| Background and objectivesBy the time this study was initiated,there were over 500 million confirmed cases and 6million deaths in the global pandemic of COVID-19.The number of confirmed cases and deaths is increasing with the emergence of more infectious strains of SARS-CoV-2,such as Omicron and Delta.Although the vast majority of COVID-19 patients recover from the acute phase,some COVID-19 patients continue to have a variety of problems that affect their social participation and health-related quality of life(HR-Qo L)after discharge from hospital.Common problems include psychiatric disorders(anxiety and depression,etc.),somatic symptoms(fatigue,etc.)and cognitive abnormalities.Therefore,there is a need for systematic follow-up of COVID-19 patients to understand their symptoms and dynamic changes in order to recognise the long-term health impact of COVID-19.Two years after the first COVID-19 patients were discharged from hospital at the start of this study,there is an urgent need to understand their long-term symptoms.We previously reported that in a cohort of 2433 hospitalised COVID-19 patients,45.0%reported at least 1 symptom 1 year after discharge,with patients with severe disease at increased risk of developing more symptoms.However,it is unclear whether symptoms associated with COVID-19 persist for longer.The aim of this study was to observe the dynamic changes in health status of COVID-19 patients from two hospitals in Wuhan 2 years after discharge,to analyse the risk factors associated with their symptom burden,and to provide a reference for improving health-related quality of life in COVID-19 patients.Methods1.Screening the study population.Inclusion criteria: all patients with laboratory-confirmed novel coronavirus pneumonia who were discharged from Wuhan Huoshenshan Hospital and Taikang Tongji Hospital between February 12 and April 10,2020,and who participated in the 1-year health follow-up(n=2433)of our subject group beforehand.All discharged patients met the unified discharge criteria of the treatment protocol for novel coronavirus pneumonia(7th edition)issued by the National Health and Wellness Commission.Exclusion criteria:(1)those who refused telephone followup;(2)those who could not be contacted;and(3)those who died.2.Develop the telephone follow-up formBased on the pre-study cohort,telephone follow-up consisted of all symptoms reported in the acute phase of the study and new symptoms at the one-year follow-up,as well as selfreported discharge from the hospital during the follow-up New symptoms(related to COVID-19)within the period and assessed according to the Likert scale(From 0(no symptoms)to 3(very severe symptoms))were present if at least 1 problem was rated as moderate or severe.And they were given a CAT score,which consisted of 8 scoring criteria: cough,coughing,chest tightness,dyspnea,limitation of activity,confidence to go out,sleep quality,and energy.3.Research stepsAll study subjects were administered telephone follow-up questionnaires,including symptom questionnaires and CAT scores,in the order of their discharge date as recorded in the electronic medical record.Study subjects were asked to report any symptoms that persisted or were new after discharge from the hospital.On the basis of the dynamic changes of symptom number between years 1 and 2,patients were classified into 4 categories:(1)patients with at least 1 symptom at both follow-up time points were defined as having symptoms persist;(2)patients with at least 1 symptom at 1-year follow-up without symptoms at 2-year follow-up were defined as having symptom relief;(3)patients without any symptom at 1-year follow-up but with at least 1 symptom at 2-year follow-up were defined as having new-onset symptoms,which included patients who had a symptom that was reported as a mild problem at year 1,but at 2-year follow-up was reported as moderate or severe problem;and(4)patients with no symptoms at all at both follow-up time points were defined as having no symptoms.4.Data organization and analysisStatistical software R version 4.1.1 and SPSS version 26.0 were used for the analysis.Continuous variables were expressed as median(IQR)followed by Mann-Whitney U test;categorical variables were expressed as absolute values and percentages and subjected to Pearson χ2 test or Fisher exact test.To reduce the risk of bias associated with missed patients,we compared clinical characteristics between enrolled patients(n = 1864)and missed patients(n = 2124).As an exploratory analysis,a 1:1 propensity score matching(PSM)was further applied between these two subgroups according to age,sex,disease severity and coexisting diseases.To identify risk factors associated with the presence of at least two symptoms at 2-year follow-up,"symptom persistence" or "new symptoms" during follow-up,and a CAT score ≥10,univariate logistic regression analysis was used to identify potential risk factors at P<0.10,which were then adjusted by a stepwise(forward:LR)selection process in a multivariate logistic regression model,while age,gender,and severity were included in the model due to their significance were forced into the model.Results1.symptoms and symptom burden of COVID-19 survivors 2 years after hospital dischargeAt 2 years after discharge,19.8% were still symptomatic,of which 12% were "persistent" and 7.8% were "new";most symptoms subsided over time,but the incidence of dyspnea did not change significantly(1 year vs.2 years,2.6% The majority of symptoms resolved over time,but the incidence of dyspnea did not change significantly(1 year vs.2 years,2.6% vs.2.0%).Notably,the "persistent symptoms" group had a much higher rate of dyspnea than the "new symptoms" group(13.4% vs.4.8%).The median CAT score for the entire cohort at 2-year follow-up was 2;the median CAT score was significantly higher in the severe group than in the non-severe group(severe vs.nonsevere,3 vs.2).6.2% had a CAT score ≥10 at 2-year follow-up,with a higher proportion in the severe group than in the non-severe group(severe vs.non-severe,9.5% vs.5.0%).survivors with a CAT score ≥10 were older,had a higher proportion of severe disease,more coexisting conditions,longer hospital stays,and greater use of oxygen therapy.The 1691 patients who were successfully propensity-matched had a similar symptom and symptom burden(CAT score)to the total enrolled population at 2-year follow-up.2.Symptom dynamics of COVID-19 survivors 2 years after hospital dischargeDuring the follow-up period,the proportion of symptomatic survivors decreased significantly(1 year vs.2 years,43.2% vs.19.8%);and the decrease was greater in the severe group compared with the non-severe group(severe group,1 year vs.2 years,52.3% vs.24.4%;non-severe group,1 year vs.2 years,39.9% vs.18.2%).The most common symptoms changed from " fatigue,sweating,chest tightness,anxiety,and myalgia " at the 1-year follow-up to "fatigue,chest tightness,anxiety,dyspnea,and myalgia " at the 2-year follow-up;however,"fatigue,anxiety,chest tightness,dyspnea,and myalgia " were the most common symptoms at the 2-year follow-up,However," fatigue,anxiety,chest tightness,dyspnea and myalgia " were the most common symptoms in the persistent symptom group,while " fatigue,anxiety,chest tightness,cough and sputum " were the most common symptoms in the new-onset symptom group.3.Analysis of risk factors for the presence of symptoms and high symptom burden in COVID-19 survivors 2 years after hospital dischargeAge,sex,disease severity,and ICU admission were associated with "symptom persistence" compared with the "symptom remission" group.Results of multivariate analysis showed that only ICU admission(OR,2.69;95% CI,1.02-7.06;P =.04)was associated with a higher risk of 2-year symptom persistence.Age(OR,1.03;95% CI,1.01-1.04;P <.001)and chronic liver disease(OR,2.22;95% CI,1.19-4.14;P =.01)were independent risk factors for the presence of more than 2 symptoms at 2-year follow-up.Coexisting cerebrovascular disease(OR,3.23;95% CI,1.36-7.69;P =.008)was associated with new-onset symptoms compared with the "asymptomatic" group.Of note,91.5% of survivors with coexisting cerebrovascular disease had 2 or more comorbidities,much higher than the proportion of survivors with other comorbidities.Multivariate analysis showed that age(OR,1.04;95%CI,1.03-1.06;P<.001),入住ICU(OR,2.83;95%CI,1.21-6.66;P=.02),and chronic liver disease(OR,2.18;95%CI,1.10-4.33;P=.03)were CAT score≥10 at 2-year follow-up of risk factors.Conclusions1.In this longitudinal cohort study of 1864 hospitalised COVID-19 patients,the most common symptoms 2 years after discharge were fatigue,chest tightness,anxiety,dyspnoea and myalgia.2.Most symptoms subsided over time,but dyspnoea persisted in "symptom persistent" patients and did not change significantly during the follow-up period.3.Patients with severe disease during hospitalisation(especially ICU admissions)were at higher risk of ’persistent symptoms’ and CAT scores ≥10. |
