Abstract
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.
Highlights
COVID-19 presents with a spectrum of clinical phenotypes, with most patients exhibiting mild-to-moderate symptoms, and 15% progressing typically within a week to severe or critical disease that requires hospitalization [1], and a minority of those develop acute respiratory disease syndrome (ARDS) requiring mechanical ventilation
We used mass cytometry to assess immune responses to Severe Acute Respiratory Syndrome (SARS)-CoV-2 infection in 52 COVID-19 patients, that were confirmed positive for viral RNA by PCR, and 62 age and gender-matched healthy controls distributed between the two cohorts
Mass cytometry analysis of peripheral blood leukocytes from two independent cohorts, from Hong Kong and Atlanta revealed several common features of immune responses induced upon SARS-CoV-2 infection
Summary
COVID-19 presents with a spectrum of clinical phenotypes, with most patients exhibiting mild-to-moderate symptoms, and 15% progressing typically within a week to severe or critical disease that requires hospitalization [1], and a minority of those develop acute respiratory disease syndrome (ARDS) requiring mechanical ventilation. COVID-19 results in functional impairment of blood myeloid cells and plasmacytoid DCs Given the earlier findings that mTOR signaling in pDCs mediates production of IFN-α in response to TLR stimulation [16] the reduced expression of pS6 in pDCs suggested that such cells may be impaired in their capacity to produce IFNα.
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