ABSTRACT
Background Although there is increasing understanding of the changes in the laboratory parameters of coronavirus disease 2019 (COVID-19), the correlation between circulating Mid-regional Proadrenomedullin (MR-proADM) and clinical outcomes of patients with COVID-19 is not fully understood. In this study, we aimed to evaluate the prognostic value of MR-proADM in patients with COVID-19.Methods The PubMed, Embase, Web of Science, Cochrane Library, Wanfang, SinoMed and Chinese National Knowledge Infrastructure (CNKI) databases were searched from 1 January 2020 to 20 March 2022 for relevant literature. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess quality bias, STATA was employed to pool the effect size by a random effects model, and potential publication bias and sensitivity analyses were performed.Results 14 studies comprising 1822 patients with COVID-19 met the inclusion criteria, there were 1145 males and 677 females, and the mean age was 64.8 years. The concentration of MR- proADM was compared between the survivors and nonsurvivors in 9 studies and the difference was significant (P < 0.01), I2 = 46%. The combined sensitivity was 0.88 [0.81–0.93], and the combined specificity was 0.77 [0.65–0.86]. We drew the SROC curve and calculated the AUC = 0.90 [0.87–0.93]. An increase of 1 nmol/L of MR-proADM was independently associated with a more than threefold increase in mortality (odds ratio 3.03, 95% confidence interval 2.26–4.06, I2 = 0.0%, P = 0.633). The predictive value of MR-proADM for death was better than many other biomarkers.Conclusion MR- proADM had a very good predictive value for the poor prognosis of COVID-19 patients. Increased levels of MR-proADM were independently associated with mortality in COVID-19 patients and may allow a better risk stratification.
Subject(s)
COVID-19 , Kallmann Syndrome , DeathABSTRACT
Understanding the mechanism of neutralizing antibodies (NAbs) against SARS-CoV-2 is critical for effective vaccines and therapeutics development. We recently reported an exceptionally potent NAb, BD-368-2, and revealed the existence of VH3-53/VH3-66 convergent NAbs in COVID-19. Here we report the 3.5-[A] cryo-EM structure of BD-368-2s Fabs in complex with a mutation-induced prefusion-state-stabilized spike trimer. Unlike VH3-53/VH3-66 NAbs, BD-368-2 fully blocks ACE2 binding by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their "up" and "down" positions. BD-368-2 also triggers fusogenic-like structural rearrangements of the spike trimer, which could impede viral entry. Moreover, BD-368-2 completely avoids the common epitope of VH3-53/VH3-66 NAbs, evidenced by multiple crystal structures of their Fabs in tripartite complexes with RBD, suggesting a new way of pairing potent NAbs to prevent neutralization escape. Together, these results rationalize a unique epitope that leads to exceptional neutralization potency, and provide guidance for NAb therapeutics and vaccine designs against SARS-CoV-2.