Immune Repertoire Sequencing Reveals an Abnormal Adaptive Immune System in COVID-19 Survivors.

Accumulating evidence suggests that SARS-CoV-2 impairs the adaptive immune system during acute infection. Still, it remains largely unclear whether the frequency and functions of T and B cells return to normal after the recovery of COVID-19. Here, we analyzed immune repertoires and SARS-CoV-2-specific neutralization antibodies in a prospective cohort of 40 COVID-19 survivors with a six-month follow-up after hospital discharge. Immune repertoire sequencing revealed abnormal T- and B-cell expression and function with large TCR/BCR clones, decreased diversity, abnormal class switch recombination and somatic hypermutation. A decreased number of B cells but an increased proportion of CD19+ CD138+ B cells were found in COVID-19 survivors. The proportion of CD4+ T cells, especially circulating follicular helper T (cTfh) cells, was increased, whereas the frequency of CD3+ CD4- T cells was decreased. SARS-CoV-2-specific neutralization IgG and IgM antibodies were identified in all survivors, especially those recorded with severe COVID-19 who showed a higher inhibition rate of neutralization antibodies. All severe cases complained of more than one COVID-19 sequelae after 6 months of recovery. Overall, our findings indicate that SARS-CoV-2-specific antibodies remain detectable even after 6 months of recovery. Because of their abnormal adaptive immune system with a low number of CD3+ CD4- T cells and high susceptibility to infections, COVID-19 patients might need more time and medical care to fully recover from immune abnormalities and tissue damage. This article is protected by copyright. All rights reserved.

Association between workplace and mental health and its mechanisms during COVID-19 pandemic: A cross-sectional, population-based, multi-country study.

BACKGROUND: The COVID-19 pandemic worsens populations' mental health. However, little is known about the COVID-19-related mental health among remote workers. METHODS: We retrieved data from survey of Health, Ageing and Retirement in Europe, covering 27 countries. Eligible people were those employed. The main outcome is the mental disorder, covering four aspects: depression, anxiety, sleep disorder, and loneliness. Country-specific weighted mixed models were fitted to estimate the association of workplaces with mental health, controlled for age, gender, education level, living alone, making ends meets, working hours, closing to suspected or confirmed COVID-19 cases, received anti-virus protection, social contact, disability, and chronic disease. Moderate analyses were conducted to explore possible mechanisms. RESULTS: 11,197 participants were included, among them 29.3% suffered at least one worse mental disorder. After controlling for covariates, compared with those who worked at the usual workplace, those who worked at home only or part of the time did not associate with worse mental disorders (p-value ≥0.1395), and those who worked at neither the usual workplace nor home had a 55% higher likelihood of suffering from worse mental disorders (OR = 1.55, 95%CI 1.03-2.36). The mediation analyses identified three indirect pathways by which workplaces influence mental health, including making ends meets, social contact, and receiving anti-virus protection. Detailed results on subtypes of mental disorders were also provided. LIMITATIONS: All assessments were self-reported, resulting in a risk of method bias. CONCLUSIONS: During the COVID-19 pandemic, working at other places, neither at the usual workplace nor home, worsened mental health. Evidence provided in this study will contribute to more nuanced and practical public health policy strategy making.

Association between inflammatory cytokines and anti-SARS-CoV-2 antibodies in hospitalized patients with COVID-19.

