ACP-Dnnel: Anti-coronavirus Peptides Prediction based on Deep Neural Network Ensemble Learning (preprint)

Background The ongoing COVID-19 pandemic has caused global economic crisis and dramatic loss of human life. There is an urgent need for safe and efficient anti-coronavirus infection drugs. Anti-coronavirus peptides (ACovPs) can inhibit coronavirus infection. With high-efficiency, low-toxicity, and broad-spectrum inhibitory effects on coronaviruses, they are promising candidates to be developed into a new type of anti-coronavirus drug. Experiment is the traditional way of ACovPs identification, which is less efficient and more expensive. With the accumulation of experimental data on ACovPs, computational prediction provides a cheaper and faster way to find anti-coronavirus peptides candidates.Methods In this study, we integrated several state-of-the-art machine learning methodologies to build nine classification models for the prediction of ACovPs. These models were pretrained using deep neural networks, and the performance of our ensemble model, ACP-Dnnel, was evaluated across three datasets and independent dataset.Results The highest accuracy of ACP-Dnnel reaches 98%, and the MCC value exceeds 0.9. On three different datasets, its average accuracy is 96.33%. After the latest independent data set validation, ACP-Dnnel improved at MCC, Sn and ACC values by 10.1%, 16.4% and 7.3% respectively. It is suggested that ACP-Dnnel can be helpful for the laboratory identification of ACovPs, speeding up the anti-coronavirus peptide drug discovery and development. We constructed the web server of anti-coronavirus peptides prediction and it is available at http://150.158.148.228:5000/.

Prognostic value of neutrophils to lymphocytes and platelets ratio for 28-day mortality in patients with acute respiratory distress syndrome: a retrospective study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a rapidly progressive and fatal respiratory failure disease that often occurs in critically ill patients. Since ARDS is associated with immune dysregulation and coagulation abnormalities, it is necessary to identify an appropriate predictor that can accurately predict ARDS mortality based on its pathophysiology. Therefore, this study aimed to evaluate the clinical value of neutrophils to lymphocytes and platelets ratio (N/LPR) in predicting 28-day mortality in ARDS patients. METHODS: From July 2018 to October 2021, the medical records of ARDS patients were retrospective reviewed. Neutrophil count, lymphocyte count, and platelet count were collected, and the neutrophil-to-lymphocyte ratio (NLR) and N/LPR were calculated. Multivariate logistic regression analyses were performed to identify independent predictors of 28-day mortality in ARDS. Receiver operating characteristic (ROC) curve with the area under curve (AUC) was used to evaluate optimal cut-off values for 28-day mortality in ARDS. Kaplan-Meier analysis was used to estimate the 28-day survival probabilities stratified by optimal cut-off values of N/LPR and NLR. RESULTS: A total of 136 ARDS patients were included in this study and were further divided into survivors (n = 69) and non-survivors (n = 67) groups according to their survival status on day 28. There were no significant differences between the two groups in age, sex, history of smoking and drinking, comorbidities, and reasons of admission (P > 0.05). Non-survivors had significantly higher neutrophil counts, NLR and N/LPR and had significantly lower platelet counts than survivors (P < 0.05). Multivariate regression analysis revealed that N/LPR, NLR and platelet counts were independent predictors for 28-day mortality in ARDS (P < 0.05). The ROC analyses showed that N/LPR with optimal cut-off value of 10.57 (sensitivity: 74.6%; specificity: 72.5%) is a more reliable predictor for 28-day mortality in ARDS than NLR and platelet count (AUC: 0.785 vs. 0.679 vs. 0.326). Further subgroup analysis confirmed that ARDS patients with N/LPR < 10.57 had significantly lower 28-day mortality than patients with N/LPR ≥ 10.57 (P < 0.001). Kaplan-Meier analysis also confirmed that ARDS patients with N/LPR < 10.57 had significantly longer survival. CONCLUSION: N/LPR is an independent risk factor associated with 28-day mortality in ARDS patients and shows better performance in predicting mortality rate than NLR.

