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Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralising public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidences to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.
Subject(s)
COVID-19ABSTRACT
Background: Little research has been done on the mental health of western Chinese university students during the Coronavirus disease (COVID-19) pandemic. This work aims to fill the gap by gaining insight into the positive psychological capital and its influencing factors among university students in western China during the COVID-19 pandemic. Methods: An online cross-sectional study was conducted in college students from a medical school. Participants were surveyed anonymously using a general information questionnaire and the Positive Psychological Capital Scale. The key factors and models affecting the psychological capital were obtained by using the gradual regression method. If P < 0.05, the difference would be considered statistically significant. Results: The total score of positive psychological capital among university students in western China was 118.51±16.91, Taking the psychological capital as the dependent variable, gender and grade as the independent variables, the key factors and models affecting the psychological capital were obtained by using the gradual regression method.The results showed that the P-value of each influencing factor was <0.05. The key influencing factors of psychological capital of college students were gender and and place of residence. Conclusion: The overall positive psychological capital of college students in western China was in good condition during the pandemic, with large room for improvement though. Gender and Residence were independent influencing factors on the positive psychological capital.
Subject(s)
COVID-19ABSTRACT
Background Pre-hospitalisation, hospitalisation and post-hospitalisation factors may significantly affect depression, anxiety and post-traumatic growth (PTG) among COVID-19 survivors. Objective Our study investigated depression, anxiety and PTG and their correlates among COVID-19 survivors. Method A cross-sectional telephone survey recruited 199 COVID-19 patients (Mean age = 42.7;53.3% females) at six-month follow-up after hospital discharge in five Chinese cities (i.e. Wuhan, Shenzhen, Zhuhai, Dongguan and Nanning). Their demographic information, clinical records and experiences during (e.g. severity of covid-19 symptoms, treatment and exposure to other patients’ suffering) and after hospitalisation (e.g. perceived impact of covid-19, somatic symptoms after hospitalisation), and psychosocial factors (e.g. perceived discrimination, self-stigma, affiliate stigma, resilience and social support) were investigated. Depressive and anxiety symptoms were measured by the Patient Health Questionnaire (PHQ-9) and the Generalised anxiety disorder (GAD-7) scale, respectively. PTG was examined by the Post-traumatic Growth Inventory (PTGI) instrument. Results The proportion of depressive symptoms <5, ≥5 and <10, ≥10 were 76.9%, 12.0% and 11.1%, respectively. The proportion of anxiety symptoms <5, ≥5 and <10, ≥10 were 77.4%, 15.1% and 7.5%, respectively. Multivariate logistic regression showed that receiving mental health care services during hospitalisation, somatic symptoms after discharge, perceived affiliate stigma and perceived impact of being infected with COVID-19 were significantly and positively associated with probable depression. Significant correlates of probable anxiety also included permanent residents of the city, somatic symptoms after discharge, perceived impact of being infected with COVID-19 and self-stigma. Social support, self-stigma and receiving mental health care services during hospitalisation were positively associated with PTG. Conclusions: The results suggest that post-hospitalisation and psychosocial factors had relatively stronger associations with depression, anxiety and PTG than pre-hospitalisation and hospitalisation factors. Promoting social support and social inclusion may be useful strategies to improve the mental health of COVID-19 survivors. HIGHLIGHTS • Post-hospitalisation and psychosocial factors had relatively stronger associations with depression, anxiety and PTG than pre-hospitalisation and hospitalisation factors, promoting social support and social inclusion may be useful strategies to improve mental health of COVID-19 survivors.
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Population antibody response is believed to be important in selection of new variant viruses. We identified that SARS-CoV-2 infections elicit a population immune response mediated by a lineage of VH1-69 germline antibodies. The representative antibody R1-32 targets a novel semi-cryptic epitope defining a new class of RBD targeting antibodies. Binding to this non-ACE2 competing epitope leading to spike destruction impairing virus entry. Based on epitope location, neutralization mechanism and analysis of antibody binding to spike variants we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of this population antibody response. These substitutions, including L452R found in the Delta variant, disrupt interaction mediated by the VH1-69 specific hydrophobic HCDR2 to impair antibody-antigen association allowing variants to escape. Lacking 452/490 substitutions, the Omicron variant is sensitive to this class of antibodies. Our results provide new insights into SARS-CoV-2 variant genesis and immune evasion.
