Yanbo Zhang

OBJECTIVE: To examine whether overall lifestyles mediate associations of socioeconomic status (SES) with mortality and incident cardiovascular disease (CVD) and the extent of interaction or joint relations of lifestyles and SES with health outcomes. DESIGN: Population based cohort study. SETTING: US National Health and Nutrition Examination Survey (US NHANES, 1988-94 and 1999-2014) and UK Biobank. PARTICIPANTS: 44 462 US adults aged 20 years or older and 399 537 UK adults aged 37-73 years. EXPOSURES: SES was derived by latent class analysis using family income, occupation or employment status, education level, and health insurance (US NHANES only), and three levels (low, medium, and high) were defined according to item response probabilities. A healthy lifestyle score was constructed using information on never smoking, no heavy alcohol consumption (women ≤1 drink/day; men ≤2 drinks/day; one drink contains 14 g of ethanol in the US and 8 g in the UK), top third of physical activity, and higher dietary quality. MAIN OUTCOME MEASURES: All cause mortality was the primary outcome in both studies, and CVD mortality and morbidity in UK Biobank, which were obtained through linkage to registries. RESULTS: US NHANES documented 8906 deaths over a mean follow-up of 11.2 years, and UK Biobank documented 22 309 deaths and 6903 incident CVD cases over a mean follow-up of 8.8-11.0 years. Among adults of low SES, age adjusted risk of death was 22.5 (95% confidence interval 21.7 to 23.3) and 7.4 (7.3 to 7.6) per 1000 person years in US NHANES and UK Biobank, respectively, and age adjusted risk of CVD was 2.5 (2.4 to 2.6) per 1000 person years in UK Biobank. The corresponding risks among adults of high SES were 11.4 (10.6 to 12.1), 3.3 (3.1 to 3.5), and 1.4 (1.3 to 1.5) per 1000 person years. Compared with adults of high SES, those of low SES had higher risks of all cause mortality (hazard ratio 2.13, 95% confidence interval 1.90 to 2.38 in US NHANES; 1.96, 1.87 to 2.06 in UK Biobank), CVD mortality (2.25, 2.00 to 2.53), and incident CVD (1.65, 1.52 to 1.79) in UK Biobank, and the proportions mediated by lifestyle were 12.3% (10.7% to 13.9%), 4.0% (3.5% to 4.4%), 3.0% (2.5% to 3.6%), and 3.7% (3.1% to 4.5%), respectively. No significant interaction was observed between lifestyle and SES in US NHANES, whereas associations between lifestyle and outcomes were stronger among those of low SES in UK Biobank. Compared with adults of high SES and three or four healthy lifestyle factors, those with low SES and no or one healthy lifestyle factor had higher risks of all cause mortality (3.53, 3.01 to 4.14 in US NHANES; 2.65, 2.39 to 2.94 in UK Biobank), CVD mortality (2.65, 2.09 to 3.38), and incident CVD (2.09, 1.78 to 2.46) in UK Biobank. CONCLUSIONS: Unhealthy lifestyles mediated a small proportion of the socioeconomic inequity in health in both US and UK adults; therefore, healthy lifestyle promotion alone might not substantially reduce the socioeconomic inequity in health, and other measures tackling social determinants of health are warranted. Nevertheless, healthy lifestyles were associated with lower mortality and CVD risk in different SES subgroups, supporting an important role of healthy lifestyles in reducing disease burden.

Importance: Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. Objective: To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. Design, Setting, and Participants: Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. Interventions: Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)-only control (n = 13 458); they received 2 intramuscular injections 21 days apart. Main Outcomes and Measures: The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. Results: Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase-polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]). Conclusions and Relevance: In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending. Trial Registration: ClinicalTrials.gov Identifier: NCT04510207; Chinese Clinical Trial Registry: ChiCTR2000034780.

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 μg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 μg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). Design, Setting, and Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. Main Outcomes and Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. Conclusions and Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.

OBJECTIVE: To investigate the association between weight changes across adulthood and mortality. DESIGN: Prospective cohort study. SETTING: US National Health and Nutrition Examination Survey (NHANES) 1988-94 and 1999-2014. PARTICIPANTS: 36 051 people aged 40 years or over with measured body weight and height at baseline and recalled weight at young adulthood (25 years old) and middle adulthood (10 years before baseline). MAIN OUTCOME MEASURES: All cause and cause specific mortality from baseline until 31 December 2015. RESULTS: During a mean follow-up of 12.3 years, 10 500 deaths occurred. Compared with participants who remained at normal weight, those moving from the non-obese to obese category between young and middle adulthood had a 22% (hazard ratio 1.22, 95% confidence interval 1.11 to 1.33) and 49% (1.49, 1.21 to 1.83) higher risk of all cause mortality and heart disease mortality, respectively. Changing from obese to non-obese body mass index over this period was not significantly associated with mortality risk. An obese to non-obese weight change pattern from middle to late adulthood was associated with increased risk of all cause mortality (1.30, 1.16 to 1.45) and heart disease mortality (1.48, 1.14 to 1.92), whereas moving from the non-obese to obese category over this period was not significantly associated with mortality risk. Maintaining obesity across adulthood was consistently associated with increased risk of all cause mortality; the hazard ratio was 1.72 (1.52 to 1.95) from young to middle adulthood, 1.61 (1.41 to 1.84) from young to late adulthood, and 1.20 (1.09 to 1.32) from middle to late adulthood. Maximum overweight had a very modest or null association with mortality across adulthood. No significant associations were found between various weight change patterns and cancer mortality. CONCLUSIONS: Stable obesity across adulthood, weight gain from young to middle adulthood, and weight loss from middle to late adulthood were associated with increased risks of mortality. The findings imply that maintaining normal weight across adulthood, especially preventing weight gain in early adulthood, is important for preventing premature deaths in later life.