Dysregulated Platelet Function and Thrombosis in Patients with Post-Acute Sequelae of COVID-19 (preprint)

Objective: Post-acute sequelae of COVID-19 (PASC, also referred as Long-COVID) sometimes follows COVID-19, a disease caused by SARS-CoV-2. While SARS-CoV-2 is well-known to promote a prothrombotic state, and especially to activate platelets acutely, less is known about the thrombosis risk in PASC. Approach and Results: PASC patients and age-matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by Light Transmission Aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under venous shear stress conditions. While only a mild increase in platelet aggregation in PASC patients through the thromboxane receptor was observed platelet activation through the glycoprotein VI (GPVI) receptor was markedly decreased in PASC patients compared to age- and sex-matched healthy controls. Thrombosis under venous shear conditions as well as Factor Xa activity were reduced in PASC patients. Plasma from PASC patients was an extremely potent activator of washed, healthy platelets - a phenomenon not observed using age- and sex-matched platelets from healthy individuals. Conclusions: PASC patients demonstrate dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating plasma-derived molecule that promotes thrombosis. A hitherto undescribed protective response appears to exists in PASC patients to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.

Mechanisms, Techniques and Devises of Airborne Virus Detection: A Review (preprint)

Airborne virus, such as COVID-19, caused pandemics all over the world. Virus-containing particles produced by infected individuals are suspended in the air for extended periods of time, actually results in viral aerosols and the spread of infectious diseases. Aerosol collection and detection devices are essential for limiting the spread of airborne virus diseases. This review provides an overview of the primary mechanisms and enhancement techniques for collecting and detecting airborne viruses. Indoor virus detection strategies for scenarios with varying ventilations are also summarized based on the excellent performance of existing advanced comprehensive devices. This review provides guidance for the development of future aerosol detection devices and aids in the control of airborne transmission diseases, such as COVID-19, monkeypox, and other airborne transmission viruses.

News from Messenger? A Cross-National Comparative Study of News Media's Audience Engagement Strategies via Facebook Messenger Chatbots

As an emerging audience engagement channel for news organizations, news chatbots can interact with and attract audiences in a conversational manner. The present study applies the comparative digital journalism frameworks and examines how society-level factors-such as media systems and information communication technology's development-explain chatbot implementation on social media platforms. We surveyed 365 news organizations across 38 countries or regions and inspected their Facebook Messenger accounts with a mixed-methods approach. We found that less than half of the surveyed news organizations implemented Messenger, and only 67 Messengers were responsive-i.e. able to produce at least one response. We used the walkthrough method to interact with the Messengers with 22 pre-defined search queries on information seeking and navigation related to COVID-19. Then we used qualitative content analysis to examine the contents generated by the Messengers. Some Messengers are out of service or could only provide limited services (e.g. generating templated responses or closed-ended options). The Messengers in different news organizations demonstrated great variations in their capacity to understand the queries and interact with the audiences and reparative strategies to handle search failure. We proposed a three-category typology of news chatbots and offered practical and constructive suggestions for news organizations.

Variations in Sulfur and Nitrogen Oxidation Rates in Summer Aerosols from 2014 to 2020 in Wuhan, China

To date, research regarding the changes of the sulfur and nitrogen rates in Wuhan during the summer is limited. In this study, we analyzed the air quality in Wuhan, China, using water-soluble ion, gaseous precursor, and weather data. A Spearman correlation analysis was then performed to investigate the temporal changes in air quality characteristics and their driving factors to provide a reference for air pollution control in Wuhan. The results indicate that SO2 in the atmosphere at Wuhan undergoes secondary conversion and photo-oxidation, and the conversion degree of SO2 is higher than that of NO2. During the summers of 2016 and 2017, secondary inorganic atmospheric pollution was more severe than during other years. The fewest oxidation days occurred in summer 2020 (11 days), followed by the summers of 2017 and 2014 (25 and 27 days, respectively). During the study period, ion neutralization was the strongest in summer 2015 and the weakest in August 2020. The aerosols in Wuhan were mostly acidic and NH4+ was an important neutralizing component. The neutralization factors of all cations showed little change in 2015. K+, Mg2+, and Ca2+ level changes were the highest in 2017 and 2020. At low temperature, high humidity, and low wind speed conditions, SO2 and NO2 were more easily converted into SO42− and NO3−.

