Inactivated SARS-CoV-2 vaccine does not increase the risk of relapse in patients with clinically inactive adult-onset Still's disease.

OBJECTIVE: A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. METHODS: We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBPCorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. RESULTS: A total of 122 patients with inactive AOSD were included, of which 49.2% (n = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% versus 6.8%), and no relapse occurred within one month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. CONCLUSION: Increased disease activity or relapse following vaccination with inactivated SARS-CoV-2 were rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS-CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2.

Counterterrorism resource allocation during a pandemic: The effects of dynamic target valuations when facing a strategic terrorist.

The outbreak of pandemics such as COVID-19 can result in cascading effects for global systemic risk. To combat an ongoing pandemic, governmental resources are largely allocated toward supporting the health of the public and economy. This shift in attention can lead to security vulnerabilities which are exploited by terrorists. In view of this, counterterrorism during a pandemic is of critical interest to the safety and well-being of the global society. Most notably, the population flows among potential targets are likely to change in conjunction with the trend of the health crisis, which leads to fluctuations in target valuations. In this situation, a new challenge for the defender is to optimally allocate his/her resources among targets that have changing valuations, where his/her intention is to minimize the expected losses from potential terrorist attacks. In order to deal with this challenge, in this paper, we first develop a defender-attacker game in sequential form, where the target valuations can change as a result of the pandemic. Then we analyze the effects of a pandemic on counterterrorism resource allocation from the perspective of dynamic target valuations. Finally, we provide some examples to display the theoretical results, and present a case study to illustrate the usability of our proposed model during a pandemic.

Status of mandatory treatment of mentally ill offenders without criminal responsibility in China: Information from 5,262 mandatory treatment judgments.

Background: To avoid public health risks, all governments ensure monitoring and treatment of mentally ill persons if they offend and assess their level of criminal responsibility. The Criminal Procedure Law of the People's Republic of China (2013) instituted special procedures. However, there are few articles in English which explain the implementation of mandatory treatment procedures in China. Methods: We collected 5,262 qualified documents from 2013 to 2021 from the China Judgments Documents Online. We analyzed social demographic characteristics, trial-related information as well as the mandatory treatment-related content, to investigate the mandatory treatment of China's mentally ill offenders without criminal responsibility, from 2013 to 2021. Simple descriptive statistics and chi-square tests were used to compare differences among several types of documents. Results: There was an overall change trend of the number of documents: increasing year by year from 2013 to 2019 after the implementation of the new law, but with sharp decrease in 2020 and 2021 during covid-19 pandemic. From 2013 to 2021, a total of 3,854 people had applications made for mandatory treatment, of whom 3,747 (97.2%) were given mandatory treatment, 107 (2.8%) had applications rejected. "Schizophrenia and other psychotic disorders" was the most common diagnosis in both groups and all offenders receiving mandatory treatment (3,747, 100.0%) were considered to have no criminal responsibility. A total of 1,294 patients had applications made for relief of mandatory treatment, of whom 827 (63.9%) were subsequently approved for relief, 467 (36.1%) were rejected. A total of 118 patients had applications for relief two or more times, and 56 (47.5%) were finally relieved. Conclusion: Our study presents the Chinese model of a criminal mandatory treatment system to the international community which has been in operation since the implementation of the new law. Legislatory changes and covid-19 pandemic can have effect on the number of mandatory treatment cases. Patients, their close relatives and mandatory treatment institutions have the right to apply for relief from mandatory treatment, but the final decision in China is taken by the court.

COVID-19 vaccine affects neither prothrombotic antibody profile nor thrombosis in primary antiphospholipid syndrome: a prospective study.

