Times Constraints, Lack of Confidence in Treatment, Stigma, and Confidentiality Concerns: Barriers to Care Among First-year Internal Medicine Residents During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has presented unprecedented challenges for frontline health care workers. First-year medical residents have been at high risk of psychological distress given these challenges as well as those related to transitioning to a provider role. Virtual peer discussion groups were organized for first-year residents (N=47) at a large, American academic medical center to process the emotional impacts from the pandemic and provide support. Residents completed an anonymous survey before the initiation of the discussion groups to assess their level of psychological distress, perceived sources of stress, impact of the pandemic on their mental health, and attitudes toward seeking mental health services. Results from the survey identified time constraints as the greatest barrier to accessing mental health care, followed by lack of confidence in treatment, stigma, and concerns about confidentiality. We discuss potential ways to address some of these barriers to improve access and acceptability of mental health support for this specific population during a pandemic.

Human Early Syncytiotrophoblasts Are Highly Susceptible to SARS-CoV-2 Infection (preprint)

The ongoing and devastating pandemic of coronavirus disease 2019 (COVID-19) has led to a global public health crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can potentially pose a serious risk to maternal and neonatal health. Cases of abnormal pregnancy and vertical transmission of SARS-CoV-2 from mother to foetus have been reported but no firm conclusions are drawn. Trophoblasts are the major constituents of the placenta to protect and nourish the developing foetus. However, direct in vivo investigation of trophoblast susceptibility to SARS-CoV-2 and of COVID-19 and pregnancy is challenging. Here we report that human early syncytiotrophoblasts (eSTBs) are highly susceptible to SARS-CoV-2 infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. From human expanded potential stem cells (hEPSCs), we derived bona fide trophoblast stem cells (TSCs) that resembled those originated from the blastocyst and the placenta in generating functional syncytiotrophoblasts (STBs) and extravillus trophoblasts (EVTs) and in low expression of HLA-A/B and amniotic epithelial (AME) cell signature. The EPSC-TSCs and their derivative trophoblasts including trophoblast organoids could be infected by SARS-CoV-2. Remarkably, eSTBs were highly susceptible to SARS-CoV-2. They expressed high levels of ACE2 and produced substantially higher amounts of virion than Vero E6 cells which are widely used in SARS-CoV-2 research and vaccine production. These findings provide experimental evidence for the clinical observations that opportunistic SARS-CoV-2 infection during pregnancy can occur. At low concentrations, two well characterized antivirals, remdesivir and GC376, effectively eliminated infection of eSTBs by SARS-CoV-2 and middle east respiratory syndrome-related coronavirus (MERS-CoV), and rescued their developmental arrest caused by the virus infection. Several human cell lines have been used in coronavirus research. However, they suffer from genetic and/or innate immune defects and have some of the long-standing technical challenges such as cell transfection and genetic manipulation. In contrast, hEPSCs are normal human stem cells that are robust in culture, genetically stable and permit efficient gene-editing. They can produce and supply large amounts of physiologically relevant normal and genome-edited human cells such as eSTBs for isolation, propagation and production of coronaviruses for basic research, antiviral drug tests and safety evaluation.

Genetic predisposition in patients with severe COVID-19.

The coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. COVID-19 has a variety of clinical manifestations, ranging from asymptomatic infection or mild symptoms to severe symptoms. Severe COVID-19 patients experience cytokine storm, resulting in multi-organ failure and even death. Male gender, old age, and pre-existing comorbidities (such as hypertension and diabetes ) are risk factors for COVID-19 severity. Recently, a series of studies suggested that genetic defects might also be related to disease severity and the cytokine storm occurence. Genetic variants in key viral immune genes, such as TLR7 and UNC13D, have been identified in severe COVID-19 patients from previous reports. In this review, we summarize the mechanisms underlying immune responses against SARS-CoV-2 and genetic variants that associated with the severity of COVID-19. The study of genetic basis of COVID-19 will be of great benefit for early disease detection and intervention.

