To provide a comprehensive systematic review and meta‐analysis regarding the cumulative incidence (incidence proportion) of human herpesvirus (HHV) reactivation among patients with coronavirus disease 2019 (COVID‐19), we searched PubMed/MEDLINE, Web of Science, and EMBASE up to 25 September 2022, with no language restrictions. All interventional and observational studies enrolling patients with confirmed COVID‐19 and providing data regarding HHV reactivation were included. The random‐effects model was used in the meta‐analyses. We included information from 32 studies. HHV reactivation was considered a positive polymerase chain reaction result taken at the time of COVID‐19 infection. Most of the included patients were severe COVID‐19 cases. The pooled cumulative incidence estimate was 38% (95% Confidence Intervals [CI], 28%–50%, I2 = 86%) for herpes simplex virus (HSV), 19% (95% CI, 13%–28%, I2 = 87%) for cytomegalovirus (CMV), 45% (95% CI, 28%–63%, I2 = 96%) for Epstein‐Barr virus (EBV), 18% (95% CI, 8%–35%) for human herpesvirus 6 (HHV‐6), 44% (95% CI, 32%–56%) for human herpesvirus 7 (HHV‐7), and 19% (95% CI, 14%–26%) for human herpesvirus 8 (HHV‐8). There was no evidence of funnel plot asymmetry based on visual inspection and Egger's regression test for the results of HSV (p = 0.84), CMV (p = 0.82), and EBV (p = 0.27) reactivation. In conclusion, the identification of HHV reactivation in severe COVID‐19 patients is helpful in the management of patients as well as the prevention of complications. Further research is required to elucidate the interaction between HHVs and COVID‐19. Systematic review registration: PROSPERO CRD42022321973.

No abstract

Background We conducted a systematic review and meta-analysis to evaluate the efficacy of ivermectin for COVID-19 patients based on current peer-reviewed RCTs and to address disputes over the existing evidence. Methods MEDLINE (Pubmed), Scopus, Web of Science, Cochrane library, Google scholar and Clinicaltrials.gov were searched for RCTs assessing the efficacy of Ivermectin up to 20 February 2022. A systematic review and meta-analysis of studies was performed based on the PRISMA 2020 statement criteria. Results 19 and 17 studies were included in this systematic review and meta-analysis, respectively. There was no significant difference in progression to severe disease (log OR − 0.27 [95% CI − 0.61 to 0.08], I2 = 42.29%), negative RT-PCR (log OR 0.25 [95% CI − 0.18–0.68], I2 = 58.73%), recovery (log OR 0.11 [95% CI − 0.22–0.45], I2 = 13.84%), duration of hospitalization (SMD − 0.40 [95% CI − 0.85–0.06], I2 = 88.90%), time to negative RT-PCR (SMD − 0.36 [95% CI − 0.89–0.17], I2 = 46.2%), and viral load (SMD -0.17 [95% CI -0.45 to 0.12], I^2 = 0%). It is worth noting that, based on low-certainty evidence, ivermectin may possibly reduce mortality (log OR − 0.67 [95% CI − 1.20 to − 0.13], I2 = 28.96%). However, studies with a higher risk of bias were more likely to indicate positive effects on the efficacy of this drug, according to our subgroup analyses based on study quality. Conclusion Ivermectin did not have any significant effect on outcomes of COVID-19 patients and as WHO recommends, use of ivermectin should be limited to clinical trials.

No abstract

Curcumin is a low‐cost and easily accessible therapeutic option for COVID‐19 patients. We aimed to conduct a meta‐analysis to assess the effect of curcumin on clinical outcomes in COVID‐19 patients. Various databases, including PubMed, the Cochrane Library and Embase were searched from inception until October 2022 for randomized controlled trials (RCTs) evaluating curcumin use in COVID‐19 patients. Results from 13 RCTs were pooled using R software version 4.1.0. Curcumin reduced the risk of all‐cause mortality (RR 0.38; 95% CI: 0.20–0.72; moderate certainty of evidence), and patients with no recovery status (RR 0.54; 95% CI: 0.42–0.70; moderate certainty of evidence) but had no effect on the incidence of mechanical ventilation and hospitalization, and the rate of a positive viral PCR test. The results of subgroup analysis suggested a higher benefit with early administration of curcumin (within 5 days of onset of symptoms) and with the use of combination regimens. Curcumin is likely to be of benefit in mild‐to‐moderate COVID‐19 patients, but large‐scale RCTs are needed to confirm these findings. The limitations of our meta‐analysis include the small sample sizes of the included RCTs and the variable formulations of curcumin used across the studies.

No abstract

Background SARS-CoV-2 exposure during pregnancy is related to adverse effects for both the mother and the infant. SARS-CoV-2 vaccination has lowered the risk of symptomatic disease substantially. Recently published studies have evaluated the outcomes of women who received the COVID-19 vaccine during pregnancy; systematic evidence regarding vaccination safety is crucial to ensure that COVID-19 vaccination is not associated with adverse pregnancy and neonatal outcomes. Methods Pubmed/MEDLINE, EMBASE, Scopus, Web of Science, and Clinicaltrials.gov were searched from each database's inception through April 7, 2022. All interventional and observational studies comparing neonatal or pregnancy outcomes between pregnant women who received COVID-19 vaccines during their pregnancy and unvaccinated pregnant women were included. The random-effects model was used in the meta-analyses. Results A total of 11 studies comprising 756,098 pregnant mothers were included. The rate of neonates with 5-min Apgar score ≤ 7 (log RR -0.08 (95% CI: -0.15 to -0.00), (P = 0.03)) and pregnant mothers with preterm birth (log RR -0.11 (95% CI: -0.21 to -0.01), (P = 0.02)) was significantly lower among vaccinated group. No significant difference was observed in adverse neonatal outcomes (log RR -0.07 (95% CI: -0.17 to 0.03)), small for gestational age (log RR -0.06 (95% CI: -0.14 to 0.02)), caesarean delivery (log RR 0.05 (95% CI: -0.05 to 0.15)), postpartum hemorrhage (log RR -0.05 (95% CI: -0.13 to 0.02)), stillbirth (log RR -0.05 (95% CI: -0.54 to 0.45)). Conclusions and relevance In this systematic review and meta-analysis, no evident differences were observed when comparing vaccinated pregnant mothers with those who had not received COVID-19 vaccines. Based on low certainty of evidence, vaccination during pregnancy was accompanied by a favorable Apgar score in neonates and fewer preterm births.

Tweetable abstract This editorial examines what has caused the evidence around ivermectin to be so controversial, provides a brief analysis of recently published evidence, and highlights why it is important to learn lessons from ivermectin for future re-purposed drugs.