COVID-19 plasma exosomes promote pro-inflammatory immune responses in peripheral blood mononuclear cells (preprint)

Elevated serum cytokine production in COVID-19 patients is associated with disease progression and severity. However, the stimulus that initiates cytokine production in patients remains to be fully revealed. Virus-infected cells can release virus-associated exosomes, extracellular vesicles (EVs) of endocytic origin, into the blood to deliver viral cargoes able to regulate immune responses. Here, we report that plasma exosomes from COVID-19 patients contain SARS-CoV-2 RNA. COVID-19 plasma exosomes stimulated robust production of interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and other inflammatory cytokines and chemokines in human peripheral mononuclear cells (PBMCs). Exosome depletion abolished these stimulated responses. COVID-19 plasma exosomes induced proinflammatoryresponses in CD4+ T cells, CD8+ T cells, and CD14+monocytes but not significantly in regulatory T cells, Th17 T cells, or memory T cells. COVID-19 plasma exosomes carry viral double-stranded RNA (dsRNA) intermediates, protect the dsRNA cargo from RNase, and deliver the dsRNA to recipient cells. COVID-19 plasma exosomes significantly increase the expression of endosomal toll-like receptor 3 (TLR3), TLR7, TLR8, and TLR9 in peripheral T cells and monocytes. Inhibition of TLR3 by a specific pharmacological inhibitor considerably reduced the production of cytokines and chemokines in CD4+ and CD8+ T cells but not in CD14+monocytes, highlighting divergent signaling pathways of immune cells in response to COVID-19 plasma exosomes. Our results indicate a novel model of crosstalk between SARS-CoV-2 infection and immune responses able to contribute to elevated cytokine production associated with COVID-19 progression, severity, and long-haul symptoms.

Integrated Immunopeptidomics and Proteomics Study Reveals Imbalanced Innate and Adaptive Immune Responses to SARS-Cov-2 Infection (preprint)

We present an integrated immunopeptidomics and proteomics study of SARS-Cov-2 infection to comprehensively decipher the changes in host cells in response to viral infection. Our results indicated that innate immune response in Calu-3 cells was initiated by TLR3, followed by activation of interferon signaling pathway. Host cells also present viral antigens to the cell surface through both Class I and Class II MHC system for recognition by adaptive immune system. SARS-Cov-2 infection led to the disruption of antigen presentation as demonstrated by higher level of HLA proteins from the flow-through of MHC immunoprecipitation. Glycosylation analysis of HLA proteins from the elution and flow-through of immunoprecipitation revealed that the synthesis and degradation of HLA protein was affected by SARS-Cov-2 infection. This study provided many useful information to study the host response to SARS-Cov-2 infection and would be helpful for the development of therapeutics and vaccine for Covid-19 and future pandemic.

Multiscale Characterization Reveals Oligomerization Dependent Phase Separation of Primer-independent RNA Polymerase nsp8 From SARS-CoV-2 (preprint)

RNA replication and transcription machinery is an important drug target for fighting against coronavirus. Non-structure protein nsp8 was proposed harboring primase activity. However, the RNA primer synthesis mechanism of nsp8 is still largely unknown. Here, we purified dimer and tetramer forms of SARS-CoV-2 nsp8. Combined with DLS, SANS and thermo-stability analysis, we found that both dimer and tetramer become loosened and destabilized with decreasing salt concentration, and the dimer form is more stable than the tetramer form. Further investigation showed that nsp8 dimer and tetramer can undergo phase separation but exhibit different phase separation behaviors. nsp8 dimer can form liquid-like droplets in the buffer with a low concentration of NaCl; phase separation of nsp8 tetramer depends on the assistance of RNA. Our findings on different phase separation behaviors of nsp8 dimer and tetramer could provide novel insight into the primer synthesis mechanism in coronavirus and facilitate developing novel therapeutic agents against SARS-CoV-2.

Improving Google Flu Trends for COVID-19 Estimates Using Weibo Posts

While incomplete non-medical data has been integrated into prediction models for epidemics, the accuracy and the generalizability of the data are difficult to guarantee. To comprehensively evaluate the ability and applicability of using social media data to predict the development of COVID-19, a new confirmed case prediction algorithm improving the Google Flu Trends algorithm is established, called Weibo COVID-19 Trends (WCT), based on the post dataset generated by all users in Wuhan on Sina Weibo. A genetic algorithm is designed to select the keyword set for filtering COVID-19 related posts. WCT can constantly outperform the highest average test score in the training set between daily new confirmed case counts and the prediction results. It remains to produce the best prediction results among other algorithms when the number of forecast days increases from one to eight days with the highest correlation score from 0.98 (p < 0.01) to 0.86 (p < 0.01) during all analysis period. Additionally, WCT effectively improves the Google Flu Trends algorithm's shortcoming of overestimating the epidemic peak value. This study offers a highly adaptive approach for feature engineering of third-party data in epidemic prediction, providing useful insights for the prediction of newly emerging infectious diseases at an early stage.

Psychological Status and Correlated Factors of Primary Medical Staff During the COVID-19 Outbreak in Hefei City, China.

