{"doi":"10.1101/2020.10.15.20208041","title":"Analysis of respiratory and systemic immune responses in COVID-19 reveals mechanisms of disease pathogenesis","abstract":"SUMMARY Immune responses to respiratory viruses like SARS-CoV-2 originate and function in the lung, yet assessments of human immunity are often limited to blood. Here, we conducted longitudinal, high-dimensional profiling of paired airway and blood samples from patients with severe COVID-19, revealing immune processes in the respiratory tract linked to disease pathogenesis. Survival from severe disease was associated with increased CD4 + T cells and decreased monocyte/macrophage frequencies in the airway, but not in blood. Airway T cells and macrophages exhibited tissue-resident phenotypes and activation signatures, including high level expression and secretion of monocyte chemoattractants CCL2 and CCL3 by airway macrophages. By contrast, monocytes in blood expressed the CCL2-receptor CCR2 and aberrant CD163 + and immature phenotypes. Extensive accumulation of CD163 + monocyte/macrophages within alveolar spaces in COVID-19 lung autopsies suggested recruitment from circulation. Our findings provide evidence that COVID-19 pathogenesis is driven by respiratory immunity, and rationale for site-specific treatment and prevention strategies.","journal":"medRxiv","year":2020,"id":119208,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9381,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":225927,"name":"Pranay Dogra","orcid":"0000-0003-2031-9855","position":1,"is_corresponding":false},{"id":225928,"name":"Joshua I. 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Yates","orcid":"0000-0003-4606-4483","position":12,"is_corresponding":false},{"id":553715,"name":"Amy Ku","orcid":"0000-0003-3251-5167","position":13,"is_corresponding":false},{"id":229314,"name":"Michael Chait","orcid":null,"position":14,"is_corresponding":false},{"id":225931,"name":"Julia Davis‐Porada","orcid":"0000-0001-9313-4590","position":15,"is_corresponding":false},{"id":109714,"name":"Jing Zhou","orcid":"0000-0001-6190-8053","position":16,"is_corresponding":false},{"id":554902,"name":"Matthew Steinle","orcid":null,"position":17,"is_corresponding":false},{"id":109727,"name":"Sean Mackay","orcid":"0009-0006-4030-916X","position":18,"is_corresponding":false},{"id":553716,"name":"Anjali Saqi","orcid":"0000-0003-3133-9886","position":19,"is_corresponding":false},{"id":104625,"name":"Matthew R. Baldwin","orcid":"0000-0003-4670-3433","position":20,"is_corresponding":false},{"id":225061,"name":"Peter A. 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