From the New England Journal of Medicine
Prevention and attenuation of COVID-19 with the BNT162b2 and mRNA-1273 vaccines. Results: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥ 14 days after dose 2), 11 partially vaccinated (≥ 14 days after dose 1 and < 14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (< 14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). Conclusions: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination.
Safety, immunogenicity, and efficacy of the BNT162b2 COVID-19 vaccine in adolescents. Results: Overall, 2260 adolescents 12 to 15 years of age received injections; 1131 received BNT162b2, and 1129 received placebo. As has been found in other age groups, BNT162b2 had a favorable safety and side-effect profile, with mainly transient mild-to-moderate reactogenicity (predominantly injection-site pain [in 79 to 86% of participants], fatigue [in 60 to 66%], and headache [in 55 to 65%]); there were no vaccine-related serious adverse events and few overall severe adverse events. The geometric mean ratio of SARS-CoV-2 50% neutralizing titers after dose 2 in 12-to-15-year-old participants relative to 16-to-25-year-old participants was 1.76 (95% confidence interval [CI], 1.47 to 2.10), which met the noninferiority criterion of a lower boundary of the two-sided 95% confidence interval greater than 0.67 and indicated a greater response in the 12-to-15-year-old cohort. Among participants without evidence of previous SARS-CoV-2 infection, no COVID-19 cases with an onset of 7 or more days after dose 2 were noted among BNT162b2 recipients, and 16 cases occurred among placebo recipients. The observed vaccine efficacy was 100% (95% CI, 75.3 to 100). Conclusions: The BNT162b2 vaccine in 12-to-15-year-old recipients had a favorable safety profile, produced a greater immune response than in young adults, and was highly effective against COVID-19.
Preliminary findings of mRNA COVID-19 vaccine safety in pregnant persons. Results: A total of 35 691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against COVID-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the COVID-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases). Conclusions: Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA COVID-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.
Effectiveness of an inactivated SARS-CoV-2 vaccine in Chile. Results: The study was conducted from February 2 through May 1, 2021, and the cohort included approximately 10.2 million persons. Among persons who were fully immunized, the adjusted vaccine effectiveness was 65.9% (95% confidence interval [CI], 65.2 to 66.6) for the prevention of COVID-19 and 87.5% (95% CI, 86.7 to 88.2) for the prevention of hospitalization, 90.3% (95% CI, 89.1 to 91.4) for the prevention of ICU admission, and 86.3% (95% CI, 84.5 to 87.9) for the prevention of COVID-19-related death. Conclusions: Our results suggest that the inactivated SARS-CoV-2 vaccine effectively prevented COVID-19, including severe disease and death, a finding that is consistent with results of phase 2 trials of the vaccine.
From the BMJ
Effect of the COVID-19 pandemic in 2020 on life expectancy across populations in the USA and other high income countries: simulations of provisional mortality data. Results: Between 2010 and 2018, the gap in life expectancy between the US and the peer country average increased from 1.88 years (78.66 v 80.54 years, respectively) to 3.05 years (78.74 v 81.78 years). Between 2018 and 2020, life expectancy in the US decreased by 1.87 years (to 76.87 years), 8.5 times the average decrease in peer countries (0.22 years), widening the gap to 4.69 years. Life expectancy in the US decreased disproportionately among racial and ethnic minority groups between 2018 and 2020, declining by 3.88, 3.25, and 1.36 years in Hispanic, non-Hispanic Black, and non-Hispanic White populations, respectively. In Hispanic and non-Hispanic Black populations, reductions in life expectancy were 18 and 15 times the average in peer countries, respectively. Progress since 2010 in reducing the gap in life expectancy in the US between Black and white people was erased in 2018–20; life expectancy in Black men reached its lowest level since 1998 (67.73 years), and the longstanding Hispanic life expectancy advantage almost disappeared. Conclusions: The US had a much larger decrease in life expectancy between 2018 and 2020 than other high income nations, with pronounced losses among the Hispanic and non-Hispanic Black populations. A longstanding and widening US health disadvantage, high death rates in 2020, and continued inequitable effects on racial and ethnic minority groups are likely the products of longstanding policy choices and systemic racism.
Risk of hospital admission for patients with SARS-CoV-2 variant B.1.1.7: cohort analysis. Results: 27 710 (4.7%) of 592 409 patients with SGTF variants and 8523 (3.5%) of 246 869 patients without SGTF variants had been admitted to hospital within one to 14 days. The stratum adjusted hazard ratio of hospital admission was 1.52 (95% confidence interval 1.47 to 1.57) for patients with COVID-19 infected with SGTF variants, compared with those infected with non-SGTF variants. The effect was modified by age (P < 0.001), with hazard ratios of 0.93–1.21 in patients younger than 20 years with versus without SGTF variants, 1.29 in those aged 20–29, and 1.45–1.65 in those aged ≥ 30 years. The adjusted absolute risk of hospital admission within 14 days was 4.7% (95% confidence interval 4.6% to 4.7%) for patients with SGTF variants and 3.5% (3.4% to 3.5%) for those with non-SGTF variants. Conclusions: The results suggest that the risk of hospital admission is higher for people infected with the B.1.1.7 variant compared with wild-type SARS-CoV-2, likely reflecting a more severe disease. The higher severity may be specific to adults older than 30 years.
Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study. Results: Over all simulation replications, the median cumulative mortality per 100 000 for standard dosing versus delayed second dose was 226 v 179, 233 v 207, and 235 v 236 for 90%, 80%, and 70% first dose efficacy, respectively. The delayed second dose strategy was optimal for vaccine efficacies at or above 80% and vaccination rates at or below 0.3% of the population per day, under both sterilizing and non-sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions between 26 and 47 per 100 000. The delayed second dose strategy for people under 65 performed consistently well under all vaccination rates tested. Conclusions: A delayed second dose vaccination strategy, at least for people aged under 65, could result in reduced cumulative mortality under certain conditions.
Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study. Results: Following vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n = 590) vs 100%, P < 0.0001 and 132.9 ± 91.7 vs 218.6 ± 82.06 BAU/mL, P < 0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n = 2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n = 6), uveitis (n = 2), and pericarditis (n = 1). Postvaccination disease activity remained stable in the majorityof patients. Conclusion: mRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.
From The Lancet
Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Findings: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65.1%] in the vaccine group and 3568 [34.9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65.4%] and 3470 [34.6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36–48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31.7 cases [14.6–59.3] per 1000 person-years) and 32 cases were reported in the placebo group (192.3 cases [135.7–261.1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83.5% (95% CI 65.4–92.1; P < 0.0001). The frequencies of any adverse events were 1259 (18.9%) in the vaccine group and 603 (16.9%) in the placebo group (P = 0.0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8.2%] participants in the vaccine group and 248 [7.0%] the placebo group, P = 0.0228). Injection-site pain was the most frequent local adverse event (157 [2.4%] in the vaccine group and 40 [1.1%] in the placebo group, P < 0.0001). Interpretation: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile.
A longitudinal study of convergence between Black and White COVID-19 mortality: A county fixed effects approach. Findings: Over this period, cumulative mortality rose by 61% and 90% for Black and White populations respectively, decreasing the mortality ratio by 0.4 (25.8%). These trends persisted when a county-level fixed-effects model was applied. Results revealed that county-level changes in prevalence nearly fully explain changes in mortality disparities over time. Interpretation: Results suggest mechanisms underpinning convergence in Black/White mortality are not driven by fixed county-level characteristics or changes in the regional dispersion of COVID-19, but instead by changes within counties. Further, declines in the Black/White mortality ratio over time appear primarily linked to county-level changes in COVID-19 prevalence rather than other county-level factors that may vary with time. Research into COVID-19 disparities should focus on mechanisms that operate within-counties and are consistent with a prevalence-disparity relationship.
Prevalence, severity and distribution of depression and anxiety symptoms using observational data collected before and nine months into the COVID-19 pandemic. Outcomes: Elevated psychological distress is primarily driven by increases in prevalence of particular symptoms. Prevalence of trouble concentrating increased six-fold from 9.6% to 72.5%. Other symptoms increased by over one-third; feeling anxious, having little interest, feeling depressed, sleep problems and being irritable, while some symptoms rose only 10% or less. Severity also increased but magnitudes are small relative to prevalence changes. Escalation in prevalence and severity are greatest for the youngest. Interpretation: Some of the least prevalent symptoms pre-pandemic became the most prevalent during the pandemic, affecting interpretation of indices validated pre-pandemic. Clinical and policy interventions should focus on specific symptoms that increased including trouble concentrating and anxiety.
Association between BNT162b2 vaccination and incidence of SARS-CoV-2 infection in pregnant women. Results: The cohort included 7530 vaccinated and 7530 matched unvaccinated women, 46% and 33% in the second and third trimester, respectively, with a mean age of 31.1 years (SD, 4.9 years). The median follow-up for the primary outcome was 37 days (interquartile range, 21–54 days; range, 0–70). There were 118 SARS-CoV-2 infections in the vaccinated group and 202 in the unvaccinated group. Among infected women, 88 of 105 (83.8%) were symptomatic in the vaccinated group vs 149 of 179 (83.2%) in the unvaccinated group (P ≥ 0.99). During 28 to 70 days of follow-up, there were 10 infections in the vaccinated group and 46 in the unvaccinated group. The hazards of infection were 0.33% vs 1.64% in the vaccinated and unvaccinated groups, respectively, representing an absolute difference of 1.31% (95% CI, 0.89%–1.74%), with an adjusted hazard ratio of 0.22 (95% CI, 0.11–0.43). Vaccine-related adverse events were reported by 68 patients; none was severe. The most commonly reported symptoms were headache (n = 10, 0.1%), general weakness (n = 8, 0.1%), nonspecified pain (n = 6, < 0.1%), and stomachache (n = 5, < 0.1%). Conclusions and relevance: In this retrospective cohort study of pregnant women, BNT162b2 mRNA vaccination compared with no vaccination was associated with a significantly lower risk of SARS-CoV-2 infection. Interpretation of study findings is limited by the observational design.
Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19. Results: A total of 10 930 patients (median age, 61 years [range of medians, 52–68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79–0.95]; P = 0.003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74–0.92; P < 0.001) for tocilizumab and 1.08 (95% CI, 0.86–1.36; P = 0.52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68–0.87) for tocilizumab and 0.92 (95% CI, 0.61–1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70–0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66–0.82) for tocilizumab, and 1.00 (95% CI, 0.74–1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85–1.16). Conclusions and relevance: In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.
Frequency of thrombocytopenia and platelet factor 4/heparin antibodies in patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. Results: Of 865 patients (median age, 40 years [interquartile range, 29–53 years], 70% women), 73 (8.4%; 95% CI, 6.8%–10.5%) had thrombocytopenia, which was mild (100–149 × 103/μL) in 52 (6.0%), moderate (50–99 × 103/μL) in 17 (2.0%), and severe (< 50 × 103/μL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, < 0.1%–0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%–4%) had platelet factor 4/heparin antibodies. Conclusions and relevance: In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.