Effect of warning signs on the epidemic spreading of the COVID-19 pandemic

Early warning signs of the outbreak of pandemic disease become a high profile from the beginning and they remind more susceptible individuals to keep social distance on social occasions. However, these signs have no way to the Susceptible–Infected–Recovered (SIR) models which have been concerned by medical scientists. Warning signs imply the risk level of the pandemic disease evaluated by the government. The response of susceptible population (S-population) to the warning signs is represented by a chicken game. In order to get a better payoff, the more beneficial behavior of the S-population may be induced in the autonomous society based on the SIR model. We emphasize that participants can choose their strategies whether to follow the health rules or not without coercion in the chicken game while the warning signs released by the policy makers can encourage S-population to choose beneficial behavior, instead of purely following the healthy rules or not. The agile policy helps S-population to make a choice on the basis of risk interests but without losing to protect themselves in a serious pandemic situation. Comparing the classic SIR model with our signal-SIR model, the serious pandemic signal released by the policy makers and the disease awareness to it together play an important role in the outbreak period of the pandemic disease. [ FROM AUTHOR]

The salvage therapy utilizing human umbilical cord-derived mesenchymal stem cells to treat severe COVID-19 patients: case series (preprint)

Background: COVID-19 has become one of the biggest challenges globally, yet no specifically effective medication has been developed. Mesenchymal stem cells (MSCs) exhibit properties of immune regulation and regeneration, which may suppress the over-inflammatory response and promote recovery of lung damage caused by COVID-19 and offer the potential as a therapeutic option. Methods: At the very beginning of COVID-19 epidemic in 2020, we investigated the use of human umbilical cord-derived MSCs (hUC-MSCs) as a salvage therapy in five severe COVID-19 patients, with each patient receiving intravenous infusion of hUC-MSCs three times. Results: All patients showed significant improvement in clinical manifestations, including laboratory biomarkers and findings of lung computed tomography images, after at least one dose of MSC therapy. Conclusion: These results suggest that MSC therapy is safe and can reduce the inflammatory response and alleviate the clinical symptoms of critically ill COVID-19 patients.

Targets and cross-reactivity of human T cell recognition of Common Cold Coronaviruses (preprint)

The Coronavirus (CoV) family includes a variety of viruses able to infect humans. Endemic CoVs that can cause common cold belong to the alphaCoV and betaCoV genera, with the betaCoV genus also containing subgenera with zoonotic and pandemic concern, including sarbecoCoV (SARS-CoV and SARS-CoV-2) and merbecoCoV (MERS-CoV). It is therefore warranted to explore pan-CoV vaccine concepts, to provide adaptive immune protection against new potential CoV outbreaks, particularly in the context of betaCoV sub lineages. To explore the feasibility of eliciting CD4+ T cell responses widely cross-recognizing different CoVs, we utilized samples collected pre-pandemic to systematically analyze T cell reactivity against representative alpha (NL63) and beta (OC43) common cold CoVs (CCC). Similar to previous findings on SARS-CoV-2, the S, N, M, and nsp3 antigens were immunodominant for both viruses while nsp2 and nsp12 were immunodominant for NL63 and OC43, respectively. We next performed a comprehensive T cell epitope screen, identifying 78 OC43 and 87 NL63-specific epitopes. For a selected subset of 18 epitopes, we experimentally assessed the T cell capability to cross-recognize sequences from representative viruses belonging to alphaCoV, sarbecoCoV, and beta-non-sarbecoCoV groups. We found general conservation within the alpha and beta groups, with cross-reactivity experimentally detected in 89% of the instances associated with sequence conservation of >67%. However, despite sequence conservation, limited cross-reactivity was observed in the case of sarbecoCoV (50% of instances), indicating that previous CoV exposure to viruses phylogenetically closer to this subgenera is a contributing factor in determining cross-reactivity. Overall, these results provided critical insights in the development of future pan-CoV vaccines.

