Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10 10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10 10 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov , NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more t...

BackgroundThe effects of convalescent plasma (CP) therapy hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect CP on clinical improvement in these patients.MethodsThis is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment.ResultsA total of 160 (80 in each arm) patients (66.3% were critically ill and 33.7%, severe) completed the trial. The median age was 60.5 years (interquartile range [IQR], 48–68), 58.1% were men and the median time from symptom onset to randomisation was 10 days (IQR, 8–12). Neutralising antibodies titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC and 65.0% in the SOC group (difference, −3.7%; 95% Confidence Interval [CI], −18.8%-11.3%). The results were similar in the subgroups of severe and critically ill. There was no significant difference between CP+SOC and SOC groups in prespecified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratorial markers values on days 3, 7 and 14 were similar between groups.ConclusionsCP+SOC did not result in a higher proportion of clinical improvement on at day 28 in hospitalised patients with COVID-19 compared to SOC alone.

Several COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARS-CoV-2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (−2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K.

Background The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant of concern (VOC) Gamma (P.1) has increased transmissibility and resulted in elevated hospitalization, intensive care unit occupancy and mortality rates in Brazil. It is not known whether this VOC is also associated with more severe clinical course of disease. Methods This was a retrospective cohort study with non-elderly patients hospitalized for COVID-19 from June to December/2020 (first period) and February to May/2021 (second period) at a reference hospital in Brazil. Two cohorts were performed: the main cohort, composed by patients with SARS-CoV-2 lineages confirmed by whole genome sequencing; and the sensitivity cohort, composed by all eligible patients admitted before and after the emergence of Gamma. The primary outcome was the incidence rate of need of advanced ventilatory support. Results In the main cohort a total of 86 (43 Gamma and 43 non-Gamma) patients were included. Baseline characteristics were similar, except that Gamma patients had lower median Charlson’s comorbidity score. The crude and adjusted incidence rates of advanced respiratory support (adjusted Hazard Ratio [aHR], 1.78; 95% Confidence Interval [CI], 1.05–3.03), invasive respiratory support (aHR, 2.64; 95% CI, 1.34–5.19) and 28-day mortality from onset of symptoms (aHR, 4.73; 95% CI, 1.15–19.41) and adjusted 28-day mortality from hospital admission (aHR, 3.72; 95% CI, 1.19–11.65) were significantly higher in patients infected by Gamma. These patients had significantly lower days alive and free of supplemental oxygen support. The sensitivity cohort included 433 patients: 259 from the first and 174 from the second period (before and after the emergence of Gamma, respectively). Baseline characteristics were similar, except for a higher incidence of severe distress respiratory syndrome in patients from second group at admission. Patients from the second period had significantly higher incidence rates of advanced respiratory support (aHR, 2.04; 95% CI, 1.60–2.59), invasive ventilatory support (aHR, 2.72; 95%CI, 2.05–3.62), and 28-day mortality from the onset of symptoms (aHR, 2.62; 95%CI, 1.46–4.72). Conclusions Our study suggests that in non-elderly hospitalized patients, COVID-19 caused by Gamma VOC may present a more severe clinical course, with increased need of advanced respiratory support and higher 28-day mortality.

The SARS-CoV-2 variant of concern (VOC) gamma (P.1) has increased transmissibility and resulted in elevated hospitalization and mortality rates in Brazil. We investigated the clinical course of COVID-19 caused by gamma and non-VOCs at a reference hospital in Brazil in a retrospective cohort study with nonelderly hospitalized patients from two periods, before and after the emergence of gamma. Cohort 1 included patients from both periods whose samples would be eligible for whole-genome sequencing (WGS). Cohort 2 was composed of randomly selected patients from Cohort 1 whose samples were submitted to WGS. A total of 433 patients: 259 from the first and 174 from the second period. Baseline characteristics were similar, except for a higher incidence of severe distress respiratory syndrome at admission in patients from the second period. Patients from the second period had significantly higher incidence rates of advanced respiratory support (adjusted hazard ratio [aHR]: 2.04; 95% confidence interval [CI], 1.60–2.59), invasive ventilatory support (aHR: 2.72; 95% CI: 2.05–3.62), and 28-day mortality from the onset of symptoms (aHR: 2.62; 95% CI: 1.46–4.72). A total of 86 (43 gamma and 43 nongamma) patients composed Cohort 2. Patients with confirmed gamma VOC infections had higher advanced ventilatory support and mortality rates than non–gamma-infected patients. Our study suggests that nonelderly patients hospitalized for COVID-19 in the second period (used as a proxy of gamma infection) had a more severe clinical course. This might have contributed to higher hospitalization and death rates observed in the second wave in Brazil.

