Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses.

SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19. However, the effects of viremia on immune responses in blood cells remain unclear. The current study comprehensively examined transcriptional signatures of PBMCs involving T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) respectively, from three different groups including individuals with moderate (nM), or severe disease with (vS) or without (nS) detectable plasma viral load. Whole transcriptome analysis demonstrated that all seven immune cell subsets were associated with disease severity regardless of cell type. Supervised clustering analysis demonstrated that mDCs and pDCs gene signatures could distinguish disease severity. Notably, transcriptional signatures of the vS group were enriched in pathways related to DNA repair, E2F targets, and G2M checkpoints; in contrast, transcriptional signatures of the nM group were enriched in interferon responses. Moreover, we observed an impaired induction of interferon responses accompanied by imbalanced cell-intrinsic immune sensing and an excessive inflammatory response in patients with severe disease (nS and vS). In sum, our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in COVID-19 patients.

Tasks of COVID-19 prevention and control management teams at primary health care facilities in mainland China: a nationwide online cross-sectional survey.

BACKGROUND: This research aimed to investigate the tasks performed by Coronavirus Disease 2019(COVID-19) prevention and control management teams at primary healthcare (PHC) facilities during COVID-19 pandemic across the mainland China. METHODS: An online survey was performed and COVID-19 prevention and control management teams at PHC facilities were invited to participate in this research. The top 7 most important tasks in the three different periods of COVID-19 containment were selected and ranked. Participations of tasks were surveyed. RESULTS: A total of 998 valid responses (an effective rate of 99.11%) were collected. The respondents were divided into Group A (≤5 respondents within each PHC facility, n1 = 718) and Group B (> 5 respondents within each PHC facility, n2 = 280). The consensus was selected from top 7 most important tasks including screening at travel centers/intervals and screening at entry centers, at-home/centralized quarantine management, transferring, pre-examination/triage and fever sentinel surveillance clinic/fever clinic. Pre-examination/triage and fever sentinel surveillance clinic/fever clinic works became more significant in the regular prevention and control period. Adjusted analysis found that team members of Group A with a college, undergraduate college and graduate school educational background were less involved in pre-examination/triage works (aOR: 0.28; 95%CI: 0.09-0.86, P = 0.026; aOR: 0.30; 95%CI: 0.10-0.90, P = 0.031; aOR: 0.21; 95%CI: 0.05-0.82, P = 0.024). Those who were over the median age were twice more likely to be engaged in managing fever sentinel surveillance of clinic/fever clinic visitors (aOR: 2.18; 95%CI: 1.16-4.08, P = 0.015). Those being specialized in nursing and other specialties were less likely to participate in fever sentinel surveillance of clinic/fever clinic works (aOR: 0.44; 95%CI: 0.24-0.81, P = 0.009; aOR: 0.30; 95%CI: 0.16-0.58, P < 0.001). Those came from central and western China were less likely to participate in centralized quarantine management (aOR: 0.61; 95%CI: 0.38-0.98, P = 0.042; aOR: 0.64; 95%CI: 0.42-0.97, P = 0.037). Team members came from central and western China were twice less likely to participate in screening at travel centers/intervals (aOR: 1.75; 95%CI: 1.14-2.70, P = 0.011; aOR: 1.63; 95%CI: 1.07-2.48, P = 0.024). CONCLUSION: In mainland China, team members of COVID-19 prevention and control at PHC facilities are mainly responsible for screening, quarantine, transferring and monitoring during the COVID-19 pandemic. Pre-examination/triage and the fever sentinel surveillance clinic/fever clinic were gradually valued. Team members with lower educational background are competent in pre-examination/triage works, but more experienced general practitioners are more likely to be in charge of fever sentinel surveillance clinic/fever clinics work. The necessity of COVID-19 prevention and control management teams to participate in screening at travel centers/intervals is subjected to further discussions.

Null-free False Discovery Rate Control Using Decoy Permutations.

The traditional approaches to false discovery rate (FDR) control in multiple hypothesis testing are usually based on the null distribution of a test statistic. However, all types of null distributions, including the theoretical, permutation-based and empirical ones, have some inherent drawbacks. For example, the theoretical null might fail because of improper assumptions on the sample distribution. Here, we propose a null distribution-free approach to FDR control for multiple hypothesis testing in the case-control study. This approach, named target-decoy procedure, simply builds on the ordering of tests by some statistic or score, the null distribution of which is not required to be known. Competitive decoy tests are constructed from permutations of original samples and are used to estimate the false target discoveries. We prove that this approach controls the FDR when the score function is symmetric and the scores are independent between different tests. Simulation demonstrates that it is more stable and powerful than two popular traditional approaches, even in the existence of dependency. Evaluation is also made on two real datasets, including an arabidopsis genomics dataset and a COVID-19 proteomics dataset.

Vaccination coverage among COVID-19 prevention and control management teams at primary healthcare facilities in China and their attitudes towards COVID-19 vaccine: a cross-sectional online survey.