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

ObjectiveTo delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.DesignRetrospective case series.SettingTongji Hospital in Wuhan, China.ParticipantsAmong a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.Main outcome measuresClinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.ResultsThe median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83;73%) than in recovered patients (88;55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113;100%), type I respiratory failure (18/35;51%), sepsis (113;100%), acute cardiac injury (72/94;77%), heart failure (41/83;49%), alkalosis (14/35;40%), hyperkalaemia (42;37%), acute kidney injury (28;25%), and hypoxic encephalopathy (23;20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.ConclusionSevere acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Numerical investigation of airborne transmission of respiratory infections on the subway platform

Underground subway platforms are among the world’s busiest public transportation systems, but the airborne transmission mechanism of respiratory infections on these platforms has been rarely studied. Here, computational fluid dynamics (CFD) modeling is used to investigate the airflow patterns and infection risks in an island platform under two common ventilation modes: Mode 1- both sides have air inlets and outlets;Mode 2- air inlets are present at the two sides and outlets are present in the middle. Under the investigated scenario, airflow structure is characterized by the ventilation jet and human thermal plumes. Their interaction with the infector’s breathing jet imposes the front passenger under the highest exposure risk by short-range airborne route, with intake fractions up to 2.57% (oral breathing) or 0.63% (nasal breathing) under Mode 1;oral breathing of the infector may impose higher risks for the front passenger compared with nasal breathing. Pathogen are efficiently diluted as they travel further, in particular to adjacent crowds. The maximum and median value of intake fractions of passengers in adjacent crowds are respectively 0.093% and 0.016% (oral breathing), and 0.073% and 0.014% (nasal breathing) under Mode 1. Compared with Mode 1, the 2nd mode minimizes the interaction of ventilation jet and breathing jet, where the maximum intake fraction is only 0.34%, and the median value in the same crowd and other crowds are reduced by 23-63%. Combining published quanta generation rate data of COVID-19 and influenza infectors, the predicted maximum and median infection risks for passengers in the same crowds are respectively 1.46%−40.23% and 0.038%−1.67% during the 3−10 min waiting period, which are more sensitive to ventilation rate and exposure time compared with return air. This study can provide practical guidance for the prevention of respiratory infections in subway platforms.

Research development and evaluation of SARS-CoV-2 vaccines

Vaccination plays a leading role in improving immunity, reducing susceptibility and controlling the occurrence and prevalence of some infectious diseases. In this epidemic prevention and control of SARS-COV-2, the Chinese government paid more attention to the development progress of vaccine and made outstanding achievements in the world's research and development (R&D) industry. Based on a brief review of the research progress of the novel vaccine and a new understanding of the scientific issues of vaccine R&D based on the characteristics of the novel vaccine, this paper discusses the research progress and evaluation of the novel vaccine from the perspective of drug evaluation. The key to the successful development of a vaccine is the safety and effectiveness of the product. In this system engineering of R&D, the use of virus structure characteristics, forming new development pathway, through elaborate design, strict domestic and international research and evaluation standard, the scientific quality of preclinical quality and stability tests, the safety and effectiveness in animal tests, phase I, II and III clinical evaluations to achieve development goals. From the research and development to the market of vaccine is a long process, during which many key scientific problems need to be solved. Especially for a SARS-COV-2 such as novel coronavirus that spreads quickly and widely, it may face more risks and challenges. Due to the virus' wide range of popularity and rapid mutation, international coordination and cooperation are needed to obtain more comprehensive virus data, so as to ensure sufficient information and research capacity for the purpose of international sharing of results.

Discussion on Etiology and Pathogenesis of Corona Virus Disease 2019 from “Cold-dampness and Insidious Dryness”

Based on the characteristics of the epidemic situation and the authors’ understanding of the related ancient books and documents, this paper explores the etiology and pathogenesis of Corona Virus Disease 2019 (COVID-19) from 5 aspects: abnormal climate in “warm winter”, unique geographical location, pathogenesis evolution of cold and dampness mixed with insidious dryness, transmission and change of “triple energizer” of toxic pathogens, and game between healthy Qi and toxic pathogens. Combined with the special treatment of traditional Chinese medicine (TCM), the purpose is to make a modest contribution to curbing the epidemic situation with TCM.

