| Background and ObjectiveCorona Virus Disease 2019(COVID-19)is a novel infectious disease with pulmonary infectious inflammation as its main manifestation.Since December 2019,COVID-19 has become a major threat to human health and a global public health problem.Although convalescent patients with COVID-19 have recovered their physical functions after treatment,and a large number of patients with COVID-19 have been cured and discharged from hospital.Many studies have reported that the convalescent patients with COVID-19 had some clinical sequelae,including fatigue,dyspnea,cough,sleep disorder,etc.Meanwhile,as a novel infectious disease,COVID-19 can be cured clinically,but its long-term impact on patients remains to be unclear.There are still many gaps in our understanding of the clinical manifestations,functional recovery,long-term prognosis and its influencing factors of convalescing patients with COVID-19.Therefore,it is necessary to understand the sequelae of COVID-19,investigate the clinical characteristics,patterns of Chinese medicine(CM)and prognostic factors of disease for understanding the complete medical history of COVID-19,predicting the development of the disease,and determining whether specific rehabilitation treatment is needed after admission or discharge,and whether these rehabilitation treatments are effective.Through cross-sectional survey and historical cohort study design,this study investigated and analyzed the clinical manifestations,CM clinical characteristics,CM patterns,pulmonary function and body recovery of convalescent patients with COVID-19,and clarified the clinical characteristics of CM,patterns/syndrome classification of CM and prognostic factors of convalescent patients with COVID-19.The results of this study will provide reference for prospective research design and implementation,and may also provide valuable information for rehabilitation and health care strategy formulation of convalescent patients with COVID-19,which is of great significance to the development of CM prevention and rehabilitation theory of epidemic diseases and the clinical practice in CM in the future.MethodsIn this study,cross-sectional survey and historical cohort study were adopted.In view of the current understanding and existing problems of convalescent patients with COVID-19 and post-COVID-19 syndrome,the basic situation of convalescent patients with COVID-19 was investigated,and patients from designated hospitals in Wuhan were recruited for a return visit by telephone contact or advertisement.Patients returned to the hospital,and data were collected through face-to-face and telephone interviews.Researchers with unified training issued questionnaires and explained in detail the matters needing attention for filling in,and gave guidance for filling in.EpiData software was used to establish a database,and the collected data included demographic characteristics,clinical manifestations,physical examination,information of four diagnostic methods in CM,severity during admission,different interventions,laboratory examinations,pulmonary function,pulmonary CT,quality of life questionnaire and other related information.According to the data type and analysis purpose,t-test,Chi-square test,ANOVA/Welch analysis of variance and binary Logistic regression were used to analyze the data.SPSS 18.0 and R software(4.05 version)were used for statistical analysis and forest plot drawing.By systematically sorting out and analyzing the CM clinical features and CM syndrome classification of convalescent patients with COVID-19,and then using historical cohort study design,matching the relevant information of COVID-19 patients during hospitalization,the related factors affecting the prognosis of convalescent patients with COVID-19 were explored by using the Logistic regression analysis.ResultsA total of 574 convalescent patients with COVID-19 were included in the crosssectional study(discharged diagnosis included 25 mild patients and 436 common patients,with 461 non-severe patients,105 severe patients and 8 critical patients(113 severe patients).The results of baseline characteristic analysis showed that the average age of the convalescent patients was 57.7 ± 11.4 years old,of which 348 cases(60.6%)were women.The average time of onset was 29.1 ± 16.1 days,the average length of stay(LOS)was 18.49 ± 12.71 days,and the average time from discharge to this survey was 194.3 ± 14.4 days.The most common basic diseases were hypertension in 156 cases(27.2%),diabetes mellitus in 84 cases(14.6%)and coronary heart disease in 37 cases(6.4%).There was no significant difference in gender,basic disease and time