OBJECTIVE: To investigate the COVID-19 vaccination coverage rate and differences among various COVID-19 prevention primary healthcare (PHC) facilities in China and understand their attitudes towards COVID-19 vaccine. These findings are helpful to provide important suggestions to further improve national COVID-19 vaccination rate. DESIGN: A nationwide cross-sectional online survey was designed and conducted among COVID-19 prevention and control management teams at PHC facilities in mainland China. In the self-designed questionnaires, each subject was asked to evaluate on a 1-10 scale (10=extremely important/acceptable/influential) the COVID-19 vaccination importance, acceptance and factors related to vaccine hesitancy. SETTING: Subjects from 31 provinces and autonomous regions including minorities across mainland China were invited to complete the questionnaire between 22 February 2021 and 2 March 2021. PARTICIPANTS: Were selected by multistage stratified sampling, 998 valid questionnaires (valid rate 99.11%) were collected. The respondents were divided into group A (≤5 respondents within each PHC facility, n1=718) and group B (>5 respondents within each PHC facility, n2=280). OUTCOME MEASURES: Survey on vaccination rate and attitude towards COVID-19 vaccine included the following: (1) if the subjects think the vaccination is important in containment of COVID-19 pandemic (1-10 scale, 10=extremely important), (2) if they would accept COVID-19 vaccine (1-10 scale, 10=extremely acceptable) and (3) their opinions on 7 factors possibly related to vaccine hesitancy (1-10 scale, 10=extremely influential). All the items were designed based on the previous expert interviews. RESULTS: Our results showed vaccination rate was greater in group A (85.93%) than in group B (66.43%) (p<0.001). Detailed analyses revealed that in group A, male members were twice as likely to get vaccinated as compared with female members (adjusted OR (aOR): 2.07; 95% CI: 1.26 to 3.43, p=0.004). In group B, those who were at or under the median age had twice the odds of vaccination coverage compared with those who were over the median age (aOR: 2.29; 95% CI: 1.22 to 4.33, p=0.010). In addition, those who were specialised in traditional Chinese medicine were less likely to get vaccinated against COVID-19 compared with those who were specialised in general medicine, with the aOR: 0.10 (95% CI: 0.01 to 0.83, p=0.033). By analysing the factors that influenced the vaccination attitudes among the 998 respondents, we found no significant difference between the vaccinated and unvaccinated participants. However, further detailed analyses found that team members with undergraduate college education were less likely to score higher in COVID-19 vaccination importance than those with technical secondary school education (aOR: 0.35; 95% CI: 0.13 to 0.93, p=0.035); Furthermore, those with non-medical job titles had nearly twice the odds of giving a higher score for the uncertainty of vaccine efficacy compared with those with junior medical titles (aOR: 1.70; 95% CI: 1.02 to 2.85, p=0.016). Team members with a non-medical title were more likely to give a higher score for advice on social sources compared with those with a junior medical title (aOR: 1.70; 95% CI: 1.02 to 2.85, p=0.042). CONCLUSION: In PHC facilities, although there was a higher COVID-19 vaccination rate among COVID-19 prevention and control teams, some subgroups with different descriptive characters showed negative attitudes towards COVID-19 vaccination. Because primary care workers in China are highly expected to receive the vaccination, and support and educate the public for COVID-19 vaccination. Thus, it is important and necessary to continue to educate them about their vaccination concerns and change their attitudes towards vaccination. Our findings are highly beneficial for designing public vaccination education strategies.

Prevention and control of COVID-19 by primary health care facilities in China: a field-survey-based qualitative study in three typical cities.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) containment, primary health care (PHC) facilities inChina played an important role in providing both healthcare and public care services to community populations. The tasks of COVID-19 containment facilitated by PHC facilities were different among different regions and during different periods of COVID-19 pandemic. We sought to investigate the gaps on task participation, explore existing problems and provide corresponding solutions. METHODS: Semi-structured face-to-face interviews with COVID-19 prevention and control management teams of PHC facilities were conducted. Purposive stratified sampling was used and 32 team members of 22 PHC facilities were selected from Wuhan (as high-risk city), Shanghai (as medium-risk city) and Zunyi (as low-risk city). Framework analysis was employed to analyze the transcribed recordings. RESULTS: The main tasks of PHC facilities during the early period of the pandemic included assisting in contact tracing and epidemiological investigation, screening of populations at high-risk at travel centers/internals, house-by-house, or pre-examination/triage within PHC facilities; at-home/ centralized quarantine management; the work of fever sentinel clinics. Further analyses revealed the existing problems and suggestions for improvement or resolutions. Regular medical supply reserves were recommended because of the medical supply shortage during the pre-outbreak period. Temporarily converted quarantine wards and centralized quarantine centers could be used to deal with pressures on patients' treatment and management of the febrile patients. Only after strict evaluation of nucleic acid testing (NAT) results and housing conditions, decision on quarantine at-home or centralized quarantine centers could be made. Settings of fever sentinel clinics at PHC facilities allowed fever patients with no COVID-19 infection risks for treatment without being transferred to fever clinics of the designed secondary hospitals. Psychological intervention was sometimes in need and really helped in addressing individuals' mental pressures. CONCLUSIONS: During the COVID-19 containment, PHC facilities in China were responsible for different tasks and several problems were encountered in the working process. Accordingly, specific and feasible suggestions were put forward for different problems. Our findings are highly beneficial for healthcare teams and governments in handling similar situations.

