COVID-19 research news in brief

From the New England Journal of Medicine

Effectiveness of mRNA COVID-19 vaccine among US health care personnel: “The study included 1482 case participants and 3449 control participants. Vaccine effectiveness for partial vaccination was 77.6% (95% confidence interval [CI], 70.9 to 82.7) with the BNT162b2 vaccine (Pfizer–BioNTech) and 88.9% (95% CI, 78.7 to 94.2) with the mRNA-1273 vaccine (Moderna); for complete vaccination, vaccine effectiveness was 88.8% (95% CI, 84.6 to 91.8) and 96.3% (95% CI, 91.3 to 98.4), respectively. Vaccine effectiveness was similar in subgroups defined according to age (<50 years or ≥50 years), race and ethnic group, presence of underlying conditions, and level of patient contact. Estimates of vaccine effectiveness were lower during weeks 9 through 14 than during weeks 3 through 8 after receipt of the second dose, but confidence intervals overlapped widely. Conclusions: The BNT162b2 and mRNA-1273 vaccines were highly effective under real-world conditions in preventing symptomatic COVID-19 in health care personnel, including those at risk for severe COVID-19 and those in racial and ethnic groups that have been disproportionately affected by the pandemic.”

Efficacy of the mRNA-1273 SARS-CoV-2 vaccine at completion of blinded phase: “The trial enrolled 30 415 participants; 15 209 were assigned to receive the mRNA-1273 vaccine, and 15 206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing COVID-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified. Conclusions: The mRNA-1273 vaccine continued to be efficacious in preventing COVID-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed.”

Protection of BNT162b2 vaccine booster against COVID-19 in Israel: “At least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the non-booster group by a factor of 11.3 (95% confidence interval [CI], 10.4 to 12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9 to 29.5). In a secondary analysis, the rate of confirmed infection at least 12 days after vaccination was lower than the rate after 4 to 6 days by a factor of 5.4 (95% CI, 4.8 to 6.1). Conclusions: In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 (Pfizer-BioNTech) vaccine at least 5 months earlier, we found that the rates of confirmed COVID-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.”

Safety and efficacy of NVX-CoV2373 COVID-19 vaccine: “A total of 15 187 participants underwent randomization, and 14 039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. Conclusions: A two-dose regimen of the NVX-CoV2373 (Novavax) vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant.”

Subcutaneous REGEN-COV antibody combination to prevent COVID-19: “Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P<0.001). In weeks 2 to 4, a total of 2 of 753 participants in the REGEN-COV group (0.3%) and 27 of 752 participants in the placebo group (3.6%) had symptomatic SARS-CoV-2 infection (relative risk reduction, 92.6%). REGEN-COV also prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%). Among symptomatic infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively), and the duration of a high viral load (>104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. Conclusions: Subcutaneous REGEN-COV prevented symptomatic COVID-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load.”

From the BMJ

Antibody and cellular therapies for treatment of COVID-19: a living systematic review and network meta-analysis: “As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of COVID-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) −4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD −4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD −3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD −4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe COVID-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical COVID-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative. Conclusion: In patients with non-severe COVID-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit.”

Risk prediction of COVID-19 related death and hospital admission in adults after COVID-19 vaccination: national prospective cohort study: “Of 6 952 440 vaccinated patients in the derivation cohort, 5 150 310 (74.1%) had two vaccine doses. Of 2031 COVID-19 deaths and 1929 COVID-19 hospital admissions, 81 deaths (4.0%) and 71 admissions (3.7%) occurred 14 days or more after the second vaccine dose. The risk algorithms included age, sex, ethnic origin, deprivation, body mass index, a range of comorbidities, and SARS-CoV-2 infection rate. Incidence of COVID-19 mortality increased with age and deprivation, male sex, and Indian and Pakistani ethnic origin. Cause specific hazard ratios were highest for patients with Down’s syndrome (12.7-fold increase), kidney transplantation (8.1-fold), sickle cell disease (7.7-fold), care home residency (4.1-fold), chemotherapy (4.3-fold), HIV/AIDS (3.3-fold), liver cirrhosis (3.0-fold), neurological conditions (2.6-fold), recent bone marrow transplantation or a solid organ transplantation ever (2.5-fold), dementia (2.2-fold), and Parkinson’s disease (2.2-fold). Other conditions with increased risk (ranging from 1.2-fold to 2.0-fold increases) included chronic kidney disease, blood cancer, epilepsy, chronic obstructive pulmonary disease, coronary heart disease, stroke, atrial fibrillation, heart failure, thromboembolism, peripheral vascular disease, and type 2 diabetes. A similar pattern of associations was seen for COVID-19 related hospital admissions. No evidence indicated that associations differed after the second dose, although absolute risks were reduced. The risk algorithm explained 74.1% (95% confidence interval 71.1% to 77.0%) of the variation in time to COVID-19 death in the validation cohort. Discrimination was high, with a D statistic of 3.46 (95% confidence interval 3.19 to 3.73) and C statistic of 92.5. Performance was similar after each vaccine dose. In the top 5% of patients with the highest predicted COVID-19 mortality risk, sensitivity for identifying COVID-19 deaths within 70 days was 78.7%. Conclusion: This population based risk algorithm performed well showing high levels of discrimination for identifying those patients at highest risk of COVID-19 related death and hospital admission after vaccination.”

