Efficacy and safety of COVID-19 vaccines.

BACKGROUND: Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally.  OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register and the COVID-19 L·OVE platform (last search date 5 November 2021). We also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing COVID-19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for all except immunogenicity outcomes.  We synthesized data for each vaccine separately and presented summary effect estimates with 95% confidence intervals (CIs).  MAIN RESULTS: We included and analyzed 41 RCTs assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty-two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty-nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromized patients. No trials included pregnant women. Sixteen RCTs had two-month follow-up or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. Overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. We identified 343 registered RCTs with results not yet available.  This abstract reports results for the critical outcomes of confirmed symptomatic COVID-19, severe and critical COVID-19, and serious adverse events only for the 10 WHO-approved vaccines. For remaining outcomes and vaccines, see main text. The evidence for mortality was generally sparse and of low or very low certainty for all WHO-approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all-cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high-certainty evidence). Confirmed symptomatic COVID-19 High-certainty evidence found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA-1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP-CorV (Sinopharm-Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID-19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA-1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP-CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants). Moderate-certainty evidence found that NVX-CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID-19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants). There is low-certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants). Severe or critical COVID-19 High-certainty evidence found that BNT162b2, mRNA-1273, Ad26.COV2.S, and BBV152 result in a large reduction in incidence of severe or critical disease due to COVID-19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA-1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants). Moderate-certainty evidence found that NVX-CoV2373 probably reduces the incidence of severe or critical COVID-19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants). Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled. Serious adverse events (SAEs) mRNA-1273, ChAdOx1 (Oxford-AstraZeneca)/SII-ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in SAEs compared to placebo (RR: mRNA-1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII-ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants. Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP-CorV, and NVX-CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP-CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX-CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants). For the evaluation of heterologous schedules, booster doses, and efficacy against variants of concern, see main text of review. AUTHORS' CONCLUSIONS: Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital.

School Closures During Social Lockdown and Mental Health, Health Behaviors, and Well-being Among Children and Adolescents During the First COVID-19 Wave: A Systematic Review.

IMPORTANCE: School closures as part of broader social lockdown measures during the COVID-19 pandemic may be associated with the health and well-being of children and adolescents. OBJECTIVE: To review published reports on the association of school closures during broader social lockdown with mental health, health behaviors, and well-being in children and adolescents aged 0 to 19 years, excluding associations with transmission of infection. EVIDENCE REVIEW: Eleven databases were searched from inception to September 2020, and machine learning was applied for screening articles. A total of 16 817 records were screened, 151 were reviewed in full text, and 36 studies were included. Quality assessment was tailored to study type. A narrative synthesis of results was undertaken because data did not allow meta-analysis. FINDINGS: A total of 36 studies from 11 countries were identified, involving a total of 79 781 children and adolescents and 18 028 parents, which occurred during the first wave of the COVID-19 pandemic (February to July 2020). All evaluated school closure as part of broader social lockdown during the first COVID-19 wave, and the duration of school closure ranged from 1 week to 3 months. Of those, 9 (25%) were longitudinal pre-post studies, 5 (14%) were cohort, 21 (58%) were cross-sectional, and 1 (3%) was a modeling study. Thirteen studies (36%) were high quality, 17 (47%) were medium quality, and 6 (17%) were low quality. Twenty-three studies (64%) were published, 8 (22%) were online reports, and 5 (14%) were preprints. Twenty-five studies (69%) concerning mental health identified associations across emotional, behavioral, and restlessness/inattention problems; 18% to 60% of children and adolescents scored above risk thresholds for distress, particularly anxiety and depressive symptoms, and 2 studies reported no significant association with suicide. Three studies reported that child protection referrals were lower than expected number of referrals originating in schools. Three studies suggested higher screen time usage, 2 studies reported greater social media use, and 6 studies reported lower physical activity. Studies on sleep (10 studies) and diet (5 studies) provided inconclusive evidence on harms. CONCLUSIONS AND RELEVANCE: In this narrative synthesis of reports from the first wave of the COVID-19 pandemic, studies of short-term school closures as part of social lockdown measures reported adverse mental health symptoms and health behaviors among children and adolescents. Associations between school closure and health outcomes and behaviors could not be separated from broader lockdown measures.

[Impact of social distancing for covid-19 on young people: type and quality of the studies found through a systematic review of the literature.] / Impatto del distanziamento sociale per covid-19 sui giovani: tipologia e qualità degli studi reperiti attraversouna revisione sistematica della letteratura.

BACKGROUND: During the first semester 2020 almost all country implemented rigid measures of social distances, including schools closure, to limit the transmission of SARS-CoV-2 infection. Up to now, however, the efficacy of school closure to reduce the spread of the disease in the community still remain unclear and no much is known about the potential negative effects of such measures on physical health and psychological wellbeing of children and adolescents, mainly if protracted for long periods. OBJECTIVE: To summarize the most relevant data of a systematic review on the impact of the 2020 school closure and social distances measures implemented in response to covid-19 pandemic on youths physical health and psychological wellbeing. In the present paper we describe the review's methodology and the characteristics and methodological quality of the retrieved studies. METHODS: We searched on 11 international databases up to 1st September 2020 to retrieve cohort studies, cross sectional surveys, uncontrolled pre-post studies and modelling studies. Methodological quality of included studies has been assessed with validated checklists. RESULTS: Sixty-four studies have been included; 42 assessed the effect of social distances measure of physical health and 27 on psychological wellbeing. All the studies have been conducted during the first wave of pandemic and assessed the short-term effect of social distances measures implemented for relatively short periods. The 32.4% of the studies has been conducted in the UK, 20.3% in Italy, 12.5% in China, 10.9% in developing countries and 9.4% in the US. 37.5% of the studies were cohort studies, 40.6% cross sectional surveys, 19.7% uncontrolled studies and 1 was a modeling study. 59.6% of the studies has been rated as high quality. The most important weakness of the cross-sectional surveys and uncontrolled studies was the scarce representativeness of the sample while 96% of the cohort studies were judged as high quality. CONCLUSIONS: A large number of acceptable quality studies have been published during the first months of pandemic to assess the impact of school closure and social distances measures on physical health and psychological wellbeing of youths. This highlights the relevance of the topic and the need to assess carefully the balance between harms and benefits of such measures in terms of actual reduction of transmission and youths' psychological and physical harms. Further studies are needed on the long-term effect of social distances measures extended over long periods.