OBJECTIVE: To explore whether inactivated COVID-19 vaccine influences the profile of prothrombotic autoantibodies and induces thrombotic events in primary antiphospholipid syndrome (APS) patients. METHODS: We enrolled 39 primary APS patients who received two doses of inactivated SARS-CoV-2 vaccine (BBIBPCorV, Sinopharm, Beijing, China) voluntarily in this prospective cohort. Prothrombotic autoantibodies were determined before vaccination and four weeks after the 2nd dose of vaccination. Thrombotic disorders were evaluated via hospital site visits and assessments. RESULTS: There was no significant difference in the presence of all eleven autoantibodies detected before and four weeks after vaccination: for aCL, IgG (14 vs. 16, P= 0.64), IgM (13 vs. 19, P= 0.34), IgA (2 vs. 3, P= 0.64); anti-ß2GP1, IgG (12 vs. 12, P= 1.00), IgM (5 vs. 8, P= 0.36), IgA (4 vs. 3, P= 0.69); aPS/PT IgG (13 vs. 16, P= 0.48), IgM (17 vs. 22, P= 0.26); LAC (22 vs. 28, P= 0.16); aPF4-heparin (0 vs. 0, P= 1.00), and antinuclear antibody (ANA) (23 vs. 26, P= 0.48). Notably, the distribution of aPL profile in pre- and post- vaccination cohort was not affected by SARS-CoV-2 vaccination: for patients with low-risk aPL profile (11 vs. 10, P= 0.799) and patients with high-risk aPL profile (28 vs. 29, P= 0.799), respectively. Furthermore, no case exhibited symptoms of the thrombotic disorder during a minimum follow-up period of 12 weeks. There was no adjustment to the ongoing treatment regimens following SARS-CoV-2 vaccination. CONCLUSIONS: Inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibodies and anti-PF4-heparin antibodies nor induces thrombotic events in primary APS patients.

An imported case of ovale malaria in Xinjiang during the epidemic period of COVID-19

On December 13, 2020, Yutian County People's hospital reported one imported malaria case in Hotan, Xinjiang. The patient had worked and lived in Yaounde, Cameroon, from January to September 2020. He was infected with malaria twice in March and May 2020. Antimalarial treatment was administrated by the team doctor for 2-3 days in each treatment. The treatment was stopped after the symptoms improved. The patient returned to China on September 16 and was hospitalized on December 13 due to a high fever of 39 degrees C and upper respiratory symptoms. Multiple detections of COVID-19 nucleic acid showed negative results. Peripheral blood from the patient was taken for Plasmodium rapid diagnostic test (RDT), which showed a positive result suggesting non Plasmodium falciparum infection. Ring stage P. ovale was found in the blood smear. Nested PCR showed positive for P. ovale. A diagnosis of imported ovale malaria was made. The patient was administrated with 4 dihydroartemisinin piperaquine tablets and 3 primaquine phosphate tablets daily. The malaria parasite test became negative after 8 days of treatment. The patient was followed up for 3 months after discharge and had no symptoms of chills or fever.

Whole genome sequence analysis of SARS-CoV-2 from 40 imported cases of confirmed COVID-19 in Sichuan

Objective To understand the genomic characteristics of SARS-CoV-2 from 40 imported cases with confirmed COVID-19 in Sichuan during January and March 2022. Methods Total viral RNA was extracted from respiratory samples of 182 confirmed COVID-19 cases who entered China through Chendu International Airport from January to March 2022.Mutation nucleic acid detection kit was used to identify the mutant strains and Illumina sequencing platform was applied for whole genome sequence（WGS） of virus.SARS-CoV-2 reference sequences were downloaded from NCBI database for genetic evolution and antigen variation analysis.The Nextclade and Pangolin online virus analysis platform were used to determine the virus family and type,and to analyze the mutation loci of the virus.The phylogenetic tree was constructed,along with the epidemiological data of cases to analyze the source and correlation of viruses. Results Among 182 imported COVID-19 cases,B.1.617.2 mutations were identified in 3 cases and B.1.1.529 mutations were detected in 57 cases.A total of 40 SARS-CoV-2 whole genome sequences with coverage>95% were obtained in this study.Nextclade typing analysis showed that 3 sequences belonged to 21J（Delta）,5 sequences belonged to 21K（Omicron）and the remaining 32 sequences belonged to 21L（Omicron）.Pangolin typing analysis showed that the 3 sequences of 21J（Delta）belonged to AY.4,AY.109and B.1.617.2,the 5sequences of 21K（Omicron）all belonged to BA.1.1,and the remaining 32 sequences of 21L（Omicron）belonged to BA.2.Our sequence results were99.7% consistency with the Omicron variants sequences in current GISAID database.Compared with the reference sequence strain Wuhan-Hu-1（NC＿045512.2）,45,47and 42nucleotide variation sites and 36,25 and 36amino acid variation sites were found in the 3 sequences of 21J（Delta）.There were average 59（26-64）nucleotide mutation sites and 48（10-53）amino acid mutation sites in the 5sequences of 21K（Omicron）.The median number of nucleotide mutation sites of 71（66-76）and amino acid mutation sites of 53（40-56）were identified in the 32sequences of 21L（Omicron）.Phylogenetic tree analysis showed that 40SARS-CoV-2WGSs were all related to the current variants of concern（VOC）. Conclusions Continuous sequencing of SARS-CoV-2whole genome from imported cases with confirmed COVID-19is of great significance for the prevention and control of the outbreak and prevalence of local epidemic caused by imported viruses in Sichuan.

