Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial

Background: Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine.Methods: In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine. 3 weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed up for 6 weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted or a cellular or recombinant quadrivalent vaccine). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reactions in the 7 days after first trial vaccination(s), with a difference of less than 25% considered non-inferior. Analyses were done on an intention-to-treat basis. Local and unsolicited systemic reactions and humoral responses were also assessed. The trial is registered with ISRCTN, ISRCTN14391248.Findings: Between April 1 and June 26, 2021, 679 participants were recruited to one of six cohorts, as follows: 129 ChAdOx1 plus cellular quadrivalent influenza vaccine, 139 BNT162b2 plus cellular quadrivalent influenza vaccine, 146 ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine, 79 BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine, 128 ChAdOx1 plus recombinant quadrivalent influenza vaccine, and 58 BNT162b2 plus recombinant quadrivalent influenza vaccine. 340 participants were assigned to concomitant administration of influenza and a second dose of COVID-19 vaccine at day 0 followed by placebo at day 21, and 339 participants were randomly assigned to concomitant administration of placebo and a second dose of COVID-19 vaccine at day 0 followed by influenza vaccine at day 21. Non-inferiority was indicated in four cohorts, as follows: ChAdOx1 plus cellular quadrivalent influenza vaccine (risk difference for influenza vaccine minus placebo –1·29%, 95% CI –14·7 to 12·1), BNT162b2 plus cellular quadrivalent influenza vaccine (6·17%, –6·27 to 18·6), BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine (–12·9%, –34·2 to 8·37), and ChAdOx1 plus recombinant quadrivalent influenza vaccine (2·53%, –13·3 to 18·3). In the other two cohorts, the upper limit of the 95% CI exceeded the 0·25 non-inferiority margin (ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine 10·3%, –5·44 to 26·0; BNT162b2 plus recombinant quadrivalent influenza vaccine 6·75%, –11·8 to 25·3). Most systemic reactions to vaccination were mild or moderate. Rates of local and unsolicited systemic reactions were similar between the randomly assigned groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected.Interpretation: Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need

Markers of physiological stress during exercise under conditions of normoxia, normobaric hypoxia, hypobaric hypoxia and genuine high altitude.

Purpose To investigate whether there is a differential response at rest and following exercise to conditions of genuine high altitude (GHA), normobaric hypoxia (NH), hypobaric hypoxia (HH) and normobaric normoxia (NN). Method Markers of sympathoadrenal and adrenocortical function (plasma normetanephrine [PNORMET], metanephrine [PMET], cortisol), myocardial injury (highly sensitive cardiac troponin T [hscTnT]) and function (N-terminal brain natriuretic peptide [NT-proBNP]) were evaluated at rest and with exercise under NN, at 3375 m in the Alps (GHA) and at equivalent simulated altitude under NH and HH. Participants cycled for 2 hours {15 minute warm-up, 105 minutes at 55% Wmax (maximal workload)} with venous blood samples taken prior (T0), immediately following (T120) and 2 hours post-exercise (T240). Results Exercise in the three hypoxic environments produced a similar pattern of response with the only difference between environments being in relation to PNORMET. Exercise in NN only induced a rise in PNORMET and PMET. Conclusion Biochemical markers that reflect sympathoadrenal, adrenocortical and myocardial responses to physiological stress demonstrate significant differences in the response to exercise under conditions of normoxia versus hypoxia while NH and HH appear to induce broadly similar responses to GHA and may therefore be reasonable surrogates

Dhaka Stress Scale-Adult: A scale for assessing psychosocial stressors among adults

Stress is an integral part of daily life and inevitable. This study was aimed to produce a culturally validated scale for measuring stressful life events of adults in Bangladesh and formulate the relative life change units of each event. The study used qualitative research, including a focus group and questionnaire, as well as quantitative statistical analysis in the validation process. Researchers first developed a provisional scale with 62 items that were translated in Bangla through a translation exercise. Using an open-ended question along with this provisional scale on 518 (260 rated on imagination and 258 on experience) subjects, researchers developed Dhaka Stress Scale-Adult with 58 items and the predictive interpretation of the overall score was made. Content validity was found excellent as I-CVI was 1 except 3 items and S-CVI was 0.91. In factor analysis on the two-factor model, no item had salient loading on more than one factor and there were 3 items failed to load on either factor. The correlation coefficient was 0.84 between this scale and the Presumptive Stressful Life Events Scale. In term of reliability, Cronbach’s alpha values were ranging from 0.53-0.88. The scale is simple to administer to assess stress and usable for both clinical and research purpose

Repetitive hypoxia rapidly depresses arousal from active sleep in newborn lambs

Arousal from sleep is an important protective mechanism that is depressed by repeated episodes of hypoxia. We aimed to determine how rapidly arousal depression occurs during repeated hypoxia and to determine if the depression is sleep state specific.Three successive 12 h overnight sleep recordings were performed in six newborn lambs instrumented to record sleep state, blood pressure, heart rate and blood gases. The first (control) and third (recovery) nights were baseline studies (inspired oxygen fraction, FI,O2 = 0.21) to determine the spontaneous arousal probability. During the second (test) study night, lambs were exposed to a 60 s episode of isocapnic hypoxia (FI,O2 = 0.10; inspired carbon dioxide fraction, FI,CO2 = 0.03) during every epoch of sleep.During quiet sleep (QS), the probability of arousing to hypoxia (56 %) remained significantly higher than the probability of arousing spontaneously (18 %) throughout the repeated hypoxic exposures (χ2 = 81.5, P < 0.001). By contrast, during active sleep (AS) arousal rapidly became depressed with repetition of the hypoxic stimulus; the probability of arousal in hypoxia (52 %) was significantly higher than the probability of spontaneous arousal (12 %) during the first ten hypoxic exposures (χ2 = 18.2, P < 0.001), but there was no difference thereafter.We conclude that, when repeated, moderate hypoxia very rapidly becomes ineffective as an arousing stimulus in AS, but not in QS. These results suggest that the arousal mechanism is particularly vulnerable to failure during AS