Risk factors for recognized and unrecognized SARS-CoV-2 infection: a seroepidemiologic analysis of the Prospective Urban Rural Epidemiology (PURE) study.

There are limited data on individual risk factors for SARS-CoV-2 infection (including unrecognized infection). In this seroepidemiologic substudy of an ongoing prospective cohort study of community-dwelling adults, participants were thoroughly characterized pre-pandemic. The SARS-CoV-2 infection was ascertained by serology. Among 8,719 participants from 11 high-, middle-, and low-income countries, 3,009 (35%) were seropositive for SARS-CoV-2. Characteristics independently associated with seropositivity were younger age (odds ratio, OR; 95% confidence interval, CI, per five-year increase: 0.95; 0.91-0.98) and body mass index >25 kg/m2 (OR, 95% CI: 1.16, 1.01-1.34). Smoking (as compared with never smoking, OR, 95% CI: 0.83, 0.70-0.97) and COVID-19 vaccination (OR, 95% CI: 0.70, 0.60-0.82) were associated with a reduced risk of seropositivity. Among seropositive participants, 83% were unaware of having been infected with SARS-CoV-2. Seropositivity and a lack of awareness of infection were more common in lower-income countries. The COVID-19 vaccination reduces the risk of SARS-CoV-2 infection (including recognized and unrecognized infections). Overweight or obesity is an independent risk factor for SARS-CoV-2 infection. Infection and lack of infection awareness are more common in lower-income countries.IMPORTANCEIn this large, international study, evidence of SARS-CoV-2 infection was obtained by testing blood specimens from 8,719 community-dwelling adults from 11 countries. The key findings are that (i) the large majority (83%) of community-dwelling adults from several high-, middle-, and low-income countries with blood test evidence of SARS-CoV-2 infection were unaware of this infection-especially in lower-income countries; and (ii) overweight/obesity predisposes to SARS-CoV-2 infection, while COVID-19 vaccination is associated with a reduced risk of SARS-CoV-2 infection. These observations are not attributable to other individual characteristics, highlighting the importance of the COVID-19 vaccination to prevent not only severe infection but possibly any infection. Further research is needed to understand the mechanisms by which overweight/obesity might increase the risk of SARS-CoV-2 infection.

Biomarkers Associated With Severe COVID-19 Among Populations With High Cardiometabolic Risk: A 2-Sample Mendelian Randomization Study.

Importance: Cardiometabolic parameters are established risk factors for COVID-19 severity. The identification of causal or protective biomarkers for COVID-19 severity may facilitate the development of novel therapies. Objective: To identify protein biomarkers that promote or reduce COVID-19 severity and that mediate the association of cardiometabolic risk factors with COVID-19 severity. Design, Setting, and Participants: This genetic association study using 2-sample mendelian randomization (MR) was conducted in 2022 to investigate associations among cardiometabolic risk factors, circulating biomarkers, and COVID-19 hospitalization. Inputs for MR included genetic and proteomic data from 4147 participants with dysglycemia and cardiovascular risk factors collected through the Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial. Genome-wide association study summary statistics were obtained from (1) 3 additional independent plasma proteome studies, (2) genetic consortia for selected cardiometabolic risk factors (including body mass index [BMI], type 2 diabetes, type 1 diabetes, and systolic blood pressure; all n >10 000), and (3) the COVID-19 Host Genetics Initiative (n = 5773 hospitalized and 15 497 nonhospitalized case participants with COVID-19). Data analysis was performed in July 2022. Exposures: Genetically determined concentrations of 235 circulating proteins assayed with a multiplex biomarker panel from the ORIGIN trial for the initial analysis. Main Outcomes and Measures: Hospitalization status of individuals from the COVID-19 Host Genetics Initiative with a positive COVID-19 test result. Results: Among 235 biomarkers tested in samples totaling 22 101 individuals, MR analysis showed that higher kidney injury molecule-1 (KIM-1) levels reduced the likelihood of COVID-19 hospitalization (odds ratio [OR] per SD increase in KIM-1 levels, 0.86 [95% CI, 0.79-0.93]). A meta-analysis validated the protective association with no observed directional pleiotropy (OR per SD increase in KIM-1 levels, 0.91 [95% CI, 0.88-0.95]). Of the cardiometabolic risk factors studied, only BMI was associated with KIM-1 levels (0.17 SD increase in biomarker level per 1 kg/m2 [95% CI, 0.08-0.26]) and COVID-19 hospitalization (OR per 1-SD biomarker level, 1.33 [95% CI, 1.18-1.50]). Multivariable MR analysis also revealed that KIM-1 partially mitigated the association of BMI with COVID-19 hospitalization, reducing it by 10 percentage points (OR adjusted for KIM-1 level per 1 kg/m2, 1.23 [95% CI, 1.06-1.43]). Conclusions and Relevance: In this genetic association study, KIM-1 was identified as a potential mitigator of COVID-19 severity, possibly attenuating the increased risk of COVID-19 hospitalization among individuals with high BMI. Further studies are required to better understand the underlying biological mechanisms.