OBJECTIVE: To investigate the mental illness and correlated factors of primary medical staff during the COVID-19 outbreak in Hefei city, China. METHODS: A total of 180 primary medical staff were randomly selected from seven community hospitals in Hefei Economic and Technological Development Zone as a study group. One hundred and eighty-two health people were recruited as the control group. The self-rating Anxiety Scale (SAS), self-rating Depression Scale (SDS) and Psychological questionnaire of public health emergencies were distributed to them for evaluation. RESULTS: The score of SAS, SDS in study group was higher than that in control group [(35.57±10.39) vs (31.31±7.98); (44.16±8.46) vs (41.47±9.47)] (t=4.371, P< 0.001; t=2.849, P=0.005). The fear subscale and total score in the psychological questionnaire of sudden public health events were negatively correlated with age (r=-0.216, P=0.004; r=-0.154, P=0.039). Marriage was negatively correlated with depression subscales in psychological questionnaires of SAS, SDS and sudden public health events (r=-0.184, P=0.013; r=-0.298, P<0.001; r=-0.161, P=0.031; r=-0.147, P=0.049). Education level was positively correlated with the total score of a psychological questionnaire for sudden public health events (r=0.151, P=0.043); Logistic regression analysis showed that marital status was a protective factor of psychological abnormality. CONCLUSION: It is necessary to pay attention to the psychological status of primary medical staff, especially the young unmarried medical staff.

Mental health status and its influencing factors of college students in Anhui Province during the coronavirus disease 2019 pandemic

[Background] As a public health emergency, the coronavirus disease 2019 (COVID-19) pandemic has brought a certain impact on the public. [Objective] This study explores the mental health status of college students in Anhui Province during the COVID-19 pandemic and analyzes possible influencing factors. [Methods] On February 2020, 493 college students from two universities in Anhui Province completed the Self-Esteem Scale (SES), the Perceived Social Support Scale (PSSS), and the Symptom Checklist 90 (SCL-90). Independent samples t test and one-way analysis of variance were used to analyze the differences of college students' mental health scores by different sociodemographic characteristics. Independent samples t test was also used to analyze the differences in mental health status between the participants and the norms. Pearson correlation analysis was used to explore the relationships between mental health, self-esteem, and perceived social support. With the total score of SCL-90 as dependent variable and the scores of SES and PSSS as independent variables, a multiple linear stepwise regression analysis was established to explore the potential influencing factors of college students' mental health during the pandemic. [Results] Finally 472 (95.74%) valid questionnaires were returned. Of them 90 (19.07%) respondents were positive at the SCL-90 scale;the highest three dimensional positive rates were anxiety (34.75%), interpersonal sensitivity (24.36%), and obsessive-compulsive (23.73%), and the lowest rate was psychiatric disorders (13.77%). The overall SCL-90 score was 139.13±31.59, and the score of the college students who were the only child was lower than that of the college students who were not the only child (t=-2.098, P < 0.05). Compared with the norms, the total score of SCL-90 and the dimensional scores of interpersonal sensitivity, depression, anxiety, phobic anxiety, and psychiatric disorders of the participants were higher (P < 0.05). The students' self-esteem score was 25.35±4.92 and perceived social support score was 60.28±12.98. The total SCL-90 score was negatively correlated with the self-esteem score (r=-0.506, P < 0.01) and the perceived social support score (r=-0.482, P < 0.01). The multiple linear stepwise regression analysis results showed that self-esteem (b=-2.590, P < 0.001) and perceived social support (b=-0.903, P < 0.001) jointly explained 38.3% of the changes in total SCL-90 score. [Conclusion] During the COVID-19 pandemic, the overall mental health status of the college students is not good. Reasonable levels of self-esteem and perceived social support are helpful to improve their mental health.

Application value of SARS-CoV-2 IgG and IgM antibodies in diagnosis and treatment of new coronavirus pneumonia

Objective: To explore the application value of chemiluminescence detection of SARS-CoV-2 IgM/IgG antibodies in the adjuvant diagnosis and treatment of coronavirus disease 2019 (COVID-19).

A COVID-19 case report from asymptomatic contact: implication for contact isolation and incubation management.

BACKGROUND: As of 2 March, 2020, at least 80 151 coronavirus disease 2019 (COVID-19) cases were reported in China. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province or were exposed to symptoms. Some patients got infected through only asymptomatic contact. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection through only asymptomatic contact. CASE PRESENTATION: A 44-year-old man, who lived in Nanchang, Jiangxi Province, China until 6 March 2020, suffered from cough on 27 January 2020. Fever symptoms appeared on 28 January, with a maximum temperature of 38.8 °C, accompanied by cough, sore throat, headache, fatigue, muscle ache, joint ache, and other symptoms. The symptoms continued until he was hospitalized on 30 January. Coronavirus conventional polymerase chain reaction assay was positive for the throat swab sample. The patient, along with his wife and son, drove from Nanchang to back to Honghu City, Hubei Province, on 23 January 2020. After staying with his parents and brother's family for 3 days, the patient drove back to Nanchang and arrived on 25 January. On the way back home, they stopped by Tongshan service area, Hubei Province, without any close contact with other people. After arriving home in Nanchang City, Jiangxi Province, none of them left their residence. In addition, his parents stayed at home for 20 days with his younger brother's family before they got back. His younger brother and one of his brother's children visited Wuhan on 5 January and came home on 6 January 2020. CONCLUSIONS: This report suggested that, in the early phase of COVID-19 pneumonia, routine screening could miss patients who were virus carriers. Highlighting travel history is of paramount importance for the early detection and isolation of severe acute respiratory syndrome coronavirus 2 cases.

