Study Of The Clinical Characteristics And Association Of Laboratory Tests And Disease Severity In Patients With Severe/critical COVID-19

Objective:Coronavirus Disease 2019(COVID-19)is an acute respiratory infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-Co V-2)infection.It is recognized that early identification of critical type patients and prevention of conversion from severe type patients to critical type patients are the key to reduce mortality and save medical costs.However,there are few studies on the COVID-19 severe/critical type patients’ clinical characteristics,liver injury,the relationship between coagulation dysfunction,inflammatory response,and immune function damage.It is not clear whether coagulationimmune dysfunction can promote disease progression and whether the related indicators can be used for identifying critical type patients.The researcher worked in Sino-French New City Branch of Tongji Hospital from February 2 to March 25,2020.During this period,the researcher participated in clinical work,and collected relevant data of patients.Through the methods of retrospective study and meta-analysis,this research analyzes the clinical characteristics,laboratory tests of COVID-19 severe/critical type patients,especially with liver injury and coagulation dysfunction,and analyse the relationship between D-dimer,inflammatory markers,cytokines,and disease severity.Moreover,this study further explored the possibility of early diagnosis of critical type patients with relevant indicators,so as to provide evidence for diagnosis and treatment of this disease.Methods:1.Clinical characteristics,laboratory tests and liver injury in COVID-19 severe/critical patientsThe medical records of 53 patients were collected from a single center in Wuhan from February 8,2020 to March 25,2020.The patients were divided into severe type group(38 patients)and critical type group(15patients).The clinical characteristics,blood cell analysis(WBC,ANC,LY,HGB,PLT),coagulation function examination(D-dimer,PT,PTA,INR),inflammatory markers(PCT,ESR,hs CRP),and liver function indexes(ALT,AST,TP,ALB,TBIL,DBIL,ALP,GGT,TC,LDH)were analyzed retrospectively.According to the degree of abnormal liver function in the process of diagnosis and treatment,the patients were divided into three groups: combined liver injury group,mild abnormal liver function group and normal liver function group.Finally,the disease outcomes of all patients were analyzed.Statistical analysis was performed using Student t test,Mann-Whitney U test,Kruskal-Wallis test,and Chi-square test.2.Association of D-dimer,inflammatory markers,cytokines abnormality and disease severity in COVID-19 severe/critical patientsThe 41 patients were divided into severe type group(28 patients)and critical type group(13 patients).The levels of D-dimer,WBC,ANC,PCT,hs CRP,IL-2R,IL-6,IL-8 and TNF-α were compared among patients with different clinical types of COVID-19.Moreover,the changes in the cytokines were analyzed in patients with different D-dimer levels.And,the levels of D-dimer and cytokines before and after anticoagulant therapy were assessed.Statistical analysis was performed using Student t test,Mann-Whitney U test,Kruskal-Wallis test,and Chi-square test.3.Meta analysis of the levels of D-dimer,hsCRP and cytokines in COVID-19 severe/critical patientsVIPub Med,EMBASE and CNKI databases were searched by computer,and references of related reviews and systematic reviews were manually searched as supplements.According to the inclusion and exclusion criteria,the literatures were screened and the quality was evaluated,and then the data were extracted for meta-analysis.The fixed / random effects model was used to calculate the weighted mean difference(WMD)and 95% CI to evaluate whether the levels of D-dimer,hs CRP,IL-6,IL-8,IL-10 and TNF-α in critical type patients were statistically different from those in severe type patients.If there were statistical differences,logistic regression analysis was used,and establish the receiver operating characteristic curve(ROC)and area under the curve(AUC)of each index for the diagnosis of critical type patients.The best diagnostic value of COVID-19 critical type patients was calculated by Youden index.Results:1.Among the 53 patients,29 were men(54.7%)and 24 were