Clinical Features And Therapy Of COVID-19 Patients And SARS-CoV-2 Bioinformatics Analysis In Zhejiang

Part Ⅰ Clinical characteristics of 788 COVID-19 patients and SARS-Co V-2 bioinformatics analysis in Zhejiang,ChinaBackground An increasing number of cases of novel coronavirus infected disease(COVID-19)have set off global alert and put heavy public health burden on China.788 cases in Zhejiang were analyzed to clarify its clinical and gene characteristics of SARS-Co V-2.Methods Information of COVID-19 confirmed patients from Jan 17 to Feb 12,2020 were collected and analyzed retrospectively,including epidemiological,demographic,clinical and laboratory data,followed by multivariate logistic-regression model to identify independent predictors of severe/critical type and bioinformatics for features of SARS-Co V-2 from Zhejiang province.Results Among 788 COVID-19 patients,the median age was 46 years and the median incubation period was 5 days,while hypertension,diabetes and chronic liver disease were the most common coexisting conditions.393(49.87%)patients had Wuhan exposure history and 195(24.75%)patients were clustered cases.78(9.90%)patients developed severe/critical types of COVID-19.Fever and cough were the most common symptoms while gastrointestinal symptoms were reported in 88(11.17%)patients.234(29.70%)patients had leukocytopenia,138(17.51%)patients had lymphocytopenia but only 27(3.43%)patients had thrombocytopenia.390(49.49%)patients had elevated C-reactive protein.All patients underwent chest radiography on admission.The radiological findings showed that 87(11.04%)non-pneumonia,170(21.57%)unilateral pneumonia,296(37.56%)bilateral pneumonia and 235(29.82%)multiple mottling and ground-glass opacity.668(84.77%)patients received antiviral treatment.8(2.28%)patients were given mechanical ventilation.319(40.48%)patients received antibiotic treatment.22(2.79%)patients were admitted to the ICU.The most common complications were ARDS and liver injury.Multivariate analysis showed any coexisting disease,fever level,myalgia,lymphocytopenia,hypoproteinemia,increased CRP and increased LDH were the independent risk factors for severe/critical COVID-19.Compared with other SARS-Co V-2 strains,35 specific gene mutations were found in SARS-Co V-2 strain(ZJ01),which was isolated in Hangzhou.The prediction of Furin cleavage site(FCS)and the sequence alignment of virus family indicated that FCS may be an important site of coronavirus evolution.ZJ01 had mutations near FCS(F1-2),which caused changes in the structure and electrostatic distribution of S protein surface,further affecting the binding capacity of Furin.Conclusion Clinical characteristics of COVID-19 patients in Zhejiang province have changed,and the symptoms and severity of illness are relatively mild compared with COVID-19 patients in the early outbreak of Wuhan.And these changes may be related to changes in the structure and electrostatic distribution of S protein surface,which caused by mutations of ZJ01 near FCS(F1-2).Part Ⅱ Clinical characteristics of 88 COVID-19 patients with gastrointestinal symptoms in Zhejiang,ChinaBackground The outbreak of coronavirus disease 2019(COVID-19)become a huge threat to human health.Previous studies mainly focused on Wuhan and typical symptoms.This study analyzed confirmed COVID-19 cases with gastrointestinal(GI)symptoms in Zhejiang province to determine its clinical characteristics.Methods COVID-19 patients admitted in hospitals of Zhejiang province from Jan 17 to Feb12,2020 were included.The epidemiological,demographic,clinical,laboratory,management and outcome datas of patients with GI symptoms were retrospectively analyzed,with multivariate analysis for risks of severe/critical types.Results Among enrolled 788 patients,88(11.2%)presented with at least one gastrointestinal symptom(nausea,vomiting and diarrhea).12(13.6%)and 6(6.8%)COVID-19 patients with GI symptoms were severe and critical types,significantly higher than 49(7.0%)and 11(1.6%)in those without(P=0.028;P=0.001,respectively).Family clustering in COVID-19 patients with GI symptoms were significantly higher than those without(30.7% vs 17.7%,P=0.004).COVID-19 patients with GI symptoms had significantly higher rates of temperature>39℃(17.0%),fatigue(35.2%),shortness of breath(11.4%)and headache(20.5%).CRP level in COVID-19 patients with GI symptoms were significantly higher than those without(15.0mg/L vs 8.0mg/L,P=0.007).COVID-19 patients with GI symptoms had significantly higher proportions of ARDS(15.9%),liver injury(19.3%),mechanical ventilation(8.0%)and ICU(6.8%)than those without(P=0.001;P=0.004;P=0.034;P=0.015,respectively).The highest temperature on admission,any coexisting disease and increased LDH were the independent risk factors for severe/critical COVID-19 patients with GI symptoms.Conclusion COVID-19 patients with GI symptoms in Zhejiang province have some particular clinical features compared with those without,including increased family clustering,relatively severe symptoms,more complications and higher proportions of severe/critical types.Part Ⅲ Analysis of clinical features in older patients with COVID-19 in Zhejiang provinceBackground Elderly COVID-19 patients