BACKGROUND: COVID-19 patients may experience "cytokine storm" when human immune system produces excessive cytokines/chemokines. However, it remains unclear whether early responses of inflammatory cytokines would lead to high or low titers of anti-SARS-CoV-2 antibodies. METHODS: This retrospective study enrolled a cohort of 272 hospitalized patients with laboratory-confirmed SARS-CoV-2. Laboratory assessments of serum cytokines (IL-2R, IL-6, IL-8, IL-10, TNF-α), anti-SARS-CoV-2 IgG/IgM antibodies, and peripheral blood biomarkers were conducted during hospitalization. RESULTS: At hospital admission, 36.4% patients were severely ill, 51.5% patients were ≥ 65 years, and 60.3% patients had comorbidities. Higher levels of IL-2R and IL-6 were observed in older patients (≥65 years). Significant differences of IL-2R (week 2 to week ≥5 from symptom onset), IL-6 (week 1 to week ≥5), IL-8 (week 2 to week ≥5), and IL-10 (week 1 to week 3) were observed between moderately-ill and severely ill patients. Anti-SARS-CoV-2 IgG titers were significantly higher in severely ill patients than in moderately ill patients, but such difference was not observed for IgM. High titers of early-stage IL-6, IL-8, and TNF-α (≤2 weeks after symptom onset) were positively correlated with high titers of late-stage IgG (≥5 weeks after symptom onset). Deaths were mostly observed in severely ill older patients (45.9%). Survival analyses revealed risk factors of patient age, baseline COVID-19 severity, and baseline IL-6 that affected survival time, especially in severely ill older patients. CONCLUSION: Early responses of elevated cytokines such as IL-6 reflect the active immune responses, leading to high titers of IgG antibodies against COVID-19.

The pooled prevalence of the mental problems of Chinese medical staff during the COVID-19 outbreak: A meta-analysis.

BACKGROUND: The COVID-19 pandemic has had a great impact on the mental health of the medical staff in China, especially those on the first-line (frontline) of the pandemic. But the profile of the mental problem of nationwide Chinese medical staff is still unclear, especially about the sleep problems. METHODS: There are five databases (PubMed, Embase, CNKI, Wanfang Database and Web of Science) searched to identify the published studies on the mental health of the medical staff in China during the COVID-19 outbreak. The pooled prevalence of mental problems of Chinese medical staff during the pandemic were calculated, especially for the first-line medical staff. Subgroup analysis and meta-regression analysis were performed to identify the potential impact factors. RESULTS: A total of 71 articles including 98,533 participants are included in this meta-analysis. The results showed that the pooled prevalence of the mental problems was as follows: anxiety problem 27%, depression problem 29%, sleep problem 40%. Subgroup analysis showed that there were significant differences in the prevalence of anxiety and depression problems between first-line and non-first-line medical staff (p < 0.01). Sex had a significant impact on the sleep of first-line medical staff (p < 0.01). LIMITATIONS: There may be heterogeneity among the included studies. The analysis of potential influencing factors remains limited. CONCLUSIONS: The prevalence of adverse mental problems among medical staff is high during the COVID-19 outbreak. We need to pay special attention to the mental health of first-line medical staff, especially the sleep problems of female first-line workers.

Oral Chinese Herbal Medicine on Immune Responses During Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

BACKGROUND: Cellular immune responses including lymphocyte functions and immune effector cells are critical for the control of coronavirus infection. Chinese herbal medicine (CHM) potentially has a therapeutic effect for treatment of coronavirus disease 2019 (COVID-19). Nevertheless, there are limited clinical practice suggestions on immunogenicity of the CHM against SARS-CoV-2. To assess the effect of oral CHM on immunogenicity and whether oral CHM improves the clinical parameters through the immunity profile during COVID-19, we performed the present study. METHODS: For this systematic review and meta-analysis, 11 databases were searched for relevant studies assessing oral CHM for COVID-19 on November 20, 2020 (updated March 9, 2021). Primary outcomes mainly included immunity profiles. Secondary outcomes included all-cause mortality; the remission time of fever, cough, chest tightness, and fatigue. The random effect was used to estimate the heterogeneity of the studies. Summary relative risks, weight mean difference and standardized mean difference were measured with 95% confidence intervals. Modified Jadad scale and Newcastle-Ottawa Scale were used to assess the risk of bias of randomized controlled trials (RCTs) and observational studies, respectively. The certainty of evidence was evaluated using the GRADE approach. RESULTS: We analyzed findings from 3,145 patients in 30 eligible studies. Compared with routine treatment, oral CHM, as an adjuvant medicine, improved lymphocyte counts, CD4+, and CD4+/CD8+ ratio with low quality of evidence; improved CD3+ with moderate quality of evidence; and reduced TNF-α with low certainty of evidence. Besides, oral CHM, as an adjuvant medicine reduced the time to clinical symptoms remission with a lower risk of all-cause mortality, compared with routine treatment alone. CONCLUSION: CHM may be recommended as an adjuvant immunotherapy for disease modification and symptom relief in COVID-19 treatment. However, large RCTs objectively assessing the efficacy of CHM on immune responses in COVID-19 are needed to confirm our findings.

