tetano
Editor, Senior Moderator
Influenza Other Respir Viruses
. 2026 Mar;20(3):e70253.
doi: 10.1111/irv.70253.
Immune Priming and the Risk of COVID-19, Influenza, and Other Acute Respiratory Infections: Insights From an N3C Cohort
Tomás M León[SUP] 1 [/SUP], Lyndsey M Muehling[SUP] 2 [/SUP], Rachel Baccile[SUP] 3 [/SUP], Olga Morozova[SUP] 4 [/SUP]; National Clinical Cohort Collaborative (N3C) COVID‐19 Consortium
Collaborators, Affiliations
Background: The emergence of SARS-CoV-2 and introduction of COVID-19 vaccines into immunologically naïve populations may alter the dynamics of other acute viral respiratory infections (viral ARIs) and vice versa. Competing forces, including viral interference, cross-reactive immunity, shared susceptibility, and immune dysregulation, may affect the risk. The potential net impact of various immune-priming events and their timing on the risk of viral ARIs is largely unknown.
Methods: Using data from the National Clinical Cohort Collaborative (N3C) COVID-19 Enclave, this retrospective population-based cohort study investigated the relationship between immune-priming events (COVID-19 and influenza vaccinations, and SARS-CoV-2, influenza, other, and unspecified viral ARIs) between January 2018 and September 2021 and the risk of viral ARIs during October 2021-April 2022. The sample included N = 608,725 individuals from seven data partners with well-ascertained COVID-19 and influenza vaccination data.
Results: Early COVID-19 vaccination (December 2020-March 2021) and SARS-CoV-2 infection during the overlapping period (October 2020-March 2021) were associated with a lower risk of all outcomes, including non-SARS-CoV-2 infections. Off-season influenza vaccination (January-June 2021) was associated with a lower risk of SARS-CoV-2 and any viral ARI. Other priming events showed mixed associations, with a lack of evidence of stronger protection from more recent immune-priming events.
Conclusions: This exploratory analysis suggests potential crossprotection between viral ARIs that may inform vaccination strategies. While ascertainment and healthcare-seeking biases in electronic health records may inflate positive associations between infection outcomes and immune priming, negative (i.e., protective) associations are of potential public health significance and warrant further investigation.
Keywords: COVID‐19 vaccines; SARS‐CoV‐2; crossreactive immunity; influenza vaccines; respiratory viruses; vaccination; viral interference.
. 2026 Mar;20(3):e70253.
doi: 10.1111/irv.70253.
Immune Priming and the Risk of COVID-19, Influenza, and Other Acute Respiratory Infections: Insights From an N3C Cohort
Tomás M León[SUP] 1 [/SUP], Lyndsey M Muehling[SUP] 2 [/SUP], Rachel Baccile[SUP] 3 [/SUP], Olga Morozova[SUP] 4 [/SUP]; National Clinical Cohort Collaborative (N3C) COVID‐19 Consortium
Collaborators, Affiliations
- PMID: 41867090
- DOI: 10.1111/irv.70253
Background: The emergence of SARS-CoV-2 and introduction of COVID-19 vaccines into immunologically naïve populations may alter the dynamics of other acute viral respiratory infections (viral ARIs) and vice versa. Competing forces, including viral interference, cross-reactive immunity, shared susceptibility, and immune dysregulation, may affect the risk. The potential net impact of various immune-priming events and their timing on the risk of viral ARIs is largely unknown.
Methods: Using data from the National Clinical Cohort Collaborative (N3C) COVID-19 Enclave, this retrospective population-based cohort study investigated the relationship between immune-priming events (COVID-19 and influenza vaccinations, and SARS-CoV-2, influenza, other, and unspecified viral ARIs) between January 2018 and September 2021 and the risk of viral ARIs during October 2021-April 2022. The sample included N = 608,725 individuals from seven data partners with well-ascertained COVID-19 and influenza vaccination data.
Results: Early COVID-19 vaccination (December 2020-March 2021) and SARS-CoV-2 infection during the overlapping period (October 2020-March 2021) were associated with a lower risk of all outcomes, including non-SARS-CoV-2 infections. Off-season influenza vaccination (January-June 2021) was associated with a lower risk of SARS-CoV-2 and any viral ARI. Other priming events showed mixed associations, with a lack of evidence of stronger protection from more recent immune-priming events.
Conclusions: This exploratory analysis suggests potential crossprotection between viral ARIs that may inform vaccination strategies. While ascertainment and healthcare-seeking biases in electronic health records may inflate positive associations between infection outcomes and immune priming, negative (i.e., protective) associations are of potential public health significance and warrant further investigation.
Keywords: COVID‐19 vaccines; SARS‐CoV‐2; crossreactive immunity; influenza vaccines; respiratory viruses; vaccination; viral interference.