Comparison of three dosing intervals for the primary vaccination of the SARS-CoV-2 mRNA Vaccine (BNT162b2) on magnitude, neutralization capacity and durability of the humoral immune response in health care workers: A prospective cohort study.

OBJECTIVES: The dosing interval of a primary vaccination series can significantly impact on vaccine immunogenicity and efficacy. The current study compared 3 dosing intervals for the primary vaccination series of the BNT162b2 mRNA COVID-19 vaccine, on humoral immune response and durability against SARS-CoV-2 ancestral and Beta variants up to 9 months post immunization. METHODS: Three groups of age- and sex-matched healthcare workers (HCW) who received 2 primary doses of BNT162b2 separated by 35-days, 35-42 days or >42-days were enrolled. Vaccine induced antibody titers at 3 weeks, 3 and 6-9 months post-second dose were assessed. RESULTS: There were 309 age- and sex-matched HCW (mean age 43 [sd 13], 58% females) enrolled. Anti-SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibody titers showed significant waning in levels beyond 35 days post first dose. The second dose induced a significant rise in antibody titers, which peaked at 3 weeks and then declined at variable rates across groups. The magnitude, consistency and durability of response was greater for anti-Spike than anti-RBD antibodies; and for IgG than IgA or IgM. Compared to the shorter schedules, a longer interval of >42 days offered the highest binding and neutralizing antibody titers against SARS-CoV-2 ancestral and Beta (B1.351) variants beyond 3 months post-vaccination. CONCLUSIONS: This is the first comprehensive study to compare 3 dosing intervals for the primary vaccination of BNT162b2 mRNA COVID-19 vaccine implemented in the real world. These findings suggest that delaying the second dose beyond 42 days can potentiate and prolong the humoral response against ancestral and Beta variants of SARS-CoV-2 up to 9 months post-vaccination.

Interaction of Depression and Unhealthy Diets on the Risk of Cardiovascular Diseases and All-Cause Mortality in the Chinese Population: A PURE Cohort Substudy.

This study aimed to identify the interaction of depression and diets on cardiovascular diseases (CVD) incident and death in China and key subpopulations. We included 40,925 participants from the Prospective Urban Rural Epidemiology (PURE)-China cohort which recruited participants aged 35-70 years from 45 urban and 70 rural communities. Depression was measured by the adapted Short-Form (CIDI-SF). The unhealthy diet was considered when the score of Alternative Healthy Eating Index was below the lowest tertile. The primary outcome was a composite outcome of incident CVD and all-cause mortality. Cox frailty models were used to examine the associations. During a median follow-up of 11.9 years (IQR: 9.6-12.6 years), depression significantly increased the risk of the composite outcome (HR = 2.00; 95% CI, 1.16-3.27), major CVD (HR = 1.82; 95% CI, 1.48-2.23), and all-cause mortality (HR = 2.21; 95% CI, 1.51-3.24) for the unhealthy diet group, but not for the healthy diet group. The interaction between depression and diet for the composite outcome was statistically significant (RERI = 1.19; 95% CI, 0.66-1.72; AP = 0.42, 95% CI, 0.27-0.61; SI = 3.30, 95% CI, 1.42-7.66; multiplicative-scale = 1.74 95% CI, 1.27-2.39), even in the subgroup and sensitivity analyses. In addition, the intake of vegetable and polyunsaturated fatty acids contributed most to the interaction of diets and depression. Depressive participants should focus on healthy diets, especially vegetables and polyunsaturated fatty acids, to avoid premature death and CVD.

