Efficacy and safety of ivermectin for treatment of non-hospitalized COVID-19 patients: a systematic review and meta-analysis of 12 randomized controlled trials with 7,035 participants.

INTRODUCTION: We systematically assessed benefits and harms of the use of ivermectin in non-hospitalized patients with early COVID-19. METHODS: Five databases were searched until October 17, 2023, for randomized controlled trials (RCTs) in adult patients with COVID-19 treated with ivermectin against standard of care (SoC), placebo, or active drug. Primary outcomes were hospitalization, all-cause mortality, and adverse events (AEs). Secondary outcomes included mechanical ventilation (MV), clinical improvement, clinical worsening, viral clearance, and severe adverse events (SAEs). Random effects meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. Pre-specified subgroup analyses (ivermectin dose, control type, risk of bias, follow-up, and country income) and trial sequential analysis (TSA) were performed. RESULTS: Twelve RCTs (n=7,035) were included. The controls were placebo in nine RCTs, SoC in two RCTs, and placebo or active drug in one RCT. Ivermectin did not reduce hospitalization (relative risk [RR], 0.81, 95% confidence interval [95%CI] 0.64-1.03; 8 RCTs, low QoE), all-cause mortality (RR 0.98, 95%CI 0.73-1.33; 9 RCTs, low QoE), or AEs (RR 0.89, 95%CI 0.75-1.07; 9 RCTs, very low QoE) vs. controls. Ivermectin did not reduce MV, clinical worsening, or SAEs and did not increase clinical improvement and viral clearance vs. controls (very low QoE for secondary outcomes). Subgroup analyses were mostly consistent with main analyses, and TSA-adjusted risk for hospitalization was similar to main analysis. CONCLUSIONS: In non-hospitalized COVID-19 patients, ivermectin did not have effect on clinical, non-clinical or safety outcomes versus controls. Ivermectin should not be recommended as treatment in non-hospitalized COVID-19 patients.

Beneficial and Harmful Effects of Monoclonal Antibodies for the Treatment and Prophylaxis of COVID-19: Systematic Review and Meta-Analysis.

BACKGROUND: We systematically assessed beneficial and harmful effects of monoclonal antibodies for coronavirus disease 2019 (COVID-19) treatment, and prophylaxis in individuals exposed to severe acute respiratory syndrome coronavirus 2. METHODS: We searched 5 engines and 3 registries until November 3, 2021 for randomized controlled trials evaluating monoclonal antibodies vs control in hospitalized or non-hospitalized adults with COVID-19, or as prophylaxis. Primary outcomes were all-cause mortality, COVID-19-related death, and serious adverse events; hospitalization for non-hospitalized; and development of symptomatic COVID-19 for prophylaxis. Inverse variance random effects models were used for meta-analyses. Grading of Recommendations, Assessment, Development, and Evaluations methodology was used to assess certainty of evidence. RESULTS: Twenty-seven randomized controlled trials were included: 20 in hospitalized patients (n = 8253), 5 in non-hospitalized patients (n = 2922), and 2 in prophylaxis (n = 2680). In hospitalized patients, monoclonal antibodies slightly reduced mechanical ventilation (relative risk [RR] 0.74; 95% confidence interval [CI], 0.60-0.9; I2 = 20%, low certainty of evidence) and bacteremia (RR 0.77; 95% CI, 0.64-0.92; I2 = 7%, low certainty of evidence); evidence was very uncertain about the effect on adverse events (RR 1.31; 95% CI, 1.02-1.67; I2 = 77%, very low certainty of evidence). In non-hospitalized patients, monoclonal antibodies reduced hospitalizations (RR 0.30; 95% CI, 0.17-0.53; I2 = 0%, high certainty of evidence) and may slightly reduce serious adverse events (RR 0.47; 95% CI, 0.22-1.01; I2 = 33%, low certainty of evidence). In prophylaxis studies, monoclonal antibodies probably reduced viral load slightly (mean difference -0.8 log10; 95% CI, -1.21 to -0.39, moderate certainty of evidence). There were no effects on other outcomes. CONCLUSIONS: Monoclonal antibodies had limited effects on most of the outcomes in COVID-19 patients, and when used as prophylaxis. Additional data are needed to determine their efficacy and safety.

Prevalence of Leishmania infection in adult HIV/AIDS patients treated in a tertiary-level care center in Brasilia, Federal District, Brazil.

In order to estimate the magnitude of Leishmania/HIV co-infection, patients with HIV/AIDS at the Brasilia University Hospital, DF, Brazil were used as subjects in a cross-sectional study. One hundred and sixty-three patients were enrolled, seven of whom had visceral leishmaniasis (VL). One hundred and twelve patients (68.7%) were men; 155 (95.1%) had been exposed to HIV infection through unprotected sex. The median age was 37 years (range: 20-74) and the median CD4+ lymphocyte count was 314 cells/microl (range: 2-1600). Symptomatic patients underwent bone marrow evaluations through direct examination of Giemsa-stained films, parasite culture and PCR assay. Blood samples were evaluated by means of an indirect immunofluorescent antibody test (IFAT), an ELISA using a soluble antigen of L. chagasi (ELISA), an ELISA with the rK39 antigen (ELISA-rK39) and a PCR targeted to the kDNA region and to the internal transcribed spacer 1 of the rDNA gene. The proportion of positive results was 2.4% for the IFAT, 12.3% for the ELISA and 4.9% for the rK39 tests. The estimated prevalence was 16%. The PCR in the blood was positive in three patients (1.8%). The prevalence of Leishmania spp. infection is high among HIV patients attending this Brazilian center suggesting that they should be routinely investigated for VL infection.