Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Arunachalam Prabhu S, Wimmers Florian, Mok Chris Ka Pun, Perera Ranawaka A P M, Scott Madeleine, Hagan Thomas, Sigal Natalia, Feng Yupeng, Bristow Laurel, Tak-Yin Tsang Owen, Wagh Dhananjay, Coller John, Pellegrini Kathryn L, Kazmin Dmitri, Alaaeddine Ghina, Leung Wai Shing, Chan Jacky Man Chun, Chik Thomas Shiu Hong, Choi Chris Yau Chung, Huerta Christopher, Paine McCullough Michele, Lv Huibin, Anderson Evan, Edupuganti Srilatha, Upadhyay Amit A, Bosinger Steve E, Maecker Holden Terry, Khatri Purvesh, Rouphael Nadine, Peiris Malik, Pulendran Bali
Аннотация
Coronavirus 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.