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Competing forces, including viral interference, cross\u2010reactive immunity, shared susceptibility, and immune dysregulation, may affect the risk. The potential net impact of various immune\u2010priming events and their timing on the risk of viral ARIs is largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using data from the National Clinical Cohort Collaborative (N3C) COVID\u201019 Enclave, this retrospective population\u2010based cohort study investigated the relationship between immune\u2010priming events (COVID\u201019 and influenza vaccinations, and SARS\u2010CoV\u20102, influenza, other, and unspecified viral ARIs) between January 2018 and September 2021 and the risk of viral ARIs during October 2021\u2013April 2022. The sample included\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009608,725 individuals from seven data partners with well\u2010ascertained COVID\u201019 and influenza vaccination data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Early COVID\u201019 vaccination (December 2020\u2013March 2021) and SARS\u2010CoV\u20102 infection during the overlapping period (October 2020\u2013March 2021) were associated with a lower risk of all outcomes, including non\u2010SARS\u2010CoV\u20102 infections. Off\u2010season influenza vaccination (January\u2013June 2021) was associated with a lower risk of SARS\u2010CoV\u20102 and any viral ARI. Other priming events showed mixed associations, with a lack of evidence of stronger protection from more recent immune\u2010priming events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This exploratory analysis suggests potential crossprotection between viral ARIs that may inform vaccination strategies. While ascertainment and healthcare\u2010seeking 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/irv.70253","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T08:42:39Z","timestamp":1774255359000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune Priming and the Risk of COVID\u201019, Influenza, and Other Acute Respiratory Infections: Insights From an N3C Cohort"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7633-677X","authenticated-orcid":false,"given":"Tom\u00e1s\u00a0M.","family":"Le\u00f3n","sequence":"first","affiliation":[{"name":"California Department of Public Health  Richmond California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3203-3264","authenticated-orcid":false,"given":"Lyndsey\u00a0M.","family":"Muehling","sequence":"additional","affiliation":[{"name":"Division of Asthma, Allergy &amp; Immunology University of Virginia School of Medicine  Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4797-8869","authenticated-orcid":false,"given":"Rachel","family":"Baccile","sequence":"additional","affiliation":[{"name":"Center for Health and Social Sciences University of Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7606-8413","authenticated-orcid":false,"given":"Olga","family":"Morozova","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences University of Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"National Clinical Cohort Collaborative (N3C) COVID\u201019 Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579\u2010022\u201000807\u20109"},{"key":"e_1_2_13_3_1","unstructured":"CDC \u201cPreliminary Estimated Flu Disease Burden 2022\u20132023 Flu Season \u201d Flu Burden December 9 2024 accessed July 9 2025 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