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Article: Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans

TitleSystems biological assessment of immunity to mild versus severe COVID-19 infection in humans
Authors
Issue Date2020
PublisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://sciencemag.org
Citation
Science, 2020, v. 369 n. 6508, p. 1210-1220 How to Cite?
AbstractCoronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators—including EN-RAGE, TNFSF14, and oncostatin M—which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.
Persistent Identifierhttp://hdl.handle.net/10722/306620
ISSN
2023 Impact Factor: 44.7
2023 SCImago Journal Rankings: 11.902
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorArunachalam, PS-
dc.contributor.authorWimmers, F-
dc.contributor.authorMok, CKP-
dc.contributor.authorPerera, RAPM-
dc.contributor.authorScott, M-
dc.contributor.authorHagan, T-
dc.contributor.authorSigal, N-
dc.contributor.authorFeng, Y-
dc.contributor.authorBristow, L-
dc.contributor.authorTsang, OTY-
dc.contributor.authorWagh, D-
dc.contributor.authorColler, J-
dc.contributor.authorPellegrini, KL-
dc.contributor.authorKazmin, D-
dc.contributor.authorAlaaeddine, G-
dc.contributor.authorLeung, WS-
dc.contributor.authorChan, JMC-
dc.contributor.authorChik, TSH-
dc.contributor.authorChoi, CYC-
dc.contributor.authorHuerta, C-
dc.contributor.authorPaine Mccullough, M-
dc.contributor.authorLv, H-
dc.contributor.authorAnderson, E-
dc.contributor.authorEdupuganti, S-
dc.contributor.authorUpadhyay, AA-
dc.contributor.authorBosinger, SE-
dc.contributor.authorMaecker, HT-
dc.contributor.authorKhatri, P-
dc.contributor.authorRouphael, N-
dc.contributor.authorPeiris, M-
dc.contributor.authorPulendran, B-
dc.date.accessioned2021-10-22T07:37:13Z-
dc.date.available2021-10-22T07:37:13Z-
dc.date.issued2020-
dc.identifier.citationScience, 2020, v. 369 n. 6508, p. 1210-1220-
dc.identifier.issn0036-8075-
dc.identifier.urihttp://hdl.handle.net/10722/306620-
dc.description.abstractCoronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators—including EN-RAGE, TNFSF14, and oncostatin M—which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.-
dc.languageeng-
dc.publisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://sciencemag.org-
dc.relation.ispartofScience-
dc.rightsScience. Copyright © American Association for the Advancement of Science.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleSystems biological assessment of immunity to mild versus severe COVID-19 infection in humans-
dc.typeArticle-
dc.identifier.emailPeiris, M: malik@hkucc.hku.hk-
dc.identifier.authorityMok, CKP=rp01805-
dc.identifier.authorityPerera, RAPM=rp02500-
dc.identifier.authorityPeiris, M=rp00410-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1126/science.abc6261-
dc.identifier.pmid32788292-
dc.identifier.pmcidPMC7665312-
dc.identifier.scopuseid_2-s2.0-85090491877-
dc.identifier.hkuros328634-
dc.identifier.volume369-
dc.identifier.issue6508-
dc.identifier.spage1210-
dc.identifier.epage1220-
dc.identifier.isiWOS:000567525400047-
dc.publisher.placeUnited States-

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