An Analysis of Eight Family Cluster Cases in Wuhan, China: Peripheral Blood Lymphocyte Count May Predict COVID-19 Mortality (preprint)

Importance: Since December 2019, a novel coronavirus (SARS-CoV-2) causing COVID-19 has spread across the world in a global pandemic. Tens of thousands of people were infected, several thousand patients died. However, key risk factors for predicting mortality remain unclear.Objective: To identify the key risk factors for COVID-19 mortality.Design, Setting, Participants: Retrospective, randomly selected eight family clusters consisting of 21 individual cases who had been confirmed positive for SARS-CoV-2 and admitted to the Wuhan Union Hospital, Wuhan, China, from February 6 to March 3 2020. This study aims to analyze the differences in mortal risk factors between fatal and non-fatal cases within each family.

Sex Differences in Severity and Mortality Among Patients With COVID-19: Evidence from Pooled Literature Analysis and Insights from Integrated Bioinformatic Analysis (preprint)

Objective: To conduct a meta-analysis of current studies that examined sex differences in severity and mortality in patients with COVID-19, and identify potential mechanisms underpinning these differences. Methods: We performed a systematic review to collate data from observational studies examining associations of sex differences with clinical outcomes of COVID-19. PubMed, Web of Science and four preprint servers were searched for relevant studies. Data were extracted and analyzed using meta-analysis where possible, with summary data presented otherwise. Publicly available bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) data were analyzed to explore the potential mechanisms underlying the observed association. Results: 39 studies met inclusion criteria, representing 77932 patients, of which 41510 (53.3%) were males. Men were at a markedly increased risk of developing severe cases compared with women. Furthermore, the pooled odds ratio (OR) of mortality for male group compared with the female group indicated significant higher mortality rate for male. Data from scRNA-seq suggest that men have a higher amount of ACE2-expressing pulmonary alveolar type II cells than women. Sex-based immunological differences exist. The expression of androgen receptor (AR) is positively correlated with ACE2, and there is evidence that AR may directly regulate the expression of ACE2. Conclusions: This meta-analysis detected an increased severity and mortality rate in the male populations with COVID-19, which might be attributable to the sex-based differences in cellular compositions and immunological microenvironments of the lung. The host cell receptor ACE2 is likely regulated by AR signaling pathway, which is identified as a potential target for prevention and treatment of SARS-Cov-2 infections in men.

A COVID-19 Case Report from Asymptomatic Contact: Implication for Contact Isolation and Incubation Management (preprint)

An outbreak caused by coronavirus disease 2019 (COVID-19) occurred in Wuhan City, Hubei Province, China, in December 2019. Up to March 2, 2020, at least 80180 cases have been reported. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province, or exposed to symptoms. Some patients got infected only from asymptomatic contacts. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection only from asymptomatic contact.

Susceptibility Analysis of COVID-19 in Smokers Based on ACE2 (preprint)

Background: Cigarette smoking (CS) is a global public health problem and a high-risk factor for various diseases. In December 2019, a novel coronavirus (HCoV-19) was identified in Wuhan, China. Because ACE2 has been identified as a receptor for HCoV-19, we hypothesize that CS affects the expression pattern of ACE2 in respiratory tract, causing differences in susceptibility to the virus. Methods: Three datasets (GSE994, GSE17913, and GSE18344), were downloaded from the Gene Expression Omnibus (GEO) database. Correlation and enrichment analysis were used to evaluate the function of ACE2. Also, the different expression of ACE2 in different groups of three datasets were analyzed. Results: Genes associated with ACE2 were enriched in important biological processes such as viral processes and immune response. Elevated ACE2 were found in intrapulmonary airways (GSE994) and oral epithelial cells (GSE17913) of smokers but not those of non-smokers or former smokers. Significant dose- and time-dependent relationships between CS and ACE2 expression were observed in mouse lung tissues, and long periods without smoking were found to significantly reduce ACE2 expression. Conclusions: Both human and rat data confirmed that CS could induce increased ACE2 in the respiratory tract, indicating that smokers have a higher susceptibility to HCoV-19.