Subject(s)
COVID-19ABSTRACT
Background As a highly infectious disease with human-to-human transmission characteristics, COVID-19 has caused panic in the general public. Those who have recovered from COVID-19 may experience discrimination and internalized stigma. They may be more likely to worry about social interaction and develop social anxiety. Objectives This study investigated the associations among hospitalization factors, social/interpersonal factors, personal factors, and social anxiety to reveal the mechanism of social anxiety in COVID-19 survivors. Methods A cross-sectional, multicenter telephone survey was conducted from July to September 2020 in five Chinese cities (i.e. Wuhan, Nanning, Shenzhen, Zhuhai, and Dongguan);adult COVID-19 survivors were recruited 6 months after they were discharged from the hospital. Linear regressions and path analysis based on the minority stress model were conducted to test the relationships among hospitalization, social/interpersonal factors, personal factors, and social anxiety. Results The response rate was 74.5% (N = 199, 55.3% females). Linear regression analyses showed that various hospitalization, social/interpersonal, and personal factors were statistically significantly associated with social anxiety. Path analysis showed that the proposed model fit the data well (χ2(df) = 3.196(3), p = .362, CFI = .999, NNFI = .996, RMSEA = .018). Internalized stigma fully mediated the association between perceived discrimination/social support and social anxiety, while it partially mediated the association between perceived affiliate stigma and social anxiety. Conclusions The results suggest that social/interpersonal and personal factors have a stronger association with social anxiety than hospitalization factors and highlight the importance of internalized stigma in understanding the mechanisms of these relationships. Clinical psychologists can refer to these modifiable psychosocial factors to develop efficient interventions for mental health promotion. HIGHLIGHTS Internalized stigma fully mediated the effects of perceived discrimination and social support on social anxiety and partially mediated the effect of perceived affiliate stigma on social anxiety.
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Objective: To explore the efficacy of anticoagulation in improving outcomes and safety of Coronavirus disease 2019 (COVID-19) patients in subgroups identified by clinical-based stratification and unsupervised machine learning. Methods: This single-center retrospective cohort study unselectively reviewed 2,272 patients with COVID-19 admitted to the Tongji Hospital between Jan 25 and Mar 23, 2020. The association between AC treatment and outcomes was investigated in the propensity score (PS) matched cohort and the full cohort by inverse probability of treatment weighting (IPTW) analysis. Subgroup analysis, identified by clinical-based stratification or unsupervised machine learning, was used to identify sub-phenotypes with meaningful clinical features and the target patients benefiting most from AC. Results: AC treatment was associated with lower in-hospital death risk either in the PS matched cohort or by IPTW analysis in the full cohort. A higher incidence of clinically relevant non-major bleeding (CRNMB) was observed in the AC group, but not major bleeding. Clinical subgroup analysis showed that, at admission, severe cases of COVID-19 clinical classification, mild acute respiratory distress syndrome (ARDS) cases, and patients with a D-dimer level ≥0.5 μg/mL, may benefit from AC. During the hospital stay, critical cases and severe ARDS cases may benefit from AC. Unsupervised machine learning analysis established a four-class clustering model. Clusters 1 and 2 were non-critical cases and might not benefit from AC, while clusters 3 and 4 were critical patients. Patients in cluster 3 might benefit from AC with no increase in bleeding events. While patients in cluster 4, who were characterized by multiple organ dysfunction (neurologic, circulation, coagulation, kidney and liver dysfunction) and elevated inflammation biomarkers, did not benefit from AC. Conclusions: AC treatment was associated with lower in-hospital death risk, especially in critically ill COVID-19 patients. Unsupervised learning analysis revealed that the most critically ill patients with multiple organ dysfunction and excessive inflammation might not benefit from AC. More attention should be paid to bleeding events (especially CRNMB) when using AC.
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Background: Corticosteroids were recommended by guidelines in severe or critical COVID -19 patients likely to have acute respiratory distress syndrome. In the treatment strategies of COVID -19 in China, corticosteroids were generally combined with some traditional Chinese medicine, especially Lianhua Qingwen Capsule (LHQW). We aimed to investigate the correlation between dexamethasone with or without LHQW and the nucleic acid negative conversion in severe patients with COVID-19. Methods: : The clinical course and nucleic acid negative conversion time of 452 consecutive symptomatic COVID-19 patients admitted to the west campus of Union Hospital in Wuhan from January 31, 2020, to March 13, 2020, were evaluated retrospectively. Results: : The duration of virus RNA from positive to negative in the participants was 28 days (interquartile range 21-34 days). Of the 452 patients, 105 (23.23%) subjects received dexamethasone, and 347 (76.77%) did not. Among patients receiving LHQW treatment, the nucleic acid negative conversion time in the dexamethasone group was shorter than that in the no dexamethasone group (𝛽, -4.77; 95% CI, -9.41, -0.12). Although among those who were receiving no LHQW treatment, the effect on shortening nucleic acid negative conversion time of dexamethasone was not observed (𝛽, 5.37; 95% CI,-4.88, 15.62; p interaction = 0.038). Additional multivariable propensity-score analyses yielded consistent results with the unmatched participants (β, -8.61; 95% CI, -16.73, -0.50). Conclusions: ： In patients hospitalized with COVID-19, the use of dexamethasone resulted in shortening nucleic acid negative conversion time among those who were receiving LHQW, suggesting that LHQW synergic with dexamethasone accelerated the SARS-CoV-2 clearance in severe patients. Trial registration： ECUH 2020-0212, a retrospective study.
