{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:25:40Z","timestamp":1792635940408,"version":"4.5.0"},"reference-count":45,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020366","name":"Massachusetts Consortium on Pathogen Readiness","doi-asserted-by":"crossref","award":["Identifying"],"award-info":[{"award-number":["Identifying"]}],"id":[{"id":"10.13039\/100020366","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020366","name":"Massachusetts Consortium on Pathogen Readiness","doi-asserted-by":"crossref","award":["targeting host cells"],"award-info":[{"award-number":["targeting host cells"]}],"id":[{"id":"10.13039\/100020366","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020366","name":"Massachusetts Consortium on Pathogen Readiness","doi-asserted-by":"crossref","award":["genes crucial in SARS-CoV-2 pathogenesis"],"award-info":[{"award-number":["genes crucial in SARS-CoV-2 pathogenesis"]}],"id":[{"id":"10.13039\/100020366","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001229","name":"G. Harold and Leila Y. Mathers Charitable Foundation","doi-asserted-by":"crossref","award":["Mathers Foundation\/SARS-CoV-2"],"award-info":[{"award-number":["Mathers Foundation\/SARS-CoV-2"]}],"id":[{"id":"10.13039\/100001229","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Department of Defense","award":["W81XWH2110029,COVID-19 Expansion for AIRe Program"],"award-info":[{"award-number":["W81XWH2110029,COVID-19 Expansion for AIRe Program"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,22]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Influenza A virus (IAV) and SARS-CoV-2 are pandemic viruses causing millions of deaths, yet their clinical manifestations are distinctly different.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>With the hypothesis that upper airway immune and epithelial cell responses are also distinct, we performed single-cell RNA sequencing (scRNA-Seq) on nasal wash cells freshly collected from adults with either acute COVID-19 or influenza or from healthy controls. We focused on major cell types and subtypes in a subset of donor samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nasal wash cells were enriched for macrophages and neutrophils for both individuals with influenza and those with COVID-19 compared with healthy controls. Hillock-like epithelial cells, M2-like macrophages, and age-dependent B cells were enriched in COVID-19 samples. A global decrease in IFN-associated transcripts in neutrophils, macrophages, and epithelial cells was apparent in COVID-19 samples compared with influenza samples. The innate immune response to SARS-CoV-2 appears to be maintained in macrophages, despite evidence for limited epithelial cell immune sensing. Cell-to-cell interaction analyses revealed a decrease in epithelial cell interactions in COVID-19 and highlighted differences in macrophage-macrophage interactions for COVID-19 and influenza.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study demonstrates that scRNA-Seq can define host and viral transcriptional activity at the site of infection and reveal distinct local epithelial and immune cell responses for COVID-19 and influenza that may contribute to their divergent disease courses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Funding<\/jats:title>\n                    <jats:p>Massachusetts Consortium on Pathogen Readiness, the Mathers Foundation, and the Department of Defense (W81XWH2110029) \u201cCOVID-19 Expansion for AIRe Program.\u201d<\/jats:p>\n                  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