Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval.

The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data for approved COVID-19 vaccines and drugs, as well as developmental pipelines, using databases from the following organizations: United States Food and Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical and Medical Devices Agency (PMDA), and ClinicalTrials.gov. In all, 387 drugs were found for initial review. After removing unrelated trials and drugs, 66 drugs were selected, including 17 approved drugs and 49 drugs under development. These drugs were classified into six categories: 1) drugs targeting the viral life cycle 2) Anti-severe acute respiratory syndrome coronavirus 2 Monoclonal Antibodies, 3) immunomodulators, 4) anti-coagulants, 5) COVID-19-induced neuropathy drugs, and 6) other therapeutics. Among the 49 drugs under development are the following: 6 drugs targeting the viral life cycle, 12 immunosuppression drugs, 2 immunostimulants, 2 HIF-PHD targeting drugs, 3 GM-CSF targeting drugs, 5 anti-coagulants, 2 COVID-19-induced neuropathy drugs, and 17 others. This review provides insight into mechanisms of action, properties, and indications for COVID-19 medications.

Prevalence and Associations Between Metabolic Syndrome Components and Hyperuricemia by Race: Findings From US Population, 2011-2020.

OBJECTIVE: We explored the trend in prevalence of hyperuricemia and metabolic syndrome in US populations and investigated associations between components of metabolic syndrome and hyperuricemia by race. METHODS: We analyzed data from the four most recent National Health and Nutrition Examination Survey (NHANES) cycles (2011 to March 2020), comprising 10,175 participants. Hyperuricemia is defined as serum urate >7.0 mg/dL (men) or >5.7 mg/dL (women), following the NHANES-III guideline. The definition of metabolic syndrome follows the National Cholesterol Education Program's Adult Treatment Panel III guideline. We estimated the prevalence of metabolic syndrome and hyperuricemia in each cycle and performed subgroup analyses with logistic regression to investigate the patterns of associated components of metabolic syndrome with hyperuricemia. RESULTS: In the most recent cycle (2017 to March 2020), the prevalence of metabolic syndrome was 45.9% and that of hyperuricemia was 20.7%. Over the 2011 to 2020 period, a significant rise in metabolic syndrome prevalence was observed among Hispanic and Asian populations, and the prevalence of hyperuricemia has increased significantly only in the Hispanic population. After adjustment for confounding factors, patients with metabolic syndrome exhibited a higher hyperuricemia in women than in men. Elevated blood pressure was the strongest factor with hyperuricemia. The association was the weakest in the Asian population. Waist circumference was the only significant factor associated with hyperuricemia in the Asian population. CONCLUSION: The prevalence of metabolic syndrome has an increasing pattern, but there was no specific decadal trend in prevalence of hyperuricemia. There is an ethnicity-specific association of metabolic syndrome and hyperuricemia, especially among Asians.

Large-scale cross-ancestry genome-wide meta-analysis of serum urate.

Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control.