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1.
Int J Epidemiol ; 2021 Sep 18.
Article in English | MEDLINE | ID: covidwho-1853082

ABSTRACT

BACKGROUND: Estimates indicate that household air pollution caused by solid fuel burning accounted for about 1.03 million premature mortalities in China in 2016. In the country's rural areas, more than half the population still relies on biomass fuels and coals for cooking and heating. Understanding the health impact of indoor air pollution and socioeconomic indicators is essential for the country to improve its developmental targets. We aimed to describe demographic and socioeconomic characteristics associated with solid fuel users in a rural area in China. We also estimated the risk of cardiovascular disease and all-cause mortality in association with solid fuel use and described the relationship between solid fuel use, socioeconomic status and mortality. We also measured the risk of long-term use, and the effect of ameliorative action, on mortality caused by cardiovascular disease and other causes. METHODS: We used the China Kadoorie Biobank (CKB) site in Pengzhou, Sichuan, China. We followed a cohort of 55 687 people over 2004-13. We calculated the mean and standard deviation among subgroups classified by fuel use types: gas, coal, wood and electricity (central heating additionally for heating). We tested the mediation effect using the stepwise method and Sobel test. We used Cox proportional models to estimate the risk of incidences of cardiovascular disease and mortality with survival days as the time scale, adjusted for age, gender, socioeconomic status, physical measurements, lifestyle, stove ventilation and fuel type used for other purposes. The survival days were defined as the follow-up days from the baseline survey till the date of death or 31 December 2013 if right-censored. We also calculated the absolute mortality rate difference (ARD) between the exposure group and the reference group. RESULTS: The study population had an average age of 51.0, and 61.9% of the individuals were female; 64.8% participants (n = 35 543) cooked regularly and 25.4% participants (n = 13 921) needed winter heating. With clean fuel users as the reference group, participant households that used solid fuel for cooking or heating both had a higher risk of all-cause mortality: hazard ratio (HR) for: cooking, 1.11 [95% confidence interval (CI) 1.02, 1.26]; heating, 1.34 (95% CI 1.16, 1.54). Solid fuel used for winter heating was associated with a higher risk of mortality caused by cerebrovascular disease: HR 1.64 (95% CI 1.12, 2.40); stroke: HR 1.70 (95% CI 1.13, 2.56); and cardiovascular disease: HR 1.49 (95% CI 1.10, 2.02). Low income and poor education level had a significant correlation with solid fuel used for cooking: odds ratio (OR) for income: 2.27 (95% CI 2.14, 2.41); education: 2.34 (95% CI 2.18, 2.53); and for heating: income: 2.69 (95% CI 2.46, 2.97); education: 2.05 (95% CI 1.88, 2.26), which may be potential mediators bridging the effects of socioeconomic status factors on cardiovascular disease and all-cause mortality. Solid fuel used for cooking and heating accounted for 42.4% and 81.1% of the effect of poor education and 55.2% and 76.0% of the effect of low income on all-cause mortality, respectively. The risk of all-cause mortality could be ameliorated by stopping regularly cooking and heating using solid fuel or switching from solid fuel to clean fuels: HR for cooking: 0.90 (95% CI 0.84, 0.96); heating: 0.76 (95% CI 0.64, 0.92). CONCLUSIONS: Our study reinforces the evidence of an association between solid fuel use and risk of cardiovascular disease and all-cause mortality. We also assessed the effect of socioeconomic status as the potential mediator on mortality. As solid fuel use was a major contributor in the effect of socioeconomic status on cardiovascular disease and all-cause mortality, policies to improve access to clean fuels could reduce morbidity and mortality related to poor education and low income.