Analysis of pathogenic bacteria, their drug resistance, and cytokines in 60 patients with a puerperal infection after a Cesarian section

Objectives: To investigate pathogenic bacteria, their drug resistance, and changes in levels of cytokines in patients with a puerperal infection after a Cesarean section.

Predicting Consumer Green Product Purchase Attitudes and Behavioral Intention During COVID-19 Pandemic.

This work has aimed to investigate the consumers' green product purchase attitudes and behavioral intention during COVID-19 pandemic. Data was collected through a survey method of 503 consumers in Malaysia. Data were analyzed using the partial least square method. The findings revealed that fear of COVID-19 pandemic has a significant impact on green product behavioral intention. Green product literacy, green product orientation, and social influence have a significant influence on green product purchase attitudes. The results also indicated that consumers' green product purchase attitudes mediate the effect of green product literacy, green product orientation, and social influence on behavioral intention. The findings of this work will provide strategically relevant references to green marketers and retail managers in the understanding of consumers' green product purchase attitudes and green product behavioral intention during the ongoing uncertainty of the COVID-19 pandemic.

Psychological experience of COVID-19 patients: A systematic review and qualitative meta-synthesis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has not only placed an unprecedented strain on healthcare systems worldwide, but has also caused irreparable physical and psychological damage to those infected. It is essential to understand the disease process and psychological experience of patients with COVID-19, to provide them with efficacious psychological guidance and interventions. This qualitative systematic review sought to explore the experience of COVID-19 patients. METHODS: The meta-analysis methodology developed by the Joanna Briggs Institute guided this systematic review and qualitative meta-analysis. Seven databases were searched, with no language restrictions. This study was registered with PROSPERO under accession number CRD42021279266. RESULTS: A total of 3107 potentially eligible articles were identified through database and reference list searches, among which 23 studies (from 10 countries) were ultimately included in our analysis. Five interrelated themes emerged: the complex psychological course of COVID-19 patients; the impact of the disease on the body; the expectation of support and guidance from multiple sources; coping strategies; and post-traumatic growth. CONCLUSIONS: Psychological distress among patients with COVID-19 was found to be widespread. Healthcare providers should pay attention to the psychological changes in patients, ensure continuity of care and provide professional support from hospital to home, and build patients' confidence so that they can return to their families and society. Long-term follow-up studies may provide deeper insight into the psychological needs of survivors.

Cocktail polysaccharides isolated from Ecklonia kurome against the SARS-CoV-2 infection.

Previous researches suggested that polysaccharides from brown algae had anti-virus activity. We hypothesized that nature polysaccharide from marine plants might have the effect on anti-SARS-CoV-2 activity. By high throughput screening to target 3CLpro enzyme using polysaccharides library, we discover a crude polysaccharide 375 from seaweed Ecklonia kurome blocked 3CLpro enzymatic activity and shows good anti-SARS-CoV-2 infection activity in cell. Further, we show that homogeneous polysaccharide 37502 from the 375 may bind to 3CLpro well and disturb spike protein binding to ACE2 receptor. The structure characterization uncovers that 37502 is alginate. These results imply that the bioactivities of 375 on SARS-CoV-2 may target multiple key molecules implicated in the virus infection and replication. The above results suggest that 375 may be a potential drug candidate against SARS-CoV-2.

What is the relationship between government response and COVID-19 pandemics? Global evidence of 118 countries.