had a relatively high proportion of total patients,and had a higher mortality rate.This study aimed to investigate the clinical characteristics of older patients with COVID-19 in Zhejiang province.Methods A retrospective study was performed,with collecting data from medical records of confirmed COVID-19 patients in Zhejiang province from Jan 17 to Feb 12,2020.Epidemiological,clinical and treatment data were analyzed between those older(≥60y)and younger(<60y)patients.Results Total 788 patients with confirmed COVID-19 were selected,and 136 were older patients with corresponding age of 68.3y±7.3y.There was a significantly higher frequency of women in the older patients compared with the younger patients(57.4% vs46.5%,P=0.021).The presence of coexisting medical condition was significantly higher in older patients compared with younger patients(55.2% vs 21.9%,P<0.001),including the rate of hypertension(39.0% vs 11.2%,P<0.001),diabetes(17.6% vs 5.1%,P<0.001),heart diseases(4.4% vs 0.8%,P=0.005)and COPD(2.2% vs 0%,P=0.005).Significantly higher rates of severe(older vs younger groups: 16.2% vs 6.0%,P<0.001)/critical(8.8%vs 0.8%,P<0.001)type,shortness of breath(12.5% vs 3.1%,P<0.001),moderate/high temperature(40.4% vs 29.6%,P=0.013;14.0% vs 7.2%,P=0.010)were observed in older patients compared with younger patients.Significantly more patients in older group had lymphocytopenia(30.9% vs 14.1%,P<0.001),lower level of haemoglobin(129g/L vs 140g/L,P<0.001)and multiple mottling and ground-glass opacity(43.4% vs27.0%,P<0.001).Higher rates of ICU admission(9.6% vs 1.4%,P<0.001),ARDS(16.9% vs 5.4%,P<0.001),mechanical ventilation(6.6% vs 1.4%,P=0.001),Intravenous immunoglobulin application(17.7% vs 5.8%,P<0.001)and methylprednisolone application(28.7% vs 9.4%,P<0.001)were also identified in older patients.By the end of Feb 12,less patients in older grouphad discharged than those in younger group(22.8% vs 44.6%,P<0.001),and duration of hospitalization in older group was longer than those in younger group(P=0.0022).Conclusion Compared with younger patinets,older COVID-19 patients in Zhejiang province have some special clinical features,including higher rates of female gender and coexisting conditions,relatively severe symptoms and severity of illness,higher proportions of severe/critical types,lower discharged rate and longer duration of hospitalization.Part Ⅳ Efficacies of arbidol combined with interferon-α and lopinavir/ritonavir in the treatment of COVID-19 patientsBackground COVID-19 has rapidly spread around the world.Effectiveness research of antiviral therapy is important for preventing and controling the epidemic.This study aimed to assessed the efficacy of combined arbidol,interferon-α and lopinavir/ritonavir for treating patients with COVID-19.Methods In this retrospective study,we enrolled 214 discharged COVID-19 patients in Zhejiang province from Jan 17 to Feb 12,2020.78 cases received treatment of combined arbidol,interferon-α and lopinavir/ritonavir(triple combination group),69 cases received treatment of combined interferon-α and lopinavir/ritonavir(dual combination group),the remaining 67 cases did not take any antiviral drugs(control group).Interferon-α,5 million U,twice daily,aerosol inhalatio;arbidol,200 mg,three times daily,orally;lopinavir/ritonavir,500 mg,twice daily,orally.The efficacies of three groups were compared.Results The average age of three groups was 43.4y±13.1y,41.1y±14.1y and 39.3y±9.3y respectively(P=0.190).There was significant difference in clinical type(P=0.005).The proportions of severe/critical types were 15.4%,11.6% and 1.5% in triple combination group,dual combination group and control group respectively.The average durations of fever in three groups were 8.0±4.2d,7.4±3.0d and 7.6±3.8d respectively(P=0.122).The average time to lung lesions improvement in three groups was 11.7±3.3d,11.4±3.2d and 11.1±4.2d respectively(P=0.743).The average durations of hospitalization in three groups were 13.5±5.0d,13.3±3.4d and 14.4±4.4d respectively(P=0.305).The median time from illness onset to discharge in three groups was 18.0d,17.0d and 17.0d respectively(P=0.254).The virus nucleic acid-negative conwersion time in three groups10.2±3.8d,9.5±3.1d and 10.0±4.9d respectively(P=0.052).Though excluding severe/critical patients to balance baseline datas,the efficacy of the three groups remained unchanged.The average durations of fever were 8.1±4.3d,7.4±3.2d and7.5±3.7d(P=0.175).The average time to lung lesions improvement was 11.6±3.1d,10.9±2.9d and 11.0d erd(P=0.636).The average durations of hospitalization were13.2±5.0d,13.1±3.2d and 14.3±4.3d(P=0.273).The average time from illness onset to discharge was 18.1±5.7d,17.0±3.9d and 17.6±4.9d(P=0.498).The virus nucleic acid-negative conwersion time was 10.1±3.8d,9.31±3.5d and 9.9±4.9d(P=0.066).Adverse reactions with gastrointestinal symptoms occurred in 9(11.5%),12(17.4%)and6(7.5%)patients,respectively in the three groups(P=0.204).Conclusion This study does not find any effects of treatment of combined interferon-α,arbidol and lopinavir/ritonavir on improving symptoms,shortening the disease course and the time of virus shedding in patients with mild to moderate COVID-19.