[Impact of social distancing for covid-19 on the psychological well-being of youths: a systematic review of the literature.] / Impatto del distanziamento sociale per covid-19 sul benessere psicologico dei giovani: una revisione sistematica della letteratura.

BACKGROUND: During the first semester 2020 almost all country implemented rigid measures of social distances, including schools closure, to limit the transmission of SARS-CoV-2 infection. Up to now, however, the efficacy of school closure to reduce the spread of the disease in the community still remains unclear and no much is known about the potential negative effects of such measures on physical health and psychological wellbeing of youths, mainly if protracted for long periods. OBJECTIVE: To summarize the data of a systematic review on the impact of the 2020 school closure and social distances measures implemented in response to covid-19 pandemic on youths' physical health and psychological wellbeing. In the present paper we describe the impact on psychological wellbeing. METHODS: We searched 11 international databases up to 1st September 2020 to retrieve cohort studies, cross sectional surveys, uncontrolled pre-post studies and modelling studies. Methodological quality of included studies has been assessed with validated checklists. RESULTS: Sixty-four studies have been included; 27 assessed the impact on psychological wellbeing. All the studies have been conducted during the first wave of pandemic and assessed the short-term effect of social distances measures implemented for relatively short periods. The majority of the studies were conducted in the UK (37,6%) and China (27%). The 42.3% has been judged of high methodological quality. Two studies reported an increase of suicides, while two studies reported a reduction of the access to Psychiatric Emergency Department, Maltreatment allegations decreased substantially, likely due to a reduction in reports rather than actual incidence. Prevalence of anxiety among adolescents ranged between 19% and 64%, depression between 22.3% and 43.7%. Among children 5-12 years old, prevalence of anxiety varied between 19% and 78%, while depression between 6.3% and 22.6%. Among pre-school children, some studies found worsening of behavioural and emotional problems while others did not. CONCLUSIONS: Most of the studies reported relevant worsening of the psychological wellbeing, mainly among adolescents. If school closure and rigid social distances measures will extend for a long time, an even more pronounced negative effect can be expected. Further studies are needed on the long-term effect of prolonged social distances measures, as well as a careful harm-benefit analysis of the impact of such measures.

[Impact of social distancing for covid-19 on youths' physical health: a systematic review of the literature.] / Impatto del distanziamento sociale per covid-19 sulla salute fisica dei giovani: una revisione sistematica della letteratura.

BACKGROUND: Schools' closure during covid-19 pandemic implemented almost all over the world, together with social distances measures and lockdown to reduce transmission, could have had negative impact on youths' health. AIM: Summarize the most relevant data from a literature systematic review on the impact on youths' physical health of the 2020 school closure and social distances measures implemented in response to covid-19 pandemic. METHODS: Authors of the original review searched on 11 international databases up to 1st September 2020 to retrieve cohort studies, cross sectional surveys, uncontrolled pre-post studies and modelling studies. Methodological quality has been assessed with validated checklists. RESULTS: Forty-two studies reporting the impact on physical health have been finally included. They have been conducted in 14 countries, most of which in Italy (30.9%) and UK (30.9%). The majority were cohort studies (40.5%) and the overall methodological quality, irrespective of study designs, was high for the 71.4% of the studies. Twenty-seven studies assessed the impact on health services utilization, whose results showed a relevant reduction of Emergency Departments accesses (64%-89.3%) and hospital admissions (31%-85%); however, an increase of acute cases was observed together with delayed admission. An important reduction of vaccine services utilization was also noted during the first period of lockdown. Domestic accidents and head trauma for suspected domestic violence increased. Health related behaviours worsened, with a relevant increase of screen time (mean of 2.9 hours to 5.1 hours), an important reduction of physical activity (up to 64%). Finally, sleep problems and increase of food consumption, particularly the unhealthy food were reported. CONCLUSIONS: Relevant negative effects of school closure and social distances measures have observed. All the studies have been conducted during the first wave of pandemic and assessed the short-term effect of closures implemented for relatively short periods. If school closure and rigid social distances measures imposition will extend for a long time, an even more pronounced negative effect can be expected. In the context of health policies, in addition to the potential benefits of school closures and social distancing measures on the containment of infection, the potential damage on the physical health of young people should be taken into account by implementing policies to safeguard their health.

Developing trustworthy recommendations as part of an urgent response (1-2 weeks): a GRADE concept paper.

OBJECTIVES: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields. STUDY DESIGN AND SETTING: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group. RESULTS: A request for developing recommendations within 2 week is the usual trigger for an urgent response. Although the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of the 4 potential approaches: adopt existing recommendations, adapt existing recommendations, develop new recommendations using existing adequate systematic review, or develop new recommendations using expert panel input; and (8) consider an updating plan. CONCLUSION: An urgent response for developing recommendations requires building a cohesive, skilled, and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise; adapting to shifting needs; complying with the principles of transparency; and properly managing conflicts of interest.