ABSTRACT
Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk and of protection, with strongest evidence for 50% inhibitory dilution (ID50) neutralizing antibody titer. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and rose to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported consistency of the ID50 titer correlate of protection across trials and vaccine types.
ABSTRACT
In the present study, serum samples of 20 hospitalized COVID-19 patients from Brazil who were infected by the earlier SARS-CoV-2 lineages B.1.1.28 and B.1.1.33, and by the variant of concern (VOC) Gamma (P.1) were tested by plaque reduction neutralization test (PRNT90) with wild isolates of a panel of SARS-CoV-2 lineages, including B.1, Zeta, N.10, and the VOCs Gamma, Alpha, and Delta that emerged in different timeframes of the pandemic. The main objectives of the present study were to evaluate if serum of COVID-19 patients infected by earlier lineages of SARS-CoV-2 were capable to neutralize recently emerged VOCs, and if PRNT90 is a reliable serologic method to distinguish infections caused by different SARS-CoV-2 lineages. Overall, sera collected from the day of admittance to the hospital to 21 days after diagnostic of patients infected by the two earlier lineages B.1.1.28 and B.1.1.33 presented neutralizing capacity for all challenged VOCs, including Gamma and Delta, that were the most prevalent VOCs in Brazil. Among all variants tested, Delta and N.10 presented the lowest mean of neutralizing antibody titers, and B.1.1.7, presented the highest titers. Four patients infected with Gamma, that emerged in December 2020, presented neutralizing antibodies for B.1, B.1.1.33 and B.1.1.28, its ancestor lineage. All of them had neutralizing antibodies under the level of detection for the VOC Delta. Interestingly, patients infected by B.1.1.28 presented very similar mean of neutralizing antibody titers for both B.1.1.33 and B.1.1.28. Findings presented here indicate that most patients infected in early stages of COVID-19 pandemic presented neutralizing antibodies up to 21 days after diagnostic capable to neutralize wild types of all recently emerged VOCs in Brazil, and that the PRNT90 it is not a reliable serologic method to distinguish natural infections caused by different SARS-CoV-2 lineages.
ABSTRACT
The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma during late 2020 and early 2021 in Brazilian settings with high seroprevalence raised some concern about the potential role of reinfections in driving the epidemic. Very few cases of reinfection associated with the VOC Gamma, however, have been reported. Here we describe 25 cases of SARS-CoV-2 reinfection confirmed by real-time RT-PCR twice within months apart in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected between March and December 2020 with distinct viral lineages, including B.1.1, B.1.1.28, B.1.1.33, B.1.195 and P.2, and then reinfected with the VOC Gamma between 3 to 12 months after primo-infection. The overall mean cycle threshold (Ct) value of the first (25.7) and second (24.5) episodes were roughly similar for the whole group and 14 individuals displayed mean Ct values < 25.0 at reinfection. Sera of 14 patients tested by plaque reduction neutralization test after reinfection displayed detectable neutralizing antibodies against Gamma and other SARS-CoV-2 variants (B.1.33, B.1.1.28 and Delta). All individuals have milder or no symptoms after reinfection and none required hospitalization. The present study demonstrates that the VOC Gamma was associated with reinfections during the second Brazilian epidemic wave in 2021 and raised concern about the potential infectiousness of reinfected subjects. Although individuals here analyzed failed to mount a long-term sterilizing immunity, they developed a high anti-Gamma neutralizing antibody response after reinfection that may provide some protection against severe disease.
ABSTRACT
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. ObjectiveTo evaluate the clinical efficacy and safety of convalescent plasma among adults hospitalized with severe and critical COVID-19. DesignRandomized, double-blind, controlled, multicenter, phase 2 trial conducted from April 21st to November 27th, 2020. SettingFive hospitals in New York City (NY, USA) and Rio de Janeiro (Brazil). ParticipantsHospitalized patients aged [≥]18 years with laboratory-confirmed COVID-19, infiltrates on chest imaging and oxygen saturation [≤] 94% on room air or requirement for supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. InterventionParticipants were randomized 2:1 to a single transfusion of either 1 unit of convalescent or normal control plasma. MeasurementsThe primary outcome was clinical status at 28 days, 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 normal control plasma. At 28 days, no significant improvement in clinical status was observed in participants randomized to convalescent plasma (with an odds ratio (OR) of a 1-point improvement in the scale: 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 (n=40) from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected. Serious adverse events occurred in 39/147 (27%) participants who received convalescent plasma and 26/72 (36%) participants who received control plasma. LimitationsSome participants did not receive high-titer convalescent plasma. ConclusionIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in 28 days clinical status. The significant reduction in mortality associated with convalescent plasma, however, may warrant further evaluation. RegistrationClinicalTrials.gov, NCT04359810 FundingAmazon Foundation Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT04359810
