Background COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. Methods This systematic review was registered at PROSPERO under CRD42020177154. We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. Results Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10 mg/L, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49 U/L, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88 pg/mL, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 to 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). Discussion This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors that predict severe COVID-19 outcomes and will inform clinical scores to support early decision-making.

The merozoite surface protein 1 (MSP1) is the most abundant protein on the surface of the invasive merozoite stages of Plasmodium falciparum and has long been considered a key target of protective immunity. However, previous studies focused on small C-terminal fragments and potentially missed the opportunity to identify important epitopes that are relevant for protection. We used samples from a controlled human malaria challenge (CHMI) study in semi-immune volunteers to show that levels of pre-challenge antibodies directed against the full-length MSP1 (MSP1FL) are significantly correlated with protection from malaria. Furthermore, we showed that anti-MSP1FLantibodies induced five distinct Fc-mediated effector mechanisms: complement fixation, phagocytosis, respiratory burst, degranulation and IFNγ production, each of which was strongly associated with protection. The breadth of Fc-mediated effector functions was the strongest correlate of protection. Our findings suggest that MSP1FLis an important target of functional antibodies that contribute to a protective immune response against malaria and support the development of MSP1FL-based vaccines.