2.
Circ Res ; 130(7): 963-977, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1731376

ABSTRACT

BACKGROUND: Increasing evidence suggests that cardiac arrhythmias are frequent clinical features of coronavirus disease 2019 (COVID-19). Sinus node damage may lead to bradycardia. However, it is challenging to explore human sinoatrial node (SAN) pathophysiology due to difficulty in isolating and culturing human SAN cells. Embryonic stem cells (ESCs) can be a source to derive human SAN-like pacemaker cells for disease modeling. METHODS: We used both a hamster model and human ESC (hESC)-derived SAN-like pacemaker cells to explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the pacemaker cells of the heart. In the hamster model, quantitative real-time polymerase chain reaction and immunostaining were used to detect viral RNA and protein, respectively. We then created a dual knock-in SHOX2:GFP;MYH6:mCherry hESC reporter line to establish a highly efficient strategy to derive functional human SAN-like pacemaker cells, which was further characterized by single-cell RNA sequencing. Following exposure to SARS-CoV-2, quantitative real-time polymerase chain reaction, immunostaining, and RNA sequencing were used to confirm infection and determine the host response of hESC-SAN-like pacemaker cells. Finally, a high content chemical screen was performed to identify drugs that can inhibit SARS-CoV-2 infection, and block SARS-CoV-2-induced ferroptosis. RESULTS: Viral RNA and spike protein were detected in SAN cells in the hearts of infected hamsters. We established an efficient strategy to derive from hESCs functional human SAN-like pacemaker cells, which express pacemaker markers and display SAN-like action potentials. Furthermore, SARS-CoV-2 infection causes dysfunction of human SAN-like pacemaker cells and induces ferroptosis. Two drug candidates, deferoxamine and imatinib, were identified from the high content screen, able to block SARS-CoV-2 infection and infection-associated ferroptosis. CONCLUSIONS: Using a hamster model, we showed that primary pacemaker cells in the heart can be infected by SARS-CoV-2. Infection of hESC-derived functional SAN-like pacemaker cells demonstrates ferroptosis as a potential mechanism for causing cardiac arrhythmias in patients with COVID-19. Finally, we identified candidate drugs that can protect the SAN cells from SARS-CoV-2 infection.


Subject(s)
COVID-19 , Ferroptosis , Humans , Myocytes, Cardiac/metabolism , SARS-CoV-2 , Sinoatrial Node/metabolism
3.
PLoS One ; 16(7): e0255373, 2021.
Article in English | MEDLINE | ID: covidwho-1334777

ABSTRACT

BACKGROUND: Blood pressure (BP) categories are useful to simplify preventions in public health, and diagnostic and treatment approaches in clinical practice. Updated evidence about the associations of BP categories with cardiovascular diseases (CVDs) and its subtypes is warranted. METHODS AND FINDINGS: About 0.5 million adults aged 30 to 79 years were recruited from 10 areas in China during 2004-2008. The present study included 430 977 participants without antihypertension treatment, cancer, or CVD at baseline. BP was measured at least twice in a single visit at baseline and CVD deaths during follow-up were collected via registries and the national health insurance databases. Multivariable Cox regression was used to estimate the associations between BP categories and CVD mortality. Overall, 16.3% had prehypertension-low, 25.1% had prehypertension-high, 14.1% had isolated systolic hypertension (ISH), 1.9% had isolated diastolic hypertension (IDH), and 9.1% had systolic-diastolic hypertension (SDH). During a median 10-year follow-up, 9660 CVD deaths were documented. Compared with normal, the hazard ratios (95% CI) of prehypertension-low, prehypertension-high, ISH, IDH, SDH for CVD were 1.10 (1.01-1.19), 1.32 (1.23-1.42), 2.04 (1.91-2.19), 2.20 (1.85-2.61), and 3.81 (3.54-4.09), respectively. All hypertension subtypes were related to the increased risk of CVD subtypes, with a stronger association for hemorrhagic stroke than for ischemic heart disease. The associations were stronger in younger than older adults. CONCLUSIONS: Prehypertension-high should be considered in CVD primary prevention given its high prevalence and increased CVD risk. All hypertension subtypes were independently associated with CVD and its subtypes mortality, though the strength of associations varied substantially.


Subject(s)
Blood Pressure , Hemorrhagic Stroke , Hypertension , Myocardial Ischemia , Adult , Age Factors , Aged , China/epidemiology , Disease-Free Survival , Female , Follow-Up Studies , Hemorrhagic Stroke/mortality , Hemorrhagic Stroke/physiopathology , Humans , Hypertension/mortality , Hypertension/physiopathology , Male , Middle Aged , Myocardial Ischemia/mortality , Myocardial Ischemia/physiopathology , Survival Rate
4.
J Clin Endocrinol Metab ; 106(5): e2025-e2034, 2021 04 23.
Article in English | MEDLINE | ID: covidwho-1199961

