Immunogenetics of resistance to SARS-CoV-2 infection in discordant couples

BackgroundDespite the high number of individuals infected by SARS-CoV-2 who develop COVID-19 symptoms worldwide, many exposed individuals remain asymptomatic and/or stay uninfected. This could be explained by a combination of environmental (exposure, previous infection), epigenetic, and genetic factors. Aiming to identify genetic variants involved in SARS-CoV-2 resistance, we analyzed 86 discordant Brazilian couples where one was infected and symptomatic while the partner remained asymptomatic and seronegative despite sharing the same bedroom during the infection. The discordant partners had comparable ages, and genetic ancestry proportions. MethodsWhole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic MHC and LRC. ResultsWe observed a minor impact in antigen-presentation genes and KIR genes associated with resistance. Interestingly, genes related to immune modulation, mainly involved in NK cell killing activation/inhibition harbor variants potentially contributing to infection resistance. We hypothesize that individuals prone to produce higher amounts of MICA (possibly soluble), LILRB1, LILRB2, and low amounts of MICB, would be more susceptible to infection. ConclusionAccording to this hypothesis, quantitative differences in these NK activity-related molecules could contribute to resistance to COVID-19 down regulating NK cell cytotoxic activity in infected individuals but not in resistant partners.

Effect of comprehensive intervention on hypertension control program in workplaces in China / 中华流行病学杂志

Objective: To evaluate the effect of comprehensive intervention program on hypertension control in workplaces in China. Methods: The study design was a non-randomized controlled trial. First, 20 sub-centers were selected across China, then hypertension patients in 2-4 workplaces were selected as the intervention group, and hypertension patients in 1 comparable workplace selected, as the control group in each sub-center. The comprehensive intervention strategy which integrating workplace primary prevention of cardiovascular diseases and standardized management of hypertension was adopted in the intervention group for at least 2 years. Patients in the control group continued their usual health care, and only baseline data and 2-year data was collected. Analyses were conducted for hypertension patients in 30 stated-owned enterprises (SOEs), including 20 for the intervention group and 10 for the control group. The primary outcome was the control rate ofhypertension while the intervention effect (IE) was estimated by using the formula: differential value of intervention group[rate (mean)]-differential value of control group[rate (mean)]. Results: Overall, 2 622 patients completed the 2-year follow-up, of which 2 055 were in the intervention group and 567 in the control group, respectively. After 2 years of intervention, the IE on the level of SBP and DBP for intervention group and control group were-7.5 and-3.9 mmHg, respectively (P<0.05). BMI decreased by 0.4 kg/m(2), with the regular exercise rate as 36.4% and alcohol consumption rate decreased by 14.0%, respectively (P<0.05). The smoking rate decreased by 6.1% (P>0.05). The overall hypertension control rate was 25.0%, and further subgroup analysis showed that our intervention program was particularly effective for those with high education level (27.6%), white-collar employees (41.9%), and those from SOEs whose affiliated hospital had been separated away (41.9%). Conclusion: The comprehensive intervention program could greatly improve the hypertension control in the workplaces in China.

