Pre-existing anti-HCoV-OC43 immunity influences the durability and cross-reactivity of humoral response to SARS-CoV-2 vaccination

Purpose This study was conducted in order to properly understand whether prior seasonal human coronavirus (HCoV) immunity could impact the potential cross-reactivity of humoral responses induced by SARS-CoV-2 vaccine, thereby devising universal coronavirus vaccines for future outbreaks. Methods We performed enzyme-linked immunosorbent assay (ELISA) to quantify the immunoglobulin G (IgG) antibody levels to spike (S) protein and S1 subunit of HCoVs (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E), and ELISA [anti-RBD and anti-nucleoprotein (N)], chemiluminescence immunoassay assays (anti-RBD), pseudovirus neutralization test, and authentic viral neutralization test to detect the binding and neutralizing antibodies to SARS-CoV-2 in the vaccinees. Results We found that the antibody of seasonal HCoVs did exist before vaccination and could be boosted by SARS-CoV-2 vaccine. A further analysis demonstrated that the prior S and S1 IgG antibodies of HCoV-OC43 were positively correlated with anti-RBD and neutralization antibodies to SARS-CoV-2 at 12 and 24 weeks after the second vaccination, and the correlation is more statistically significant at 24 weeks. The persistent antibody levels of SARS-CoV-2 were observed in vaccinees with higher pre-existing HCoV-OC43 antibodies. Conclusion Our data indicate that inactivated SARS-CoV-2 vaccination may confer cross-protection against seasonal coronaviruses in most individuals, and more importantly, the pre-existing HCoV-OC43 antibody was associated with protective immunity to SARS-CoV-2, supporting the development of a pan-coronavirus vaccine.

Understanding Agri-Food Traceability System User Intention in Respond to COVID-19 Pandemic: The Comparisons of Three Models.

Scientists believed the outbreak of COVID-19 could be linked to the consumption of wild animals, so food safety and hygiene have become the top concerns of the public. An agri-food traceability system becomes very important in this context because it can help the government to trace back the entire production and delivery process in case of food safety concerns. The traceability system is a complicated digitalized system because it integrates information and logistics systems. Previous studies used the technology acceptance model (TAM), information systems (IS) success model, expectation confirmation model (ECM), or extended model to explain the continuance intention of traceability system users. Very little literature can be found integrating two different models to explain user intention, not to mention comparing three models in one research context. This study proposed the technology acceptance model (TAM), technology acceptance model-information systems (TAM-IS) success, and technology acceptance model-expectation confirmation model (TAM-ECM) integrated models to evaluate the most appropriate model to explain agri-food traceability system during the COVID-19 pandemic. A questionnaire was designed based on a literature review, and 197 agri-food traceability system users were sampled. The collected data were analyzed by partial least square (PLS) to understand the explanatory power and the differences between the three models. The results showed that: (1) the TAM model has a fair explanatory power of continuance intention (62.2%), but was recommended for its' simplicity; (2) the TAM-IS success integrated model had the best predictive power of 78.3%; and (3) the system providers should raise users' confirmation level, so their continuance intention could be reinforced through mediators, perceived value, and satisfaction. The above findings help to understand agri-food traceability system user intention, and provide theoretical and practical implications for system providers to refine their system design.

Characteristics of Peripheral Blood Cells in COVID-19 Patients Revealed by a Retrospective Cohort Study (preprint)

Background Peripheral hematological changes in severe COVID-19 patients may reflect the immune reaction during SARS-CoV-2 infection. Characteristics of peripheral blood cells as early signals were needed to be investigated for clarifying its associations with the fatal outcomes in COVID-19 patients. Methods A retrospective cohort study was performed and the hospitalized COVID-19 patients were recruited in wards of Tongji Hospital (Wuhan, China). Characteristics of peripheral blood cells in survivors and non-survivors were analyzed. Also the comparison among patients with different level of eosinophils was performed. Results198 patients were included in this study, of whom 185 were discharged and 13 died in hospital. Compared to the survivors, counts of lymphocytes, monocytes, eosinophils and basophils were significantly decreased in non-survivors. According to the level of eosinophils, patients were divided into low EOS group (< 0.02×109/L) and normal EOS group (≥ 0.02×109/L). Patients in the low EOS group showed a significantly higher fever compared to normal EOS group. The proportion of patients in low EOS group who used glucocorticoids increased significantly than the other group. Death rate in the low EOS group was higher and no patient death in normal EOS group. Moreover, positive correlation was found between the counts of lymphocytes and eosinophils in patients with glucocorticoids use but not in patients without the treatment. Conclusions Hematological changes differed between survivors and non-survivors with COVID-19. Lymphopenia and eosinopenia could serve to predict the poor prognosis of COVID-19 patients. Initial counts of eosinophils may guide us in usage of glucocorticoids for COVID-19 treatment. 

