by socioeconomic factors and the implementation of school closures, mask mandates, stay-at-home orders, and lockdowns shortly after the first positive case of COVID-19 was detected in Michigan March 10, 2020.

“Discrepancies in adherence to these guidelines between influenza vaccinated and unvaccinated patients could bias the observed association. A prospective study accounting for these differences is needed to explore the possible protective effect of the influenza vaccine on COVID-19 susceptibility and outcomes,” wrote the investigators.

In addition, the reduced COVID-19 risks in vaccinated patients may be due to bias from a healthy patient population that is more likely to receive preventive therapies.

However, the investigators noted that there is a “hypothetical, yet plausible immunologic mechanism” associated with influenza vaccines that could result in trained immunity, where a vaccine results in an adaptive immune response that can be activated in response to a nonspecific antigen, such as how a particular tuberculosis vaccine has shown to be effective against yellow fever and malaria.

“Even if the direct link between the prevention of COVID-19 and the influenza vaccine is minimal, through an overall reduction in the number of patients presenting to their providers with viral-like symptoms necessitating work up for COVID-19 or requiring hospitalization for complications of influenza, vaccination will preserve health care resources for those with COVID-19,” wrote the investigators.

Limitations of the study included that the patients and data were specific to Michigan and mostly collected from large hospitals, not community settings.

“Until the COVID-19 vaccine becomes widely available, the influenza vaccine should be promoted to reduce the burden of disease during this pandemic,” the investigators said.


Conlon A, Ashur C, Washer L, Eagle KA, Hofmann Bowman MA. Impact of the influenza vaccine on COVID-19 infection rates and severity. Am J Infect Control. Published online February 22, 2021. doi:10.1016/j.ajic.2021.02.012

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