Sentinel surveillance for viral hepatitis C in China, 2016-2017 / 中华流行病学杂志

Objective: To understand the prevalence of hepatitis C virus (HCV) infection in 5 populations in China during 2016-2017 and provide evidence for the estimation of prevalence trend of hepatitis C and evaluation on the prevention and control effect. Methods: A total of 87 national sentinel surveillance sites for hepatitis C were set up in 31 provinces (autonomous regions and municipalities) of China to obtain the information about HCV infection prevalence in 5 populations, including volunteer blood donors, people receiving physical examination, patients receiving invasive diagnosis and treatment, patients receiving hemodialysis, and clients visiting family planning outpatient clinics. From April to June, 2016 and 2017, cross-sectional surveys were repeatedly conducted in the 5 populations and blood samples were collected from them for HCV antibody detection. Results: In 2016, 86 sentinel sites completed the surveillance (one sentinel site was not investigated), and 115 841 persons were surveyed. The overall HCV positive rate was 0.38% (442/115 841, 95%CI: 0.23%-0.53%). In 2017, all the 87 sentinel sites completed the surveillance, and 120 486 persons were surveyed. The overall HCV positive rate was 0.37% (449/120 486, 95%CI: 0.23%-0.52%). In 2016 and 2017, the anti-HCV positive rates were 4.46% (223/5 005, 95%CI: 2.18%-6.73%) and 4.39% (216/4 919, 95%CI: 2.29%-6.50%) respectively in hemodialysis patients, 0.85% (44/5 200, 95%CI: 0.27%-1.42%) and 0.70% (36/5 150, 95%CI: 0.15%-1.24%) respectively in patients receiving invasive diagnosis and treatment and remained to be ≤0.25% in volunteer blood donors, people receiving physical examination and clients visiting family planning outpatient clinics. Results for the comparison of the anti-HCV positive rates in the 5 populations indicated that the differences were significant (F=23.091, P<0.001 in 2016 and F=20.181, P<0.001 in 2017). Conclusions: Data from the sentinel surveillance of HCV infection on prevalence in China showed that the anti-HCV positive rates varied in the 5 populations during 2016-2017. The anti-HCV positive rate appeared the highest in the hemodialysis patients, followed by that in the patients receiving invasive diagnosis and treatment, and the prevalence of HCV infection in other 3 populations were at low levels.

Association between high-sensitivity C-reactive protein and both cardiovascular, total mortality events in middle-aged Chinese adults / 中华流行病学杂志

Objective: To estimate the association between high-sensitivity C-reactive protein (hs-CRP) and cardiovascular events as well as all-cause mortality events. Methods: During 2009- 2010, out of the 11 623 individuals, 1 000 participants aged 35-64 years, were recruited and divided into 12 age-groups, to have received a study on CVD risk factors. Information on the risk factors of cardiovascular diseases was also collected. Fasting blood sample was gathered for all the participants, with hs-CRP tested. Participants in 7 out of the 12 sites were followed, with 6.21 years (36 075 person-years) as the median follow-up period. Cardiovascular and all-cause mortality events were collected. A total of 6 177 participants had been followed after excluding participants who had baseline infections, or did not take hs-CRP test/physical examination at the baseline. Finally, 5 984 participants were included for analysis. Participants were categorized into three groups based on the hs-CRP (mg/L) values: <1, 1-3 and >3, respectively. Cox proportional hazards regression model was used to analyze the relationships between hs-CRP with cardiovascular events or all-cause mortality events, after adjusting for confounding factors. Results: Mean age of the participants was 50.2 years. The incidence rates of cardiovascular disease events were 3.6/1 000 person-years, 7.1/1 000 person-years,and 10.4/1 000 person-years among three groups and 3.0/1 000 person-years, 5.7/1 000 person-years, 9.1/1 000 person-years for all-cause mortality events, respectively. After adjusting for confounding factors, the hazard risks (HR) for cardiovascular events were 1.33 (95%CI: 0.95-1.84) in the hs-CRP 1-3 mg/L group and 1.76 (95%CI: 1.20-2.60) in the hs-CRP>3 mg/L group when comparing with the hs-CRP<1 mg/L group (trend test P=0.003). The HRs for all-cause mortality events were 1.76 (95%CI: 1.23-2.54) and 2.64 (95%CI: 1.74-4.01) (trend test P<0.001), respectively. Conclusion: Hs-CRP appeared an independent predictor for cardiovascular events and all-cause mortality events.

A Meta-analysis on the relations between short-term exposure to PM(2.5) and both mortality and related emergency visits in China / 中华流行病学杂志

