The global Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has affected more than eight million people. There is an urgent need to investigate how the adaptive immunity is established in COVID-19 patients. In this study, we profiled adaptive immune cells of PBMCs from recovered COVID-19 patients with varying disease severity using single-cell RNA and TCR/BCR V(D)J sequencing. The sequencing data revealed SARS-CoV-2-specific shuffling of adaptive immune repertories and COVID-19-induced remodeling of peripheral lymphocytes. Characterization of variations in the peripheral T and B cells from the COVID-19 patients revealed a positive correlation of humoral immune response and T-cell immune memory with disease severity. Sequencing and functional data revealed SARS-CoV-2-specific T-cell immune memory in the convalescent COVID-19 patients. Furthermore, we also identified novel antigens that are responsive in the convalescent patients. Altogether, our study reveals adaptive immune repertories underlying pathogenesis and recovery in severe versus mild COVID-19 patients, providing valuable information for potential vaccine and therapeutic development against SARS-CoV-2 infection.
BackgroundIL-10+ regulatory B (Bregs), CD4+Foxp3+ regulatory T (Tregs), and CD4+CXCR5+Foxp3+ follicular regulatory T (TFR) cells regulate the progression of infection disease. This study aimed at examining how those cells associated with the development of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) in a Chinese population.MethodsThe numbers of circulating IL-10+ Bregs, Tregs and TFR cells in 31 CHC, 58 CHB patients and 22 healthy controls (HC) were examined by flow cytometry. The potential association of those cells with clinical measures was analyzed.ResultsThe numbers of CD5+CD19+CD1dhighIL-10+ Bregs, Tregs and TFR cells and the levels of serum IL-10, IFN-γ and IL-2 in the CHB, and IL-10 and IFN-γ in the CHC patients were significantly higher than that in the HC (p < 0.05). Furthermore, the numbers of circulating IL-10+ Bregs and the levels of serum IL-10, but not other cytokines tested were positively correlated with the levels of serum HBV DNA and ALT in the HBeAg− CHB patients as well as HCV RNA and ALT in CHC patients. Additionally, the numbers of circulating TFR cells were positively correlated with the levels of serum HBV DNA and ALT in the CHB patients as well as HCV RNA and ALT in the CHC patients.ConclusionsIncreased numbers of circulating IL-10+ Bregs and TFR cells are associated with poor virus eradication and liver injury in CHB and CHC patients. Furthermore, the levels of serum IL-10 is associated with the hepatic flares.
No therapeutics have been proven effective yet for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the efficacy and safety of Triazavirin therapy for COVID-19, we conducted a randomized, double-blinded controlled trial involving hospitalized adult patients with COVID-19. Participants were enrolled from ten sites, and were randomized into two arms of the study with a ratio of 1:1. Patients were treated with Triazavirin 250 mg versus a placebo three or four times a day for 7 d. The primary outcome was set as the time to clinical improvement, defined as normalization of body temperature, respiratory rate, oxygen saturation, cough, and absorption of pulmonary infection by chest computed tomography (CT) until 28 d after randomization. Secondary outcomes included individual components of the primary outcome, the mean time and proportion of inflammatory absorption in the lung, and the conversion rate to a repeated negative SARS-CoV-2 nucleic acid test of throat swab sampling. Concomitant therapeutic treatments, adverse events, and serious adverse events were recorded. Our study was halted after the recruitment of 52 patients, since the number of new infections in the participating hospitals decreased greatly. We randomized 52 patients for treatment with Triazavirin ( n = 26) or a placebo ( n = 26). We found no differences in the time to clinical improvement (median, 7 d versus 12 d; risk ratio (RR), 2.0; 95% confidence interval (CI), 0.7–5.6; p = 0.2), with clinical improvement occurring in ten patients in the Triazavirin group and six patients in the placebo group (38.5% vs. 23.1%, RR, 2.1; 95% CI, 0.6–7.0; p = 0.2). All components of the primary outcome normalized within 28 d, with the exception of absorption of pulmonary infection (Triazavirin 50.0%, placebo 26.1%). Patients in the Triazavirin group used less frequent concomitant therapies for respiratory, cardiac, renal, hepatic, or coagulation supports. Although no statistically significant evidence was found to indicate that Triazavirin benefits COVID-19 patients, our observations indicated possible benefits from its use to treat COVID-19 due to its antiviral effects. Further study is required for confirmation.
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