Variations in the financial impact of the COVID-19 pandemic across 5 continents: A cross-sectional, individual level analysis.

BACKGROUND: COVID-19 has caused profound socio-economic changes worldwide. However, internationally comparative data regarding the financial impact on individuals is sparse. Therefore, we conducted a survey of the financial impact of the pandemic on individuals, using an international cohort that has been well-characterized prior to the pandemic. METHODS: Between August 2020 and September 2021, we surveyed 24,506 community-dwelling participants from the Prospective Urban-Rural Epidemiology (PURE) study across high (HIC), upper middle (UMIC)-and lower middle (LMIC)-income countries. We collected information regarding the impact of the pandemic on their self-reported personal finances and sources of income. FINDINGS: Overall, 32.4% of participants had suffered an adverse financial impact, defined as job loss, inability to meet financial obligations or essential needs, or using savings to meet financial obligations. 8.4% of participants had lost a job (temporarily or permanently); 14.6% of participants were unable to meet financial obligations or essential needs at the time of the survey and 16.3% were using their savings to meet financial obligations. Participants with a post-secondary education were least likely to be adversely impacted (19.6%), compared with 33.4% of those with secondary education and 33.5% of those with pre-secondary education. Similarly, those in the highest wealth tertile were least likely to be financially impacted (26.7%), compared with 32.5% in the middle tertile and 30.4% in the bottom tertile participants. Compared with HICs, financial impact was greater in UMIC [odds ratio of 2.09 (1.88-2.33)] and greatest in LMIC [odds ratio of 16.88 (14.69-19.39)]. HIC participants with the lowest educational attainment suffered less financial impact (15.1% of participants affected) than those with the highest education in UMIC (22.0% of participants affected). Similarly, participants with the lowest education in UMIC experienced less financial impact (28.3%) than those with the highest education in LMIC (45.9%). A similar gradient was seen across country income categories when compared by pre-pandemic wealth status. INTERPRETATION: The financial impact of the pandemic differs more between HIC, UMIC, and LMIC than between socio-economic categories within a country income level. The most disadvantaged socio-economic subgroups in HIC had a lower financial impact from the pandemic than the most advantaged subgroup in UMIC, with a similar disparity seen between UMIC and LMIC. Continued high levels of infection will exacerbate financial inequity between countries and hinder progress towards the sustainable development goals, emphasising the importance of effective measures to control COVID-19 and, especially, ensuring high vaccine coverage in all countries. FUNDING: Funding for this study was provided by the Canadian Institutes of Health Research and the International Development Research Centre.

Household and personal air pollution exposure measurements from 120 communities in eight countries: results from the PURE-AIR study.

