A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19.

BACKGROUNDAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.METHODSWe conducted a randomized, double-blind, controlled trial among adults hospitalized with severe and critical COVID-19 at 5 sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized 2:1 to receive a single transfusion of either convalescent plasma or normal control plasma. The primary outcome was clinical status at 28 days following randomization, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.RESULTSOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to receive normal control plasma. At 28 days, no significant improvement in the clinical scale was observed in participants randomized to convalescent plasma (OR 1.50, 95% confidence interval [CI] 0.83-2.68, P = 0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, P = 0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected.CONCLUSIONIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in day 28 clinical status. However, convalescent plasma was associated with significantly improved survival. A possible explanation is that survivors remained hospitalized at their baseline clinical status.TRIAL REGISTRATIONClinicalTrials.gov, NCT04359810.FUNDINGAmazon Foundation, Skoll Foundation.

Efficacy of Three Antiretroviral Regimens Initiated during Pregnancy: Clinical Experience in Rio de Janeiro.

Few studies have compared the clinical efficacy and adverse events of combined antiretroviral therapy (cART) regimens in pregnant women seeking obstetrical care. The objective of this study was to compare the efficacy (virus load response), adverse events, and obstetrical and neonatal outcomes of three different regimens of cART in HIV-infected pregnant women initiating treatment in Rio de Janeiro, Brazil. This was a retrospective cohort study of cART-naive pregnant women who initiated either ritonavir-boosted protease inhibitors (atazanavir or lopinavir), efavirenz, or raltegravir plus a backbone regimen. From 2014 to 2018, 390 pregnant women were followed over time. At baseline, the median viral load (VL) for HIV was 4.1 log copies/ml. Among participants who received cART for 2 to 7 weeks, the VL decline was greater for raltegravir (2.24 log copies/ml) than for efavirenz or protease inhibitors (P < 0.001). Virologic suppression was achieved in 87% of women on raltegravir near delivery versus 73% on efavirenz and 70% on protease inhibitors (P = 0.011). Patients on raltegravir achieved virologic suppression faster than those on other regimens (P = 0.019). Overall, the HIV perinatal infection rate was 1.5%. This clinical study compared three potent and well-tolerated cART regimens and demonstrated that a higher proportion of participants on raltegravir achieved an undetectable HIV VL near delivery (P = 0.011) compared to the other arms. These findings suggest that raltegravir-containing regimens are optimal regimens for women with HIV initiating treatment late in pregnancy.

High rates of baseline antiretroviral resistance among HIV-infected pregnant women in an HIV referral centre in Rio de Janeiro, Brazil.

In order to understand antiretroviral resistance during pregnancy and its impact on HIV vertical transmission, we performed a cross-sectional analysis of 231 HIV-infected pregnant women who fulfilled Brazilian guidelines for antiretroviral testing and had antiretroviral genotypic testing performed between April 2010 and October 2012. At entry into prenatal care, the mean CD4 cell count for this cohort of patients was 406 cells/mm(3) (95% CI: 373-438 cells/mm(3)), while the mean HIV RNA was 24,394 copies/ml (95% CI: 18,275-30,513 copies/ml). Thirty-six women (16%) had detectable antiretroviral-resistant mutations. By 34 weeks gestation, 75% had achieved HIV RNA <400 copies/ml. Our logistic regression model showed the odds of harbouring antiretroviral-resistant virus with a baseline CD4 cell count of <200 cells/mm(3) was eight times that of subjects with CD4 cell counts >500 CD4 cells/mm(3) (95% CI 1.5-42.73). Six infants were HIV infected, four born to mothers with detectable viraemia at 34 weeks and two born to mothers who were lost to follow up. Antiretroviral resistance is common in prenatal care but did not increase vertical transmission if viral load was appropriately suppressed. Genotyping should be considered in Brazil in order to assist initiation of appropriate combination antiretroviral therapy during pregnancy to suppress viral load to avoid vertical transmission.

Hemoptise/s e síndrome de angústia respiratória aguda como expressöes clínicas dominantes no curso da leptospirose / Massive hemoptysis and adult respiratory distress syndrome like clinical manifestations in leptospirosis

Säo apresentados, a guisa de exemplos, três casos de leptospirose com manifestaçöes clínicas respiratórias e alteraçöes radiográficas e gasométricas compatíveis com envolvimento pulmonar importante. Em dois casos, episódios de hemoptises francas foram assinalados, fato näo raramente detectado na leptospirose e que confunde com freqüência o diagnóstico. Como a doença é endêmica, com elevada prevalência em nosso meio, decidimos mostrar algumas características, clínicas do envolvimento do aparelho respiratório, fazendo uma revisäo de alguns trabalhos sobre o tema