{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:48:15Z","timestamp":1790743695752,"version":"4.1.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-20-COVI-0053"],"award-info":[{"award-number":["ANR-20-COVI-0053"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-LABX-69-01"],"award-info":[{"award-number":["ANR-10-LABX-69-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-20-COVI-0053"],"award-info":[{"award-number":["ANR-20-COVI-0053"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-LABX-69-01"],"award-info":[{"award-number":["ANR-10-LABX-69-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Immunol"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Coordinated local mucosal and systemic immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either protect against coronavirus disease 2019 (COVID-19) pathologies or fail, leading to severe clinical outcomes. To understand this process, we performed an integrated analysis of SARS-CoV-2 spike-specific antibodies, cytokines, viral load and bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct patients with COVID-19 during acute infection. Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and also with spike-specific neutralizing antibodies. By contrast, nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities. Potential pathogenic microorganisms, often implicated in secondary respiratory infections, were associated with mucosal inflammation and elevated in severe COVID-19. Our results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes.<\/jats:p>","DOI":"10.1038\/s41590-021-01028-7","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T06:04:51Z","timestamp":1630476291000},"page":"1428-1439","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":158,"title":["Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection"],"prefix":"10.1038","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0202-612X","authenticated-orcid":false,"given":"Nika\u00efa","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4127-1152","authenticated-orcid":false,"given":"Pedro","family":"Goncalves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5478-482X","authenticated-orcid":false,"given":"Bruno","family":"Charbit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludivine","family":"Grzelak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Beretta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Planchais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timoth\u00e9e","family":"Bruel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Rouilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-0984","authenticated-orcid":false,"given":"Vincent","family":"Bondet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Hadjadj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"Yatim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Pere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah H.","family":"Merkling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amine","family":"Ghozlane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solen","family":"Kern\u00e9is","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7858-7866","authenticated-orcid":false,"given":"Frederic","family":"Rieux-Laucat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Terrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0729-1475","authenticated-orcid":false,"given":"Olivier","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Mouquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8875-2308","authenticated-orcid":false,"given":"Darragh","family":"Duffy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7146-1862","authenticated-orcid":false,"given":"James P.","family":"Di Santo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,1]]},"reference":[{"key":"1028_CR1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","volume":"395","author":"C Huang","year":"2020","unstructured":"Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497\u2013506 (2020).","journal-title":"Lancet"},{"key":"1028_CR2","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","volume":"584","author":"EJ Williamson","year":"2020","unstructured":"Williamson, E. J. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 584, 430\u2013436 (2020).","journal-title":"Nature"},{"key":"1028_CR3","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1056\/NEJMra2026131","volume":"383","author":"DC Fajgenbaum","year":"2020","unstructured":"Fajgenbaum, D. C. & June, C. H. Cytokine storm. N. Engl. J. Med. 383, 2255\u20132273 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1028_CR4","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.immuni.2020.07.026","volume":"53","author":"R Zhou","year":"2020","unstructured":"Zhou, R. et al. Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses. Immunity 53, 864\u2013877 (2020).","journal-title":"Immunity"},{"key":"1028_CR5","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1126\/science.abc6027","volume":"369","author":"J Hadjadj","year":"2020","unstructured":"Hadjadj, J. et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 369, 718\u2013724 (2020).","journal-title":"Science"},{"key":"1028_CR6","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1016\/j.cell.2021.02.029","volume":"184","author":"JL Schultze","year":"2021","unstructured":"Schultze, J. L. & Aschenbrenner, A. C. COVID-19 and the human innate immune system. Cell 184, 1671\u20131692 (2021).","journal-title":"Cell"},{"key":"1028_CR7","doi-asserted-by":"publisher","first-page":"eabc8511","DOI":"10.1126\/science.abc8511","volume":"369","author":"D Mathew","year":"2020","unstructured":"Mathew, D. et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 369, eabc8511 (2020).","journal-title":"Science"},{"key":"1028_CR8","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1016\/j.cell.2020.05.015","volume":"181","author":"A Grifoni","year":"2020","unstructured":"Grifoni, A. et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 181, 1489\u20131501 (2020).","journal-title":"Cell"},{"key":"1028_CR9","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41577-020-0331-4","volume":"20","author":"M Merad","year":"2020","unstructured":"Merad, M. & Martin, J. C. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat. Rev. Immunol. 20, 355\u2013362 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"1028_CR10","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1016\/S0140-6736(20)30920-X","volume":"395","author":"H Li","year":"2020","unstructured":"Li, H. et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet 395, 1517\u20131520 (2020).","journal-title":"Lancet"},{"key":"1028_CR11","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/s41591-020-0868-6","volume":"26","author":"W Sungnak","year":"2020","unstructured":"Sungnak, W. et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat. Med. 26, 681\u2013687 (2020).","journal-title":"Nat. Med."},{"key":"1028_CR12","doi-asserted-by":"publisher","unstructured":"Cervia, C. et al. Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19. J. Allergy Clin. Immunol https:\/\/doi.org\/10.1016\/j.jaci.2020.10.040 (2020).","DOI":"10.1016\/j.jaci.2020.10.040"},{"key":"1028_CR13","doi-asserted-by":"publisher","first-page":"eabe5511","DOI":"10.1126\/sciimmunol.abe5511","volume":"5","author":"B Isho","year":"2020","unstructured":"Isho, B. et al. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci. Immunol. 5, eabe5511 (2020).","journal-title":"Sci. Immunol."},{"key":"1028_CR14","doi-asserted-by":"publisher","unstructured":"Sterlin, D. et al. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci. Transl. Med. https:\/\/doi.org\/10.1126\/scitranslmed.abd2223 (2020).","DOI":"10.1126\/scitranslmed.abd2223"},{"key":"1028_CR15","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/s41591-020-0897-1","volume":"26","author":"Q-X Long","year":"2020","unstructured":"Long, Q.-X. et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat. Med. 26, 845\u2013848 (2020).","journal-title":"Nat. Med."},{"key":"1028_CR16","doi-asserted-by":"publisher","first-page":"eabc3103","DOI":"10.1126\/scitranslmed.abc3103","volume":"12","author":"L Grzelak","year":"2020","unstructured":"Grzelak, L. et al. A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations. Sci. Transl. Med. 12, eabc3103 (2020).","journal-title":"Sci. Transl. Med."},{"key":"1028_CR17","doi-asserted-by":"publisher","first-page":"eabe0240","DOI":"10.1126\/sciimmunol.abe0240","volume":"5","author":"K R\u00f6ltgen","year":"2020","unstructured":"R\u00f6ltgen, K. et al. Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome. Sci. Immunol. 5, eabe0240 (2020).","journal-title":"Sci. Immunol."},{"key":"1028_CR18","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/s41591-021-01318-5","volume":"27","author":"D Planas","year":"2021","unstructured":"Planas, D. et al. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat. Med. 27, 917\u2013924 (2021).","journal-title":"Nat. Med."},{"key":"1028_CR19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3390\/proteomes7030029","volume":"7","author":"MB O\u2019Rourke","year":"2019","unstructured":"O\u2019Rourke, M. B. et al. What is normalization? the strategies employed in top-down and bottom-up proteome analysis workflows. Proteomes 7, 29 (2019).","journal-title":"Proteomes"},{"key":"1028_CR20","doi-asserted-by":"publisher","unstructured":"Bastard, P. et al. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science https:\/\/doi.org\/10.1126\/science.abd4585 (2020).","DOI":"10.1126\/science.abd4585"},{"key":"1028_CR21","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41586-020-2588-y","volume":"584","author":"C Lucas","year":"2020","unstructured":"Lucas, C. et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 584, 463\u2013469 (2020).","journal-title":"Nature"},{"key":"1028_CR22","doi-asserted-by":"publisher","first-page":"eaah3565","DOI":"10.1126\/sciimmunol.aah3565","volume":"1","author":"EA Moseman","year":"2016","unstructured":"Moseman, E. A., Wu, T., Torre, J. C., Schwartzberg, P. L. & McGavern, D. B. Type I interferon suppresses virus-specific B cell responses by modulating CD8+ T cell differentiation. Sci. Immunol. 1, eaah3565 (2016).","journal-title":"Sci. Immunol."},{"key":"1028_CR23","doi-asserted-by":"publisher","unstructured":"Veyer, D. et al. Highly sensitive quantification of plasma SARS-CoV-2 RNA sheds light on its potential clinical value. Clin. Infect. Dis. https:\/\/doi.org\/10.1093\/cid\/ciaa1196 (2020).","DOI":"10.1093\/cid\/ciaa1196"},{"key":"1028_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19057-5","volume":"11","author":"J Fajnzylber","year":"2020","unstructured":"Fajnzylber, J. et al. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat. Commun. 11, 5493 (2020).","journal-title":"Nat. Commun."},{"key":"1028_CR25","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1056\/NEJMc2001737","volume":"382","author":"L Zou","year":"2020","unstructured":"Zou, L. et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N. Engl. J. Med. 382, 1177\u20131179 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1028_CR26","doi-asserted-by":"publisher","first-page":"e1005633","DOI":"10.1371\/journal.ppat.1005633","volume":"12","author":"SD Brugger","year":"2016","unstructured":"Brugger, S. D., Bomar, L. & Lemon, K. P. Commensal-pathogen interactions along the human nasal passages. PLoS Pathog. 12, e1005633 (2016).","journal-title":"PLoS Pathog."},{"key":"1028_CR27","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1186\/s12859-020-03666-4","volume":"21","author":"S Volant","year":"2020","unstructured":"Volant, S. et al. SHAMAN: a user-friendly website for metataxonomic analysis from raw reads to statistical analysis. BMC Bioinformatics 21, 345 (2020).","journal-title":"BMC Bioinformatics"},{"key":"1028_CR28","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","volume":"13","author":"BJ Callahan","year":"2016","unstructured":"Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581\u2013583 (2016).","journal-title":"Nat. Methods"},{"key":"1028_CR29","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1084\/jem.20171079","volume":"215","author":"VK Ridaura","year":"2018","unstructured":"Ridaura, V. K. et al. Contextual control of skin immunity and inflammation by Corynebacterium. J. Exp. Med. 215, 785\u2013799 (2018).","journal-title":"J. Exp. Med."},{"key":"1028_CR30","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1038\/s41590-020-0721-6","volume":"21","author":"J Di Domizio","year":"2020","unstructured":"Di Domizio, J. et al. The commensal skin microbiota triggers type I IFN\u2013dependent innate repair responses in injured skin. Nat. Immunol. 21, 1034\u20131045 (2020).","journal-title":"Nat. Immunol."