BACKGROUND: Approximately 2·8 billion people are exposed to household air pollution from cooking with polluting fuels. Few monitoring studies have systematically measured health-damaging air pollutant (ie, fine particulate matter [PM2·5] and black carbon) concentrations from a wide range of cooking fuels across diverse populations. This multinational study aimed to assess the magnitude of kitchen concentrations and personal exposures to PM2·5 and black carbon in rural communities with a wide range of cooking environments. METHODS: As part of the Prospective Urban and Rural Epidemiological (PURE) cohort, the PURE-AIR study was done in 120 rural communities in eight countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Data were collected from 2541 households and from 998 individuals (442 men and 556 women). Gravimetric (or filter-based) 48 h kitchen and personal PM2·5 measurements were collected. Light absorbance (10-5m-1) of the PM2·5 filters, a proxy for black carbon concentrations, was calculated via an image-based reflectance method. Surveys of household characteristics and cooking patterns were collected before and after the 48 h monitoring period. FINDINGS: Monitoring of household air pollution for the PURE-AIR study was done from June, 2017, to September, 2019. A mean PM2·5 kitchen concentration gradient emerged across primary cooking fuels: gas (45 µg/m3 [95% CI 43-48]), electricity (53 µg/m3 [47-60]), coal (68 µg/m3 [61-77]), charcoal (92 µg/m3 [58-146]), agricultural or crop waste (106 µg/m3 [91-125]), wood (109 µg/m3 [102-118]), animal dung (224 µg/m3 [197-254]), and shrubs or grass (276 µg/m3 [223-342]). Among households cooking primarily with wood, average PM2·5 concentrations varied ten-fold (range: 40-380 µg/m3). Fuel stacking was prevalent (981 [39%] of 2541 households); using wood as a primary cooking fuel with clean secondary cooking fuels (eg, gas) was associated with 50% lower PM2·5 and black carbon concentrations than using only wood as a primary cooking fuel. Similar average PM2·5 personal exposures between women (67 µg/m3 [95% CI 62-72]) and men (62 [58-67]) were observed. Nearly equivalent average personal exposure to kitchen exposure ratios were observed for PM2·5 (0·79 [95% 0·71-0·88] for men and 0·82 [0·74-0·91] for women) and black carbon (0·64 [0·45-0·92] for men and 0·68 [0·46-1·02] for women). INTERPRETATION: Using clean primary fuels substantially lowers kitchen PM2·5 concentrations. Importantly, average kitchen and personal PM2·5 measurements for all primary fuel types exceeded WHO's Interim Target-1 (35 µg/m3 annual average), highlighting the need for comprehensive pollution mitigation strategies. FUNDING: Canadian Institutes for Health Research, National Institutes of Health.

Household, Community, Sub-National and Country-level Predictors of Primary Cooking Fuel Switching in Nine Countries from the PURE Study.

INTRODUCTION: Switching from polluting (e.g. wood, crop waste, coal) to clean cooking fuels (e.g. gas, electricity) can reduce household air pollution (HAP) exposures and climate-forcing emissions. While studies have evaluated specific interventions and assessed fuel-switching in repeated cross-sectional surveys, the role of different multilevel factors in household fuel switching, outside of interventions and across diverse community settings, is not well understood. METHODS: We examined longitudinal survey data from 24,172 households in 177 rural communities across nine countries within the Prospective Urban and Rural Epidemiology (PURE) study. We assessed household-level primary cooking fuel switching during a median of 10 years of follow up (~2005-2015). We used hierarchical logistic regression models to examine the relative importance of household, community, sub-national and national-level factors contributing to primary fuel switching. RESULTS: One-half of study households (12,369) reported changing their primary cooking fuels between baseline and follow up surveys. Of these, 61% (7,582) switched from polluting (wood, dung, agricultural waste, charcoal, coal, kerosene) to clean (gas, electricity) fuels, 26% (3,109) switched between different polluting fuels, 10% (1,164) switched from clean to polluting fuels and 3% (522) switched between different clean fuels. Among the 17,830 households using polluting cooking fuels at baseline, household-level factors (e.g. larger household size, higher wealth, higher education level) were most strongly associated with switching from polluting to clean fuels in India; in all other countries, community-level factors (e.g. larger population density in 2010, larger increase in population density between 2005-2015) were the strongest predictors of polluting-to-clean fuel switching. CONCLUSIONS: The importance of community and sub-national factors relative to household characteristics in determining polluting-to-clean fuel switching varied dramatically across the nine countries examined. This highlights the potential importance of national and other contextual factors in shaping large-scale clean cooking transitions among rural communities in low- and middle-income countries.