Exploring the self-reported physical fitness and self-rated health, mental health disorders, and body satisfaction among Chinese adolescents: A cross-sectional study

Background Physical activity (PA) and Physical fitness (PF) have received tremendous attention in the field of physical and mental health. However, limited attention has been given to the associations of self-reported physical fitness with some health-related outcomes. Given the COVID-19 pandemic is still active in many Chinese regions, assessing health-related physical fitness (HRPF) in adolescents using field-based assessment (such as a shuttle run for cardiorespiratory fitness) is unrealistic, therefore, this study was conducted via a self-reported questionnaire. Purpose The present cross-sectional study was aimed at delving into the relationship between self-reported physical fitness with self-rated health, depression, anxiety, and body satisfaction in adolescents. Three thousand eight hundred and seven study participants from 12 public schools in South-eastern China were recruited and 2,407 of them provided valid data on variables that this study needed for analysis. Materials and methods Study participants were asked to self-report their sociodemographic factors (e.g., sex, grade, age), independence, and outcomes. Generalized linear models were used to explore the associations of self-reported physical fitness (comprising general physical fitness, cardiorespiratory fitness, muscular strength, speed and agility, and flexibility) with depression, anxiety, and body satisfaction. A total of 2,407 children and adolescents with a mean age of 13.82 (±2.1) years were included in the final study analysis. Results Higher self-reported levels of general physical fitness and cardiorespiratory fitness were associated with better self-rated health, and body satisfaction but with lower risks of depression and anxiety. Conclusion The current study offered evidence on the roles of self-reported physical fitness and health-related outcomes. To facilitate health in children and adolescents, advocating fitness education, and promotion could be a feasible approach.

Nursing students' perceptions and experiences of e-internships during the COVID-19 pandemic: A phenomenological study.

BACKGROUND: Clinical internship is an indispensable stage for nursing students to graduate successfully and become qualified nurses. However, COVID-19, a novel coronavirus disease with strong human-to-human transmission, hit China in late 2019 and forced the Chinese government to suspend classes and clinical internships. To cope with this situation, e-internship, which facilitate varied interactions without the need for direct contact, is used as an alternative strategy to help nursing students continue their internships. OBJECTIVES: To describe the perceptions and experiences of undergraduate nursing students in e-internships during the COVID-19 pandemic. METHODS: A descriptive phenomenological design was adopted. Seventeen undergraduate nursing students in a major teaching hospital in Changsha, China, were recruited into the study. Data were collected through semi-structured, in-depth, face-to-face interviews. The interviews were transcribed verbatim and analyzed using Colaizzi's approach. RESULTS: Four themes were captured from the data analysis: perceived images of clinical nurses in e-internships, psychological experience, perceived benefits of e-internships, and perceived limitations of e-internships. CONCLUSIONS: Our findings suggest that e-internship is a suitable method for training and cultivating undergraduate nursing students during a crisis. To enhance the efficiency of e-internships, guidelines and standards should be formulated, and effective measures should be taken to build better e-internship platforms. In the future, we suggest combine on-site internships with e-internships, thereby fully using their advantages, and improve the efficiency of internships as much as possible.

Postpartum Depressive Symptoms, Perceived Social Support and Their Associations of Women Under Different COVID-19 Pandemic Severities: Analysis of A Chinese Nationwide Multicenter Study (preprint)

Background The evidence for associations of mental health with COVID-19 pandemic severity is scarce in postpartum women. We aimed to investigate the associations of postpartum depressive symptoms (PDS), perceived social support (PSS) with COVID-19 pandemic severity, respectively, and to explore the associations between PSS and PDS under different pandemic severities.Methods This was a nationwide multicenter study. An online survey was launched from January 23 through February 29, 2020 in mainland China. Participants’ PDS and PSS were measured by Edinburgh Postnatal Depression Scale and Multidimensional Scale of Perceived Social Support, respectively.Results The final sample consisted of 452 participants from 19 hospitals in 19 provinces/municipalities of mainland China. After covariate adjustment, women in Hubei Province experienced higher PDS levels than those in moderate (β coefficient = − 3.883, p = 0.001) and high (β coefficient = − 3.760, p = 0.005) pandemic severity; women in moderate pandemic severity reported higher PSS levels not only than those in high (β coefficient = − 4.947, p = 0.008) pandemic severity and Hubei Province (β coefficient = − 6.480, p = 0.049), but also than low (β coefficient = − 7.428, p = 0.005) pandemic severity. Also, no significant associations were found between PSS and pandemic severity for women with moderate-to-severe PDS (p > 0.05). There were significantly negative associations between PSS and PDS for women under low (OR = 0.837, p = 0.039), moderate (OR = 0.919, p < 0.001), and high (OR = 0.951, p = 0.012) pandemic severity, and no significant association between PSS and PDS was observed in Hubei Province after covariate adjustment (p > 0.05).Conclusion Women in Hubei Province experienced higher PDS levels than those in moderate and high pandemic severity. Women in moderate pandemic severity reported higher PSS levels not only than those in high pandemic severity and Hubei Province, but also than low pandemic severity, and no associations were found between PSS and pandemic severity for women with moderate-to-severe PDS. There were negative associations between PSS and PDS for women in low, moderate and high pandemic severity, but no association between PSS and PDS of women in Hubei Province.