Objective: To carry out a quantitative estimate that related to the effects of short-term exposure to PM(2.5) on all-cause mortality and emergency visits in China by using the systematic review and Meta-analysis. Methods: We selected all the studies published before March 2018 from China National Knowledge Infrastructure, Wanfang database, PubMed and EMBASE and data on relative risk (RR), excess risk (ER) and their 95%CIs: appeared in these papers were extracted. According to the differences in the size or direction (heterogeneity) of the results, we computed summary estimates of the effect values using a random-effect or fixed effect model. We also conducted the subgroup analysis and Meta-analysis to have assessed the selected studies for the evidence of study bias. Results: A total of 33 original studies, indexed in databases, were identified. Among those studies, 39 sets of data on mortality and 4 sets of data on emergency were valid to show that within the daily concentration range from 47.7 to 176.7 μg/m(3), for 10 μg/m(3) increases in PM(2.5) concentrations, it would increase the daily numbers of deaths by 0.49% (95%CI: 0.39%-0.59%) and 0.30% (95%CI: 0.10%-0.51%) for all-cause deaths and all-cause emergency-room visits, respectively. For subgroup analysis, the combined effect of PM(2.5) in causing short-term all-cause deaths in the northern areas (ER=0.42%, 95%CI: 0.30%-0.54%) seemed lower than that in the southern areas (ER=0.63%, 95%CI: 0.44%-0.82%). The combined effect of PM(2.5) concentration below 75 μg/m(3) (ER=0.50%, 95%CI: 0.37%-0.62%) was higher than that of PM(2.5) concentration ≥75 μg/m(3) (ER=0.39%, 95%CI: 0.26%-0.52%). Conclusion: Within the concentration range from 47.7 to 176.7 μg/m(3), short-term exposure to current level of PM(2.5) might increase both the all-cause daily mortality and daily emergency visits in China.

Interactive effects between health literacy and mobile phone dependence as well as its relation with unintentional injuries in middle school students / 中华流行病学杂志

Objective: To investigate the interaction between health literacy, mobile phone dependence and unintentional injuries in middle school students, and to provide guidance for prevention on unintentional injuries in adolescents. Methods: From November 2015 to January 2016, a questionnaire survey was conducted among 22 628 middle school students in Shenyang of Liaoning province, Bengbu of Anhui province, Xinxiang of Henan province, Ulanqab of Inner Mongolia Autonomous Region, Chongqing and Yangjiang of Guangdong province. Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ), Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU), and Unintentional Injuries Assessment Scale and demographic variables were used to measure the health literacy, mobile phone dependence and unintentional injuries among the Chinese middle school students. Results: The detection rates of mobile phone dependence and unintentional injuries were 25.4% and 46.7%, respectively. The rates of unintentional injuries of middle school students with mobile phone dependence and with low, medium and high health literacy were 53.6%, 44.4% and 48.8%, 48.1%, 41.7%. Factors as mobile phone dependence, low and middle health literacy were positively related to unintentional injuries (OR=1.452, 1.196, 1.364). However, the multiplicative interaction between mobile phone dependence and health literacy on unintentional injuries was noticed significant (OR=1.217, 95%CI: 1.041-1.422). Conclusions: Our results showed that the prevalence of unintentional injuries was relatively high in middle school students. Health literacy and mobile phone dependence seemed related to unintentional injuries. Interaction between health literacy and mobile phone dependence on unintentional injuries appeared significant.

Caspase 7: increased expression and activation after traumatic brain injury in rats.

Caspases, a cysteine proteinase family, are required for the initiation and execution phases of apoptosis. It has been suggested that caspase 7, an apoptosis executioner implicated in cell death proteolysis, is redundant to the main executioner caspase 3 and it is generally believed that it is not present in the brain or present in only minute amounts with highly restricted activity. Here we report evidence that caspase 7 is up-regulated and activated after traumatic brain injury (TBI) in rats. TBI disrupts homeostasis resulting in pathological apoptotic activation. After controlled cortical impact TBI of adult male rats we observed, by semiquantitative real-time PCR, increased mRNA levels within the traumatized cortex and hippocampus peaking in the former about 5 days post-injury and in the latter within 6-24 h of trauma. The activation of caspase 7 protein after TBI, demonstrated by immunoblot by the increase of the active form of caspase 7 peaking 5 days post-injury in the cortex and hippocampus, was found to be up-regulated in both neurons and astrocytes by immunohistochemistry. These findings, the first to document the up-regulation of caspase 7 in the brain after acute brain injury in rats, suggest that caspase 7 activation could contribute to neuronal cell death on a scale not previously recognized.