Diversity and independent evolutionary profiling of rodent-borne pathogens in tropical island, China (preprint)

The risk of emerging infectious diseases (EID) is increasing globally. More than 60% of EIDs worldwide are caused by animal-borne pathogens, and most viral pathogens are rodent-borne. This study aimed to characterise the virome and analyse the phylogenetic evolution and diversity of rodent-borne viruses in Hainan Province, China. We collected 588 anal and throat samples from rodents, combined them into 28 pools according to their species and location, and processed them for next-generation sequencing and bioinformatics analysis. The diverse viral reads closely related to mammals were assigned to 15 viral families. Molecular clues of the important rodent-borne viruses were further identified by polymerase chain reaction for phylogenetic analysis and annotation of genetic characteristics such as coronavirus, arenavirus, picornavirus. We identified a pestivirus in Leopoldoms edwardsi and two bocaviruses in Rattus andamanensis and Leopoldoms edwardsi from the national nature reserves of Jianfengling and Bangxi with low amino acid identity to known pathogens are proposed as the novel species, and their rodent hosts have not been previously reported to carry these viruses. These results expand our knowledge of viral classification and host range and suggest that there are highly diverse, undiscovered viruses that have evolved independently in their unique wildlife hosts in inaccessible areas, which may cause zoonosis if they cross their host barrier. Our virome and phylogenetic analyses of rodent-borne viruses provide basic data for the prevention and control of human infectious diseases caused by rodent-borne viruses in the subtropical area of China.

Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2

Monoclonal antibodies (mAbs) targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have demonstrated clinical efficacy in preventing or treating coronavirus disease 2019 (COVID-19), resulting in the emergency use authorization (EUA) for several SARS-CoV-2 targeting mAb by regulatory authority. However, the continuous virus evolution requires diverse mAb options to combat variants. Here we describe two fully human mAbs, amubarvimab (BRII-196) and romlusevimab (BRII-198) that bind to non-competing epitopes on the receptor binding domain (RBD) of spike protein and effectively neutralize SARS-CoV-2 variants. A YTE modification was introduced to the fragment crystallizable (Fc) region of both mAbs to prolong serum half-life and reduce effector function. The amubarvimab and romlusevimab combination retained activity against most mutations associated with reduced susceptibility to previously authorized mAbs and against variants containing amino acid substitutions in their epitope regions. Consistently, the combination of amubarvimab and romlusevimab effectively neutralized a wide range of viruses including most variants of concern and interest in vitro. In a Syrian golden hamster model of SARS-CoV-2 infection, animals receiving combination of amubarvimab and romlusevimab either pre- or post-infection demonstrated less weight loss, significantly decreased viral load in the lungs, and reduced lung pathology compared to controls. These preclinical findings support their development as an antibody cocktail therapeutic option against COVID-19 in the clinic.

Global dynamics of Porcine Epidemic Diarrhea Virus evolution and transmission (preprint)

With a possible origin from bats, the alphacoronavirus Porcine epidemic diarrhea virus (PEDV) causes significant hazards and widespread epidemics in the swine population. However, the ecology, evolution, and spread of PEDV are still unclear. Here, from 149,869 fecal and intestinal tissue samples of pigs collected in an 11-year survey, we identified PEDV as the most dominant virus in diarrheal animals. Global whole genomic and evolutionary analyses of 672 PEDV strains revealed the fast-evolving PEDV genotype 2 (G2) strains as the main epidemic viruses worldwide, which seems to correlate with the use of G2-targeting vaccines. The evolving pattern of the G2 viruses presents geographic bias as they evolve tachytely in South Korea but undergo the highest recombination in China. Therefore, we clustered six PEDV haplotypes in China, whereas South Korea held five haplotypes, including a unique haplotype G. In addition, an assessment of the spatiotemporal spread route of PEDV indicates Germany and Japan as the primary hubs for PEDV dissemination in Europe and Asia, respectively. Overall, our findings provide novel insights into the epidemiology, evolution, and transmission of PEDV, and thus may lay a foundation for the prevention and control of PEDV and other coronaviruses.

