Final efficacy analysis, interim safety analysis, and immunogenicity of a single dose of recombinant novel coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: an international, multicentre, randomised, double-blinded, placebo-controlled phase 3 trial.

BACKGROUND: The Ad5-nCoV vaccine is a single-dose adenovirus type 5 (Ad5) vectored vaccine expressing the SARS-CoV-2 spike protein that was well-tolerated and immunogenic in phase 1 and 2 studies. In this study, we report results on the final efficacy and interim safety analyses of the phase 3 trial. METHODS: This double-blind, randomised, international, placebo-controlled, endpoint-case driven, phase 3, clinical trial enrolled adults aged 18 years older at study centres in Argentina, Chile, Mexico, Pakistan, and Russia. Participants were eligible for the study if they had no unstable or severe underlying medical or psychiatric conditions; had no history of a laboratory-confirmed SARS-CoV-2 infection; were not pregnant or breastfeeding; and had no previous receipt of an adenovirus-vectored, coronavirus, or SARS-CoV-2 vaccine. After informed consent was obtained, 25 mL of whole blood was withdrawn from all eligible participants who were randomised in a 1:1 ratio to receive a single intramuscular dose of 0·5 mL placebo or a 0·5 mL dose of 5 × 1010 viral particle (vp)/mL Ad5-nCoV vaccine; study staff and participants were blinded to treatment allocation. All participants were contacted weekly by email, telephone, or text message to self-report any symptoms of COVID-19 illness, and laboratory testing for SARS-CoV-2 was done for all participants with any symptoms. The primary efficacy objective evaluated Ad5-nCoV in preventing symptomatic, PCR-confirmed COVID-19 infection occurring at least 28 days after vaccination in all participants who were at least 28 days postvaccination on Jan 15, 2021. The primary safety objective evaluated the incidence of any serious adverse events or medically attended adverse events postvaccination in all participants who received a study injection. This trial is closed for enrolment and is registered with ClinicalTrials.gov (NCT04526990). FINDINGS: Study enrolment began on Sept 22, 2020, in Pakistan, Nov 6, 2020, in Mexico, Dec 2, 2020, in Russia and Chile, and Dec 17, 2020, in Argentina; 150 endpoint cases were reached on Jan 15, 2021, triggering the final primary efficacy analysis. One dose of Ad5-nCoV showed a 57·5% (95% CI 39·7-70·0, p=0·0026) efficacy against symptomatic, PCR-confirmed, COVID-19 infection at 28 days or more postvaccination (21 250 participants; 45 days median duration of follow-up [IQR 36-58]). In the primary safety analysis undertaken at the time of the efficacy analysis (36 717 participants), there was no significant difference in the incidence of serious adverse events (14 [0·1%] of 18 363 Ad5-nCoV recipients and 10 [0·1%] of 18 354 placebo recipients, p=0·54) or medically attended adverse events (442 [2·4%] of 18 363 Ad5-nCoV recipients and 411 [2·2%] of 18 354 placebo recipients, p=0·30) between the Ad5-nCoV or placebo groups, or any serious adverse events considered related to the study product (none in both Ad5-nCoV and placebo recipients). In the extended safety cohort, 1004 (63·5%) of 1582 of Ad5-nCoV recipients and 729 (46·4%) of 1572 placebo recipients reported a solicited systemic adverse event (p<0·0001), of which headache was the most common (699 [44%] of Ad5-nCoV recipients and 481 [30·6%] of placebo recipients; p<0·0001). 971 (61·3%) of 1584 Ad5-nCoV recipients and 314 (20·0%) of 1573 placebo recipients reported an injection-site adverse event (p<0·0001), of which pain at the injection site was the most frequent; reported by 939 (59%) Ad5-nCoV recipients and 303 (19%) placebo recipients. INTERPRETATION: One dose of Ad5-nCoV is efficacious and safe in healthy adults aged 18 years and older. FUNDING: CanSino Biologics and the Beijing Institute of Biotechnology.

Effect of beta-endorphin on calcium uptake in the brain.

The uptake of 45Ca2+ by nerve-ending fractions from brains of mice was inhibited in vitro by 10(-9)M concentrations of beta-endorphin and in mice injected intraventricularly with 7 picomoles of beta-endorphin. That the effect was a specific opiate agonist response of beta-endorphin was demonstrated by use of the opiate antagonist, naloxone, which reversed the action. A role for beta-endorphin in the regulation of calcium flux and neurotransmitter release should be considered.

Cohort study of rotavirus serotype patterns in symptomatic and asymptomatic infections in Mexican children.

A cohort of 200 Mexican children from a low income periurban community was monitored from birth to the age of 2 years to determine the serotype-specific incidence, morbidity and seasonal pattern of symptomatic and asymptomatic human rotavirus (HRV) infections. A total of 177 HRV infections occurred in 134 (67%) children; 50% of these infections were asymptomatic. The incidence of all HRV infections was 0.6 episode/child year and was inversely related to age (r = -0.93; P < 0.01). The incidence of HRV-associated diarrhea was 0.3 episode/child year, with the highest frequency and severity occurring in infants between 4 and 6 months of age. HRV infections were more frequent each autumn, with a changing sequential pattern of predominant serotypes. Overall serotype 3 (34%) was the most frequent, followed by serotypes 1 (16%), 2 (15%) and 4 (6%). The 4 serotypes were associated with a similar risk for diarrhea and severity of diarrhea. In 23 (26%) HRV diarrhea-associated infections, an additional enteropathogen was identified; these mixed infections were more frequent in older children (chi square, 4.45; P < 0.05) but were not more severe (chi square, 0.02; P > 0.05). Our data indicate that HRV infections were common early in life, seasonal, frequently asymptomatic and caused by a variety of serotypes, none of which was a risk factor for diarrhea or severity of diarrhea.