Association of Web-Based Physical Education With Mental Health of College Students in Wuhan During the COVID-19 Outbreak: Cross-Sectional Survey Study.

BACKGROUND: The COVID-19 outbreak has affected people's health worldwide. For college students, web-based physical education is a challenge, as these course are normally offered outdoors. OBJECTIVE: The aim of this study was to use data from a web-based survey to evaluate the relationship between the mental health status of college students and their sports-related lifestyles. Problems related to web-based physical education were also examined. METHODS: A web-based survey was conducted by snowball sampling from May 8 to 11, 2020. Demographic data, mental health status, and sports-related lifestyles of college students in Wuhan as well as issues related to web-based physical education were collected. Mental health status was assessed by the Depression, Anxiety, and Stress Scale (DASS-21). RESULTS: The study included 1607 respondents from 267 cities. The average scores of the DASS-21 subscales (2.46 for depression, 1.48 for anxiety, and 2.59 for stress) were significantly lower in our study than in a previous study (P<.05). Lower DASS-21 scores were significantly correlated with regular exercise, maintaining exercise habits during the outbreak of COVID-19, exercising more than 1 to 2 times a week, exercise duration >1 hour, and >2000 pedometer steps (all P<.05). None of the three forms of web-based physical education was preferred by more than 50% of respondents. Frequent technical problems were confronted by 1087/1607 students (67.6%). Shape-up exercises (846/1607, 52.6%), a designed combination of exercises (710/1607, 44.2%), and Chinese kung fu (559/1607, 34.8%) were suggested sports for web-based physical education. CONCLUSIONS: Mental status was significantly correlated with regular exercise and sufficient exercise duration. Professional physical guidance is needed for college students in selected sports. Exercises not meeting students' preferences, frequent technical problems, and the distant interaction involved in web-based physical education were the main problems that should be solved in future.

Clinical characteristics and outcome of influenza virus infection among adults hospitalized with severe COVID-19: A retrospective cohort study from Wuhan, China (preprint)

BackgroundCoronavirus disease 2019 (COVID-19) is an emerging infectious disease that rapidly spreads worldwide and co-infection of COVID-19 and influenza may occur in some cases. We aimed to describe clinical features and outcomes of severe COVID-19 patients with co-infection of influenza virus.MethodsRetrospective cohort study was performed and a total of 140 patients with severe COVID-19 were enrolled in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan city, Hubei province, China. The demographic, clinical features, laboratory indices, treatment and outcomes of these patients were collected.ResultsOf 140 severe COVID-19 hospitalized patients, including 73 patients (52.14%) with median age 62 years were influenza virus IgM-positive and 67 patients (47.86%) with median age 66 years were influenza virus IgM-negative. 76 (54.4%) of severe COVID-19 patients were males. Chronic comorbidities consisting mainly of hypertension (45.3%), diabetes (15.8%), chronic respiratory disease (7.2%), cardiovascular disease (5.8%), malignancy (4.3%) and chronic kidney disease (2.2%). Clinical features, including fever (≥38°C), chill, cough, chest pain, dyspnea, diarrhea and fatigue or myalgia were collected. Fatigue or myalgia was less found in COVID-19 patients with IgM-positive (33.3% vs 50/7%, P = 0.0375). Higher proportion of prolonged activated partial thromboplastin time (APTT) > 42 s was observed in COVID-19 patients with influenza virus IgM-negative (43.8% vs 23.6%, P = 0.0127). Severe COVID-19 Patients with influenza virus IgM positive have a higher cumulative survivor rate than that of patients with influenza virus IgM negative (Log-rank P= 0.0308). Considering age is a potential confounding variable, difference in age was adjusted between different influenza virus IgM status groups, the HR was 0.29 (95% CI, 0.081-1.100). Similarly, difference in gender was adjusted as above, the HR was 0.262 (95% CI, 0.072-0.952) in the COX regression model.ConclusionsInfluenza virus IgM positive may be associated with decreasing in-hospital death.

