A new framework for calibrating COVID-19 SEIR models with spatial-/time-varying coefficients using genetic and sliding window algorithms (preprint)

A susceptible-exposed-infected-removed (SEIR) model assumes spatial-/time-varying coefficients to model the effect of non-pharmaceutical interventions (NPIs) on the regional and temporal distribution of COVID-19 disease epidemics. A significant challenge in using such model is their fast and accurate calibration to observed data from geo-referenced hospitalized data, i.e., efficient estimation of the spatial-/time-varying parameters. In this work, a new calibration framework is proposed towards optimizing the spatial-/time-varying parameters of the SEIR model. We also devise a method for combing the overlapping sliding window technique (OSW) with a genetic algorithm (GA) calibration routine to automatically search the segmented parameter space. Parallelized GA is used to reduce the computational burden. Our framework abstracts the implementation complexity of the method away from the user. It provides high-level APIs for setting up a customized calibration system and consuming the optimized values of parameters. We evaluated the application of our method on the calibration of a spatial age-structured microsimulation model using a single objective function that comprises observed COVID-19-related ICU demand. The results reflect the effectiveness of the proposed method towards estimating the parameters in a changing environment.

Prevalence and Associated Factors of Depression Among Frontline Nurses in Wuhan 6 Months After the Outbreak of COVID-19: A Cross-Sectional Study

Background Due to the COVID-19 pandemic, frontline nurses have experienced psychological problems. However, the depression of frontline nurses in Wuhan 6 months after the outbreak of COVID-19 has not been studied adequately. The purpose of this study was to investigate the depression of frontline nurses in Wuhan 6 months after the COVID-19 outbreak and to analyze possible risk and protective factors. Material/Methods Data were collected through Wenjuanxing from 612 frontline nurses in Wuhan national COVID-19-designated hospitals between July 27, 2020, and August 12, 2020. The levels of depression, family functioning, and psychological resilience were assessed among frontline nurses in Wuhan with a depression scale, family function scale, and 10-item psychological resilience scale, respectively. The factors associated with depressive symptoms were identified using the chi-square test and binary logistic regression analysis. Results A total of 126 respondents were included in the study. The overall prevalence of depression was 25.2%. The need for mental health services was a potential risk factor for depressive symptoms, while family functioning and psychological resilience were potential protective factors. The COVID-19 pandemic poses a major challenge to the depressive symptoms of frontline nursing in Wuhan, highlighting the need for all frontline nurses in Wuhan to be screened for depression regularly for timely intervention. Conclusions To mitigate the impact of the pandemic on depression, psychological interventions for frontline nurses need to be implemented to preserve their mental health.

Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron Variant in Shanghai, China:a retrospective analysis (preprint)

Objectives: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during Omicron variant outbreak. Methods: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, household vaccination rates were collected through electronic health records and telephone interviews. Results: The total of 603 pediatric cases confirmed with COVID-19 was included in this study. Both Univariate and multivariate analysis were performed to filter independent factors for the duration to viral RNA negative conversion. Data on cases re-detected SARS-CoV-2after showing negative results on RT-PCR test (intermittent negative status) were also analyzed. The median duration of virus shedding was 12(Interquartile Qange,IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patient who had abnormal defecation or with more severe condition would delay virological clearance, while patient accepted 2 doses vaccination or with higher household vaccination rates would accelerate virological clearance. Loss of appetite (Odds Ratio (OR) :5.343; 95%CI: 3.307-8.632) and abnormal defecation (OR:2.840; 95%CI: 1.736-4.645) were significantly associated with intermittent negative status. Conclusion: These findings could provide clues for early identification of pediatric patients with prolonged viral shedding, enriching the evidence for development of prevention and control strategies especially the vaccination policies for children and adolescents.

Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron Variant in Shanghai, China (preprint)

Abstract Objectives: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during Omicron variant outbreak. Methods: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, household vaccination rates were collected through electronic health records and telephone interviews. Results: The total of 603 pediatric cases confirmed with COVID-19 was included in this study. Both Univariate and multivariate analysis were performed to filter independent factors for the duration to viral RNA negative conversion. Data on cases re-detected SARS-CoV-2 after showing negative results on RT-PCR test (intermittent negative status) were also analyzed. The median duration of virus shedding was 12(Interquartile Qange,IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patient who had abnormal defecation or with more severe condition would delay virological clearance, while patient accepted 2 doses vaccination or with higher household vaccination rates would accelerate virological clearance. Loss of appetite (Odds Ratio (OR) :5.343; 95%CI: 3.307-8.632) and abnormal defecation (OR:2.840; 95%CI: 1.736-4.645) were significantly associated with intermittent negative status. Conclusion: These findings could provide clues for early identification of pediatric patients with prolonged viral shedding, enriching the evidence for development of prevention and control strategies especially the vaccination policies for children and adolescents.

Structural and computational insights into the SARS-CoV-2 Omicron RBD-ACE2 interaction (preprint)

Since SARS-CoV-2 Omicron variant (B.1.1.529) was reported in November 2021, it has quickly spread to many countries and outcompeted the globally dominant Delta variant in several countries. The Omicron variant contains the largest number of mutations to date, with 32 mutations located at spike (S) glycoprotein, which raised great concern for its enhanced viral fitness and immune escape[1-4]. In this study, we reported the crystal structure of the receptor binding domain (RBD) of Omicron variant S glycoprotein bound to human ACE2 at a resolution of 2.6 Å. Structural comparison, molecular dynamics simulation and binding free energy calculation collectively identified four key mutations (S477N, G496S, Q498R and N501Y) for the enhanced binding of ACE2 by the Omicron RBD compared to the WT RBD. Representative states of the WT and Omicron RBD-ACE2 systems were identified by Markov State Model, which provides a dynamic explanation for the enhanced binding of Omicron RBD. The effects of the mutations in the RBD for antibody recognition were analyzed, especially for the S371L/S373P/S375F substitutions significantly changing the local conformation of the residing loop to deactivate several class IV neutralizing antibodies.

Structural and computational insights into the SARS-CoV-2 Omicron RBD-ACE2 interaction (preprint)

Since SARS-CoV-2 Omicron variant (B.1.1.529) was reported in November 2021, it has quickly spread to many countries and outcompeted the globally dominant Delta variant in several countries. The Omicron variant contains the largest number of mutations to date, with 32 mutations located at spike (S) glycoprotein, which raised great concern for its enhanced viral fitness and immune escape[1-4]. In this study, we reported the crystal structure of the receptor binding domain (RBD) of Omicron variant S glycoprotein bound to human ACE2 at a resolution of 2.6 angstrom. Structural comparison, molecular dynamics simulation and binding free energy calculation collectively identified four key mutations (S477N, G496S, Q498R and N501Y) for the enhanced binding of ACE2 by the Omicron RBD compared to the WT RBD. Representative states of the WT and Omicron RBD-ACE2 systems were identified by Markov State Model, which provides a dynamic explanation for the enhanced binding of Omicron RBD. The effects of the mutations in the RBD for antibody recognition were analyzed, especially for the S371L/S373P/S375F substitutions significantly changing the local conformation of the residing loop to deactivate several class IV neutralizing antibodies.