Domestic Violence Victimization Among Men Who Have Sex with Men in China During the COVID-19 Lockdown.

Many countries worldwide have implemented dedicated measures, such as shelter at home, to contain the spread of the COVID-19 virus. However, those mitigation measures may have major implications for individuals living with someone abusive or controlling. Domestic violence (DV) may be one of the unintended consequences of public health measures due to increased various stressors and reduced access to support and services. There has been a lack of empirical research on DV victimization among gender and sexual minorities, a population vulnerable to interpersonal violence and its associated adverse health outcomes. This study investigates the prevalence of DV victimization among men who have sex with men (MSM) in Jiangsu Province, China, during the COVID-19 lockdown and its correlates with COVID-19-related psychosocial and health stressors. A total of 413 MSM were recruited via snowball sampling, venue-based, and internet-based sampling from four cities in Jiangsu Province. After providing informed consent, all participants completed study questionnaires, followed by HIV testing. Over a quarter of the participants (27.4%) reported DV victimization during the COVID-19 lockdown, including experience of verbal, physical, or sexual abuse. After adjusting sociodemographic factors, DV victimization was associated with various adverse experiences during the COVID-19 lockdown, including increased stress or anxiety level, increased alcohol use, and housing instability. Study findings underscore the prevalence of DV victimization among MSM during the COVID-19 pandemic in China. The results can inform public health efforts to raise awareness and address DV victimization among MSM in the low- and middle-income country context during the COVID-19 pandemic. Adequate health and social services and economic resources are also critical to address the needs of MSM experiencing DV victimization.

COVID-19, Diabetes, and Associated Health Outcomes in China: Results from a Nationwide Survey of 10 545 Adults.

This study examined the associations between diabetes and self-reported/familial COVID-19 infection and investigated health-related outcomes among those with diabetes during China's nationwide quarantine. The 2020 China COVID-19 Survey was administered anonymously via social media (WeChat). It was completed by 10 545 adults in all of mainland China's 31 provinces. The survey consisted of 74 items covering sociodemographic characteristics, preventive measures for COVID-19, lifestyle behaviors, and health-related outcomes during the period of quarantine. Regression models examined associations among study variables. Diabetes was associated with a six-fold increased risk of reporting COVID-19 infection among respondents or their family members. Among people with diabetes, individuals who rarely wore masks had double the risk of suspected COVID-19 infection compared with those who always wore masks, with an inverse J-shaped relationship between face mask wearing and suspected COVID-19 infection. People with diabetes tended to have both poor knowledge of COVID-19 and poor compliance with preventive measures, despite perceiving a high risk of personal infection (40.0% among respondents reporting diabetes and 8.0% without diabetes). Only 54-55% of these respondents claimed to consistently practice preventive measures, including wearing face masks. Almost 60% of those with diabetes experienced food or medication shortages during the quarantine period, which was much higher than those without diabetes. Importantly, respondents who experienced medication shortages reported a 63% higher COVID-19 infection rate. Diabetes was associated with an increased risk of self-reported personal and family member COVID-19 infection, which is mitigated by consistent use of face masks.

Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19.

Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+ TFH cell differentiation together with an increase in T-bet+ TH1 cells and aberrant extra-follicular TNF-α accumulation. Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+ TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections, and suggest that achieving herd immunity through natural infection may be difficult.

The Loss of Bcl-6 Expressing T Follicular Helper Cells and the Absence of Germinal Centers in COVID-19.

Humoral responses in COVID-19 disease are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined postmortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers, a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+TFH cell differentiation together with an increase in T-bet+TH1 cells and aberrant extra-follicular TNF-a accumulation.  Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections and suggest that achieving herd immunity through natural infection may be difficult. Funding: This work was supported by NIH U19 AI110495 to SP, NIH R01 AI146779 to AGS, NIH R01AI137057 and DP2DA042422 to DL, BMH was supported by NIGMS T32 GM007753, TMC was supported by T32 AI007245. Funding for these studies from the Massachusetts Consortium of Pathogen Readiness, the Mark and Lisa Schwartz Foundation and Enid Schwartz is also acknowledged. Conflict of Interest: None. Ethical Approval: This study was performed with the approval of the Institutional Review Boards at the Massachusetts General Hospital and the Brigham and Women's Hospital.