Epidemiological and clinical features of imported and local patients with coronavirus disease 2019 (COVID-19) in Hainan, China (preprint)

Background: Hainan Island, which is a popular tourist destination, received many imported cases of Coronavirus disease 2019 (COVID-19) but successfully contained the epidemic within one month. We described the epidemiological and clinical characteristics of COVID-19 in Hainan and compared these features between imported and local cases to provide information for other international epidemic areas. Methods: : We included 91 patients (56 imported and 35 local cases) from two designated hospitals for COVID-19 in Haikou, China, from January 20 to February 19, 2020. Data on the demographic, epidemiological, clinical and laboratory characteristics were extracted from medical records. Patients were followed until April 21, 2020, and the levels of antibodies at the follow-ups were also analyzed. Results: : Of the 91 patients, 78 (85.7%) patients were diagnosed within the first three weeks after the first case was identified (Day 1: Jan 22, 2020), while the number of local cases started to increase during the third week. No new cases occurred after Day 29. Fever and cough were two main clinical manifestations. In total, 15 (16.5%) patients were severe, 14 (15.4%) had complicated infections, nine (9.9%) were admitted to the ICU, and three died. The median duration of viral shedding in feces was longer than that in nasopharyngeal swabs (19 days vs 16 days, P =0.007). Compared with local cases, imported cases were older and had a higher incidence of fever and concurrent infections. There was no difference in outcomes between the two groups. IgG was positive in 92.8% patients (77/83) in the follow-up at week 2 after discharge, while 88.4% patients (38/43) had a reduction in IgG levels in the follow-up at week 4 after discharge, and the median level was lower than that in the follow-up at week 2 (10.95 S/CO vs 15.02 S/CO, P<0.001). Conclusion: Imported cases were more severe than local cases but had similar prognoses. The level of IgG antibodies declined from week 6 to week 8 after onset. The short epidemic period in Hainan suggests that the epidemic could be quickly brought under control if proper timely measures were taken.

Time-series plasma cell-free DNA analysis reveals disease severity of COVID-19 patients (preprint)

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. Detection of individuals at high risk for critical condition is crucial for control of the disease. Herein, for the first time, we profiled and analyzed plasma cell-free DNA (cfDNA) of mild and severe COVID-19 patients. We found that in comparison between mild and severe COVID-19 patients, Interleukin-37 signaling was one of the most relevant pathways; top significantly altered genes included POTEH, FAM27C, SPATA48, which were mostly expressed in prostate and testis; adrenal glands, small intestines and liver were tissues presenting most differentially expressed genes. Our data thus revealed potential tissue involvement, provided insights into mechanism on COVID-19 progression, and highlighted utility of cfDNA as a noninvasive biomarker for disease severity inspections.

Epidemiological and clinical features of imported and local patients with coronavirus disease 2019 (COVID-19) in Hainan, China (preprint)

Background Hainan Island, a popular tourist destination, had received many imported cases of Coronavirus disease 2019 (COVID-19), but successfully contained the epidemics in one month. We described epidemiological and clinical characteristics of COVID-19 in Hainan and compared these features between imported and local cases to provide information for other international epidemic areas. Methods We included 91 patients (56 imported and 35 local cases) from two designed hospitals for COVID-19 in Haikou, China, from January 20 to February 19, 2020. Data on demographic, epidemiological, clinical and laboratory characteristics were extracted from medical records. Results Of the 91 patients, 78 (85.7%) patients were diagnosed within the first three weeks after the first case identified (Day 1: Jan 22, 2020), while the number of local cases started to increase from the third week. No new cases occurred after Day 29. Fever and cough were two main clinical manifestations. 15 (16.5%) were severe, 14 (15.4%) had complicated infections, nine (9.9%) were admitted to ICU, and three died. Median duration of viral shedding in feces was longer than that in nasopharyngeal swabs (19 days vs 16 days, P =0.007). Compared with local cases, imported cases were older, have higher incidence of fever and concurrent infections. There was no difference in outcomes between the two groups. Conclusion Imported cases were more severe than local cases, but could have similar prognosis. The short epidemic period in Hainan suggests that the epidemics could be quickly brought under control if proper timely measures were taken.