ABSTRACT

PURPOSE: Comorbidities making up metabolic syndrome (MetS), such as obesity, type 2 diabetes, and chronic cardiovascular disease can lead to increased risk of coronavirus disease-2019 (COVID-19) with a higher morbidity and mortality. SARS-CoV-2 antibodies are higher in severely or critically ill COVID-19 patients, but studies have not focused on levels in convalescent patients with MetS, which this study aimed to assess. METHODS: This retrospective study focused on adult convalescent outpatients with SARS-CoV-2 positive serology during the COVID-19 pandemic at NewYork Presbyterian/Weill Cornell. Data collected for descriptive and correlative analysis included SARS-COV-2 immunoglobin G (IgG) levels and history of MetS comorbidities from April 17, 2020 to May 20, 2020. Additional data, including SARS-CoV-2 IgG levels, body mass index (BMI), hemoglobin A1c (HbA1c) and lipid levels were collected and analyzed for a second cohort from May 21, 2020 to June 21, 2020. SARS-CoV-2 neutralizing antibodies were measured in a subset of the study cohort. RESULTS: SARS-CoV-2 IgG levels were significantly higher in convalescent individuals with MetS comorbidities. When adjusted for age, sex, race, and time duration from symptom onset to testing, increased SARS-CoV-2 IgG levels remained significantly associated with obesity (P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with HbA1c ≥6.5% compared to those with HbA1c <5.7% (P = 0.0197) and remained significant on multivariable analysis (P = 0.0104). A positive correlation was noted between BMI and antibody levels [95% confidence interval: 0.37 (0.20-0.52) P < 0.0001]. Neutralizing antibody titers were higher in COVID-19 individuals with BMI ≥ 30 (P = 0.0055). CONCLUSION: Postconvalescent SARS-CoV-2 IgG and neutralizing antibodies are elevated in obese patients, and a positive correlation exists between BMI and antibody levels.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/immunology , Immunoglobulin G/immunology , Metabolic Syndrome/immunology , Adult , Antibodies, Neutralizing/blood , COVID-19/blood , COVID-19/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/virology , Female , Humans , Immunoglobulin G/blood , Male , Metabolic Syndrome/blood , Metabolic Syndrome/virology , Middle Aged , Obesity/blood , Obesity/immunology , Obesity/virology , Retrospective Studies
6.
JAMA Netw Open ; 4(3): e214302, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1144219

ABSTRACT

Importance: Accumulating evidence suggests that children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to manifest mild symptoms and are at a lower risk of developing severe respiratory disease compared with adults. It remains unknown how the immune response in children differs from that of adolescents and adults. Objective: To investigate the association of age with the quantity and quality of SARS-CoV-2 antibody responses. Design, Setting, and Participants: This cross-sectional study used 31 426 SARS-CoV-2 antibody test results from pediatric and adult patients. Data were collected from a New York City hospital from April 9 to August 31, 2020. The semiquantitative immunoglobin (Ig) G levels were compared between 85 pediatric and 3648 adult patients. Further analysis of SARS-CoV-2 antibody profiles was performed on sera from 126 patients aged 1 to 24 years. Main Outcomes and Measures: SARS-CoV-2 antibody positivity rates and IgG levels were evaluated in patients from a wide range of age groups (1-102 years). SARS-CoV-2 IgG level, total antibody (TAb) level, surrogate neutralizing antibody (SNAb) activity, and antibody binding avidity were compared between children (aged 1-10 years), adolescents (aged 11-18 years), and young adults (aged 19-24 years). Results: Among 31 426 antibody test results (19 797 [63.0%] female patients), with 1194 pediatric patients (mean [SD] age, 11.0 [5.3] years) and 30 232 adult patients (mean [SD] age, 49.2 [17.1] years), the seroprevalence in the pediatric (197 [16.5%; 95% CI, 14.4%-18.7%]) and adult (5630 [18.6%; 95% CI, 18.2%-19.1%]) patient populations was similar. The SARS-CoV-2 IgG level showed a negative correlation with age in the pediatric population (r = -0.45, P < .001) and a moderate but positive correlation with age in adults (r = 0.24, P < .001). Patients aged 19 to 30 years exhibited the lowest IgG levels (eg, aged 25-30 years vs 1-10 years: 99 [44-180] relative fluorescence units [RFU] vs 443 [188-851] RFU). In the subset cohort aged 1 to 24 years, IgG, TAb, SNAb and avidity were negatively correlated with age (eg, IgG: r = -0.51; P < .001). Children exhibited higher median (IQR) IgG levels, TAb levels, and SNAb activity compared with adolescents (eg, IgG levels: 473 [233-656] RFU vs 191 [82-349] RFU; P < .001) and young adults (eg, IgG levels: 473 [233-656] RFU vs 85 [38-150] RFU; P < .001). Adolescents also exhibited higher median (IQR) TAb levels, IgG levels, and SNAb activity than young adults (eg, TAb levels: 961 [290-2074] RFU vs 370 [125-697]; P = .006). In addition, children had higher antibody binding avidity compared with young adults, but the difference was not significant. Conclusions and Relevance: The results of this study suggest that SARS-CoV-2 viral specific antibody response profiles are distinct in different age groups. Age-targeted strategies for disease screening and management as well as vaccine development may be warranted.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibody Affinity/immunology , Antibody Formation/immunology , COVID-19 , SARS-CoV-2 , Age Factors , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Serological Testing/methods , COVID-19 Serological Testing/statistics & numerical data , Child , Correlation of Data , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , New York City/epidemiology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
7.
BMJ ; 372: n415, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1102165