The SARS-CoV-2 RNA with mild pulmonary consolidation lasts longer in non-severe COVID-19 patients: an observational study (preprint)

Background: Since December 2019, COVID-19 has rapidly swept the world. It is particularly important to understand the dynamic changes of the whole disease course of non-severe patients from the onset to the follow-up after discharge.Methods: On February 1, 2020, 18 cases of non-severe COVID-19 appeared in a hospital in Beijing. All patients were SARS-CoV-2 RNA positive by RT-PCR for pharyngeal swabs. We recorded the clinical information and viral dynamics of these patients from the onset of the disease to 2 months after discharge. According to the severity of lung consolidation, 18 patients were divided into two groups (mild pulmonary consolidation group [imaging score ≤10]; severe pulmonary consolidation group [imaging score >10]).Results: Eighteen patients (median age 43) were included, including 14 females. Fever (11/18) and cough (8/18) were the most common symptoms. The duration of SARS-CoV-2 RNA positive in mild pulmonary consolidation group was significantly longer than severe pulmonary consolidation group (the median time was 30 days and 13 days, respectively, P= 0.0031). Two months after discharge, almost all patients were followed up for IgM antibody disappearance and IgG antibody production.Conclusion: In non-severe COVID-19 patients, the positive duration of the SARS-CoV-2 RNA in patients with mild pulmonary consolidation was longer than the severe pulmonary consolidation. However, it is necessary for a large sample to verify our conclusions.

Influence of influenza A virus in COVID-19 patients: A retrospective cohort study (preprint)

Background and objective: Coronavirus disease (COVID-19) is currently an urgent global issue, but we cannot ignore the impact of influenza A since there is an overlap of infection time and region and similar clinical manifestations and chest computed tomography (CT) images for influenza A and COVID-19 infections. We compared patients who had a COVID-19 infection and co-infection with the influenza A virus.Methods: We retrospectively reviewed patients who met the inclusion criteria for this study.Results: There were 213 patients included in this study, of whom 106 were females and 107 were males, with a median age of 63 years. All patients were diagnosed with COVID-19 and were subsequently divided into influenza positive (n = 97) and influenza negative (n = 116) groups according to the serum test results for the influenza A IgM antibody. The two groups had similar symptoms, outcomes, CT manifestation and CT scores, except for lymphadenopathy (6.2% in the influenza positive group vs. 14.7% in the negative group, P = 0.047). However, in the subgroup analysis, male or younger patients (age <= 60 years) in the influenza negative group had higher CT scores than patients in the influenza positive group (P < 0.05).Conclusions: COVID-19 patients who had co-infection with the influenza A virus showed similar symptoms, outcomes, CT manifestation and CT scores to influenza negative patients. However, male patients and younger patients had higher CT scores in the influenza negative group.

Clinical characteristics and prognostic factors in elderly patients with COVID-19 (preprint)

Background: The COVID-19 pandemic posed tremendous threats to the world. Elderly patients were among the high-risk population, and apt to experience worse outcomes.Methods: Elderly patients (age ≥60 years old) were enrolled from January 28 to February 29, 2020, in Tongji Hospital, one of designated COVID-19 medical centers in Wuhan, China. A retrospective study was performed to describe clinical characteristics and outcomes of elderly COVID-19 patients. COX regression was used to analyze predictors for 28-day mortality. Linear regression models were constructed to analyze factors associated with length of hospital stay (LOS).Result: A total of 186 elderly patients (aged 70.4 ± 7.1 years, 95 males (51.6%)) were enrolled, 120 patients (64.5%) were severe or critical type, and mortality rate was 16.1%. Patients in non-survival group had a higher smoking rate, more symptoms of dyspnea, lab results indicative of poorer health. Age (HR 1.128, 95% CI 1.066-1.194), lymphocyte count (HR 0.261, 95% CI 0.073-0.930), LDH (HR 1.003, 95% CI 1.002-1.005), procalcitonin (HR 1.061, 95% CI 1.002-1.125), and qSOFA (HR 3.162, 95% CI 1.646-6.072) were independently associated with 28-day mortality. CURB-65 plus LDH on admission were predictors of mortality by ROC analysis (AUROC=0.891). Among surviving patients, consolidation on CTs, elevated ferritin level and neutrophil count were associated with increased LOS.Conclusion: High incidence of comorbidities and mortality were observed in elderly patients. Decreased lymphocyte, older age, higher qSOFA score, procalcitonin and LDH levels were independent factors associated with mortality, CURB-65 plus LDH could be a predictive model of fatal outcome. Consolidation on CTs, elevated ferritin and neutrophil level correlated with increased LOS. Further prospective studies should be performed to test our findings and explore potential treatments.