Using daily data of novel coronavirus pneumonia (COVID-19) covering 118 countries from January 1 to April 13, 2021, this research examines the relationship between the government response stringency index (GRSI) and COVID-19 pandemic. The empirical results show that GRSI significantly negatively impacts confirmed cases, and the effects are especially larger around 14 to 21 days after the implementation of the government response. These results are robust through analysis with sub-samples of Asian countries and non-Asian countries, proving that public prevention policies of being isolated for 14 days and being observed for 7 days are effective. The Dumitrescu-Hurlin causality test uncovers a statistically significant bi-directional correlation between government response stringency and COVID-19 pandemic when analyzing the full samples. In terms of the sub-samples, a bi-directional relationship exists between government response stringency and confirmed cases, while one-way causality runs only from government response stringency to deaths in Asian countries. We offer a policy implication that countries all over the world should continue to carry out public prevention policies, and governments in non-Asian countries should be more concerned about confirmed cases.

Development and clinical evaluation of a rapid antibody lateral flow assay for the diagnosis of SARS-CoV-2 infection.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has quickly spread worldwide since its outbreak in December 2019. One of the primary measures for controlling the spread of SARS-CoV-2 infection is an accurate assay for its diagnosis. SARS-CoV-2 real-time PCR kits suffer from some limitations, including false-negative results in the clinic. Therefore, there is an urgent need for the development of a rapid antibody test kit for COVID-19 diagnosis. METHODS: The nuclear capsid protein (N) and spike protein 1 (S1) fragments of SARS-CoV-2 were expressed in Escherichia coli, and rapid antibody-based tests for the diagnosis of SARS-CoV-2 infection were developed. To evaluate their clinical applications, the serum from COVID-19 patients, suspected COVID-19 patients, recovering COVID-19 patients, patients with general fever or pulmonary infection, doctors and nurses who worked at the fever clinic, and health professionals was analyzed by the rapid antibody test kits. The serum from patients infected with Mycoplasma pneumoniae and patients with respiratory tract infection was further analyzed to test its cross-reactivity with other respiratory pathogens. RESULTS: A 47 kDa N protein and 67 kDa S1 fragment of SARS-CoV-2 were successfully expressed, purified, and renatured. The rapid antibody test with recombinant N protein showed higher positive rate than the rapid IgM antibody test with recombinant S1 protein. Clinical evaluation showed that the rapid antibody test kit with recombinant N protein had 88.56 % analytical sensitivity and 97.42 % specificity for COVID-19 patients, 53.48 % positive rate for suspected COVID-19 patients, 57.14 % positive rate for recovering COVID-19 patients, and 0.5-0.8 % cross-reactivity with other respiratory pathogens. The analytical sensitivity of the kit did not significantly differ in COVID-19 patients with different disease courses (p < 0.01). CONCLUSIONS: The rapid antibody test kit with recombinant N protein has high specificity and analytical sensitivity, and can be used for the diagnosis of SARS-CoV-2 infection combined with RT-PCR.

Does COVID-19 pandemic hurt stock prices of solar enterprises?

This research examines the relationships between stock prices of solar enterprises and the COVID-19 pandemic for 18 enterprises from OECD countries and 3 enterprises from non-OECD countries from January 2, 2020 to March 8, 2021. The empirical results show that there exists a cointegration relationship between the pandemic and solar stock prices. Moreover, the effects of COVID-19 pandemic on solar stock prices exhibit heterogeneity, as the COVID-19 pandemic affects solar stock prices negatively in the full sample and OECD countries, whereas the pandemic negatively affects solar stock prices in both the short run and long run, but the effects are not significant in non-OECD countries. We conduct a series of robustness tests, including changing variables and employing the Markov switching regression for time-series analysis, and the results support our main findings. According to the empirical results, investors should be prudent about investing in solar enterprises, while policymakers should balance pandemic control and maintain economic performance when implementing prevention policies.

Investigation into molecular mechanisms and high-frequency core TCM for pulmonary fibrosis secondary to COVID-19 based on network pharmacology and data mining.