ABSTRACT

OBJECTIVE: To assess excess all cause and cause specific mortality during the three months (1 January to 31 March 2020) of the coronavirus disease 2019 (covid-19) outbreak in Wuhan city and other parts of China. DESIGN: Nationwide mortality registries. SETTING: 605 urban districts and rural counties in China's nationally representative Disease Surveillance Point (DSP) system. PARTICIPANTS: More than 300 million people of all ages. MAIN OUTCOME MEASURES: Observed overall and weekly mortality rates from all cause and cause specific diseases for three months (1 January to 31 March 2020) of the covid-19 outbreak compared with the predicted (or mean rates for 2015-19) in different areas to yield rate ratio. RESULTS: The DSP system recorded 580 819 deaths from January to March 2020. In Wuhan DSP districts (n=3), the observed total mortality rate was 56% (rate ratio 1.56, 95% confidence interval 1.33 to 1.87) higher than the predicted rate (1147 v 735 per 100 000), chiefly as a result of an eightfold increase in deaths from pneumonia (n=1682; 275 v 33 per 100 000; 8.32, 5.19 to 17.02), mainly covid-19 related, but a more modest increase in deaths from certain other diseases, including cardiovascular disease (n=2347; 408 v 316 per 100 000; 1.29, 1.05 to 1.65) and diabetes (n=262; 46 v 25 per 100 000; 1.83, 1.08 to 4.37). In Wuhan city (n=13 districts), 5954 additional (4573 pneumonia) deaths occurred in 2020 compared with 2019, with excess risks greater in central than in suburban districts (50% v 15%). In other parts of Hubei province (n=19 DSP areas), the observed mortality rates from pneumonia and chronic respiratory diseases were non-significantly 28% and 23% lower than the predicted rates, despite excess deaths from covid-19 related pneumonia. Outside Hubei (n=583 DSP areas), the observed total mortality rate was non-significantly lower than the predicted rate (675 v 715 per 100 000), with significantly lower death rates from pneumonia (0.53, 0.46 to 0.63), chronic respiratory diseases (0.82, 0.71 to 0.96), and road traffic incidents (0.77, 0.68 to 0.88). CONCLUSIONS: Except in Wuhan, no increase in overall mortality was found during the three months of the covid-19 outbreak in other parts of China. The lower death rates from certain non-covid-19 related diseases might be attributable to the associated behaviour changes during lockdown.


Subject(s)
COVID-19/mortality , Cause of Death , Adult , China/epidemiology , Disease Outbreaks , Female , Humans , Male , Noncommunicable Diseases/mortality , Pneumonia/mortality , Population Surveillance , Registries , SARS-CoV-2 , Wounds and Injuries/mortality
9.
Clin Chim Acta ; 509: 117-125, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-526557

ABSTRACT

BACKGROUND: In the ongoing COVID-19 pandemic, there is an urgent need for comprehensive performance evaluation and clinical utility assessment of serological assays to understand the immune response to SARS-CoV-2. METHODS: IgM/IgG and total antibodies against SARS-CoV-2 were measured by a cyclic enhanced fluorescence assay (CEFA) and a microsphere immunoassay (MIA), respectively. Independent performance evaluation included imprecision, reproducibility, specificity and cross-reactivity (CEFA n = 320, MIA n = 364). Clinical utility was evaluated by both methods in 87 patients at initial emergency department visit, 28 during subsequent hospitalizations (106 serial samples), and 145 convalescent patients. Totally 916 patients and 994 samples were evaluated. RESULTS: Agreement of CEFA and MIA was 90.4%-94.5% (Kappa: 0.81-0.89) in 302 samples. CEFA and MIA detected SARS-CoV-2 antibodies in 26.2% and 26.3%, respectively, of ED patients. Detection rates increased over time reaching 100% after 21 days post-symptom onset. Longitudinal antibody kinetic changes by CEFA and MIA measurements correlated well and exhibited three types of seroconversion. Convalescent sera showed a wide range of antibody levels. CONCLUSION: Rigorously validated CEFA and MIA assays are reliable for detecting antibodies to SARS-CoV-2 and show promising clinical utility when evaluating immune response in hospitalized and convalescent patients, but are not useful for early screening at patient's initial ED visit.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus , Clinical Laboratory Techniques/trends , Coronavirus Infections/blood , Emergency Service, Hospital/trends , Hospitalization/trends , Pneumonia, Viral/blood , Adult , Aged , Aged, 80 and over , Betacoronavirus/isolation & purification , COVID-19 , Clinical Laboratory Techniques/methods , Cohort Studies , Convalescence , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Female , Humans , Immunoassay/methods , Longitudinal Studies , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , SARS-CoV-2
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