Associations between coping styles, gender, their interaction and non-suicidal self-injury among middle school students in rural west China: A multicentre cross-sectional study

Background To investigate the association between coping styles, gender, their interactions and non-suicidal self-injurious (NSSI) behaviors among middle school students in rural western China under COVID-19. Methods A multicentre cross-sectional study method was used to conduct an online survey of 8,361 students from 23 middle schools in the northern Sichuan region by clustering sampling, using the General Information Questionnaire, the Ottawa Self-Injury Inventory, and the Coping Style Scale for Middle School Students. Results The past year prevalence of NSSI among middle school students in rural west China was 5.7%. The differences in scores between those with and without NSSI on all dimensions of coping styles were statistically significant (p < 0.001). Multivariate logistic regression analysis revealed that vocational high school (OR = 1.67), girls (OR = 2.5), single parent with divorced parents (OR = 1.89), remarriage with divorced parents (OR = 1.81), and tolerance (OR = 1.17), venting emotions (OR = 1.15) and fantasy/denial (OR = 1.07) in coping styles may increase the risk of NSSI among middle school students, while problem solving (OR = 0.9) and seeking social support (OR = 0.9) among coping styles may reduce the risk of NSSI among middle school students. The interaction results show that gender has a moderating role in the process of endurance, avoidance, venting of emotions, and fantasy/denial influencing non-suicidal self-injury in middle school students. Conclusion There is an association between coping styles and self-injury among middle school students in rural areas in western China, with gender playing a moderating role. Active attention should be paid to students' coping styles and encouraging them to adopt positive coping styles as well as avoid negative coping styles, especially in the case of girls, which can help prevent self-injury.

Computational pipeline provides mechanistic understanding of Omicron variant of concern neutralizing engineered ACE2 receptor traps (preprint)

The SARS-CoV-2 Omicron variant, with 15 mutations in Spike receptor binding domain (Spike-RBD), renders virtually all clinical monoclonal antibodies against WT SARS-CoV-2 ineffective. We recently engineered the SARS-CoV-2 host entry receptor, ACE2, to tightly bind WT-Spike-RBD and prevent viral entry into host cells (receptor traps). Here we determine cryo-EM structures of our receptor traps in complex with full length Spike. We develop a multi-model pipeline combining Rosetta protein modeling software and cryo-EM to allow interface energy calculations even at limited resolution and identify interface side chains that allow for high affinity interactions between our ACE2 receptor traps and Spike-RBD. Our structural analysis provides a mechanistic rationale for the high affinity (0.53 - 4.2nM) binding of our ACE2 receptor traps to Omicron-RBD confirmed with biolayer interferometry measurements. Finally, we show that ACE2 receptor traps potently neutralize Omicron- and Delta- pseudotyped viruses, providing alternative therapeutic routes to combat this evolving virus.

Early Detection of Emerging SARS-CoV-2 Variants of Interest for Experimental Evaluation (preprint)

Since the beginning of the COVID-19 pandemic, SARS-CoV-2 has demonstrated its ability to rapidly and continuously evolve, leading to the emergence of thousands of different sequence variants, many with distinctive phenotypic properties. Fortunately, the broad availability of next generation sequencing (NGS) technologies across the globe has produced a wealth of SARS-CoV-2 genome sequences, offering a comprehensive picture of how this virus is evolving so that accurate diagnostics and reliable therapeutics for COVID-19 can be maintained. The millions of SARS-CoV-2 sequences deposited into genomic sequencing databases, including GenBank, BV-BRC, and GISAID are annotated with the dates and geographical regions of sample collection, and can be aligned to the Wuhan-Hu-1 reference genome to extract the constellation of nucleotide and amino acid substitutions. By aggregating these data into concise datasets, the spread of variants through space and time can be assessed. Variant tracking efforts have focused on the spike protein due to its critical role in viral tropism and antibody neutralization. To identify emerging variants of concern as early as possible, we developed a computational pipeline to process the genomic data from public databases and assign risk scores based on both epidemiological and functional parameters. Epidemiological dynamics are used to identify variants exhibiting substantial growth over time and across geographical regions. In addition, experimental data that quantify Spike protein regions critical for adaptive immunity are used to predict variants with consequential immunogenic or pathogenic impacts. These growth assessment and functional impact scores are combined to produce a Composite Score for any set of Spike substitutions detected. With this systematic approach to routinely score and rank emerging variants, we have established a method to identify threatening variants early and prioritize them for experimental evaluation.