Clinical characteristics and outcome of influenza virus infection among adults hospitalized with severe COVID-19: A retrospective cohort study from Wuhan, China (preprint)

Background Coronavirus disease 2019 (COVID-19) is an emerging infection disease that rapidly spreads worldwide. Clinical features and outcomes of severe COVID-19 patients with influenza virus IgM positive during the influenza season need to be described.Methods Retrospective cohort study of 140 patients with severe COVID-19 hospitalized in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan, Hubei province, China. The demographic, clinical feature, laboratory, treatment and outcome were collected and analyzed.Results Of 140 severe COVID-19 hospitalized patients, 73 patients were with median age of 66 years old with identification of influenza virus IgM-positive and 67 patients were with median age of 62 years old in influenza virus IgM-negative group. Nearly half of severe COVID-19 patients in this research are male. Majority of the severe COVID-19 patients had chronic underlying conditions. Wheeze was the clinical feature of severe COVID-19 patients with influenza IgM-positive (26.4% vs 9.0%, P = 0.008). On contrary, fatigue or myalgia was the feature of the COVID-19 patients without IgM-positive (38.4% vs 58.2%, P = 0.019). In laboratory examination, increased levels of ferritin and prolonging APTT were showed in severe COVID-19 patients without influenza IgM-positive compared with patients in the other group with significant differences. Death rate in the group of severe COVID-19 patients with influenza IgM-positive is higher than it is in other group with significant differences (14.9% vs 4.1%, P = 0.040). In univariate regression analysis, several factors were associated with higher risk of death, which included LDH, troponin, NT-proBNP, D-dimer, PT, APTT, lymphocytes, platelet and eGFR. However, influenza virus IgM positive was associated with lower risk of death. Multivariate Regression analysis showed that troponin and lymphocyte were independently associated with higher risk of death.Conclusion The characteristics of patients hospitalized with severe COVID-19 with identification of influenza virus IgM-positive were described. It hints proof of seasonal influenza which may overlap with COVID-19 and may cause a crisis we could confront in the future.

Trends and prediction in daily incidence and deaths of COVID-19 in the United States: a search-interest based model (preprint)

Background and Objectives: The coronavirus disease 2019 (COVID-19) infected 586,000 patients in the U.S. However, the COVDI-19 daily incidence and deaths in the U.S. are poorly understood. Internet search interest was found highly correlated with COVID-19 daily incidence in China, but not yet applied to the U.S. Therefore, we examined the association of search interest with COVID-19 daily incidence and deaths in the U.S. Methods: We extracted the COVDI-19 daily incidence and death data in the U.S. from two population-based datasets. The search interest of COVID-19 related terms was obtained using Google Trends. Pearson correlation test and general linear model were used to examine correlations and predict future trends, respectively. Results: There were 555,245 new cases and 22,019 deaths of COVID-19 reported in the U.S. from March 1 to April 12, 2020. The search interest of COVID, COVID pneumonia, and COVID heart were correlated with COVDI-19 daily incidence with about 12-day of delay (Pearson r=0.978, 0.978 and 0.979, respectively) and deaths with 19-day of delay (Pearson r=0.963, 0.958 and 0.970, respectively). The COVID-19 daily incidence and deaths appeared to both peak on April 10. The 4-day follow-up with prospectively collected data showed moderate to good accuracies for predicting new cases (Pearson r=-0.641 to -0.833) and poor to good acuracies for daily new deaths (Pearson r=0.365 to 0.935). Conclusions: Search terms related to COVID-19 are highly correlated with the trends in COVID-19 daily incidence and deaths in the U.S. The prediction-models based on the search interest trend reached moderate to good accuracies.

Modes of contact and risk of transmission in COVID-19 among close contacts (preprint)

Background Rapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Guangzhou and elsewhere in China. Modes of contact and risk of transmission among close contacts have not been well estimated. Methods We included 4950 closes contacts from Guangzhou, and extracted data including modes of contact, laboratory testing, clinical characteristics of confirmed cases and source cases. We used logistic regression analysis to explore the risk factors associated with infection of close contacts. Results Among 4950 closes contacts, the median age was 38.0 years, and males accounted for 50.2% (2484). During quarantine period, 129 cases (2.6%) were diagnosed, with 8 asymptomatic (6.2%), 49 mild (38.0%), and 5 (3.9%) severe to critical cases. The sensitivity of throat swab was 71.32% and 92.19% at first to second PCR test. Among different modes of contact, household contacts were the most dangerous in catching with infection of COVID-19, with an incidence of 10.2%. As the increase of age for close contacts and severity of source cases, the incidence of COVID-19 presented an increasing trend from 1.8% (0-17 years) to 4.2% (60 or over years), and from 0.33% for asymptomatic, 3.3% for mild, to 6.2% for severe and critical source cases, respectively. Manifestation of expectoration in source cases was also highly associated with an increased risk of infection in their close contacts (13.6%). Secondary cases were in general clinically milder and were less likely to have common symptoms than those of source cases. Conclusions In conclusion, the proportion of asymptomatic and mild infections account for almost half of the confirmed cases among close contacts. The household contacts were the main transmission mode, and clinically more severe cases were more likely to pass the infection to their close contacts. Generally, the secondary cases were clinically milder than those of source cases.

Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs (preprint)

ABSTRACT Background As core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing. Results We perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novel COCH + fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues. Conclusions The adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.