Introducão A linhagem Gamma (P.1) do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tem transmissibilidade aumentada e resultou em aumento de hospitalizações, ocupação de leitos de terapia intensiva e taxas de mortalidade no Brasil. A associação dessa linhagem com um curso mais severo de doença ainda não foi determinado. Métodos Esta foi uma coorte retrospectiva avaliando pacientes não idosos hospitalizados por COVID-19 de junho a dezembro de 2020 (primeiro período) e fevereiro a maio de 2021 (segundo período) em um hospital de referência no Brasil. Duas coortes foram incluídas: a principal, composta de pacientes com linhagens de SARS-CoV-2 confirmada por sequenciamento genético, e a coorte de sensibilidade, composta por todos os pacientes elegíveis admitidos antes e depois da emergência da Gamma. O desfecho primário foi a taxa de incidência de necessidade de suporte ventilatório avançado. Resultados Na coorte principal, 86 (43 Gamma e 43 não-Gamma) pacientes foram incluídos. Características na admissão foram semelhantes, à exceção de que pacientes infectados pela Gamma tinham uma mediana menor no escore de comodidades de Charlson's. As taxas de incidência bruta e ajustada de suporte ventilatório avançado (hazard ratio ajustada [aHR], 1.78; intervalo de confiança 95% [CI], 1.05-3.03) e mortalidade em 28 dias do inicio de sintomas (aHR, 4.73; 95% CI, 1.15-19.41) e mortalidade em 28 dias da hospitalização (aHR, 3.72; 95% CI, 1.19-11.65) foram significativamente maiores em pacientes infectados pela Gamma. Estes pacientes tinham significativamente menos dias de vida e sem necessidade de oxigênio suplementar. A coorte de sensibilidade incluiu 433 pacientes: 259 do primeiro e 174 do segundo período (antes e depois da emergência da Gamma, respectivamente). Características de base eram semelhantes, à exceção de maior incidência de síndrome respiratória aguda grave na admissão em pacientes do segundo grupo. Pacientes do segundo período tinham significativamente maiores taxas de incidência de necessidade de suporte ventilatório avançado (aHR, 2.04; 95% CI, 1.60-2.59), suporte ventilatório invasivo (aHR, 2.72; 95% CI, 2.05-3.62), e mortalidade em 28 dias do início dos sintomas (aHR, 2.62; 95% CI, 1.46-4.72). Conclusão Nosso estudo sugere que em pacientes hospitalizados não idosos, COVID-19 causada pela linhagem Gamma pode apresentar quadro clinico mais severo, com maior necessidade de suporte ventilatório avançado e mortalidade em 28 dias.

Objective To describe the IMPACTO-MR, a Brazilian nationwide intensive care unit platform study focused on the impact of health care-associated infections due to multidrug-resistant bacteria. Methods We described the IMPACTO-MR platform, its development, criteria for intensive care unit selection, characterization of core data collection, objectives, and future research projects to be held within the platform. Results The core data were collected using the Epimed Monitor System® and consisted of demographic data, comorbidity data, functional status, clinical scores, admission diagnosis and secondary diagnoses, laboratory, clinical, and microbiological data, and organ support during intensive care unit stay, among others. From October 2019 to December 2020, 33,983 patients from 51 intensive care units were included in the core database. Conclusion The IMPACTO-MR platform is a nationwide Brazilian intensive care unit clinical database focused on researching the impact of health care-associated infections due to multidrug-resistant bacteria. This platform provides data for individual intensive care unit development and research and multicenter observational and prospective trials.

No abstract