Gastrointestinal Symptoms Are Associated with Increased Risk of Progression from Non- severe to Severe Illness in COVID-19 Patients (preprint)

BackgroundThe involvement of gastrointestinal (GI) symptoms in the progression of illness in COVID-19 patients has not been illustrated, with the association between GI symptoms and illness severity remaining controversial. The present study aimed to evaluate the association between GI symptoms and the illness progression, severity, and prognosis in COVID-19 patients.MethodsThis study retrospectively recruited consecutive patients with laboratory-confirmed COVID-19 from three hospitals in Wuhan. The severity of illness was classified as non-severe and severe for analyses. The primary outcome was the association between GI symptoms and progression from non-severe to severe illness (PNTS) in COVID-19 patients. ResultsOf the 934 COVID-19 patients (mean age 59.3 years; 43.7% males), the prevalence of overall and specific GI symptoms at/prior to admission were 59.9% and 13.0%, respectively. Patients with GI symptoms were associated with increased risk of fever (56.1% vs. 48.1%; P=0.02), increased IL-6 (18.2% vs. 11.7%; P=0.04), ground-glass opacity (56.8% vs. 43.1%; P<0.001), bilateral pneumonia (80.4% vs. 72.3%; P=0.005), secondary infections (12.6% vs. 6.5%;, P=0.003), and hypoalbuminemia (26.2% vs. 18.4%; P=0.01). Patients with GI symptoms had a higher risk for PNTS (2.9% vs. 0.6%; P=0.02), even after full adjustments (OR, 6.50; (95%CI:1.34-31.6); P=0.02), but comparable risk for severe illness or deaths. GI symptoms and the specific GI symptoms were identified as the independent risk factors for PNTS.Conclusions The occurrence of GI symptoms is proved to be an independent risk factor for PNTS, which might be a predicting indicator in the prevention of illness deterioration at an early stage.

Improved Cloud Auditing Protocol and Its Application for Pandemic Data Management

Data integrity verification mechanisms play an important role in cloud environments. Recently, a lightweight identity-based cloud storage audit scheme has been proposed;this paper points out security vulnerabilities of their OffTagGen algorithm. That is, the attackers such as malicious cloud servers can forge the tags, which can destroy data integrity. By improving the construction of OffTagGen algorithm, an improved security cloud auditing protocol is proposed in this work to better protect user’s privacy. The analysis shows that the new protocol is effective and resistant to attacks.

Prevalence and predictors of post-traumatic stress disorder in patients with cured coronavirus disease 2019 (COVID-19) one month post-discharge Prevalencia y predictores de TEPT en pacientes recuperados de COVID-19 un mes después del alta 新型冠状病毒肺炎患者 (COVID-19) 出院一个月后创伤后应激障碍的患病率和预测因素

Background: Coronavirus disease 2019 (COVID-19) can place an immense psychological strain on the infected patient. The psychological distress can linger after the initial recovery from the infection. Objective: This study aimed to evaluate the prevalence and predictors of provisional post-traumatic stress disorder (PTSD) in patients with cured COVID-2019. Methods: The baseline survey was conducted from 10 to 25 February 2020 in patients with COVID-19 in a designated hospital. Demographic and clinical characteristics were acquired, and depression and anxiety levels were assessed, using the 9-item Patient Health Questionnaire and 7-item Generalized Anxiety Disorder scale, respectively. A follow-up survey was conducted 1 month post-discharge. PTSD symptoms were measured by the Impact of Event Scale-6 (IES-6) and patients’ perception of supportive care during hospitalization was investigated using a self-developed questionnaire. Results: In total, 114 patients completed both the baseline and follow-up surveys. Of these, 41 (36.0%) met the cut-off score for provisional PTSD diagnosis according to the IES-6. Female gender [odds ratio (OR) = 4.69, 95% confidence interval (CI) 1.54–14.37], educational level of high school or below (OR = 15.49, 95% CI 1.13–212.71), higher anxiety levels (OR = 1.34, 95% CI 1.12–1.61) and lower perceptions of emotional support during hospitalization (OR = 0.41, 95% CI 0.17–0.96) predicted a higher risk for provisional PTSD. Conclusions: PTSD is commonly seen in patients with COVID-19 1 month post-discharge. Female patients, and patients with lower educational levels, higher anxiety levels and lower perceptions of emotional support during hospitalization may be more likely to develop PTSD in the near future. Enhancing emotional support during hospitalization could help to prevent PTSD in patients with COVID-19. HIGHLIGHTS More than one-third ofpatients met the diagnostic criteria of probable PTSD 1 month post-discharge. Providing timely emotional support during hospitaliza-tion may be one of the key measures for preventing PTSD in patients with COVID-19.