CPAP delivered outside critical care during the second wave of COVID-19: outcomes from a UK respiratory surge unit: “88 patients were included in the analysis. 56/88 (64%) were deemed suitable for escalation to invasive mechanical ventilation (IMV) and received CPAP as a trial; 32/88 (36%) received CPAP as a ceiling of care. Median age was 63 years (IQR: 56–74) and 58/88 (66%) were men. Median SpO2/FiO2 immediately prior to CPAP initiation was 95 (92–152). Among patients for escalation to IMV, the median time on CPAP was 6 days (IQR 4–7) and survival at day 30 was 84% (47/56) with 14/56 (25%) escalated to IMV. Of those patients for whom CPAP was ceiling of care, the median duration of CPAP was 9 days (IQR 7–11) and 18/32 (56%) survived to day 30. Pulmonary barotrauma occurred in 9% of the cohort. There were no associations found on multivariant analysis that were associated with all-cause 30-day mortality. Conclusions: With adequate planning and resource redistribution, CPAP may be delivered effectively outside of a traditional critical care setting for the treatment of respiratory failure due to COVID-19. Clinicians delivering CPAP to patients with COVID-19 pneumonitis should be alert to the dangers of pulmonary barotrauma. Among patients who are for escalation of care, the use of CPAP may avoid the need for IMV in some patients. Our data support the NHS England recommendation to consider CPAP as a ceiling of care.”

Incidence of “new-onset” constipation and associated factors during lockdown due to the COVID-19 pandemic: “Out of 678 subjects evaluated, 170 (25%, 95% CI: 21.7 to 28.4) developed symptoms of ‘new-onset’ constipation, with a significant decrease in the number of daily bowel movements (p<0.05) and stool consistency (p<0.05) during lockdown. Furthermore, in the ‘new-onset’ constipation population there was a higher proportion of subjects (79 (47%) of 170) who stopped exercising during the pandemic compared with the subjects who did not develop constipation symptoms (187 (37%) of 508, p=0.03, OR: 1.49, 95% CI: 1.0 to 2.1). The multivariate analysis (logistic regression) showed that female sex (p=0.001), water intake (p=0.039), and physical activity (p=0.012) were associated with ‘new-onset’ constipation. Conclusions: In our study on an open population in Mexico, we found that one-fourth of the population developed ‘new-onset’ constipation symptoms during the lockdown imposed due to the COVID-19 pandemic. A reduction of physical activity and less water consumption were associated factors.”

Association of changes in work due to COVID-19 pandemic with psychosocial work environment and employee health: a cohort study of 24 299 Finnish public sector employees: “After adjusting for sex, age, socioeconomic status and lifestyle risk score, working from home (44%) was associated with greater increase in worktime control (standardised mean difference (SMD)_Exposed=0.078, 95% CI 0.066 to 0.090; SMD_Non-exposed=0.025, 95% CI 0.014 to 0.036), procedural justice (SMD_Exposed=0.101, 95% CI 0.084 to 0.118; SMD_Non-exposed=0.053, 95% CI 0.038 to 0.068), workplace social capital (SMD_Exposed=0.094, 95% CI 0.077 to 0.110; SMD_Non-exposed=0.034, 95% CI 0.019 to 0.048), less decline in self-rated health (SMD_Exposed=−0.038, 95% CI −0.054 to –0.022; SMD_Non-exposed=−0.081, 95% CI −0.095 to –0.067), perceived work ability (SMD_Exposed=−0.091, 95% CI −0.108 to –0.074; SMD_Non-exposed=−0.151, 95% CI −0.167 to –0.136) and less increase in psychological distress (risk ratio (RR)_Exposed=1.06, 95% CI 1.02 to 1.09; RR_Non-exposed=1.16, 95% CI 1.13 to 1.20). New tasks (6%) were associated with greater increase in psychological distress (RR_Exposed=1.28, 95% CI 1.19 to 1.39; RR_Non-exposed=1.10, 95% CI 1.07 to 1.12) and team reorganisation (5%) with slightly steeper decline in perceived work ability (SMD_Exposed=−0.151 95% CI −0.203 to –0.098; SMD _Non-exposed=−0.124, 95% CI −0.136 to –0.112). Conclusion: Employees who worked from home during the pandemic had more favourable psychosocial work environment and health, whereas those who were exposed to work task changes and team reorganisations experienced more adverse changes.”