from onset to follow-up between non-severe group and severe group(all P>0.05),but there was significant difference in age,onset time,LOS and time from discharge to investigation between the two groups(P<0.05).It is found that convalescent patients still have persistent chest CT abnormalities,decreased pulmonary function,persistent fatigue,respiratory symptoms and decreased quality of life 5-8 months after discharge.More than half(55.9%)of convalescent patients with COVID-19 have one ormore common symptoms.Among them,the incidence of fatigue,dyspnea and chest tightness was higher.114 patients(19.9%)reported that they were more afraid of cold than before,and there was significant difference between severe group(26.5%)and non-severe group(18.2%)(P<0.05).For the first time,it was found that 256 patients(45.4%)had decreased balance capability through one-leg upright balance test,and the difference between severe group(63.4%)and non-severe group(41%)was statistically significant(P<0.05),and 12.0%of convalescent patients had decreased memory,and the incidence in severe group was statistically significant compared with non-severe group(P<0.05).29.4%of the convalescent patients had the main psychological and mental manifestations characterized by sleep disorder,and a few showed anxiety and post-traumatic stress disorder.Except for aversion to cold,expectoration,memory impairment and balance loss,there was no significant difference in sequelae between severe and non-severe patients(P>0.05).A total of 342 convalescent patients completed the pulmonary function examination during the follow-up period.Among the 342 convalescent patients,193 patients still had pulmonary function impairment,among which 110 patients(32.4%)had abnormal DLCO%,105 patients(30.7%)had MMEF%<65%,128 patients(37.4%)had FEF 50%<65%,240 patients(70.2%)had FEF 75%<65%.Most convalescent patients still have small airway obstruction.However,there was no significant difference between the severe group and the non-severe group(P>0.05).A total of 563 patients completed lung CT examination during the follow-up period of rehabilitation.A total of 287 patients(51.0%)had CT abnormalities.The incidence rate of CT abnormalities in severe cases(65.2%)was higher than that in non-severe cases(47.5%),and the difference was statistically significant(P=0.001).In addition,univariate analysis showed that the incidence of lesions in right middle lobe,right lower lobe,left upper lobe and semi-ground glass shadow in severe group was higher than that in non-severe group,and the differences were statistically significant(P<0.05).Lymphocyte subsets test showed that 252(43.9%)T lymphocyte counts were lower than normal,231(40.2%)CD8+T lymphocyte counts were lower,260(45.3%)CD4+T lymphocyte counts were lower,119(20.7%)B lymphocyte counts were lower,54(9.4%)NK lymphocyte counts were lower.Qualitative detection of SARS-COV-2 IgG and IgM antibody in 573 convalescent patients showed that there were 546(95.1%)convalescent patients with positive or weakly positive IgG antibody,and there was no significant difference in the positive rate between severe and non-severe patients(95.6%)(P>0.05).There were still 107 patients(18.6%)who were positive or weakly positive for IgM antibody,and there was no significant difference in the positive rate between severe patients and nonsevere patients(P>0.05).According to the descriptive statistics of CM clinical manifestations of convalescent patients,the frequency of common remaining symptoms from high to low is as follows:fatigue(275 cases,47.9%),dry mouth(215 cases,37.5%),insomnia(169 cases,29.4%),chest tightness(169 cases,29.4%),shortness of breath(165 cases,28.7%),bitter taste(120 cases,20.9%),chills(114 cases,19.9%),spontaneous sweating(78 cases,13.6%)and cough(66 cases,11.5%).Through cluster analysis,the main CM syndrome types of convalescent patients with COVID-19 were divided into five types:① 156 cases(27.2%)with deficiency of both qi and yin,symptoms:fatigue,fatigue,chest tightness,dry mouth and insomnia,thin and white fur,thin and smooth pulse;②126 cases(22.0%)with phlegm blocking and stagnation of heat,symptoms:fatigue,dry mouth,insomnia,thick fur,yellow and white,and thin and smooth pulse;③126 cases(22.0%)with Qi deficiency,phlegm and blood stasis,symptoms:fatigue,fatigue,chest tightness,insomnia,dry mouth,constipation,slippery pulse,dark red tongue,petechia and yellow fur;④ 102 cases(17.8%)with deficiency of yang-qi and cold,symptoms:fatigue,chest tightness,shortness of breath,chills,spontaneous sweating,dry mouth,thin pulse,pale red tongue and thin white fur;⑤102 cases(17.8%)with spleen deficiency and