Working conditions and health status of 6,317 front line public health workers across five provinces in China during the COVID-19 epidemic: a cross-sectional study (preprint)

Background: Public health workers at the Chinese Centre for Disease Control and Prevention (China CDC) and primary health care institutes (PHIs) were among the main workers who implemented prevention, control, and containment measures. However, their efforts and health status have not been well documented. We aimed to investigate the working conditions and health status of front line public health workers in China during the COVID-19 epidemic. Methods: : Between 18 February and 1 March 2020, we conducted an online cross-sectional survey of 2,313 CDC workers and 4,004 PHI workers in five provinces across China experiencing different scales of COVID-19 epidemic. We surveyed all participants about their work conditions, roles, burdens, perceptions, mental health, and self-rated health using a self-constructed questionnaire and standardised measurements (i.e., Patient Health Questionnaire and General Anxiety Disorder scale). To examine the independent associations between working conditions and health outcomes, we used multivariate regression models controlling for potential confounders. Results: : The prevalence of depression, anxiety, and poor self-rated health was 21.3%, 19.0%, and 9.8%, respectively, among public health workers (27.1%, 20.6%, and 15.0% among CDC workers and 17.5%, 17.9%, and 6.8% among PHI workers). The majority (71.6%) made immense efforts in both field and non-field work. Nearly 20.0% have worked all night for more than 3 days, and 45.3% had worked throughout the Chinese New Year holiday. Three risk factors and two protective factors were found to be independently associated with all three health outcomes in our final multivariate models: working all night for >3 days (multivariate odds ratio [ORm]=1.67~1.75, p <0.001), concerns about infection at work (ORm=1.46~1.89, p <0.001), perceived troubles at work (ORm=1.10~1.28, p <0.001), initiating COVID-19 prevention work after January 23 (ORm=0.78~0.82, p =0.002~0.008), and ability to persist for > 1 month at the current work intensity (ORm=0.44~0.55, p <0.001). Conclusions: : Chinese public health workers made immense efforts and personal sacrifices to control the COVID-19 epidemic and faced the risk of mental health problems. Efforts are needed to improve the working conditions and health status of public health workers and thus maintain their morale and effectiveness during the fight against COVID-19.

Difficulties of Prevention and Control Staff in COVID-19 Outbreak: A Cross-sectional Study Based on Five Provinces (preprint)

Objectives: The aim of this study is to address the difficulties encountered by epidemic control staff in the early and middle stages of their efforts to combat COVID-19, compare the gaps among different types of institutions, and identify shortcomings in epidemic control. Methods: Using multi-stage sampling, a survey of primary (“primary-urban” and “primary-rural”) and non-primary (“CDC”) public health workers involved in the prevention and control of COVID-19 in five provinces, including Hubei, Guangdong, Sichuan, Jiangsu and Gansu, was conducted from 18 February to 1 March 2020 through a self-administered questionnaire.Results: A total of 9475 outbreak prevention and control workers were surveyed, of which 40.0% were from the primary-rural, 27.0% were from the primary-urban and 33.0% were CDC. Resources shortage was reported at 27.9%, with the primary-rural being the worst affected (OR=1.201, 95%CI: 1.073-1.345). Difficulties in data processing were reported at 31.5%, with no significant differences among institutions. Communication and coordination difficulties were reported at 29.8%, with the CDC being the most serious (the rural primary: OR=0.520, 95%CI: 0.446-0.606; the primary-urban: OR=0.533, 95%CI: 0.454-0.625). Work object difficulties were reported at 20.2%, with the primary-urban being the worst (OR=1.368, 95%CI: 1.199-1.560). Psychological distress was reported at 48.8%, with no significant differences among institutions.Conclusions: Psychological distress is the most serious problem in the prevention and control of COVID-19, and the resources shortage in primary-rural, communication and coordination difficulties in CDC, and difficulties in working with the target population in the primary-urban deserve attention. This study will provide a scientific basis for improving the national public health emergency management system, especially for reducing the urban-rural differences in emergency response capacity.

Clinical Features of Hemodialysis (HD) patients confirmed with Coronavirus Disease 2019 (COVID-19): a Retrospective Case-Control Study (preprint)

Background: Since December 2019, Coronavirus Disease 2019(COVID-19) occurred in wuhan, China, and outbreaked rapidly into a global pandemic. This current poses great challenges to hemodialysis (HD) patients. Objective: To make a comprehensive evaluation and comparison between HD patients confirmed with COVID-19 and the general HD patients. Methods: HD patients confirmed with COVID-19 in Wuhan No.5 Hospital were admitted as confirmed group from Jan 10 to Mar 15, 2020. And HD patients not infected in our dialysis center were chosen as control group. General characteristics, laboratory indicators were retrospectively collected, analyzed and compared. Results: A total of 142 cases were admitted, including 43 cases in confirmed group and 99 in control group. Body mass index (BMI) was slightly lower in confirmed group than that in control group (P=0.011). The proportion of one or less underlying disease in confirmed group(51.16%) was higher than that in control group(14.14%)(P< 0.001), and the proportion of three or more underlying diseases in confirmed group(11.63%) was lower than that in control group(52.53%)(P< 0.001). Patients in confirmed group exhibited significantly lower hemoglobin, lymphocyte count, and lymphocyte percentage, but higher neutrophil percentage, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, aspartate transaminase, and alkaline phosphatase. There was no significant difference in age, gender, dialysis age, primary disease, the using of ACEI/ARB, platelet-to-lymphocyte ratio (PLR) , and other indicators between the two groups. Conclusions: Faced with Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV-2), HD patients with lower BMI and hemoglobin were more susceptible to be infected, which might be related to malnutrition. Once confirmed with COVID-19, HD patients expressed obviously disregulated in inflammation and immune.

Crystal structure of SARS-CoV-2 main protease in complex with a Chinese herb inhibitor shikonin (preprint)

Main protease (Mpro, also known as 3CLpro) has a major role in the replication of coronavirus life cycle and is one of the most important drug targets for anticoronavirus agents. Here we report the crystal structure of main protease of SARS-CoV-2 bound to a previously identified Chinese herb inhibitor shikonin at 2.45 angstrom resolution. Although the structure revealed here shares similar overall structure with other published structures, there are several key differences which highlight potential features that could be exploited. The catalytic dyad His41-Cys145 undergoes dramatic conformational changes, and the structure reveals an unusual arrangement of oxyanion loop stabilized by the substrate. Binding to shikonin and binding of covalent inhibitors show different binding modes, suggesting a diversity in inhibitor binding. As we learn more about different binding modes and their structure-function relationships, it is probable that we can design more effective and specific drugs with high potency that can serve as effect SARS-CoV-2 anti-viral agents.

Structure of SARS-CoV-2 main protease in the apo state reveals the inactive conformation (preprint)

Mpro is of considerable interest as a drug target in the treatment of COVID-19 since the proteolytic activity of this viral protease is essential for viral replication. Here we report the first insight of the structure Mpro for SARS-CoV-2 in the inactive conformation under conditions close to the physiological state (pH 7.5) to an overall resolution of 1.9 [A]. The comparisons of Mpro in different states reveal that substrate binding site and the active site are more flexible in the inactive conformation than that in the active conformations. Notably, compared with the active conformation of the apo state structure in pH7.6 of SARS, the SARS-CoV-2 apo state is in the inactive conformation under condition close to physiological state (pH7.5). Two water molecules are present in the oxyanion hole in our apo state structure, whereas in the ligand-bound structure, water molecular is absence in the same region. This structure provides novel and important insights that have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational, structure-based, approaches for the design of specific SARS-CoV-2 ligands as new therapeutic agents.

Taking the pulse of COVID-19: A spatiotemporal perspective (preprint)

The sudden outbreak of the Coronavirus disease (COVID-19) swept across the world in early 2020, triggering the lockdowns of several billion people across many countries, including China, Spain, India, the U.K., Italy, France, Germany, and most states of the U.S. The transmission of the virus accelerated rapidly with the most confirmed cases in the U.S., and New York City became an epicenter of the pandemic by the end of March. In response to this national and global emergency, the NSF Spatiotemporal Innovation Center brought together a taskforce of international researchers and assembled implemented strategies to rapidly respond to this crisis, for supporting research, saving lives, and protecting the health of global citizens. This perspective paper presents our collective view on the global health emergency and our effort in collecting, analyzing, and sharing relevant data on global policy and government responses, geospatial indicators of the outbreak and evolving forecasts; in developing research capabilities and mitigation measures with global scientists, promoting collaborative research on outbreak dynamics, and reflecting on the dynamic responses from human societies.

