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...
In the early 2015, several cases of patients presenting symptoms of mild fever, rash,
conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all
patients lived in a dengue endemic area, molecular and serological diagnosis for
dengue resulted negative. Chikungunya virus infection was also discarded.
Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase
chain reaction from the sera of eight patients and the result was confirmed by DNA
sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the
Asian clade. This is the first report of ZIKV infection in Brazil.
The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.).
An unusually high incidence of microcephaly in newborns has recently been observed in
Brazil. There is a temporal association between the increase in cases of microcephaly
and the Zika virus (ZIKV) epidemic. Viral RNA has been detected in amniotic fluid
samples, placental tissues and newborn and fetal brain tissues. However, much remains
to be determined concerning the association between ZIKV infection and fetal
malformations. In this study, we provide evidence of the transplacental transmission
of ZIKV through the detection of viral proteins and viral RNA in placental tissue
samples from expectant mothers infected at different stages of gestation. We observed
chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry
in Hofbauer cells and some histiocytes in the intervillous spaces. We also
demonstrated the neurotropism of the virus via the detection of viral proteins in
glial cells and in some endothelial cells and the observation of scattered foci of
microcalcifications in the brain tissues. Lesions were mainly located in the white
matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain
reaction. We believe that these findings will contribute to the body of knowledge of
the mechanisms of ZIKV transmission, interactions between the virus and host cells
and viral tropism.
IMPORTANCEOlder patients and those with comorbidities who are infected with SARS-CoV-2 may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody for the treatment of high-risk patients to prevent COVID-19 progression.OBJECTIVE To evaluate the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease.DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial including 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites in Brazil, Canada,
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