Summary Currently severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission has been on the rise worldwide. Predicting outcome in COVID‐19 remains challenging, and the search for more robust predictors continues. We made a systematic meta‐analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non‐severe patients of COVID‐19, serum levels of Interleukins (IL)‐2, IL‐2R, IL‐4, IL‐6, IL‐8, IL‐10 and tumor necrosis factor α were significantly up‐regulated in severe patients, with the largest inter‐group differences observed for IL‐6 and IL‐10. In contrast, IL‐5, IL‐1β and Interferon (IFN)‐γ did not show significant inter‐group difference. Four mediators of T cells count, including CD3 + T, CD4 + T, CD8 + T, CD4 + CD25 + CD127 ‐ Treg, together with CD19 + B cells count and CD16 + CD56 + NK cells were all consistently and significantly depressed in severe group than in non‐severe group. SARS‐CoV‐2 specific IgA and IgG antibodies were significantly higher in severe group than in non‐severe group, while IgM antibody in the severe patients was slightly lower than those in the non‐severe patients, and IgE antibody showed no significant inter‐group differences. The combination of cytokines, especially IL‐6 and IL‐10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS‐CoV‐2 infection.

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Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality, however with no effective therapy available. Methods The effect of favipiravir (FPV) in treating SFTS was evaluated by an integrated analysis on data collected from a single-arm study (n=428), a surveillance study (n=2350) and published data from a randomized controlled trial study (n=145). A 1:1 propensity score matching was performed to include 780 patients: 390 received FPV and 390 received supportive therapy only. Case fatality rates (CFRs), clinical progress, and adverse effects were compared. Findings FPV treatment had significantly reduced CFR from 20.0% to 9.0% (odds ratio 0.38, 95% confidence interval 0.23-0.65), however showing heterogeneity when patients were grouped by age, onset-to-admission interval, initial viral load and therapy duration. The effect of FPV was significant only among patients aged ≤70 years, with onset-to-admission interval ≤5 days, therapy duration ≥5 days or baseline viral load ≤1 × 10 6 copies/mL. Age-stratified analysis revealed no benefit in the aging group >70 years, regardless of their sex, onset-to-admission interval, therapy duration or baseline viral load. However, for both ≤60 and 60-70 years groups, therapy duration and baseline viral load differentially affected FPV therapy efficiency. Hyperuricemia and thrombocytopenia, as the major adverse response of FPV usage, were observed in >70 years patients. Interpretation FPV was safe in treating SFTS patients but showed no benefit for those aged >70 years. Instant FPV therapy could highly benefit SFTS patients aged 60-70 years. Funding China Natural Science Foundation (No. 81825019, 82073617 and 81722041) and China Mega-project for Infectious Diseases (2018ZX10713002 and 2015ZX09102022).