The Prevalence of Mental Problems for Chinese Children and Adolescents During COVID-19 in China: A Systematic Review and Meta-Analysis.

The outbreak of coronavirus disease 2019 (COVID-19) has caused mental problems among the public and medical staff in China, especially for children and adolescents, a vulnerable group that might present with more mental problems. It seems that there is a rapid growth in the mental problems (such as depression or anxiety) of Chinese children and adolescents during the outbreak of COVID-19. Although several studies reported the prevalence of depression or anxiety problems for children and adolescents, the results are different across different age groups and sex groups. Moreover, the sample size of these studies was small. In the present study, we aim to perform a meta-analysis to identify the confirmed prevalence of depression and anxiety problems for Chinese children and adolescents during home confinement. Five databases were searched including PubMed, Web of Science, PsycINFO, Google Scholar, and the China National Knowledge Infrastructure (CNKI), and both inclusion and exclusion criteria were developed. Finally, a total of 12 studies were included in this meta-analysis. The protocol of this systematic review was registered with INPLASY (protocol ID: INPLASY202150032). It found that the pooled prevalence of mental problems was 28% (95% confidence interval, CI: 0.22-0.34), and the depression and anxiety problem for children and adolescents in China was 22% (95% CI: 0.16-0.30) and 25% (95% CI: 0.20-0.32) based on a random effect model, separately. Subgroup analysis was used to identify that there are no differences between different age groups (primary and middle school vs. high school) (p = 0.26). Meta-regression analysis was performed and the results showed that the moderator of boy percentage was a significant factor (p = 0.04). It indicated that there was an increasing number of children and adolescents with mental problems during the home confinement. It suggested that we should pay more attention to this vulnerable population during a public health crisis in the future, especially for the girls groups, and more detailed implements for mental health management were needed and should be prepared. Systematic Review: The protocol of this systematic review was registered with INPLASY. The protocol ID was INPLASY202150032.

Coordinated Management of COVID-19 Response: Lessons From Whole-of-Society and Whole-of-Health Strategies in Wuhan, China.

Background: The outbreak of novel coronavirus disease 2019 (COVID-19) has been challenging globally following the scarcity of medical resources after a surge in demand. As the pandemic continues, the question remains on how to accomplish more with the existing resources and improve the efficiency of existing health care delivery systems worldwide. In this study, we reviewed the experience from Wuhan - the first city to experience a COVID-19 outbreak - that has presently shown evidence for efficient and effective local control of the epidemic. Material and Methods: We performed a retrospective qualitative study based on the document analysis of COVID-19-related materials and interviews with first-line people in Wuhan. Results: We extracted two themes (the evolution of Wuhan's prevention and control strategies on COVID-19 and corresponding effectiveness) and four sub-themes (routine prevention and control period, exploration period of targeted prevention and control strategies, mature period of prevention and control strategies, and recovery period). How Wuhan combatted COVID-19 through multi-tiered and multi-sectoral collaboration, overcoming its fragmented, hospital-centered, and treatment-dominated healthcare system, was illustrated and summarized. Conclusion: Four lessons for COVID-19 prevention and control were summarized: (a) Engage the communities and primary care not only in supporting but also in screening and controlling, and retain community and primary care as among the first line of COVID-19 defense; (b) Extend and stratify the existing health care delivery system; (c) Integrate person-centered integrated care into the whole coordination; and (d) Delink the revenue relationship between doctors and patients and safeguard the free-will of physicians when treating patients.

Traditional Chinese Medicine (TCM) in the treatment of COVID-19 and other viral infections: Efficacies and mechanisms.