A scoping review of 2019 Novel Coronavirus during the early outbreak period: Epidemiology, causes, clinical manifestation and diagnosis, prevention and control (preprint)

Background: The 2019-nCoV has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. This epidemic had spread to 19 countries with 11791 confirmed cases, including 213 deaths, as of January 31, 2020. The World Health Organization declared it as a Public Health Emergency of International Concern.Methods: A scoping review of 65 research articles published until January 31, 2020 were analyzed and discussed for a better understanding of the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, publishing dates, journal language, and authors’ affiliations, as well as methodological characteristics were analyzed. All findings and statements that are mentioned regarding the outbreak in this review are based on published information as listed in the references.Results: Most of the publications were in English language (89.23%). The largest proportion of articles were related to causes (38.46%) and majority (67.69%), and were published by Chinese scholars. Research articles initially focused on causes while there was an increase of the articles related to prevention and control over time. Studies thus far have shown origination in connection to a seafood market in Wuhan, but specific animal association has not been confirmed. The reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines are being discussed for reducing the transmission. To date, no specific antiviral treatment is proven effective, hence, infected people primarily rely on symptomatic treatment and supportive care. Conclusions: There has been a rapid surge in research in response to the outbreak of 2019-nCoV. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies had relevance to the control of a public emergency, more high-quality research need to be conducted to provide valid and reliable ways to manage this kind of public health emergency in both short-and long-terms.

Crystal structure of the 2019-nCoV spike receptor-binding domain bound with the ACE2 receptor (preprint)

A novel and highly pathogenic coronavirus (2019-nCoV) has caused an outbreak in Wuhan city, Hubei province of China since December 2019, and soon spread nationwide and spilled over to other countries around the world. To better understand the initial step of infection at atomic-level, we determined the crystal structure of the 2019-nCoV spike receptor-binding domain (RBD) bound with the cell receptor ACE2 at 2.45 [A] resolution. The overall ACE2-binding mode of the 2019-nCoV RBD is nearly identical to that of the SARS-CoV RBD, which also utilizes ACE2 as the cell receptor. Structural analysis identified residues in 2019-nCoV RBD critical for ACE2 binding, and majority of which are either highly conserved or shared similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly argue for a convergent evolution between 2019-nCoV and SARS-CoV RBD for improved binding to ACE2 despite of being segregated in different genetic lineages in the betacoronavirus genus. The epitopes of two SARS-CoV antibodies targeting the RBD are also analyzed with the 2019-nCoV RBD, providing insights into future identification of cross-reactive antibodies.

A Literature Review of 2019 Novel Coronavirus During the Early Outbreak Period: Epidemiology, Causes, Clinical Manifestation and Diagnosis, Prevention and Control (preprint)

The 2019-nCoV has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. This epidemic had spread to 19 countries with 11,791 confirmed cases, including 213 deaths, as of January 31, 2020. The World Health Organization declared it as a Public Health Emergency of International Concern. This study analyzed and discussed 70 research articles published until January 31, 2020 for a better understanding of the epidemiology, causes, clinical diagnosis, prevention and control of this virus. Studies thus far have shown origination in connection to a seafood market in Wuhan, but specific animal association has not been confirmed. The reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines are effective for reducing the transmission. To date, no specific antiviral treatment is proven effective, hence, infected people primarily rely on symptomatic treatment and supportive care. Although these studies had relevance to control a public emergency, more research need to be conducted to provide valid and reliable ways to manage this kind of public health emergency in both short- and long- term.