From the Lancet

Willingness of children and adolescents to have a COVID-19 vaccination: Results of a large whole schools survey in England: “27 910 students from 180 schools answered the vaccine hesitancy question between 14 May and 21 July 2021, of whom 13 984 (50.1%) would opt-in to take a vaccination, 10 322 (37.0%) were undecided, and 3604 (12.9%) would opt-out. A lower percentage of younger students reported that they would opt-in to vaccination, for example, 35.7% of 9-year-olds and 51.3% of 13-year-olds compared to 77.8% of 17-year-olds would opt-in to take a vaccination. Students who were ‘opt-out’ or ‘undecided’ (a combined ‘vaccine hesitant’ group) were more likely to come from deprived socioeconomic contexts with higher rates of home rental versus home ownership and their school locations were more likely to be in areas of greater deprivation. They were more likely to smoke or vape, spend longer on social media, feel that they did not belong in their school community but had lower levels of anxiety and depression. The vaccine hesitant students – the undecided and opt-out groups – were similar in profile, although the opt-out students had higher reported confirmed or probable previous COVID-19 infection than the opt-in group, whereas those undecided, did not. Interpretation: If government vaccination strategies move towards vaccinating younger school-aged students, efforts to increase vaccination uptake may be necessary. Compared with students who would opt-in, those who were vaccine hesitant had greater indicators of social deprivation and felt a lack of community cohesion by not feeling a sense of belonging at their school. There were indications that those students who would opt-out had higher levels of marginalisation and mistrust. If programs are rolled out, focus on hesitant younger students will be important, targeting more marginalised and deprived young people with information from trusted sources utilising social media; improving access to vaccination centres with provision both in and outside school; and addressing fears and worries about the effects of the vaccine. The main limitation of this study is that the participant group may not be wholly representative of England or the UK, which may bias population-level estimates of willingness to be vaccinated.”

Daily testing for contacts of individuals with SARS-CoV-2 infection and attendance and SARS-CoV-2 transmission in English secondary schools and colleges: an open-label, cluster-randomised trial: “Between March 18 and May 4, 2021, 204 schools were taken through the consent process, during which three decided not to participate further. 201 schools were randomly assigned (control group n=99, intervention group n=102) in the 10-week study (April 19–May 10, 2021), which continued until the pre-appointed stop date (June 27, 2021). 76 control group schools and 86 intervention group schools actively participated; additional national data allowed most non-participating schools to be included in analysis of coprimary outcomes. 2432 (42·4%) of 5763 intervention group contacts participated in daily contact testing. There were 657 symptomatic PCR-confirmed infections during 7 782 537 days-at-risk (59·1 per 100 000 per week) in the control group and 740 during 8 379 749 days-at-risk (61·8 per 100 000 per week) in the intervention group (intention-to-treat adjusted incidence rate ratio [aIRR] 0·96 [95% CI 0·75–1·22]; p=0·72; CACE aIRR 0·86 [0·55–1·34]). Among students and staff, there were 59 422 (1·62%) COVID-19-related absences during 3 659 017 person-school-days in the control group and 51 541 (1·34%) during 3 845 208 person-school-days in the intervention group (intention-to-treat aIRR 0·80 [95% CI 0·54–1·19]; p=0·27; CACE aIRR 0·61 [0·30–1·23]). Interpretation: Daily contact testing of school-based contacts was non-inferior to self-isolation for control of COVID-19 transmission, with similar rates of symptomatic infections among students and staff with both approaches. Infection rates in school-based contacts were low, with very few school contacts testing positive. Daily contact testing should be considered for implementation as a safe alternative to home isolation following school-based exposures.”

Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990–2050: “In 2019, health spending globally reached $8·8 trillion (95% uncertainty interval [UI] 8·7–8·8) or $1132 (1119–1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40·4 billion (0·5%, 95% UI 0·5–0·5) was development assistance for health provided to low-income and middle-income countries, which made up 24·6% (UI 24·0–25·1) of total spending in low-income countries. We estimate that $54·8 billion in development assistance for health was disbursed in 2020. Of this, $13·7 billion was targeted toward the COVID-19 health response. $12·3 billion was newly committed and $1·4 billion was repurposed from existing health projects. $3·1 billion (22·4%) of the funds focused on country-level coordination and $2·4 billion (17·9%) was for supply chain and logistics. Only $714·4 million (7·7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34·3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448–1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation: Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all.”

From JAMA

Trajectory of COVID-19 vaccine hesitancy over time and association of initial vaccine hesitancy with subsequent vaccination: “This cohort study found that COVID-19 vaccine hesitancy is not a stable trait precluding vaccination but, instead, is labile. Hesitancy decreased between late 2020 and early 2021, with nearly one-third (32%) of persons who were initially hesitant being vaccinated at follow-up and more than one-third (37%) transitioning from vaccine hesitant into vaccine willing. Early plans regarding vaccination frequently deviated from later action in vaccine seeking. Self-reported vaccination status was congruent with biological tests, indicating that it is a valid metric. Changes in hesitancy have not alleviated health inequities in vaccines received, and further studies are needed to explore the reasons why vaccine hesitancy is changing over time by group. Our analysis is limited in that vaccines were not available to all respondents until April 19, 2021, and our follow-up period ended before this date. Conclusions: Vaccine hesitancy is waning, yet inequities in receipt remain. There is a clear public health opportunity to convert higher vaccine willingness into successfully delivered vaccinations.”