Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused significant health and economic havoc around the globe. One of the early agents targeted for repurposing to treat and prevent COVID-19 was hydroxychloroquine (HCQ). In this systematic review and meta-analysis, HCQ is evaluated for its potential role in decreasing mortality in hospitalized patients with COVID-19. We searched PubMed, Web of Science, and medRxiv databases using combinations of the terms "COVID-19", "SARS-CoV-2", "coronavirus", "hydroxychloroquine", and "mortality". Articles were selected for further review based on the content of their abstracts. Studies were excluded if they were of poor methodological quality, were not based in the inpatient setting, or did not have available data to assess the primary outcome of death between patients treated with HCQ versus standard of care. Once the final dataset was compiled, a meta-analysis using the random-effects model was performed. Our search identified 14 studies involving 24,780 patients of whom 12,707 patients were on HCQ alone or in combination with other adjuvant therapies. HCQ alone or in combination with other drugs did not significantly decrease mortality in hospitalized patients with COVID-19 (odds ratio [OR], 0.95; 95% CI, 0.72-1.26; p = 0.732; I2 = 91.05). Similar findings were observed in all subgroup analyses. HCQ did not significantly impact mortality in hospitalized patients with COVID-19. Additional well-designed studies are essential due to the heterogeneity in available studies.

Linezolid (LZD) has a longstanding reported association with the onset of serotonin toxicity (ST), secondary to drug-drug interactions with serotoninergic agents. There have been no conclusive data supporting the incidence or contributing risk factors to date. The study evaluated the incidence of ST in patients treated with LZD and serotonergic agents concomitantly versus LZD alone. The secondary objectives included a comparison of ST incidence in patients treated with one serotonergic agent + LZD versus two or more serotonergic agents + LZD. The studies used for this meta-analysis were retrieved from PubMed, Scopus, and Google Scholar. All studies including a comparison between LZD alone and LZD + a serotonergic agent published between 1 January 2000 and 1 October 2023 and meeting the quality standards were considered for inclusion. Fourteen studies were identified, with five meeting all inclusion and exclusion criteria with no significant heterogeneity. For the analysis of LZD monotherapy vs. SA combination therapy, four studies with 6025 patients total were analyzed and yielded an odds ratio of 1.78 (CI [1.04, 3.02]; I2 = 49%; GRADE certainty: low). Four studies and 2501 patients were included in the analysis of one versus more than one SA with an odds ratio of 5.18 (CI [1.05, 25.49]; I2 = 44.87; GRADE certainty: moderate). The Newcastle-Ottawa score, visual inspection of the funnel plot, and Egger's statistic were used to evaluate quality and heterogeneity. The Peto method was used to calculate the summary odds ratios. All analyses were performed using Comprehensive Meta-Analysis version 3.0 and R, while GRADE was used to evaluate the quality of the final recommendation. The number of concomitant serotonergic agents may play a role in the development of serotonin toxicity in patients prescribed linezolid. In patients requiring linezolid therapy and serotonergic agents, risk versus benefit analysis should pay attention to the number of interacting drugs.