Small business owners’ Fintech credit in crises: Theory and evidence from farmers under the COVID-19

This paper examines the COVID-19 impact on Chinese farmers’ peer-to-peer (P2P) borrowings using transaction-level data. Our difference-in-differences estimation results suggest that farmers from the most pandemic-affected region, Hubei province, substantially reduced their P2P loans by 13% compared to other areas. Besides, we find a significantly lower equilibrium interest rate change, indicating a more dominant force on the demand side. Finally, we evaluate the lockdown policy, showing that provinces with larger logistics capacities exhibit more considerable credit declines. Overall, our study suggests that Fintech lending functions as an alternative financing channel during the pandemic, though the demand shrinkage dominates the supply.

Declined eGFR Associated With Poor Prognosis in COVID-19 Patients in Wuhan, China: A Retrospective Cohort Study (preprint)

Background: Increasing evidence revealed that kidney was one of the targets of SARS-CoV-2. However, the incidences of kidney abnormalities were significantly different, from 0·5 to 75·4% in coronavirus disease 2019 (COVID-19) patients. The association of kidney injury with prognosis remain controversial.Methods: In this retrospective cohort study, laboratory confirmed COVID-19 in patients with severe type were enrolled. Demographic, clinical, and laboratory data were collected. Association of estimated glomerular filtration rate (eGFR) with 28-days mortality was analyzed.Findings: The total 28-days mortality of hospitalization was 22·3% (79/354). Non-survivors had a significantly declined eGFR levels than survivors (75·95 [IQR: 47·22,92·84] ml/min/1·73m2 vs. 96·43 [IQR: 84·11,108·47] ml/min/1·73m2, P <0·0001). The 28-days mortality in declined eGFR group (<90 ml/min/1·73m2) was significantly higher than that in normal eGFR group (38·5% vs. 10·7%, P <0·0001). Multivariate logistic regression revealed that the independent risk factors of 28-days outcome included lower eGFR (OR: 3·97, 95%CI: 1·42-11·11), elevated WBC (OR: 7·08, 95%CI: 3·15-15·90), lymphopenia (OR: 2·58, 95%CI: 1·21-5·49), and IL-6 (OR: 7·90, 95%CI: 2·19-28·49). Kaplan-Meier analysis indicated the survival disadvantage in patients with declined eGFR. ROC curve showed the eGFR cut-off value for predicting 28-days death was 82·2 μmol/L, with the sensitivity of 76·7%, and specialty of 66·3%.Interpretation: Declined eGFR was associated with poor prognosis, and could be used an independent risk factor of 28-days mortality in COVID-19 patients. Early detection, and surveillance for eGFR may benefit to identify patients with high-risk of progression.Funding Information: Program of Key Talents of Medical Science in Jiangsu Province, Suzhou science and technology development plan.Declaration of Interests: The authors have declared that no conflict of interest exists.Ethics Approval Statement: This study was approved by the institutional review boards at the First Affiliated Hospital of Soochow University and Wuhan Tongji Hospital. As COVID-19 is an emerging infectious disease, the written informed consent was exempted.

