Efficacy of Aromatherapy at Relieving the Work-Related Stress of Nursing Staff from Various Hospital Departments during COVID-19.

This study aimed to evaluate the efficacy of aromatherapy in relieving the stress of nursing staff working in different departments during COVID-19. A total of 26 nursing staff from Taiwan were recruited for this study. Bergamot essential oil was diffused for over a four-week period in four different hospital departments. We assessed heart rate variability indicators, Nurse Stress Checklist, and Copenhagen Burnout Inventory before and after the intervention. The results of the analysis showed that during a high workload period, aromatherapy had no significant effect on regulating physical stress. Subjective measurements showed a significant impact on work concern and personal fatigue. Moreover, there were large differences among the four departments; the aromatherapy treatment had a weak effect on those with a heavy workload, whereas those with a lighter workload showed a stronger effect. Finally, this study provides practical results about aromatherapy stress reduction applied during the pandemic on first-line medical staff.

Sex Differences in Students’ Performance in VR-based Learning of Gross Anatomical Education (preprint)

Background: Studying anatomy has always challenged medical students. The coronavirus disease 2019 pandemic has transformed medical education worldwide, and virtual reality (VR) has recently emerged as a useful learning tool to promote memorization through understanding and visualization. With a remarkable rise in the use of remote learning methods during the pandemic, more schools are adopting distance learning through VR for anatomy. However, scholars have yet to explore the potential sex differences among students who use VR-based anatomical learning. Thus, we investigated the effects of teaching strategies on learners’ experiences with and performance in an anatomy course using VR-based learning. Method: Fifty first-year medical students enrolled in a human anatomy course were provided with VR devices for anatomical learning. They received a questionnaire comprising four determinants of experience: demographic background, discomfort symptoms, satisfaction levels, and opinions about the VR-based learning experience after their final examination. Student performance was then compared to previous performances over three-semester years when traditional teaching methods were used. A three-way mixed-model ANOVA was used to test the effects of sex, examination, and teaching methods on the examination scores. Results: VR-based learning resulted in better exam scores when compared to the traditional learning method. Female students experienced significantly higher disorientation symptoms compared with male students, and male students showed significant improvement in laboratory examination performance. Results showed that VR-based teaching can facilitate gross anatomical learning among first-year medical students and improve the laboratory performance of male students. Conclusion: Medical schools can use VR to teach anatomy effectively; however, faculty should be prepared to support inexperienced users when learning to use a VR system. Future research should further explore sex differences for reliability.

Angiotensin-converting enzyme 2 SNPs as the common genetic loci and optimal early identification genetic markers for COVID-19 (preprint)

Background: Angiotensin-converting enzyme 2 (ACE2) is implicated as a host cell receptor that causes infection in the pathogenesis of Coronavirus disease 2019 (COVID-19), and its genetic polymorphisms in the ACE2 gene may promote cardiovascular disease and systemic inflammatory injury in COVID-19. Hence, genetic background may potentially explain the broad inter-individual variation of disease susceptibility and/or severity. Methods The genetic susceptibility to COVID-19 by examining single-nucleotide polymorphisms (SNPs) of ACE2 was analyzed in 196 patients with COVID-19 and 210 normal controls using TaqMan genotyping assay. Results We demonstrated that ACE2 SNP rs4646142, rs6632677, and rs2074192 were associated with COVID-19 (all P < 0.05), and the differences of ACE2 SNPs rs4646142 and rs6632677 were correlated with COVID-19 related systemic inflammatory injury and cardiovascular risk. Specially, rs4646142 was associated with high-sensitive C-reactive protein (hs-CRP), prealbumin (PAB), apolipoprotein A (APOA), high-density lipoprotein (HDL), and acid glycoprotein (AGP). Rs6632677 was also associated with elevated CRP and haptoglobin (HPT). Conclusions Our results suggest that early identification of these individuals can provide a possible strategy for preventing the spread of the COVID-19, and ACE2 SNPs rs4646142 and rs6632677 may be a common genetic loci and optimal early identification genetic marker for COVID-19 with cardiovascular risks.

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients (preprint)

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.

