COVID-19 vaccination during pregnancy: a systematic review and meta-analysis.

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.

A twisting tale of misinformation: should ivermectin be approved as a treatment for COVID-19 disease?

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.

A twisting tale of misinformation: should ivermectin be approved as a treatment for COVID-19 disease?

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.

Reactivation of herpesviruses during COVID-19: A systematic review and meta-analysis.

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.

Ivermectin under scrutiny: a systematic review and meta-analysis of efficacy and possible sources of controversies in COVID-19 patients.

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.

Comparative study of CNR1 and CNR2 cannabinoid receptors expression levels in COVID-19 patients with and without diabetes mellitus: Recommendations for future research targets.

BACKGROUND AND AIMS: The COVID-19 pandemic has prompted researchers to look for effective therapeutic targets. The effect of endocannabinoid system against infectious diseases is investigated for several years. In this study, we evaluated the expression level of CNR1 and CNR2 genes in patients with COVID-19 with and without diabetes to provide new insights regarding these receptors and their potential effect in COVID-19 disease. METHODS: In this study, peripheral blood monocytes cells (PBMCs) were isolated from eight different groups including COVID-19 patients, diabetic patients, and healthy individuals. RNA were extracted to evaluate the expression level of CNR1 and CNR2 genes using real-time PCR. The correlation between the expression levels of these genes in different groups were assessed. RESULTS: A total of 80 samples were divided into 8 groups, with each group consisting of ten samples. When comparing severe and moderate COVID-19 groups to healthy control group, the expression levels of the CNR1 and CNR2 genes were significantly higher in the severe and moderate COVID-19 groups. There were no significant differences between the mild COVID-19 group and the healthy control group. It was found that the expression levels of these genes in patients with diabetes who were infected with SARS-COV-2 did not differ across COVID-19 groups with varying severity, but they were significantly higher when compared to healthy controls. CONCLUSION: Our study suggests the possible role of endocannabinoid system during SARS-COV-2 pathogenicity as the expression of CNR1 and CNR2 were elevated during the disease.

Pooled Prevalence Estimate of Ocular Manifestations in COVID-19 Patients: A Systematic Review and Meta-Analysis.

Background: There are reports of ocular tropism due to respiratory viruses such as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Various studies have shown ocular manifestation in coronavirus disease-2019 (COVID-19) patients. We aimed to identify ophthalmic manifestations in COVID-19 patients and establish an association between ocular symptoms and SARS-CoV-2 infection. Methods: A systematic search of Medline, Scopus, Web of Science, Embase, and Cochrane Library was conducted for publications from December 2019 to April 2021. The search included MeSH terms such as SARS-CoV-2 and ocular manifestations. The pooled prevalence estimate (PPE) with 95% confidence interval (CI) was calculated using binomial distribution and random effects. The meta-regression method was used to examine factors affecting heterogeneity between studies. Results: Of the 412 retrieved articles, 23 studies with a total of 3,650 COVID-19 patients were analyzed. The PPE for any ocular manifestations was 23.77% (95% CI: 15.73-31.81). The most prevalent symptom was dry eyes with a PPE of 13.66% (95% CI: 5.01-25.51). The PPE with 95% CI for conjunctival hyperemia, conjunctival congestion/conjunctivitis, and ocular pain was 13.41% (4.65-25.51), 9.14% (6.13-12.15), and 10.34% (4.90-15.78), respectively. Only two studies reported ocular discomfort and diplopia. The results of meta-regression analysis showed that age and sample size had no significant effect on the prevalence of any ocular manifestations. There was no significant publication bias in our meta-analysis. Conclusion: There is a high prevalence of ocular manifestations in COVID-19 patients. The most common symptoms are dry eyes, conjunctival hyperemia, conjunctival congestion/conjunctivitis, ocular pain, irritation/itching/burning sensation, and foreign body sensation.

Complete genome sequencing and molecular characterization of SARS-COV-2 from COVID-19 cases in Alborz province in Iran.

Iran was among countries which was hard hit at the early stage of the coronavirus disease 2019 (COVID-19) pandemic and dealt with the second wave of the pandemic in May and June 2020; however, there are a very limited number of complete genome sequences of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from Iran. In this study, complete genome sequences of the virus in the samples obtained from three patients in Alborz province in May and June 2020 were generated and analyzed using bioinformatic methods. The sequenced genomes were positioned in a cluster with B.4 lineage along with the sequences from other countries namely, United Arab Emirates and Oman. There were seven single nucleotide variations (SNVs) in common in all samples and only one of the sequenced genomes showed the D614G amino acid substitution. Three SNVs, 1397 G > A, 28688T > C, 29742 G > T, which had already been reported in February, were found with high frequency in all the sequenced genomes in this study, implying that viral diversity reflected in the early stages of viral transmission in Iran were established in the second wave. Considering the importance of molecular epidemiology in response to ongoing pandemic, there is an urgent need for more complete genome sequencing and comprehensive analyses to gain insight into the transmission, adaptation and evolution of the virus in Iran.

Effect of Ammonium Chloride in addition to standard of care in outpatients and hospitalized COVID-19 patients: A randomized clinical trial.

OBJECTIVE: The COVID-19 pandemic has called an urgent need for drug repurposing to improve the outcome of the disease. Quaternary ammonium compounds have been demonstrated to have antiviral effects and may be of use against SARS-CoV-2 infections. DESIGN: In this double-blind, single-center study, we enrolled patients with positive PCR test and/or CT findings for COVID-19. The participants of each group were randomly assigned to Diphenhydramine Compound (Diphenhydramine + Ammonium Chloride) plus standard of care or to Diphenhydramine alone and standard of care groups. The primary outcome was all-cause mortality within 30 days of randomization. Secondary outcomes include viral burden, clinical status, assessed by a 5-point ordinal scale, and length of stay in hospitalized patients. RESULTS: A total of 120 patients were included in the trial, 60 of which were assigned to the Ammonium Chloride group. The primary endpoint was not statistically different between the two groups (HR: 3.02 (95% CI, 0.57-16.06; p = 0.195)). Recovery time and viral burden were significantly lower in the Ammonium Chloride group, corresponding to an odds ratios of 1.8 (95% CI, 1.15-2.83; p = 0.01) and 7.90 (95% CI, 1.62-14.17; p = 0.014), respectively. CONCLUSION: The findings of this study advocate the careful addition of Ammonium Chloride to standard of care for COVID-19 patients.