Declined eGFR Associated with Poor Prognosis in COVID-19 Patients in Wuhan, China: A Retrospective Cohort Study (preprint)

Background: Increasing evidence revealed that kidney was one of the targets of SARS-CoV-2. However, the incidences of kidney abnormalities were significantly different, from 0.5 to 75.4% in coronavirus disease 2019 (COVID-19) patients. The association of kidney injury with prognosis remain controversial. Methods: : In this retrospective cohort study, laboratory confirmedCOVID-19inpatients with severe type were enrolled. Demographic, clinicaland laboratory data were collected. Association of estimated glomerular fifiltration rate (eGFR)with 28-days mortality was analyzed. Results: : The total 28-days mortality of hospitalizationwas 22.3% (79/354). Non-survivors had a significantly declined eGFR levels than survivors (75.95 [IQR: 47.22,92.84] ml/min/1.73m 2 vs. 96.43 [IQR: 84.11,108.47] ml/min/1.73m 2 , P <0.001). The 28-days mortality in declined eGFR group (<90 ml/min/1.73m 2 ) was significantly higher than that in normal eGFR group (38.5% vs. 10.7%, P <0.001). Multivariate logistic regression revealed that the independent risk factors of 28-days outcome included lower eGFR (OR: 3.97, 95%CI: 1.42-11.11), elevated WBC (OR: 7.08, 95%CI: 3.15-15.90), lymphopenia (OR: 2.58, 95%CI: 1.21-5.49)andIL-6 (OR: 7.90, 95%CI: 2.19-28.49). Kaplan-Meier analysis indicated the survival disadvantage in patients with declined eGFR. ROC curve showed the eGFR cut-off value for predicting 28-days death was 82.2 μmol/L, with the sensitivity of 76.7% and speciality of 66.3%. Conclusion: Declined eGFR was associated with poor prognosis and could be used an independent risk factor of 28-days mortality in COVID-19 patients. Early detection and surveillance for eGFR may benefit to identify patients with high-risk ofprogression.

Long-term variations of aerosol optical properties over Wuhan with polarization lidar

Aerosols greatly impact the global and regional climate system and public health. We conducted lidar measurements at Wuhan (30.53°N, 114.37°E) from October 2010 to June 2020 and analyzed the massive dataset with an automatic lidar processing algorithm, to investigate the long-term variations of aerosols. Lidar-derived total aerosol optical depth (AOD) at 532 nm shows an interannual decrease of −0.049 since 2010. Compared with AODs in other megacities worldwide, the AOD for Wuhan shows the largest decrease rate. After separating AOD contributions from boundary layer (BL) and free troposphere (FT), different evolution patterns are revealed with AOD decrease rates of −0.009 and −0.044 per year for FT and BL, respectively, which indicates more than 80% of AOD decrease are associated with reductions of local emissions. In addition, BL AOD was always larger than FT AOD before COVID-19 lockdown. However, this relation was conversed thereafter, with the lowest value of 0.125 for BL AOD since 2010, which is only the half of FT AOD within the same period. This feature corroborates strong influences of COVID-19 lockdown on human activities and local emissions. These findings can improve our understandings of regional aerosol responses to pollution controls and aerosol direct impacts on regional climate.

High-content screening of coronavirus genes for innate immune suppression revealsenhanced potency of SARS-CoV-2 proteins (preprint)

Suppression of the host intracellular innate immune system is an essential aspect of viral replication. Here, we developed a suite of medium-throughput high-content cell-based assays to reveal the effect of individual coronavirus proteins on antiviral innate immune pathways. Using these assays, we screened the 196 protein products of seven coronaviruses (SARS-CoV-2,SARS-CoV-1, 229E, NL63, OC43, HKU1 and MERS). This includes a previously unidentified gene in SARS-CoV-2 encoded within the Spike gene. We observe immune-suppressing activity in both known host-suppressing genes (e.g., NSP1, Orf6, NSP3, and NSP5) as well as other coronavirus genes, including the newly identified SARS-CoV-2 protein. Moreover, the genes encoded by SARS-CoV-2 are generally more potent immune suppressors than their homologues from the other coronaviruses. This suite of pathway-based and mechanism-agnostic assays could serve as the basis for rapid in vitro prediction of the pathogenicity of novel viruses based on provision of sequence information alone.