Clinical analysis of nine cases with critical corona virus disease 2019 in Hainan province / 中华传染病杂志

Objective To explore the clinical features of critical cases of coronavirus disease 2019 (COVID-19). Methods The clinical data of nine patients who were diagnosed with critical COVID-19 in Hainan General Hospital from January 21, 2020 to February 6, 2020 were retrospectively analyzed. RT-PCR testing for 2019 novel coronavirus (2019-nCoV) was performed with multi-sites synchronize specimens including pharyngeal swab, blood, excrement, and urine. The serum levels of leucocyte, C-reactive protein, procalcitonin and lactic acid between the improved group (five cases) and the deteriorated group (four cases) were compared. The t test was used for comparison of normally distributed continuous data between groups. Results There were eight males (88.9%) and 1 female enrolled. The patients aged 28-77 years old, with an age of (52.9±18.0) years. By March 4, 2020, all five cases in improved group were cured and discharged, three cases in deteriorated group died and 1case remained in critical condition. All multi-sites specimens of patients in improved group turned negative in 2-4 weeks of illness onset, while those of cases in deteriorated group showed sustained viral nucleic acid positive (up to 48th day of illness onset). The white blood cell counts ((13.52±8.24)×10 9 /L vs (10.49±4.46) ×10 9 /L), C-reactive protein ((139.71±87.46) mg/L vs (78.60±55.40) mg/L) and procalcitonin ((2.32±4.03) ng/mL vs (0.28±0.58) ng/mL) , lactic acid ((3.70±4.14) mmol/L vs (2.33±0.53) mmol/L) in deteriorated group were all significantly higher than those in improved group ( t =2.908, 5.009, 4.391 and 2.942, respectively, all P <0.01). A rapid rise of serum IL-6 level up to 8 500 pg/mL was observed in one patient three days prior to death. Conclusion Among the patients with critical COVID-19, serum levels of inflammatory cytokines of the death cases are higher than those of improved and discharged cases.

Single-cell atlas of a non-human primate reveals new pathogenic mechanisms of COVID-19 (preprint)

Stopping COVID-19 is a priority worldwide. Understanding which cell types are targeted by SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state influence viral entry is fundamental for accelerating therapeutic and preventative approaches. In this endeavor, we profiled the transcriptome of nine tissues from a Macaca fascicularis monkey at single-cell resolution. The distribution of SARS-CoV-2 facilitators, ACE2 and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, kidney, and liver. Through co-expression analysis, we identified immunomodulatory proteins such as IDO2 and ANPEP as potential SARS-CoV-2 targets responsible for immune cell exhaustion. Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 expression that could promote viral entry. Our work constitutes a unique resource for understanding the physiology and pathophysiology of two phylogenetically close species, which might guide in the development of therapeutic approaches in humans. Bullet pointsO_LIWe generated a single-cell transcriptome atlas of 9 monkey tissues to study COVID-19. C_LIO_LIACE2+TMPRSS2+ epithelial cells of lung, kidney and liver are targets for SARS-CoV-2. C_LIO_LIACE2 correlation analysis shows IDO2 and ANPEP as potential therapeutic opportunities. C_LIO_LIWe unveil a link between IL6, STAT transcription factors and boosted SARS-CoV-2 entry. C_LI

No SARS-CoV-2 in expressed prostatic secretion of patients with coronavirus disease 2019: a descriptive multicentre study in China (preprint)

Abstract Purpose: The aim of the present study was to assess whether SARS-CoV-2 can be detected in the expressed prostatic secretion (EPS) of patients with corona virus disease 2019 (COVID-19). Methods: 18 cases of COVID-19, and 5 suspected cases, were selected from three medical centers to detect the RNA expression of SARS-CoV-2 in their EPS with RT-PCR. Results: Results were negative in all EPS samples for SARS-CoV-2 of suspected and confirmed patients. Conclusions: No SARS-CoV-2 was expressed in EPS of patients with COVID-19.