},{"key":"1028_CR31","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1016\/j.jaci.2018.09.041","volume":"143","author":"F Lan","year":"2019","unstructured":"Lan, F. et al. IFN-\u03bb1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps. J. Allergy Clin. Immunol. 143, 1416\u20131425 (2019).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1028_CR32","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/j.cell.2020.04.022","volume":"181","author":"L Schaupp","year":"2020","unstructured":"Schaupp, L. et al. Microbiota-induced type I interferons instruct a poised basal state of dendritic cells. Cell 181, 1080\u20131096 (2020).","journal-title":"Cell"},{"key":"1028_CR33","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.immuni.2012.04.011","volume":"37","author":"MC Abt","year":"2012","unstructured":"Abt, M. C. et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37, 158\u2013170 (2012).","journal-title":"Immunity"},{"key":"1028_CR34","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1016\/j.cell.2020.10.047","volume":"183","author":"KL Stefan","year":"2020","unstructured":"Stefan, K. L., Kim, M. V., Iwasaki, A. & Kasper, D. L. Commensal microbiota modulation of natural resistance to virus infection. Cell 183, 1312\u20131324 (2020).","journal-title":"Cell"},{"key":"1028_CR35","doi-asserted-by":"publisher","first-page":"e01969","DOI":"10.1128\/mBio.01969-20","volume":"11","author":"HH Mostafa","year":"2020","unstructured":"Mostafa, H. H. et al. Metagenomic next-generation sequencing of nasopharyngeal specimens collected from confirmed and suspect COVID-19 patients. Mbio 11, e01969\u201320 (2020).","journal-title":"Mbio"},{"key":"1028_CR36","doi-asserted-by":"publisher","unstructured":"Wang, Z. et al. Enhanced SARS-CoV-2 neutralization by dimeric IgA. Sci. Transl. Med. https:\/\/doi.org\/10.1126\/scitranslmed.abf1555 (2020).","DOI":"10.1126\/scitranslmed.abf1555"},{"key":"1028_CR37","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/mi.2015.126","volume":"9","author":"M Weitnauer","year":"2016","unstructured":"Weitnauer, M., Mijo\u0161ek, V. & Dalpke, A. H. Control of local immunity by airway epithelial cells. Mucosal Immunol. 9, 287\u2013298 (2016).","journal-title":"Mucosal Immunol."},{"key":"1028_CR38","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1126\/science.abd4570","volume":"370","author":"Q Zhang","year":"2020","unstructured":"Zhang, Q. et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 370, 422 (2020).","journal-title":"Science"},{"key":"1028_CR39","doi-asserted-by":"publisher","unstructured":"Galani, I. -E. et al. Untuned antiviral immunity in COVID-19 revealed by temporal type I\/III interferon patterns and flu comparison. Nat. Immunol. https:\/\/doi.org\/10.1038\/s41590-020-00840-x (2020).","DOI":"10.1038\/s41590-020-00840-x"},{"key":"1028_CR40","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41577-020-00429-3","volume":"20","author":"JS Lee","year":"2020","unstructured":"Lee, J. S. & Shin, E.-C. The type I interferon response in COVID-19: implications for treatment. Nat. Rev. Immunol. 20, 585\u2013586 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"1028_CR41","doi-asserted-by":"publisher","unstructured":"WHO Solidarity Trial Consortium. Repurposed antiviral drugs for COVID-19\u2014Interim WHO Solidarity Trial Results. N. Engl. J. Med. https:\/\/doi.org\/10.1056\/NEJMoa2023184 (2020).","DOI":"10.1056\/NEJMoa2023184"},{"key":"1028_CR42","doi-asserted-by":"publisher","first-page":"ofaa407","DOI":"10.1093\/ofid\/ofaa407","volume":"7","author":"B Sierra","year":"2020","unstructured":"Sierra, B. et al. Association of early nasopharyngeal immune markers with COVID-19 clinical outcome: predictive value of CCL2\/MCP-1. Open Forum Infect. Dis. 7, ofaa407 (2020).","journal-title":"Open Forum Infect. Dis."},{"key":"1028_CR43","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.chom.2020.04.017","volume":"27","author":"Z Zhou","year":"2020","unstructured":"Zhou, Z. et al. Heightened innate immune responses in the respiratory tract of COVID-19 patients. Cell Host Microbe 27, 883\u2013890 (2020).","journal-title":"Cell Host Microbe"},{"key":"1028_CR44","doi-asserted-by":"publisher","unstructured":"Pairo-Castineira, E. et al. Genetic mechanisms of critical illness in COVID-19. Nature https:\/\/doi.org\/10.1038\/s41586-020-03065-y (2020).","DOI":"10.1038\/s41586-020-03065-y"},{"key":"1028_CR45","doi-asserted-by":"publisher","first-page":"637430","DOI":"10.3389\/fmicb.2021.637430","volume":"12","author":"MP Ventero","year":"2021","unstructured":"Ventero, M. P. et al. Nasopharyngeal microbial communities of patients infected with SARS-CoV-2 that developed COVID-19. Front. Microbiol. 