Subject(s)
COVID-19 , Conversion Disorder , Respiratory Distress SyndromeABSTRACT
As a classic parameter from the binomial distribution, the binomial proportion has been well studied in the literature owing to its wide range of applications. In contrast, the reciprocal of the binomial proportion, also known as the inverse proportion, is often overlooked, even though it also plays an important role in various fields including clinical studies and random sampling. The maximum likelihood estimator of the inverse proportion suffers from the zero-event problem, and to overcome it, alternative methods have been developed in the literature. Nevertheless, there is little work addressing the optimality of the existing estimators, as well as their practical performance comparison. Inspired by this, we propose to further advance the literature by developing an optimal estimator for the inverse proportion in a family of shrinkage estimators. We further derive the explicit and approximate formulas for the optimal shrinkage parameter under different settings. Simulation studies show that the performance of our new estimator performs better than, or as well as, the existing competitors in most practical settings. Finally, to illustrate the usefulness of our new method, we also revisit a recent meta-analysis on COVID-19 data for assessing the relative risks of physical distancing on the infection of coronavirus, in which six out of seven studies encounter the zero-event problem.
Subject(s)
COVID-19ABSTRACT
Object: A recently developing pneumonia called COVID-19 which caused by SARS-CoV-2 has quickly spread across the world. Lymphopenia and a proinflammatory cytokine storm frequently happened in severe COVID-19 patients. But no specific immunomodulate therapy on COVID-19 had been reported. In this retrospect case control study, we observed the potential therapeutic effect of recombinant human interleukin-2 (rIL-2) on severe COVID-19 patients in a hospital in Wuhan, China. Methods: Fifty nine severe cases with COVID-19 admitted in hospital from January 29, 2020 to February 29, 2020 were included in this study. Twenty patients received a one-week to 10 days subcutaneous injection of the recombinant human interleulin-2 1 million IU per day other than regular treatment were classified as rIL-2 group. Twenty from thirty nine patients with regular treatment without intervention of rIL-2 were matched as the control group. Clinical characteristic such as age, gender, symptoms, signs, laboratory data and comorbidities were paired in these two groups. Changes of lymphocytes counts, IL-6 and C- reactive protein (CRP) before and after rIL-2 treatment and differences between rIL-2 group and non-rIL-2 group were analyzed.Results: There were a clearly visible increasing in lymphocyte counts and a decreasing in CRP level in non rIL-2 group and rIL-2 group. The difference of the change of lymphocyte counts were significant in rIL-2 group and non-rIL-2 group (p<0.01). Though CRP decreased more in rIL-2 group, it did not show a significant difference between the two groups (p>0.05).Conclusion: RIL-2 might be a prospective adjuvant therapy for severe COVID-19 patients by increasing lymphocytes number.
Subject(s)
Pneumonia , COVID-19 , LymphopeniaABSTRACT
BACKGROUND and OBJECTIVE The rhythms of life, work and entertainment behaviours are considered as the external behavioural manifestations of biological rhythm.To evaluate the distinctive disrupted rhythms of behaviours and their associations with mental health problems in people with different backgrounds under the stress of COVID-19 epidemic.SUBJECTS AND METHODS A cross-sectional study was conducted from 10-17 March 2020 under the stress of COVID-19 epidemic.A structured e-questionnaire containing general information,rhythm scale(subscale1 for life-work rhythms and subscale2 for entertainment rhythm) and Zung's self-rating depression and anxiety scale(SDS and SAS) were filled and the data were analysed.RESULTS Overall 5854 participants were included.Significant differences were found in rhythm, SDS and SAS scores among people with different backgrounds (all P<0.05). Subjects with female gender and poor health status were mostly suffered from disrupted rhythms of life- work-entertainment behaviours, combined with depression and anxiety. Nurses and subjects being divorced or with chronic disease with psychosomatic diseases were mostly suffered from disrupted rhythms of life-work behaviours, combined with depression and anxiety. Subjects with aged 26-30 years, or annual income of 50,000-100,000CY were mostly suffered from disrupted rhythms of life-work combined with depression. Subjects with income over 300,000CY were mostly suffered from disrupted rhythm of entertainment combined with anxiety.The prevalence rates of depression and anxiety in people with the high-scores of rhythm disruption increased by 34.50% and 47.16%, respectively, compared with those with low-scores.People with the high-scores of rhythm disruption had higher SDS and SAS scores, compared to those with low scores (all P<0.001). The independent related factors of disrupted rhythms included gender,age,marital status, health status,annual income and chronic diseases with psychosomatic diseases using logistic regression.The disrupted rhythms of life and work behaviours was positively correlated with both SDS and SAS scores.CONCLUSIONS The disrupted rhythms of life, work and entertainment behaviours were closely associated with mental health problems.The disrupted rhythms of behaviours are frequent and fluxible,triggering more severe mental health problems under the stress of COVID-19 epidemic.The physicians should be aware of their importance when evaluating their interviewees or patients’ mental health and achieving maximization of therapeutic efficacy by integrating the intervention of circadian rhythm and its behaviour.