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Longitudinal transcriptional analysis of peripheral blood leukocytes in COVID-19 convalescent donors.
Gedda, Mallikarjuna R; Danaher, Patrick; Shao, Lipei; Ongkeko, Martin; Chen, Leonard; Dinh, Anh; Thioye Sall, Mame; Reddy, Opal L; Bailey, Christina; Wahba, Amy; Dzekunova, Inna; Somerville, Robert; De Giorgi, Valeria; Jin, Ping; West, Kamille; Panch, Sandhya R; Stroncek, David F.
Afiliação
  • Gedda MR; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Danaher P; Section of Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Shao L; NanoString Technologies, Seattle, WA, 98109, USA.
  • Ongkeko M; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Chen L; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Dinh A; Blood Services Section, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Thioye Sall M; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Reddy OL; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Bailey C; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Wahba A; NanoString Technologies, Seattle, WA, 98109, USA.
  • Dzekunova I; NanoString Technologies, Seattle, WA, 98109, USA.
  • Somerville R; NanoString Technologies, Seattle, WA, 98109, USA.
  • De Giorgi V; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Jin P; Infectious Disease Section, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • West K; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Panch SR; Blood Services Section, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Stroncek DF; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 20892, USA. srpanch@uw.edu.
J Transl Med ; 20(1): 587, 2022 12 12.
Article em En | MEDLINE | ID: mdl-36510222
BACKGROUND: SARS-CoV2 can induce a strong host immune response. Many studies have evaluated antibody response following SARS-CoV2 infections. This study investigated the immune response and T cell receptor diversity in people who had recovered from SARS-CoV2 infection (COVID-19). METHODS: Using the nCounter platform, we compared transcriptomic profiles of 162 COVID-19 convalescent donors (CCD) and 40 healthy donors (HD). 69 of the 162 CCDs had two or more time points sampled. RESULTS: After eliminating the effects of demographic factors, we found extensive differential gene expression up to 241 days into the convalescent period. The differentially expressed genes were involved in several pathways, including virus-host interaction, interleukin and JAK-STAT signaling, T-cell co-stimulation, and immune exhaustion. A subset of 21 CCD samples was found to be highly "perturbed," characterized by overexpression of PLAU, IL1B, NFKB1, PLEK, LCP2, IRF3, MTOR, IL18BP, RACK1, TGFB1, and others. In addition, one of the clusters, P1 (n = 8) CCD samples, showed enhanced TCR diversity in 7 VJ pairs (TRAV9.1_TCRVA_014.1, TRBV6.8_TCRVB_016.1, TRAV7_TCRVA_008.1, TRGV9_ENST00000444775.1, TRAV18_TCRVA_026.1, TRGV4_ENST00000390345.1, TRAV11_TCRVA_017.1). Multiplexed cytokine analysis revealed anomalies in SCF, SCGF-b, and MCP-1 expression in this subset. CONCLUSIONS: Persistent alterations in inflammatory pathways and T-cell activation/exhaustion markers for months after active infection may help shed light on the pathophysiology of a prolonged post-viral syndrome observed following recovery from COVID-19 infection. Future studies may inform the ability to identify druggable targets involving these pathways to mitigate the long-term effects of COVID-19 infection. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04360278 Registered April 24, 2020.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: COVID-19 Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: COVID-19 Idioma: En Ano de publicação: 2022 Tipo de documento: Article