dampness,symptoms:fatigue,shortness of breath,chest tightness,dry mouth,tooth marks on the edge of tongue,pale red tongue with thick fur and smooth pulse.Deficiency of both qi and yin is the most common CM syndrome type of convalescent patients in non-severe group,while phlegm resistance and stagnation of heat is the most common syndrome type in rehabilitation period in severe group.By multivariate Logistic regression analysis,after adjusting for gender,age,LOS,onset time,basic diseases,treatment,and whether to continue rehabilitation after discharge,compared with non-severe group,the odds ratio(OR)of pulmonary diffusion dysfunction in severe group was 2.18(95%CI:1.10-4.31),and the OR of one-leg upright balance test was 2.34,95%CI:1.27-4.31,and CD4+abnormality was 1.76(95%CI:1.02-3.00).Other general malaise symptoms such as fatigue,sweating,muscle soreness,chest tightness and pain,shortness of breath,cough and expectoration,digestive tract symptoms,nervous system symptoms,psychological state and other variables were not statistically significant.A historical cohort study was designed to match the relevant information of convalescent patients during admission.A total of 342 convalescent patients who completed pulmonary function examination were included in this study.The average age of 342 patients was 60.0±10.2 years old,including 217 females(63.5%),82 severe patients and 260 nonsevere patients.The mean time of onset was 28.8±16.2 days and the mean LOS was 19.6±13.2 days.These 342 patients were divided into normal pulmonary function group(149 cases)and abnormal pulmonary function group(193 cases).In the abnormal pulmonary function group,143 cases were non-severe patients and 50 cases were severe patients.There was no significant difference between non-severe patients and severe patients(P>0.05).Among the basic diseases,94 cases(27.5%)with hypertension were the most common,among which 4 cases(1.2%)had a history of COPD before onset.227(66.4%)convalescent patients continued to do rehabilitation treatment after discharge,and sports rehabilitation was the main treatment(51.2%).During the treatment,most patients(92.1%)were treated with CM.By comparison,there was no significant difference between the two groups in age,gender,onset time,LOS,hospitalization classification,basic diseases,treatment methods,biochemical indexes related to the first admission and whether there was rehabilitation treatment after discharge(P>0.05).The comparison of D-dimer in the first examination of admission showed that the convalescent patients with abnormal pulmonary function were slightly higher than those with normal pulmonary function,but the difference was not statistically significant(P=0.072).Multivariate Logistic regression analysis showed that there was no significant difference between the two groups in age,sex,onset time,LOS,admission classification,basic diseases,treatment methods,biochemical indexes related to the first admission and whether there was rehabilitation treatment after discharge(P>0.05).A total of 338 of the 342 convalescent patients included in the historical cohort study had chest CT examination.The patients were divided into normal CT group(151 cases)and abnormal CT group(187 cases).In the abnormal CT group,the OR of age was 1.05(95%CI:1.02-1.07),the OR of onset time was 0.98(95%CI:0.97-1.00),the OR of diabetes mellitus was 1.95(95%CI:1.08-3.53),coronary heart disease was 3.11(95%CI:1.13-8.58),respiratory disease was 9.38(95%CI:1.20-73.46).Multivariate Logistic regression analysis showed that age and respiratory diseases were independent risk factors for abnormal CT findings in convalescent patients.ConclusionsConvalescent patients with COVID-19 still have clinical sequelae 5-8 months after discharge,and some patients have incomplete rehabilitation of pulmonary function.Attention should be paid to the long-term rehabilitation of convalescent patients.The main CM syndromes of convalescent patients include deficiency of both qi and yin,phlegm blocking and stagnation of heat,qi deficit plus phlegm and blood stasis&internal resistance,deficiency of yang and cold,deficiency of spleen and dampness,with deficiency syndrome as the main pathogenesis.Age,gender,onset time,LOS,admission type,basic diseases,treatment methods,biochemical indexes related to the first admission and whether there is rehabilitation treatment after discharge have no effect on the rehabilitation of pulmonary function in convalescent patients with COVID-19.Age and respiratory diseases are independent risk factors for abnormal chest CT findings in convalescent patients. |
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