COVID-19 has remained an uncontained, worldwide pandemic. While battling for the disease in China, six Traditional Chinese Medicine (TCM) recipes have been shown to be remarkably effective for treating patients with COVID-19. The present review discusses principles of TCM in curing infectious disease, and clinical evidence and mechanisms of the 6 most effective TCM recipes used in treating COVID-19 in 92% of all of the confirmed cases in China. Applications of TCM and specific recipes in the treatment of other viral infections, such as those caused by SARS-CoV, MERS-CoV, hepatitis B virus, hepatitis C virus, influenza A virus (including H1N1 and H7N9), influenza B, dengue virus as well as Ebola virus, are also discussed. Among the 6 TCM recipes, Jinhua Qinggan (JHQG) granules and Lianhua Qingwen (LHQW) capsules are recommended during medical observation; Lung Cleansing and Detoxifying Decoction (LCDD) is recommended for the treatment of both severe and non-severe patients; Xuanfeibaidu (XFBD) granules are recommended for treating moderate cases; while Huashibaidu (HSBD) and Xuebijing (XBJ) have been used in managing severe cases effectively. The common components and the active ingredients of the six TCM recipes have been summarized to reveal most promising drug candidates. The potential molecular mechanisms of the active ingredients in the six TCM recipes that target ACE2, 3CLpro and IL-6, revealed by molecular biological studies and/or network pharmacology prediction/molecular docking analysis/visualization analysis, are fully discussed. Therefore, further investigation of these TCM recipes may be of high translational value in enabling novel targeted therapies for COVID-19, potentially via purification and characterization of the active ingredients in the effective TCM recipes.

The comparative analysis of epidemiological characteristics between COVID-19 and SARS

Both COVID-19 and SARS are two serious infectious diseases caused by coronaviruses. The cause of both is still unknown and there are currently no effective treatments. Therefore, it is important to understand the epidemiological and pathological characteristics of COVID-19 and SARS for its prevention and treatment. This article reviewed the literature, combined with the latest research status at home and abroad, to explore the two diseases of COVID-19 and SARS from the etiology, spatial, time and population distributions and pathology. The results show that the two infectious diseases have many of the same clinical characteristics. There are some differences in the disease process, severity, and imaging. COVID-19 have stronger infectivity than SARS, but its mortality is lower than SARS, and the pathological changes of the two are also different. The article also compared the experiences and lessons learned during the SARS epidemic, sorted out the loopholes and deficiencies in disease prevention and control during the COVID-19 epidemic, and made recommendations for the problems at the current stage, so as to provides the certain scientific basis for preventing and treating the two diseases, and their pathogenesis research.

Heat Conduction and Antibacterial Hexagonal Boron Nitride/Polypropylene Nanocomposite Fibrous Membranes for Face Masks with Long-Time Wearing Performance.

Wearing surgical masks is one of the best protective measures to protect humans from viral invasion during the 2019 coronavirus (COVID-19) outbreak. However, wearing surgical masks for extended periods will cause uncomfortable sweltering sense to users and are easy to breed bacteria. Here, we reported a novel fibrous membrane with outstanding comfortability and antibacterial activity prepared by PP ultrafine fiber nonwovens and antibacterial functionalized h-BN nanoparticles (QAC/h-BN). The thermal conductivity of commercial PP nonwovens was only 0.13 W m-1 K-1, but that of the QAC/h-BN/PP nanocomposite fibrous membranes can reach 0.88 W m-1 K-1, an enhancement of 706.5% than commercial PP nonwovens. The surface temperature of commercial PP surgical masks was 31.8 °C when the wearing time was 60 min. In contrast, QAC/h-BN/PP surgical masks can reach 33.6 °C at the same tested time, exhibiting stronger heat dissipation than commercial PP surgical masks. Besides, the antibacterial rates of QAC/h-BN/PP nanocomposite fibrous membranes were 99.3% for E. coli and 96.1% for S. aureus, and their antibacterial mechanism was based on "contact killing" without the release of unfavorable biocides. We think that the QAC/h-BN/PP nanocomposite fibrous membranes could provide better protection to people.