{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:39:00Z","timestamp":1792571940257,"version":"4.5.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":197,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Respiratory viral infections continue to impose a large burden of hospitalization, organ failure and death, particularly among older adults and people with cardiometabolic disease. Whether prior semaglutide exposure is associated with lower post-infection severity across distinct respiratory viruses remains uncertain. We analyzed de-identified longitudinal electronic health record data from a federated U.S. network spanning more than 29 million patients. Adults with documented COVID-19 or influenza infection were classified by pre-infection semaglutide use versus metformin use without prior GLP-1 receptor agonist exposure and one-to-one propensity matched on demographics, BMI, HbA1c, vaccination status, prior infection status, antiviral use, healthcare utilization extent, and baseline comorbidities, yielding matched cohorts of N\u2009=\u20097092 for COVID-19 and N\u2009=\u20091920 for influenza (flu). In the COVID-19 cohort, semaglutide exposure was associated with significantly lower 30-day mortality (0.3% vs 0.8%, RR 0.39, P\u2009&amp;lt;\u2009.001), hospitalization (5.3% vs 7.4%, RR 0.72, P\u2009&amp;lt;\u2009.001), and the composite disease severity outcome (8.2% vs 10.6%, RR 0.77, P\u2009&amp;lt;\u2009.001). Differences in rates of intensive care admission (1.4% vs 1.8%, RR 0.79, P\u2009=\u2009.07) and mechanical ventilation (0.7% vs 0.9%, RR 0.76, P\u2009=\u2009.14) were not statistically significant. In the flu cohort, semaglutide use was also associated with significantly lower mortality (0.2% vs 0.7%, RR 0.29, P\u2009=\u2009.02), hospitalization (6.5% vs 9.6%, RR 0.68, P\u2009&amp;lt;\u2009.001), and the composite outcome (10.3% vs 14.6%, RR 0.70, P\u2009&amp;lt;\u2009.001); ICU admissions (1.9% vs 2.7%, RR 0.71, P\u2009=\u2009.11) and mechanical ventilation (0.7% vs 0.9%, RR 0.78, P\u2009=\u2009.48) were not statistically significant. Among organ-specific outcomes, for which P values were adjusted for multiple comparisons, a significant risk reduction was observed for acute kidney injury (COVID-19 RR 0.73, P\u2009=\u2009.02; flu RR 0.58, P\u2009=\u2009.03) in the 30-day observation period, whereas reductions in acute coronary syndrome (COVID-19 RR 0.67, P\u2009=\u2009.14; flu RR 1.00, P\u2009=\u20091.00) and acute respiratory failure (COVID-19 RR 0.84, P\u2009=\u2009.17; flu RR 0.74, P\u2009=\u2009.27) were not statistically significant against the metformin comparator. Within the COVID-19 cohort, prior semaglutide exposure was associated with lower composite COVID-19 severity across the full study period, reaching significance in both vaccinated (RR 0.81, P\u2009=\u2009.04) and unvaccinated (RR 0.76, P\u2009&amp;lt;\u2009.001) patients, and during the pandemic period ending May 11, 2023, reaching significance in unvaccinated patients (RR 0.76, P\u2009=\u2009.001) but not vaccinated patients (RR 0.85, P\u2009=\u2009.20). When restricting to those treated with standard-of-care therapeutics during the COVID-19 pandemic era, semaglutide users had significantly lower 30-day composite risk among those receiving Paxlovid within \u00b17\u2009days of infection (9.6% vs 12.7%; RR 0.76, P\u2009=\u2009.02). Among those initiating corticosteroids \u00b17\u2009days of infection, the composite outcome remained significantly lower (27.3% vs 36.3%; RR 0.75, P\u2009=\u2009.007). Among the influenza cohort, semaglutide was associated with a reduced risk of the composite outcome among unvaccinated patients (RR 0.69, P\u2009&amp;lt;\u2009.001), but this trend was not statistically significant among vaccinated patients (RR 0.74, P\u2009=\u2009.06). Notably, semaglutide use was associated with significantly lower composite risk among Medicare-eligible adults aged \u226565\u2009years for both COVID-19 (11.2% vs 12.9%; RR 0.86, P\u2009=\u2009.04) and influenza (17.0% vs 23.7%; RR 0.72, P\u2009=\u2009.003). Finally, composite risk did not vary significantly across pre-infection weight loss strata of &amp;lt;5%, 5%\u201315%, and \u226515% for COVID (P\u2009=\u2009.89) or flu (P\u2009=\u2009.54), or across dosage strata of 0.25\u20130.5, 1.0, and 1.7\u20132.4\u2009mg\/week for COVID (P\u2009=\u2009.50) or flu (P\u2009=\u2009.32), suggesting semaglutide-associated lower COVID and influenza severity may not be related to substantial weight loss or maximal dosing. Taken together, this study motivates prospective evaluation of low-dose semaglutide to blunt the severity of respiratory viral infections.<\/jats:p>","DOI":"10.1093\/biomethods\/bpag042","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:40:44Z","timestamp":1784288444000},"source":"Crossref","is-referenced-by-count":0,"title":["Semaglutide use linked to lower COVID-19 and influenza severity with better renal outcomes after pandemic or seasonal infection"],"prefix":"10.1093","volume":"11","author":[{"given":"Robert","family":"Matson","sequence":"first","affiliation":[{"name":"nference , 1 Main Street, East Arcade Building, Cambridge, MA 02142,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2819-3214","authenticated-orcid":false,"given":"A J","family":"Venkatakrishnan","sequence":"additional","affiliation":[{"name":"nference , 1 Main Street, East Arcade Building, Cambridge, MA 02142,","place":["United States"]},{"name":"Metabolism Agentic Intelligence Atlas (MAIA) , Cambridge, MA, Cambridge, MA 02142,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Murugadoss","sequence":"additional","affiliation":[{"name":"nference , 1 Main Street, East Arcade Building, Cambridge, MA 02142,","place":["United States"]},{"name":"Metabolism Agentic Intelligence Atlas (MAIA) , Cambridge, MA, Cambridge, MA 02142,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7434-9211","authenticated-orcid":false,"given":"Venky","family":"Soundararajan","sequence":"additional","affiliation":[{"name":"nference , 1 Main Street, East Arcade Building, Cambridge, MA 02142,","place":["United States"]},{"name":"Metabolism Agentic Intelligence Atlas (MAIA) , Cambridge, MA, Cambridge, MA 02142,","place":["United 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