Genetic diversity of porcine deltacoronavirus in Guangxi Province from 2017 to 2019

To understand the genetic diversity of porcine deltacoronavirus(PDCo V) in Guangxi Province, clinical diarrhea samples were collected from suspected piglets in Guangxi Province from2017 to 2019, detected by RT-PCR for PDCoV, and the positive samples were used for amplification and sequence of S, M, N genes. Finally, 16 S, M and N gene sequences of PDCoV were obtained. Homology analysis showed that the S, M, N gene nucleotide identity among Guangxi strains were 95.8% -99.9%, 95.9%-100% and 97.9%-99.9%, respectively. The nucleotide identity of S, M and N genes among Guangxi strains and other reference strains were 95.1%-100%, 95.0%-100%and 96.3%-99.9%, respectively. Sequence alignment showed that S1 protein existed amino acid mutations and insertions, and there were some variations among different epidemic strains. Phylogenetic trees based on S, M and N genes obtained similar topological diagram and all strains could be divided into Group I, Group II and GroupIII, of which Group I came from USA, Japan and Korea, Group II came from China, and Group III came from China, Vietnam, Laos and Thailand. Most strains from Guangxi Province distributed in Group II, individual strain distributed in Group III and some strains formed a single small branch. The evolutionary rates of S, M and N genes of Guangxi strains and other reference strains were 2.57 x 10-4, 2.07 x 10-4, 1.70 x 10-4 substitutions/site/year, respectively, showing that the evolutionary rate of S gene was the fastest. The results indicated that the S, M, N genes of PDCo V strains from Guangxi Province had some variations and existed genetic diversity.

Associations of sport participation, muscle-strengthening exercise and active commuting with self-reported physical fitness in school-aged children.

Background: Numerous studies suggest a positive association between physical activity and physical fitness in schoolchildren. However, little is known about some neglected forms of physical activity and their associations with physical fitness. This study was conducted via a self-reported questionnaire, owing to the COVID-19 pandemic in many regions in China. Purpose: This study explores the associations between participating in sports, muscle-strengthening exercises, and active commuting with self-reported physical fitness assessed by the International Fitness Scale (IFIS). Methods: A total of 3,807 study participants (ages 11-17) from 12 public schools in South-eastern China were recruited, with 2,407 providing valid data on variables for analysis. Study participants were asked to self-report their sociodemographic factors (i.e., sex, grade, age), participation in sports (never, 1-3 times per month, 1-2 times per week, and 3 or more times per week), muscle-strengthening exercise (0-7 days) and active commuting (0-5 days). Generalized linear models were used to explore the associations between sports participation, muscle-strengthening exercise, and active commuting with self-reported physical fitness (comprising general physical fitness, cardiorespiratory fitness, muscular strength, speed and agility, and flexibility). A total of 2,407 children and adolescents with a mean age of 13.82 (±2.1) years were included in the study's final analysis. Results: The study found no significant association between active commuting and physical fitness. Regarding participating in sports and muscle-strengthening exercises, positive, significant associations were found, which showed that a higher frequency of participating in sports and more participation in muscle-strengthening exercises are associated with improved physical fitness. Conclusion: This study offered evidence on the roles of some aspects of physical activity in physical fitness. To promote health in children and adolescents, they should be encouraged to participate in more sports and engage in muscle-strengthening exercises.