BACKGROUND: The complication, pulmonary fibrosis (PF) secondary to COVID-19, may have a second wave of late mortality, given the huge number of individuals infected by COVID-19. However, the molecular mechanisms of PF secondary to COVID-19 haven't been fully elucidated, making the identification of novel strategies for targeted therapy challenging. This study aimed to systematically identify the molecular mechanisms and high-frequency core traditional Chinese medicine (TCM) targeting PF secondary to COVID-19 through network pharmacology and data mining. METHODS: The molecular mechanisms of PF secondary to COVID-19 were identified by mapping the COVID-19 differentially expressed gene and known targets associated with PF, protein-protein interactions network analysis, and enrichment pathway analysis; then the high-frequency core TCM targeting PF secondary to COVID-19 were identified by data mining and "Key targets related to PF secondary to COVID-19 - Ingredients" and "Key ingredients-key herbs" network analysis; and last we validated the interaction between the key ingredients and key targets by molecular docking. RESULTS: The molecular mechanisms of PF secondary to COVID-19 were mainly related to tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interaction pathway, and NF-κB signaling pathway. Among these, cytokines interleukin 6 (IL-6), TNF, and IL-1ß were identified as the key targets associated with PF secondary to COVID-19. The high-frequency core TCM targeting these key targets were identified, including ingredients of quercetin, epigallocatechin-3-gallate, emodin, triptolide, resveratrol, and herb of Polygonum cuspidatum. Finally, our results were validated by quercetin and resveratrol both well docked to IL-6, TNF, and IL-1ß protein, with the estimated docking energy <0 kcal/mol. CONCLUSIONS: This study identified the cytokines-related molecular mechanisms of PF secondary to COVID-19, and the high-frequency core TCM against PF by targeting IL-6, TNF, and IL-1ß. Which provides new ideas for the discovery of small molecular compounds with potential therapeutic effects on PF secondary to COVID-19.

Lacking Communication Would Increase General Symptom Index Scores of Medical Team Members During COVID-19 Pandemic in China: A Retrospective Cohort Study.

There are few studies on the psychological status of medical staff during the COVID-19 outbreak. Our study addresses whether lack of communication affects the psychological status of medical team members supporting Wuhan during the COVID-19 pandemic in China. We used general symptom index (GSI) scores of the Symptom Checklist-90 (SCL-90) to evaluate participants' psychological status. We adopted a stratified sampling method and selected the fourth team, with a total of 137 members, as participants. In total 76.6% and 69.7% of female and male participants, respectively, had bachelor's degrees; 41.6% and 21.2% of female and male participants, respectively, were unmarried. Regarding communication, 14.29% and 6.06% of female and male participants, respectively, reported a lack of communication with the team (LCWT). Additionally, 13.0% and 6.1% of female and male participants, respectively, experienced fear of being infected (FoBI). LCWT and FoBI were positively correlated with GSI score (estimated change = 0.2, 95% CI [0.1-0.3]). When adjusted for gender, age, and FoBI, LCWT was positively correlated with GSI score (P < .05). Increasing communication among medical team members can reduce GSI scores.

Cytokine Storm in Coronavirus Disease 2019 and Adult-Onset Still's Disease: Similarities and Differences.

The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still's disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1ß, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared with those in active AOSD. There were no significant differences on the cytokine of IL-1ß and TNF-α. Fold changes of IL-18 were defined as the mean expression level ratio of severe COVID-19 to healthy controls in the COVID-19 study and active AOSD to healthy controls in our study, individually. Although the fold change of IL-18 in patients with AOSD was significantly higher than patients with severe COVID-19 (fold change: 594.00 vs 2.17), there was no statistical comparability. In addition, the level of ferritin was higher in active AOSD in comparison with severe COVID-19. Our findings suggest that severe COVID-19 and active AOSD have differences in cytokine panel and ferritin level, indicating the pathogenic role of ferritin in overwhelming inflammation. And it paves the way to make efficacy therapeutic strategy targeting the hyperinflammatory process in COVID-19 according to AOSD management, especially in severe COVID-19.

More Accurate Estimates of the Accuracy of RT-PCR and Chest CT Tests for COVID-19 (preprint)

In this article, we propose a novel statistical method for estimating the accuracy of chest computed tomography (CT) and reverse transcription polymerase chain reaction (RT-PCR) tests in the diagnosis of coronavirus disease 2019 (COVID-19), with a correction for imperfect gold standard and verification bias simultaneously. These two types of bias are often involved in estimating the diagnostic accuracy of COVID-19 tests. Imperfect gold standard bias arises when estimating accuracy measures of chest CT while using the RT-PCR test as a gold standard, despite its tendency to produce false negative results. Meanwhile, verification bias occurs in some studies where the results from chest CT are verified by RT-PCR test in a subsample of suspected cases that is not representative of the original population. Consequently, the accuracy estimates of chest CT and RT-PCR tests could be seriously biased and lead to invalid inference. Our proposed method is able to correct these two types of bias in providing unbiased and more accurate estimates of sensitivity and specificity of the two tests. Our results suggest that chest CT has higher sensitivity and lower specificity than RT-PCR, and the accuracy estimates can serve as an important reference for assessing and comparing the performance of these two tests in the diagnosis of COVID-19, and could guide policy recommendations for the implementation of these tests.