Modeling the Opening SARS-CoV-2 Spike: an Investigation of its Dynamic Electro-Geometric Properties (preprint)

The recent COVID-19 pandemic has brought about a surge of crowd-sourced initiatives aimed at simulating the proteins of the SARS-CoV-2 virus. A bottleneck currently exists in translating these simulations into tangible predictions that can be leveraged for pharmacological studies. Here we report on extensive electrostatic calculations done on an exascale simulation of the opening of the SARS-CoV-2 spike protein, performed by the Folding@home initiative. We compute the electric potential as the solution of the non-linear Poisson-Boltzmann equation using a parallel sharp numerical solver. The inherent multiple length scales present in the geometry and solution are reproduced using highly adaptive Octree grids. We analyze our results focusing on the electro-geometric properties of the receptor-binding domain and its vicinity. This work paves the way for a new class of hybrid computational and data-enabled approaches, where molecular dynamics simulations are combined with continuum modeling to produce high-fidelity computational measurements serving as a basis for protein bio-mechanism investigations.

Analysis of the Effect of Proton Pump Inhibitors on the Course of Common COVID-19 (preprint)

Background/aims: This study is to evaluate the effect of proton pump inhibitors on the course of common COVID-19.Methods: Clinical data of common COVID-19 patients admitted to the Shanghai Public Health Clinical Center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses.Results: A total of 154 COVID-19 common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of the SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of the hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of the SARS-CoV-2 clearance and the discharge, all P > 0.05. Multivariate analysis showed that chronic gastropathy prolonged the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension, chronic obstructive pulmonary disease, chronic liver disease and malignant tumor all increased the duration of hospital stay for COVID-19, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of the hospital stay in COVID-19 patients was shortened by the SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05.Conclusion:  Proton pump inhibitors use has no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19.

Functional mapping of B-cell linear epitopes 1 of SARS-CoV-2 in COVID-19 convalescent population (preprint)

Pandemic SARS-CoV-2 has infected over 10 million people and caused over 500,000 mortalities. Vaccine development is in urgent need to stop the pandemic. Despite great progresses on SARS-CoV-2 vaccine development, the efficacy of the vaccines remains to be determined. Deciphering the interactions of the viral epitopes with their elicited neutralizing antibodies in the convalescent COVID-19 population inspires the vaccine development. In this study, we devised a peptide array composed of 20-mer overlapped peptides of spike (S), membrane (M) and envelope (E) proteins, and performed a screening with 120 COVID-19 convalescent serums and 24 non-COVID-19 serums. We identified five SARS-CoV-2-specific dominant epitopes that reacted with above 40% COVID-19 convalescent serums. Epitopes in the receptor-binding domain (RBD) of S ill reacted with the convalescent serums. Of note, two peptides non-specifically interacted with most of the non-COVID-19 serums. Neutralization assay indicated that only five serums completely blocked viral infection at the dilution of 1:200. By using a peptide-compete neutralizing assay, we found that three dominant epitopes partially competed the neutralization activity of several convalescent serums, suggesting antibodies elicited by these epitopes played an important role in neutralizing viral infection. The epitopes we identified in this study may serve as vaccine candidates to elicit neutralizing antibodies in most vaccinated people or specific antigens for SARS-CoV-2 diagnosis.

Pharmacokinetics and Pharmacodynamics of Vancomycin in Severe COVID-19 Patients: a Preliminary Study in a Chinese Tertiary Hospital (preprint)

Vancomycin plays an important role in the treatment of concurrent infections in severe coronavirus disease 2019 (COVID-19) patients. However, few is known about its pharmacokinetics (PK) in these patients. Here we performed therapeutic drug monitoring (TDM) of intravenous vancomycin with or without nasal administration in these patients. Drug dosage was adjusted depending on vancomycin concentration. A population PK model was developed using NONMEM software. Therapeutic effects, and vancomycin-related adverse events were monitored. A total of 63 samples from 8 patients were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The mean trough and peak concentration were 13.79±6.61 (4.63-34.2) mg/L (n=36) and 30.97±9.71 (17-49.9) mg/L (n=27), respectively. 25.4% of serum vancomycin concentration was beyond optimal range. Dose adjustments were made for 3 patients. The PK of vancomycin was consistent with two-compartment model, with the clearance and distribution volume in the central compartment of 4.3 L/h and 2.0 L, respectively. The AUC0-24/MIC of vancomycin was 848±566 h. Target infection was clinically cured in all patients, and no vancomycin-associated nephrotoxicity was detected during the TDM process. In conclusion, the PK studies of vancomycin in COVID-19 patients are needed to optimize drug dosage. Based on our PK model, the clearance of vancomycin was 4.3 L/h. 