Comparison of initial clinic characteristics of hospitalized patients in Suzhou City during the COVID-19 Omicron wave with ancestral variant wave.

BACKGROUND: Recently, the SARS-CoV-2 variant of concern, Omicron (B.1.1.529), was identified as responsible for a novel wave of COVID-19 worldwide. Here, we compared initial clinical features of hospitalized COVID-19 patients during recent wave (Omicron Variant) with those in ancestral variant wave (2020). METHODS: This is a cohort study of electronic health record (EHR) data from a signal center in the China. The clinical data of 116 cases of Omicron hospitalized in 2022 and 87 cases hospitalized in 2020 were collected. The comparisons were performed with the Mann-Whitney U test, Fisher exact test or the chi-square test, and multivariable logistic regression analysis. RESULTS: Clinically, compared with 2020-cohort, Omicron-cohort was more inclined to cluster in younger population and had more nonsymptomatic (25.0%) and nonsevere cases, as well as suffered from comparable extrapulmonary complication. Radiologically, although the major computed tomography (CT) findings of both cohorts were ground-glass opacities (GGOs), crazy-paving pattern was relatively less seen in the Omicron-cohort. Based on multiple logistic regression analysis, Omicron-cohort was associated with a lower risk of complaining with fever, the presence of lung opacity, and increased Sequential Organ Failure Assessment (SOFA) score. CONCLUSION: This study provided the data of different patterns of clinic characteristics and reduced severity from infections that occurred in Omicron variant as compared with the outbreak of the epidemic in 2020 wave (ancestral variant).

Online Teaching Quality Evaluation of Business Statistics Course Utilizing Fermatean Fuzzy Analytical Hierarchy Process with Aggregation Operator

Due to the full-scale outbreak of COVID-19, many universities have adopted the way of online teaching to ensure the orderly development of teaching plans and teaching contents. However, whether online and offline teaching can develop homogeneously and how to ensure the teaching effect is a major challenge for colleges and universities. Therefore, it is urgent to construct a reasonable index system and evaluation approach for the quality of network teaching. Combined with the influencing factors and characteristics of online teaching, this study first puts forward a multi-index evaluation index system and then proposes a novel evaluation method for online teaching based on the analytical hierarchy process (AHP) and Dombi weighted partitioned Muirhead Mean (PMM) operator under Fermatean fuzzy (FF) environment. This presented method not only adapts to changeable evaluation information but also handles the elusive interrelationships among indexes, realizing the flexibility and comprehensiveness both in form and in the polyaddition process. The applicability and feasibility of this presented method are then discussed through the practical online teaching quality evaluation of a business statistics course case, and a group of tentative about the sensitivity analysis and comparative analysis further demonstrates the effectiveness and flexibility of the proposed method.

Sociodemographic Correlates of Organized Sports Participation in a Sample of Middle School Students in China.

Background: Organized sport participation (OSP) is considered as one method with the potential to increase overall physical activity (PA) levels in young people. It is essential to understand the correlates of OSP to inform future PA interventions. Purpose: This study aimed to explore the sociodemographic correlates of OSP among middle school students from the Nanjing City of China. Methods: A total of 7,097 adolescents (50.1% girls) aged 12-15 years from Nanjing, China, were recruited in this survey. Self-reported data on sex, grade, race, residence areas, proficient sport skills, and parental highest education were obtained. OSP was assessed by the question asked in the questionnaire on whether participants were involved in any "sports club or team" with the binary answer options of "yes" and "no," for statistical analysis purposes. Generalized linear models were used to determine the correlates of OSP. Results: Only 16.6% reported participating in any organized sport over the past whole year, while boys (OR = 1.34, 95% CI: 1.18-1.53) and 7th graders (OR = 1.40, 95% CI: 1.18-1.65) were more likely to participate in organized sport. Adolescents being Han ethnicity were less likely to either participate in organized sport (OR = 0.60, 95% CI: 0.40-0.92), or masterless (one or two) proficient sport skills [OR (one) = 0.27, 95%CI: 0.20-0.37; OR (two) = 0.43, 95% CI: 0.36-0.50]. Besides, both residence area and parental highest education were not significantly associated with OSP among the participating adolescents. Conclusion: The current study confirmed that only one-sixth of adolescents participate in the organized sport over the past year. At-risk population subgroups include girls, older adolescents, being Han ethnicity, and those proficient in fewer sport skills. Sex, grades, race, and proficient sport skills were significant correlates of OSP. School, community, and families need to provide more resources and support for disadvantaged populations in OSP.