Genetic evolution analysis of SARS-CoV-2 ORF 1ab/S/M protein and screening of epitopes of mRNA vaccine

Objective　To analyze the genetic and evolutionary properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF 1ab/S/M proteins and select antigen epitope sequences of mRNA vaccines. Methods　We analyzed the worldwide SARS-CoV-2 genome sequences in this study and have focused on the protein and nucleic acid sequences of the ORF 1ab/S/M. The neighbor-joining tree was employed to map the global distribution of genetic differences. Based on current research on SARS-CoV-2 and SARS-CoV-2 genetic differences, we predicted candidate mRNA vaccines for SARS-CoV-2. Results　The SARS-CoV-2 ORF 1ab nucleic acid sequence similarity is 100.0%, while the homology is 99.3% in the global hot region;the S-protein nucleic acid sequence similarity is 100.0%, while the homology is 97.5%;the M-protein nucleic acid sequence similarity is 100.0%, while the homology is 99.9%. Global distribution of ORF 1ab/S/M proteins indicates that there is a significant genetic difference between the Americas and Eurasia. Potential vaccine antigen epitope mRNA sequences (11 B cell responses and 13 T cell responses) were selected for SARS-CoV-2 ORF 1ab protein;6 B cell responses and 4 T cell responses antigen epitope mRNA sequences were selected for the Spike protein;3 B cell responses and 7 T cell responses antigen epitope mRNA sequences were selected for the membrane protein. Conclusion　There are significant genetic differences in the global hot spot of SARS-CoV-2 in the Americas and Eurasia. Through our new antigen design strategy to screen linear epitopes, we predicted many sequences in ORF 1ab/S/M coding region that potentially raising an immune response. Our study will benefit the discovery of the mRNA vaccine (tandem antigen epitope sequence), antibody discovery, and potentially understanding related immune mechanisms.

Prognostic Assessment of COVID-19 in the Intensive Care Unit by Machine Learning Methods: Model Development and Validation.

BACKGROUND: Patients with COVID-19 in the intensive care unit (ICU) have a high mortality rate, and methods to assess patients' prognosis early and administer precise treatment are of great significance. OBJECTIVE: The aim of this study was to use machine learning to construct a model for the analysis of risk factors and prediction of mortality among ICU patients with COVID-19. METHODS: In this study, 123 patients with COVID-19 in the ICU of Vulcan Hill Hospital were retrospectively selected from the database, and the data were randomly divided into a training data set (n=98) and test data set (n=25) with a 4:1 ratio. Significance tests, correlation analysis, and factor analysis were used to screen 100 potential risk factors individually. Conventional logistic regression methods and four machine learning algorithms were used to construct the risk prediction model for the prognosis of patients with COVID-19 in the ICU. The performance of these machine learning models was measured by the area under the receiver operating characteristic curve (AUC). Interpretation and evaluation of the risk prediction model were performed using calibration curves, SHapley Additive exPlanations (SHAP), Local Interpretable Model-Agnostic Explanations (LIME), etc, to ensure its stability and reliability. The outcome was based on the ICU deaths recorded from the database. RESULTS: Layer-by-layer screening of 100 potential risk factors finally revealed 8 important risk factors that were included in the risk prediction model: lymphocyte percentage, prothrombin time, lactate dehydrogenase, total bilirubin, eosinophil percentage, creatinine, neutrophil percentage, and albumin level. Finally, an eXtreme Gradient Boosting (XGBoost) model established with the 8 important risk factors showed the best recognition ability in the training set of 5-fold cross validation (AUC=0.86) and the verification queue (AUC=0.92). The calibration curve showed that the risk predicted by the model was in good agreement with the actual risk. In addition, using the SHAP and LIME algorithms, feature interpretation and sample prediction interpretation algorithms of the XGBoost black box model were implemented. Additionally, the model was translated into a web-based risk calculator that is freely available for public usage. CONCLUSIONS: The 8-factor XGBoost model predicts risk of death in ICU patients with COVID-19 well; it initially demonstrates stability and can be used effectively to predict COVID-19 prognosis in ICU patients.