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Using SARS\u2010CoV\u20102 infection as a model of acute viral challenge, we investigated how aging alters myeloid responses in the lungs. Across infected mouse models and human cohorts, disease severity was associated with a pronounced shift in myeloid balance, characterized by an increased neutrophil\u2010to\u2010monocyte ratio. Neutrophils exhibited prolonged retention within the pulmonary microvasculature and formed large co\u2010aggregates with monocytes. In parallel, severe disease was associated with a defect in classical monocyte activation in the lungs, notably through reduced PD\u2010L1 upregulation. This defect was not observed in the circulation, indicating tissue\u2010dependent dysregulation of inflammatory and regulatory markers. Aging further accentuated this imbalance. Both aged mice and elderly patients displayed a reduced proportion of PD\u2010L1\u2010expressing lung monocytes, despite enhanced pulmonary neutrophil recruitment. This age\u2010associated alteration distinguished severe from non\u2010severe disease and characterized a maladaptive myeloid response to acute viral challenge. Together, these findings identify impaired, compartment\u2010specific myeloid immune regulation as a central feature of age\u2010related vulnerability to severe infection. They highlight that tissue\u2010dependent regulatory failure compounds inflammatory excess as a key determinant of disease outcome and suggest that restoring myeloid regulatory function may offer therapeutic benefit in older individuals during acute respiratory infections.<\/jats:p>","DOI":"10.1111\/acel.70588","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T11:26:42Z","timestamp":1781263602000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Opposing Association of Lung Neutrophils and PD\u2010L1\n                    <sup>+<\/sup>\n                    Monocytes in Age\u2010Related Severity of SARS\u2010CoV\u20102 Infection"],"prefix":"10.1111","volume":"25","author":[{"given":"Serban","family":"Morosan","sequence":"first","affiliation":[{"name":"Department of Exact Sciences \u201cIon Ionescu de la Brad\u201d Iasi University of Life Sciences  Ia\u0219i 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