The Associations of Active Travel to School With Physical Activity and Screen Time Among Adolescents: Do Individual and Parental Characteristics Matter?

Little is known about the relationship of active travel to school (ATS) with physical activity (PA) and screen time (ST) by individual and parental characteristics among adolescents, especially in China. To address the research gap, this study aimed to explore the difference of sex, age, living environment, parental occupation and education level in the relationship of ATS with PA and ST among students of grades 7-12 (aged 10-18 years) using cross-sectional data. In 13 cities of Hubei province, China, students from 39 public schools were recruited to engage in the survey. In total, 5,898 students (response rate = 89.6%) were invited into this study. Participants were required to report their ATS (including its types), PA and ST as well as sociodemographic information using a validated questionnaire. Descriptive analyses were used to report the information of all variables. Regression models were used to analyse the relationships of ATS and its types with PA and ST. In a total of 4,128 participants (boys: 50.9%; younger adolescents: 61.9%) included in the final analysis, the proportion of those with ATS was 47.3%. Regarding the types of ATS, walking accounted for over 30%, while cycling was 13.2%. Participants with ATS were more likely to have sufficient PA (OR = 1.26, 95% CI: 1.14-1.39), especially among boys, younger adolescents and those with lower parental education level. However, ATS was not associated with ST (OR = 0.94, 95% CI: 0.86-1.01). Participants with cycling had a higher odds ratio of being physically active (OR for cycling = 1.47, 95% CI: 1.27-1.70; OR for walking = 1.18, 95% CI: 1.06-1.32). The association of ATS types with PA and ST differed by gender, age, living environment and parental educational level as well as occupations. ATS may be a useful approach to increase PA among adolescents, but this should be explained by individual and parental characteristics.

Rare Variants in Inborn Errors of Immunity Genes Associated with Covid-19 Severity (preprint)

Covid-19 is a contagious disease caused by SARS-CoV-2, a novel severe acute respiratory syndrome coronavirus. Common variants and networks underlying host genetic mechanisms have been extensively studied to identify disease-associated genetic factors. However, there are few studies about the rare variants, typically inborn errors of immunity, in understanding the host genetics behind Covid-19 infection, especially in the Chinese population. To fill this gap, we investigate likely-deleterious missense and high-confidence predicted loss-of-function variants by (a) performing gene- and pathway-level association analyses, (b) examining known genes involved in type I interferon signaling and others previously reported in Covid-19 disease, and (c) identifying candidate genes with accumulating mutations and their potential protein-protein interactions with known genes. Based on our analyses, several putative genes and pathways are uncovered and worth further investigation, for example, genes IL12RB1, TBK1, and TLR3, and pathways Tuberculosis (hsa:05152), Primary Immunodeficiency (hsa:05340), and Influenza A (hsa:05164). These regions generally play an essential role in regulating antiviral innate immunity responses to foreign pathogens and in responding to many inflammatory diseases. We believe that to some extent, as an acute inflammatory disease, Covid-19 is also affected by these inborn errors of immunity. We hope that the identification of these rare genetic factors will provide new insights into the genetic architecture of Covid-19.

