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Background: The role of ivermectin in the treatment of COVID-19 is still under debate, yet the drug has been widely used in some parts of the world, as shown by impressive market data. The available body of evidence may have changed over the last months, as studies have been retracted and "standards of care" (SOC) used in control groups have changed with rapidly evolving knowledge on COVID-19. This review aims to summarize and critically appraise the evidence of randomized controlled trials (RCTs) of ivermectin, assessing clinical outcomes in COVID-19 patients.Methods: RCTs evaluating the effects of ivermectin in adult patients with COVID-19 were searched through June 22, 2022, in four databases, L.OVE platform, clinical trial registries and pre-prints platforms. Primary endpoints included all-cause mortality and invasive ventilation requirement. Secondary endpoint was the occurrence of adverse events. Risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Meta-analysis included only studies which compared ivermectin to placebo or SOC. Random-effects were used to pool the risk ratios (RRs) of individual trials. The quality of evidence was evaluated using GRADE. The protocol was register in PROSPERO (CRD42021257471).Results: Twenty-five RCTs fulfilled inclusion criteria (n = 6310). Of those, 14 compared ivermectin with placebo, in night ivermectin associated with SOC was compared to SOC and two studies compared ivermectin to an active comparator. Most RCTs had some concerns or high risk of bias, mostly due to lack of concealment of the randomization sequence and allocation, lack of blinding and high number of missing cases. Ivermectin did not show an effect in reducing mortality (RR = 0.76; 95%CI: 0.52-1.11) or mechanical ventilation (RR = 0.74; 95%CI: 0.48-1.16). This effect was consistent when comparing ivermectin vs. placebo, and ivermectin associated with SOC vs. SOC, as well as in sensitivity analysis. Additionally, there was very low quality of evidence regarding adverse effects (RR = 1.07; 95%CI: 0.84-1.35).Conclusions: The evidence suggests that ivermectin does not reduce mortality risk and the risk of mechanical ventilation requirement. Although we did not observe an increase in the risk of adverse effects, the evidence is very uncertain regarding this endpoint. [ABSTRACT FROM AUTHOR]

Potential medium- and long-term neurodevelopmental sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy have not been ruled out. We aimed to systematically review and summarize the evidence regarding the effects of intrauterine exposure to SARS-CoV-2 on infant development and behavior. Scopus, PubMed, Web of Science, CINAHL, and PsycNet databases were searched for studies published up to February 6, 2023, investigating the effects of gestational SARS-CoV-2 on infant development and behavior. We performed narrative synthesis according to updated protocols. Studies using comparison groups and with the Ages and Stages Questionnaires-Third Edition (ASQ-3) scores available were included in a meta-analysis performed according to Cochrane protocols. We used the Newcastle–Ottawa Quality Assessment Scale to analyze the risk of bias. Heterogeneity was calculated using the I2 statistic. The search identified 2,782 studies. After removing duplicates and applying the eligibility criteria, we performed a narrative synthesis of 10 included studies and a meta-analysis of three. There was no evidence of higher developmental delay rates in infants exposed to SARS-CoV-2 during pregnancy compared to non-exposed infants. However, the exposed infants scored lower than either the non-exposed children or pre-pandemic cohorts in some domains. Pooled results from the random-effects model indicated that SARS-CoV-2-exposed infants had lower scores on fine motor (mean difference [MD] = -4.70, 95% confidence interval [CI]: -8.76; -0.63), and problem-solving (MD = -3.05, 95% CI: -5.88; -0.22) domains than non-exposed infants (heterogeneity: I2 = 69% and 88%, respectively). There was no difference between the exposed and non-exposed infants in the communication, gross motor, and personal-social ASQ-3 domains. Conclusion: We did not find evidence confirming the association between SARS-CoV-2 gestational exposure and neurodevelopmental delays. However, the meta-analysis indicated that gestational exposure negatively affected fine motor and problem-solving skills. Robust evidence on this topic is still incipient, and the available studies present methodological inconsistencies that limit the drawing of clear-cut conclusions. PROSPERO registration: #CRD42022308002; March 14, 2022. What is Known: • COVID-19 is associated with adverse pregnancy outcomes potentially linked to neurodevelopmental delays. • SARS-CoV-2 vertical transmission is rare; however, infections during pregnancy can be deleterious to the fetus, possibly mediated by maternal immune activation and other inflammatory mechanisms. What is New: • No evidence of increased developmental delay rates among SARS-CoV-2 gestational-exposed infants was found. However, a meta-analysis of three studies showed lower scores in fine motor and personal social ASQ-3 domains among exposed infants. • SARS-CoV-2 gestational exposure and the pandemic can affect child development via many mechanisms. Potential neurodevelopmental sequelae of SARS-CoV-2 exposure during gestation have not been ruled out. [ABSTRACT FROM AUTHOR]