12, 637430 (2021).","journal-title":"Front. Microbiol."},{"key":"1028_CR46","doi-asserted-by":"publisher","unstructured":"Giron, L. B. et al. Severe COVID-19 is fueled by disrupted gut barrier integrity. Preprint at medRxiv https:\/\/doi.org\/10.1101\/2020.11.13.20231209 (2020).","DOI":"10.1101\/2020.11.13.20231209"},{"key":"1028_CR47","doi-asserted-by":"publisher","unstructured":"Yang, X. et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir. Med. https:\/\/doi.org\/10.1016\/S2213-2600(20)30079-5 (2020).","DOI":"10.1016\/S2213-2600(20)30079-5"},{"key":"1028_CR48","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","volume":"72","author":"MM Bradford","year":"1976","unstructured":"Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248\u2013254 (1976).","journal-title":"Anal. Biochem."},{"key":"1028_CR49","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1111\/j.1537-2995.2006.00976.x","volume":"46","author":"MER Darnell","year":"2006","unstructured":"Darnell, M. E. R. & Taylor, D. R. Evaluation of inactivation methods for severe acute respiratory syndrome coronavirus in noncellular blood products. Transfusion 46, 1770\u20131777 (2006).","journal-title":"Transfusion"},{"key":"1028_CR50","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1084\/jem.20161451","volume":"214","author":"MP Rodero","year":"2017","unstructured":"Rodero, M. P. et al. Detection of interferon alpha protein reveals differential levels and cellular sources in disease. J. Exp. Med. 214, 1547\u20131555 (2017).","journal-title":"J. Exp. Med."},{"key":"1028_CR51","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/S1473-3099(20)30200-0","volume":"20","author":"F-X Lescure","year":"2020","unstructured":"Lescure, F.-X. et al. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect. Dis. 20, 697\u2013706 (2020).","journal-title":"Lancet Infect. Dis."},{"key":"1028_CR52","doi-asserted-by":"publisher","unstructured":"Veyer, D. et al. Highly sensitive quantification of plasma SARS-CoV-2 RNA shelds light on its potential clinical value. Clin. Infect. Dis. https:\/\/doi.org\/10.1093\/cid\/ciaa1196 (2020).","DOI":"10.1093\/cid\/ciaa1196"},{"key":"1028_CR53","doi-asserted-by":"publisher","first-page":"e106267","DOI":"10.15252\/embj.2020106267","volume":"39","author":"J Buchrieser","year":"2020","unstructured":"Buchrieser, J. et al. Syncytia formation by SARS-CoV-2-infected cells. EMBO J. 39, e106267 (2020).","journal-title":"EMBO J."},{"key":"1028_CR54","doi-asserted-by":"publisher","unstructured":"Chakraborty, S. et al. Divergent early antibody responses define COVID-19 disease trajectories. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2021.05.25.445649 (2021).","DOI":"10.1101\/2021.05.25.445649"},{"key":"1028_CR55","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.1016\/S0140-6736(15)60342-7","volume":"385","author":"M Castelino","year":"2015","unstructured":"Castelino, M. et al. The skin microbiome in psoriatic arthritis: methodology development and pilot data. Lancet 385, S27 (2015).","journal-title":"Lancet"}],"container-title":["Nature Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41590-021-01028-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-021-01028-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-021-01028-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:01:53Z","timestamp":1776855713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41590-021-01028-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,1]]},"references-count":55,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["1028"],"URL":"https:\/\/doi.org\/10.1038\/s41590-021-01028-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.03.01.21251633","asserted-by":"object"}]},"ISSN":["1529-2908","1529-2916"],"issn-type":[{"value":"1529-2908","type":"print"},{"value":"1529-2916","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,1]]},"assertion":[{"value":"10 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}