The SARS-CoV-2 Omicron (B.1.1.529) variant exhibits altered pathogenicity, transmissibility, and fitness in the golden Syrian hamster model (preprint)

The newly emerging SARS-CoV-2 Omicron (B.1.1.529) variant first identified in South Africa in November 2021 is characterized by an unusual number of amino acid mutations in its spike that renders existing vaccines and therapeutic monoclonal antibodies dramatically less effective. The in vivo pathogenicity, transmissibility, and fitness of this new Variant of Concerns are unknown. We investigated these virological attributes of the Omicron variant in comparison with those of the currently dominant Delta (B.1.617.2) variant in the golden Syrian hamster COVID-19 model. Omicron-infected hamsters developed significantly less body weight losses, clinical scores, respiratory tract viral burdens, cytokine/chemokine dysregulation, and tissue damages than Delta-infected hamsters. The Omicron and Delta variant were both highly transmissible (100% vs 100%) via contact transmission. Importantly, the Omicron variant consistently demonstrated about 10-20% higher transmissibility than the already-highly transmissible Delta variant in repeated non-contact transmission studies (overall: 30/36 vs 24/36, 83.3% vs 66.7%). The Delta variant displayed higher fitness advantage than the Omicron variant without selection pressure in both in vitro and in vivo competition models. However, this scenario drastically changed once immune selection pressure with neutralizing antibodies active against the Delta variant but poorly active against the Omicron variant were introduced, with the Omicron variant significantly outcompeting the Delta variant. Taken together, our findings demonstrated that while the Omicron variant is less pathogenic than the Delta variant, it is highly transmissible and can outcompete the Delta variant under immune selection pressure. Next-generation vaccines and antivirals effective against this new VOC are urgently needed.

Unemployment in the Time of COVID-19: A Flow-Based Approach to Real-time Unemployment Projections

This paper presents a flow-based methodology for real-time unemployment rate projections and shows that this approach performed considerably better at the onset of the COVID-19 recession in the spring 2020 in predicting the peak unemployment rate as well as its rapid decline over the year. It presents an alternative scenario analysis for 2021 based on this methodology and argues that the unemployment rate is likely to decline to 5.4 percent by the end of 2021. The predictive power of the methodology comes from its combined use of real-time data with the flow approach.

Analysis of network usage and influencing factors among college students returning to a vocational college during COVID-19 epidemic

Objective: To understand the current situation and influencing factors of Internet addiction among college students after returning to school during the COVID-19 epidemic, and to provide scientific basis for timely intervention measures to adjust the risk factors of Internet addiction.

Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patient's immunological status and found dramatic changes in the IGH within the patient's immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion, and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones 2-3 weeks after the onset of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34, and IGHV4-39 in COVID-19 patients were more abundant than those of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.

Plasma cell-free DNA promise disease monitoring and tissue injury assessment of COVID-19 (preprint)

COVID-19 is a huge threat to global health. Due to the lack of definitive etiological therapeutics currently, effective disease monitoring is of high clinical value for better healthcare and management of the large number of COVID-19 patients. In this study, we recruited 37 COVID-19 patients, collected 176 blood samples upon diagnosis and during treatment, and analyzed cell-free DNA (cfDNA) in these samples. We report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA characteristics reflect patient-specific physiological conditions during treatment. Further analysis on tissue origin tracing of cfDNA reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, we demonstrate the translational merit of cfDNA as valuable analyte for effective disease monitoring, as well as tissue injury assessment in COVID-19 patients.

A Chinese host genetic study discovered type I interferons and causality of cholesterol levels and WBC counts on COVID-19 severity (preprint)

As of early May 2021, the ongoing pandemic COVID-19 has caused over 160 million of infections and over 3 million deaths worldwide. Many risk factors, such as age, gender, and comorbidities, have been studied to explain the variable symptoms of infected patients. However, these effects may not fully account for the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory features. Based on these findings, we performed Mendelian randomization (MR) analysis to investigate the causality of laboratory traits on disease severity. From the MR study, we identified two causal traits, cholesterol levels and WBC counts. The functional gene related to cholesterol levels is ApoE and people with particular ApoE genotype are more likely to have higher cholesterol levels, facilitating the process that SARS-CoV-2 binds on its receptor ACE2 and aggravating COVID-19 disease. The functional gene related to WBC counts is MHC system that plays a central role in the immune system. The host immune response to the SARS-CoV-2 infection greatly affects the patients severity status and clinical outcome. Additionally, our gene-based and GSEA analysis revealed interferon pathways, including type I interferon receptor binding, regulation of IFNA signaling, and SARS coronavirus and innate immunity. We hope that our work will make a contribution in studying the genetic mechanisms of disease illness and serve as useful reference for the clinical diagnosis and treatment of COVID-19.