COVID-19 severity is associated with immunopathology and multi-organ damage (preprint)

COVID-19 is characterised by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand how host responses contribute to COVID-19 pathophysiology, we used a multi-omics approach to identify molecular markers in peripheral blood and plasma samples that distinguish COVID-19 patients experiencing a range of disease severities. A large number of expressed genes, proteins, metabolites and extracellular RNAs (exRNAs) were identified that exhibited strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients, indicative of multi-organ damage. The continuous activation of IFN-I signalling and neutrophils, as well as a high level of inflammatory cytokines, were observed in severe disease patients. In contrast, COVID-19 in mild patients was characterised by robust T cell responses. Finally, we show that some of expressed genes, proteins and exRNAs can be used as biomarkers to predict the clinical outcomes of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19 and will help guide future studies in this area.

Analysis of the effect of proton pump inhibitors on the course of common COVID-19 (preprint)

Background/aimsTo evaluate the effect of proton pump inhibitors on the course of common COVID-19. MethodsClinical data of common COVID-19 patients admitted to the Shanghai public health clinical center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses. ResultsA total of 154 COVID-19 common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of SARS-CoV-2 clearance and the cumulative incidence of discharge, and the same after Propensity Score Match, all P > 0.05. Multivariate analysis suggested that chronic gastropathy prolonged the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension, chronic obstructive pulmonary disease, chronic liver disease and malignant tumor all increased the duration of hospital stay for COVID-19, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of hospital stay in COVID-19 patients was shortened by SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05. ConclusionProton pump inhibitors use have no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19.

Risk assessment and prediction of severe or critical illness of COVID-19 in the elderly (preprint)

Background: This study aims to investigate the clinical characteristics and risk prediction of severe or critical events of COVID-19 in the elderly patients in China. Methods: The clinical data of COVID-19 in the elderly patients admitted to the Shanghai Public Health Clinical Center during the period of January 20, 2020 to March 16, 2020 were collected. A retrospective cohort study design was conducted to screen out independent factors through Cox univariable regression analysis and multivariable regression analysis, and the efficacy of risk prediction of severe or critical illness was examined through the receiver operating characteristic (ROC) curve. Results: A total of 110 elderly patients with COVID-19 were enrolled. 52 (47.3%) were males and 21 (19.1%) had severe or critical illness. Multivariable regression analysis showed that CD4 cells and D-dimer were independent risk factors. D-dimer, CD4 cells, and D-dimer/CD cells ratios with cut off values of 0.65 (mg/L), 268 (cell/ul) and 431 were in the prediction of severe or critical illness of the elderly COVID-19. The AUC value of D-dimer, CD4 cells, CD4 cells/D-dimer ratio, the tandem group and the parallel group were 0.703, 0.804, 0.794, 0.812 and 0.694, respectively. Conclusions: D-dimer, CD4 cells and their combination have risk assessment value in predicting severe or critical illness of COVID-19 in the elderly.

Neutralizing Antibody Responses to SARS-CoV-2 in a COVID-19 Recovered Patient Cohort and Their Implications (preprint)

Background: The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease. However, the characteristics of these antibodies have not been well studied in association with the clinical manifestations in patients. Methods: Plasma collected from 175 COVID-19 recovered patients with mild symptoms were screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-specific NAbs and the spike-binding antibodies were monitored at the same time. Findings: SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-2-specific NAbs were detected in patients from day 10-15 after the onset of the disease and remained thereafter. The titers of NAb among these patients correlated with the spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were variable in different patients. Elderly and middle-age patients had significantly higher plasma NAb titers (P<0·0001) and spike-binding antibodies (P=0·0003) than young patients. Notably, among these patients, there were ten patients whose NAb titers were under the detectable level of our assay (ID50: < 40); while in contrast, two patients, showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb titers were positive correlated with plasma CRP levels but negative correlated with the lymphocyte counts of patients at the time of admission, indicating an association between humoral response and cellular immune response. Interpretation: The variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression. The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment. Funding Statement: This work was supported by the National Major Science and Technology Projects of China (2017ZX10202102 and 2018ZX10301403), National Natural Science Foundation of China (31771008), Hundred Talent Program of Shanghai Municipal Health Commission (2018BR08), and Chinese Academy of Medical Sciences (2019PT350002). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was conducted under a clinical protocol approved by the Investigational Review Board in the Shanghai Public Health Clinical Center (Study number: YJ-2020-S021-01). All participants signed an informed consent approved by the IRB.

Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications (preprint)

Background The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease. However, the characteristics of these antibodies have not been well studied in association with the clinical manifestations in patients. Methods Plasma collected from 175 COVID-19 recovered patients with mild symptoms were screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-specific NAbs and the spike-binding antibodies were monitored at the same time. Findings SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-2-specific NAbs were detected in patients from day 10-15 after the onset of the disease and remained thereafter. The titers of NAb among these patients correlated with the spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were variable in different patients. Elderly and middle-age patients had significantly higher plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young patients. Notably, among these patients, there were ten patients whose NAb titers were under the detectable level of our assay (ID50: < 40); while in contrast, two patients, showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb titers were positive correlated with plasma CRP levels but negative correlated with the lymphocyte counts of patients at the time of admission, indicating an association between humoral response and cellular immune response. Interpretation The variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression. The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Chinese Academy of Medical Sciences

Clinical analysis of risk factors for severe patients with novel coronavirus pneumonia / 中华传染病杂志

Objective To analyze the clinical features of patients with coronavirus disease 2019 (COVID-19) in Shanghai and to investigate the risk factors for disease progression to severe cases. Methods The clinical data of 292 adult patients with COVID-19 hospitalized in Shanghai Public Health Clinical Center from January 20, 2020 to February 10, 2020 were retrospectively analyzed, including 21 severe patients and 271 mild patients. The demographic characteristics, epidemiological history, history of underlying diseases and laboratory examinations were compared between the two groups. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using hi-square test. The binary logistic regression equation was used to analyze the risk factors for the progression of patients to severe cases. Results Among the 292 patients, 21 were severe cases with the rate of 7.2% (21/292). One patient died, and the mortality rate was 4.8% in severe patients. The severe patients aged (65.0±15.7) years old, 19 (90.5%) were male, 11 (52.4%) had underlying diseases, 7 (33.3%) had close relatives diagnosed with COVID-19. The mild patients aged (48.7±15.7) years old, 135 (49.8%) were male, 74 (27.3%) had underlying diseases, 36 (13.3%) had close relatives diagnosed with COVID-19. The differences between two groups were all significant statistically ( t =-4.730, χ 2 =12.930, 5.938 and 4.744, respectively, all P <0.05). Compared with the mild patients, the levels of absolute numbers of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine, serum cystatin C, C reactive protein (CRP), procalcitonin , D -dimer, pro-B-type natriuretic peptide (proBNP), serum myoglobin, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum troponin I (cTnI) in severe patients were all significantly higher ( U =2 091.5, 1 928.0, 1 215.5, 729.0, 1 580.5, 1 375.5, 917.5, 789.5, 1 209.0, 1 434.0, 638.0, 964.5, 1 258.0 and 1 747.5, respectively, all P <0.05), while the levels of lymphocyte count, albumin, transferrin, CD3 + T lymphocyte count, CD8 + T lymphocyte count and CD4 + T lymphocyte count in severe patients were all significantly lower ( U =1 263.5, t =4.716, U =1 214.0, 962.0, 1 167.5 and 988.0, respectively, all P <0.05). Further logistic regression analysis showed that the albumin (odds ratio ( OR )=0.806, 95% CI 0.675-0.961), CRP ( OR =1.016, 95% CI 1.000-1.032), serum myoglobin ( OR =1.010, 95% CI 1.004-1.016), CD3 + T lymphocyte count ( OR =0.996, 95% CI 0.991-1.000) and CD8 + T lymphocyte count ( OR =1.006, 95% CI 1.001-1.010) at admission were independent risk factors for the progression of COVID-19 patients to severe illness (all P <0.05). Conclusions Severe cases of patients with COVID-19 in Shanghai are predominantly elderly men with underlying diseases. Albumin, CRP, serum myoglobin, CD3 + T lymphocyte count and CD8 + T lymphocyte count could be used as early warning indicators for severe cases, which deserve more clinical attention.

