ABSTRACT
The current global epidemiology of COVID-19 is now characterized by the emergence and rapid spread of the SARS-CoV-2 Omicron variant on a global scale 1,2 . Despite the variant’s prompt predominance, there remain knowledge gaps in its origin and evolution history 3–6 . Here, we show that Omicron lineage SARS-CoV-2 is characterized by the feature of chimera. It was generated by genomic recombination of two early PANGO lineages of SARS-CoV-2. In the recombination event, strains with medium or high circulating intensity like SARS-CoV-2/human/USA/COR-21-434196/2021 belonging to PANGO lineage BA.1 provided the fundamental genome and served as the major parents, while the rare lineage strains like SARS-CoV-2/human/IRN/Ir-3/2019 belonging to B.35, as the minor parents, hybridized their genomic fractions into the major genomes at position 21593-23118nt. This recombination event results in 22 amino acid residue substitutions for the variant of Omicron, including 16 in the pivotal RBD of the spike protein. These substitutions have led to some subtle variations in the spatial structure and the affinity to hACE2 receptor of the spike protein 7,8 , thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics 9–12 . The global spread and explosive growth of the SARS-CoV-2 in human population increase opportunities for future recombination 13–15 .
Subject(s)
COVID-19ABSTRACT
Background: Hydroxychloroquine (HCQ) and chloroquine (CQ) have been widely used for the treatment of the coronavirus disease 2019 (COVID-19), despite limited clinical evidence and controversial early reports. The aim of this report was to provide a systematic review of the literature and meta-analysis on the use of HCQ/CQ with respect to safety and clinical efficacy of these medications. Methods: We performed a systematic search of the medical databases and included studies if they focused on patients with COVID-19 who received HCQ or CQ alone, or in combination with other treatments, and were compared with a control group. We analyzed two important clinical objectives; viral clearance rate by reverse transcription-polymerase chain reaction (RT-PCR) negativity and all-cause mortality.Results: A total of 14 studies were included in the quantitative synthesis. The use of HCQ/CQ was associated with higher viral clearance rate compared with control group (OR: 3.12, 95% CI: 2.17-4.49 p<0.0001). In the sensitivity analysis, the effect on viral clearance disappeared (OR 1.44, 95% CI: 0.87-2.37, p=0.155). The use of HCQ/CQ was associated with a higher risk of mortality (OR 1.26, 95% CI: 1.05-1.51, p<0.0001). Due to huge heterogeneity between the studies (I2 = 86%, p < 0.01), we performed a meta regression analysis. Both treatment within 24 hours (p=0.047) and comorbidities [hypertension (p=0.025), diabetes (p=0.049) and chronic lung disease (p=0.0064)] contributed to the heterogeneity. HCQ/CQ daily dose (p=0.61) and age (p=0.62) had no impact on effect size. Higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ. Overall, the use of HCQ/CQ resulted in longer QTc intervals.Conclusions: Our meta-analysis did not reveal a clinical benefit of HCQ/CQ on in-hospital outcomes for patients with COVID-19. The use of HCQ/CQ did not result in rapid viral clearance on RT-PCR. Moreover, our results showed that higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ.