Epstein Barr Virus Reactivation during COVID-19 Hospitalization Significantly Increased Mortality/Death in SARS-CoV-2(+)/EBV(+) than SARS-CoV-2(+)/EBV(-) Patients: A Comparative Meta-Analysis.

Epstein-Barr virus (EBV) reactivation in acute-phase of COVID-19 disease was recently discovered but it is not clear in terms of degree of mortality caused, and this was the aim of the current study. Six databases and three non-databases were thoroughly searched, independently. The articles related to non-human study (abstract, in vitro, in vivo, in silico, case study, poster, and review articles) were excluded for main analysis. Four articles related to mortality linked to EBV reactivation were systematically identified and included in the qualitative and quantitative analyses. Based on proportional meta-analysis of 4 studies, 34.3% or 0.343 (95% CI: 0.189-0.516; I 2 = 74.6) mortality related to EBV reactivation was identified. To address high heterogeneity, subgroup meta-analysis was carried out. Based on subgroup analysis, 26.6% or 0.266 (95% CI: 0.191-0.348; I 2 = 0) with no heterogeneity was identified. Interestingly, in comparative meta-analysis, EBV(-)/SARS-CoV-2(+) patients had statistically lesser mortality (9.9%) than EBV(+)/SARS-CoV-2(+) patients (23.6%) where RR = 2.31 (95% CI: 1.34-3.99; p = 0.003; I 2 = 6%). This finding is equivalent to the absolute mortality effect of 130 more per 1000 COVID-19 patients (95% CI: 34-296). Furthermore, based on statistical analysis, D-dimer was not statistically significantly different (p > 0.05) between the groups although studies have shown that D-dimer was statistically significantly different (p < 0.05) between these groups. Based on the inclusion and analysis of low risk of bias and high quality of articles graded with Newcastle-Ottawa Scale (NOS), when COVID-19 patients' health state is gradually worsening, EBV reactivation needs to be suspected because EBV reactivation is a possible marker for COVID-19 disease severity.

Does baricitinib reduce mortality and disease progression in SARS-CoV-2 virus infected patients? A systematic review and meta analysis.

BACKGROUND: There are conflicting reports on the results of several of the latest clinical trials related to the use of baricitinib in the management of COVID-19 patients. The aim of the current systematic review and meta-analysis was to evaluate the efficacy of baricitinib in COVID-19 patients. METHODS: Databases like ScienceDirect, PubMed/Medline, Publons, Google Scholar and other sources like ClinicalTrials.gov, Cochrane, medRxiv, Research Square and reference lists were thoroughly searched. RESULTS: Fifteen (15) articles which met the inclusion criteria were qualitatively and quantitatively analysed. Based on Cochrane and Newcastle-Ottawa Scale (NOS) risk of bias (RoB) analyses, 14/15 articles are grouped as high-quality. Meta-analyses revealed that randomised control trials (RCTs) and non-randomised control trials (nRCTs) statistically significantly reduced the mortality rate in COVID-19 patients, with a risk ratio (RR) in the fixed-effect model was RR = 0.64 [95% CI: 0.51 to 0.79; p < 0.0001] and RR = 0.58 [95% CI: 0.45 to 0.73; p < 0.00001], respectively, with insignificant heterogeneity and no publication bias found. For block/reduce disease progression (BDP), baricitinib did not statistically significantly reduce disease progression for RCTs. The RR in the random effect model was RR = 0.80 [95% CI: 0.58 to 1.10: p = 0.17], with significant heterogeneity, where I2 was 60%. On the other hand, baricitinib statistically significantly reduced disease progression in nRCTs, as the RR of the fixed effect model was RR = 0.54 [95% CI: 0.37 to 0.78; p = 0.001] with insignificant heterogeneity. CONCLUSION: The current meta-analyses revealed that baricitinib statistically significantly reduced mortality rate and disease progression in COVID-19 patients. PROSPERO REGISTRATION NUMBER: CRD42021281556.

Baricitinib for the Management of SARS-CoV-2-Infected Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Baricitinib is known to reduce mortality and disease progression in COVID-19 patients; however, the data are inconsistent. Therefore, it needs to be explored to further understand the clinical benefits of this drug in the management of COVID-19 patients. Does baricitinib statistically significantly reduce mortality and disease progression in COVID-19 patients? To answer these questions, three databases known as ScienceDirect, PubMed/MEDLINE, and Scopus and other sources, such as preprint (medRxiv) and reference lists, were thoroughly searched. Four randomised controlled trials (RCTs) were included. Based on the meta-analysis, baricitinib statistically significantly reduced mortality with the risk ratio (RR) of RR = 0.74 [95% CI: 0.58 to 0.94; p = 0.01] and moderately high heterogeneity, where I 2 = 62% and p = 0.05. On the other hand, RR = 0.84 [95% CI: 0.75 to 0.95; p = 0.005] with insignificant heterogeneity of I 2 = 20% and p = 0.28 was found for disease progression. Cochrane risk of bias (RoB) analysis revealed that three out of four articles were ranked as high-quality articles with low RoB. Based on the evidence grading, the overall certainty of evidences was moderate. In conclusion, baricitinib statistically significantly reduced mortality and disease progression in COVID-19 patients when the patients were treated with baricitinib at a dosage of 2 mg or 4 mg for a maximum duration of 14 days.