Viral and host factors related to the clinic outcome of the SARS-CoV-2 infection (preprint)

At least three months have been passed since the outbreak of the severe acute respiratory disease, COVID-19 in Wuhan city, China in December 2019, caused by the infection of a novel coronavirus, SARS-CoV-2. 1,2 . Due to its rapid spread throughout China and abroad, knowledge sharing for both its epidemiology and clinic manifestations is urgently need. Here we analyzed the clinical, molecular and immunological data from 326 confirmed cases of SARS-CoV-2 infection in Shanghai. Genomic sequences assembled from 112 quality samples together with uploaded sequences in Global Initiative on Sharing All Influenza Data (GISAID) showed a stable evolution and suggested two major lineages with differential exposure history during the earliest outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially the reduced CD4+ and CD8+ T cell counts upon admission, was predictive of disease progression. High level of IL-6 and IL-8 during treatment was observed in severe and critical patients and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such age, lymphocytopenia and its associated cytokine storm whereas viral genetic variation did not significantly affect the outcomes. This comprehensive analysis on the molecular, immunological and clinical data provides a panorama of the key determinants related to the disease outcomes which should be helpful for improving the current combat against this extremely aggressive pandemic.Authors Xiaonan Zhang, Yun Tan, Yun Ling, Gang Lu, Feng Liu, and Zhigang Yi contributed equally to this work.

Clinical Characteristics of SARS-CoV-2 Infections Involving 325 Hospitalized Patients outside Wuhan (preprint)

Background/Objective To date, the clinical features of SARS-CoV-2 infections were reported mainly based on cases in Wuhan. We aimed to report the clinical features of SARS-CoV-2 infections outside Wuhan. Methods We analyzed 325 SARS-COV-2 infection patients hospitalized in Shanghai Public Health Clinical Center. The epidemiological, demographic, and clinical data were compared between severe and non-severe cases. Results Of 325 patients, the median age was 51 years, 167 (51.4%) were men, and 107 (32.9%) had underlying diseases. 159 (48.9%) visited Wuhan or had contacted with people from Wuhan, but 57 (17.5%) had no clear epidemiological history. Compared with non-severe patients (n=299, 92%), severe patients (n=26, 8%) were older, had more common underlying disorder, more common lymphopenia, and higher D-dimer, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, procalcitonin, C-reactive-protein, and troponin I level. The common complications included secondary infection (12.3%), acute cardiac injury (9.2%), ARDS (5.5%), acute kidney injury (5.8%), and shock (4.9%). To Mar 12, 311 (95.7%) patients were discharged, 3 (0.9%) died, and 11 (3.4%) still hospitalized. Conclusions The severity rate and fatality rate were low if the measures (early isolation, early diagnosis and early management) were undertaken at the early time of the outbreak.

A simple algorithm helps early identification of SARS-CoV-2 infection patients with severe progression tendency (preprint)

Objectives We aimed to develop a simple algorithm helps early identification of SARS-CoV-2 infection patients with severe progression tendency. Methods 322 SARS-COV-2 infection patients were respectively enrolled. The univariable and multivariable analysis were computed to identify the independent predictors of severe progression, and the prediction model was established based on independent predictors. The areas under the ROC curves (AUROCs) were used to evaluate the diagnostic performances. Results Of 322 confirmed SARS-COV-2 infection patients, 11 were diagnosed as severe cases on admission, 15 developed to severe cases after admission, and 296 were non-severe cases. The multivariable analysis identified age (OR=1.061, p=0.028), lactate dehydrogenase (LDH) (OR=1.006, p=0.037), and CD4 count (OR=0.993, p=0.006) as the independent predictors of severe progression. Consequently, the age-LDH-CD4 algorithm was derived as (age×LDH)/CD4. The AUROC of the age-LDH-CD4 model was significantly higher than that of single CD4 count, LDH, or age (0.92, 0.85, 0.80, and 0.75, respectively). The age-LDH-CD4 model ≥ 82 has high sensitive (81%) and specific (93%) for the early identification of patients with severe progression tendency following SARS-CoV-2 infection. Conclusions The age-LDH-CD4 model is a simple algorithm for early identifying cases with severe progression tendency in SARS-CoV-2 infection patients, and warrants further validation. 

