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Do COVID-19 and Influenza vaccines influence susceptibility to other respiratory viruses? A population based study
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Introduction: Studies have raised concerns that Influenza and COVID-19 vaccination may influence susceptibility to other respiratory viruses (ORV), potentially increasing the risk of non-target infections. This challenges a key assumption of test-negative design studies—that vaccines do not affect the risk of other infections within the same clinical syndrome. Nevertheless, current evidence remains inconclusive. This study aimed to evaluate the association between COVID-19 and influenza vaccination and the risk of non-influenza/COVID-19 respiratory virus infections.
Methods: Test-negative design (TND) study using Portuguese data from a primary care vaccine effectiveness study (VEBIS Primary Care study) between October/2022-April/2025. Data on influenza/COVID-19 vaccination status, age, sex and chronic conditions were collected. Samples were tested by RT-PCR for influenza, SARS-CoV-2 and ORV. Patients with laboratory-confirmed influenza/COVID-19 infection were excluded. Logistic regression estimated adjusted odds ratios (aOR) of being vaccinated among cases (ORV positive) and controls (pan-negative).
Results: Of the 1096 patients included, 4.5% received the COVID-19 vaccine, 5.9% the influenza vaccine, 13.3% both, and 76.3% neither. Human Rhinovirus (44.2%), human Coronavirus (14.6%) and Respiratory Syncytial Virus (14.1%) were the viruses more frequently identified. Individuals 65+ exhibited significant lower odds of infection with ORV (OR=0.45, 95%CI:0.25-0.81) compared to younger age group (<18yo). Vaccination status, including influenza only (aOR=1.01, 95%CI:0.59‐1.72), COVID only (aOR=0.88, 95%CI:0.48‐1.59), and both vaccines (aOR=1.38, 95%CI:0.92‐2.06), were not associated to ORV infection risk.
Conclusions: Our results suggest that vaccination status—whether for influenza, COVID-19, or both—was not significantly associated with the risk of ORV infections. This supports the use of test-negative controls for influenza/COVID-19 within the same clinical syndrome, as it upholds a key TND assumption of no association between vaccination and risk of non-target infections. While mechanisms such as reduced cross-protection from natural infection or potential vaccine-induced cross-immunity have been proposed, our findings reinforce the validity of the primary methodological assumption rather than suggesting evidence for these alternative effects.
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VEBIS Lot 5 Respiratory Viruses Influenza COVID-19 Observação em Saúde e Vigilância Estados de Saúde e de Doença Infecções Respiratórias
Contexto Educativo
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Licença CC
Sem licença CC