women(45.3%);the median age was(56.79±13.17)years old.The time from onset to admission was(11.5±7.7)days.A total of 26 patients(49.1%)had underlying diseases,including 18 patients(34.0%)with hypertension and 8 patients(15.1%)with diabetes.The main clinical symptoms were fever in 45 cases(84.9%),cough in 43 cases(81.1%),anorexia in 39 cases(73.6%),dyspnea in 26 cases(49.1%).The age of critical type patients(62.27±10.71)years was higher than that of severe type patients(54.63±13.54)years,the difference was statistically significant(P<0.05).The proportion of critical type patients complicated with basic diseases,especially hypertension,cardiovascular disease and cerebrovascular disease increased than those in severe type patients,and the difference were statistically significant(P<0.05).The proportion of critical type patients with dyspnea,night sweats and fatigue symptoms increased than those in severe type patients,and the differences were statistically significant(P<0.05).WBC,ANC,ANC%,D-dimer,PCT,hs CRP,AST,TBIL,DBIL,ALP,GGT,LDH in critical type patients were higher than those in severe type patients(P<0.05).LY% and ALB in critical type patients were lower than those in severe type patients(P<0.05).Among the 53 patients,34(64%)patients had abnormal elevation of ALT,AST or TBIL,and 4(7.5%)patients met the criteria of COVID-19 with liver injury.After grouping according to the degree of liver dysfunction,ALP,GGT and D-dimer levels in the combined liver injury group were significantly higher than those in the normal liver function group,D-dimer levels in the combined liver injury group were significantly higher than those in the mild abnormal liver function group,ALP and GGT levels in the mild abnormal liver function group were significantly higher than those in the normal liver function group,and the differences were statistically significant(P<0.05).2.The clinical characteristics of 41 patients with cytokine detection results were similar to that of the 53 patients.The levels of D-dimer,WBC,ANC,PCT,hs CRP,and IL-8 in critical type patients were higher than those in severe type patients;the differences were statistically significant(P<0.05).The levels of IL-2R,IL-8 and TNF-α in patients with abnormal Ddimer were higher as compared to those in patients with normal D-dimer;the differences were statistically significant(P<0.05).The levels of D-dimer,IL-2R,IL-6 and IL-8 after preventive anticoagulant therapy were lower than those before treatment.No obvious clinical bleeding and thrombosis events were found in all patients.3.According to the inclusion and exclusion criteria,40 articles were finally included in this study,and all of them were high-quality studies after evaluation.The results of meta-analysis showed that the levels of D-dimer,hs CRP,IL-6,IL-8 and IL-10 in critical type group were significantly higher than those in severe type group(P<0.05).Based on ROC curve,the AUC of D-dimer was 0.785(95% CI: 0.671-0.899),AUC of hs CRP was 0.884(95% CI: 0.632-1.000),AUC of IL-6 was 0.819(95% CI: 0.700-0.939),which had diagnostic significance for critical type patients(P<0.05).The optimal diagnostic threshold of D-dimer was ≥2.00 mg/L(sensitivity 89.3%,specificity 64.0%);the optimal diagnostic threshold of hs CRP was ≥64.22 mg/L(sensitivity 75.0%,specificity 100%);the optimal diagnostic threshold of IL-6 was ≥33.01 ng/L(sensitivity 68.0%,specificity 92.0%).Conclusion:1.The main clinical characteristics of severe/critical type patients were fever,cough,dyspnea,and other respiratory symptoms.The main laboratory abnormalities were decreased LY,increased D-dimer and inflammatory markers(ANC,PCT,hs CRP).A considerable proportion of COVID-19 severe/critical type patients had abnormal liver function.2.The levels of D-dimer,inflammatory markers(ANC,PCT,hs CRP)and cytokines(IL-6,IL-8,IL-10)in COVID-19 critical type patients were significantly higher than those in severe type patients,and the abnormal increase of D-dimer in severe/critical type patients was accompanied by the increase of IL-2R,IL-8,TNF-α levels,which suggested that critical type patients had more serious coagulation-immune dysfunction than severe type patients.3.When D-dimer ≥2.0 mg/L,hsCRP ≥64.22 mg/L and IL-6 ≥33.01 ng/L,it is helpful for early identification of critical type patients.