Efficacies of lopinavir/ritonavir and abidol in the treatment of novel coronavirus pneumonia / 中华传染病杂志

Objective@#To evaluate the efficacies of lopinavir/ritonavir and abidol in the treatment of NCP.@*Methods@#The clinical data of 134 patients with NCP receiving treatment at Shanghai Public Health Clinical Center during Jan 20 to Feb 6, 2020 were retrospectively collected. All the patients received interferon-α2b spray and symptomatic supportive treatment, and 52 cases received oral lopinavir/ritonavir treatment, 34 cases received oral abidol treatment, the remaining 48 cases did not take any antiviral drugs. The efficacies at median day 7 among the three groups were compared by using Kruskal-Wallis or chi-square tests.@*Results@#The 134 patients included 69 males (51.5%) and 65 females, aged 35-62 years with the average of 48 years. The median time to temperature normalization in patients receiving abidol or lopinavir/ritonavir treatment was both 6 days after admission, and that was 4 days in the control group, with no significant difference (χ2=2.37, P=0.31). The median time to PCR negative in the respiratory specimens in the three groups was all 7 days after admission, and the PCR negative rates at day 7 after admission in lopinavir/ritonavir, abidol and control groups were 71.8% (28/39), 82.6% (19/23) and 77.1% (27/35), respectively, which were not significantly different (χ2=0.46, P=0.79). Radiological worsening at day 7 was observed in comparable proportions of patients in the three groups, which were 42.3% (n=22), 35.3% (n=12) and 52.1% (n=25), respectively (χ2=2.38, P=0.30) . Adverse reactions occurred in 17.3% (n=9), 8.8% (n=3) and 8.3% (n=4) patients, respectively in the three groups (χ2=2.33, P=0.33).@*Conclusions@#This study did not find any effects of lopinavir/ritonavir and abidol on relieving symptoms or accelerating virus clearance. The efficacies of these two drugs in NCP treatment need further investigation.

A descriptive study of the impact of diseases control and prevention on the epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai, lessons learned for metropolis epidemics prevention (preprint)

Objective: To describe and evaluate the impact of diseases control and prevention on epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai. Design: A retrospective descriptive study Setting: China Participants: Epidemiology information was collected from publicly accessible database. 265 patients admitted to Shanghai Public Health Center with confirmed COVID-19 were enrolled for clinical features analysis. Main outcome measure: Prevention and control measures taken by Shanghai government, epidemiological, demographic, clinical, laboratory and radiology data were collected. Weibull distribution, Chi-square test, Fisher's exact test, t test or Mann-Whitney U test were used in statistical analysis. Results: COVID-19 transmission rate within Shanghai had reduced over 99% than previous speculated, and the exponential growth has been stopped so far. Epidemic was characterized by the first stage mainly composed of imported cases and the second stage where >50% of cases were local. The incubation period was 6.4 (95% CI 5.3 to 7.6) days and the mean onset-admission interval was 5.5 days (95% CI, 5.1 to 5.9). Median time for COVID-19 progressed to severe diseases were 8.5 days (IQR: 4.8-11.0 days). By February 11th, proportion of patients being mild, moderate, severe and critically ill were 1.9%(5/265), 89.8%(238/265), 3.8%(10/265), 4.5%(12/265), respectively; 47 people in our cohort were discharged, and 1 patient died. Conclusion: Strict controlling of the transmission rate at the early stage of an epidemic in metropolis can quickly prohibit the spread of the diseases. Controlling local clusters is the key to prevent outbreaks from imported cases. Most COVID-19 severe cases progressed within 14 days of disease onset. Multiple systemic laboratory abnormalities had been observed before significant respiratory dysfunction. Keyword: COVID-19, SARS-CoV-2, epidemics dynamics, diseases control, clinical features