Background
With the COVID-19 pandemic ongoing, growing evidence shows that a considerable proportion of people who have recovered from COVID-19 have long-term effects on multiple organs and systems. Some longitudinal studies reported on persistent health effects of COVID-19, but follow-up was limited to 1 year after acute infection.
The objective of our study was to characterize the longitudinal evolution of health outcomes in hospital survivors with different initial disease severity over 2 years after acute COVID-19 infection and determine their recovery status.
Methods
We did a 2-way longitudinal cohort study of people who had survived hospitalization with COVID-19 and who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between January 7 and May 29, 2020.
We measure health outcomes 6 months (June 16 to September 3, 2020), 12 months (December 16, 2020 to February 7, 2021), and 2 years (November 16, 2021 to January 10, 2022) after the onset of symptoms with a 6-minute walk distance (6MWD) test, laboratory tests and a series of questionnaires on symptoms, mental health, health-related quality of life (HRQoL), return to work and use of health services after discharge. A subset of COVID-19 survivors received lung function testing and chest imaging at each visit.
Age-, sex-, and comorbidity-matched participants without COVID-19 infection (controls) were entered to determine the recovery status of COVID-19 survivors at 2 years.
Primary outcomes included symptoms, modified British Medical Research Council (mMRC) dyspnea scale, HRQoL, 6MWD, and return to work, and were assessed in all COVID-19 survivors who attended all three follow-up visits. Symptoms, mMRC dyspnea scale, and HRQoL were also assessed in controls.
Results
2,469 COVID-19 patients were discharged from Jin Yin-tan Hospital between January 7 and May 29, 2020. 1,192 COVID-19 survivors completed assessments at all three follow-up visits and were included in the analysis. final, 1119 (94%) of whom attended the face-to-face interview 2 years after infection. The median age at discharge was 57.0 years (48.0-65.0) and 551 (46%) were women.
The median follow-up time after symptom onset was 185.0 days (IQR 175.0-197.0) for the 6-month visit, 349.0 days (337.0-360.0) for the 12-month visit, and 685·0 days (675·0–698·0) for the 2-year visit.
The proportion of COVID-19 survivors with at least one sequelae symptom decreased significantly from 777 (68%) of 1149 at 6 months to 650 (55%) of 1190 at 2 years (p<0·0001), with Fatigue or muscle weakness is always the most common.
The proportion of COVID-19 survivors with an mMRC score of at least 1 was 168 (14%) of 1191 at 2 years, significantly lower than 288 (26%) of 1104 at 6 months (p<0·0001) .
HRQoL continued to improve in almost all domains, especially in terms of anxiety or depression: the proportion of individuals with symptoms of anxiety or depression decreased from 256 (23%) at 6 months to 143 (12%) at 1191. 2 years (p<0·0001).
The proportion of people with a 6MWD below the lower limit of the normal range continuously decreased in COVID-19 survivors overall and in the three subgroups of varying initial disease severity. 438 (89%) of 494 COVID-19 survivors had returned to their original job by 2 years.
Survivors with long COVID symptoms at 2 years had lower HRQoL, worse exercise capacity, more mental health abnormalities, and higher healthcare use after discharge than survivors without long COVID symptoms.
COVID-19 survivors still had more frequent symptoms and more problems with pain or discomfort, as well as anxiety or depression, at 2 years than controls. Furthermore, a significantly higher proportion of survivors who had received high-level respiratory support during hospitalization had impaired pulmonary diffusion (43 [65%] of 66 vs 24 [36%] of 66, p=0·0009), reduced residual volume (41 [62%] vs. 13 [20%], p<0·0001) and total lung capacity (26 [39%] vs. four [6%], p<0·0001) than controls .
Interpretation
Regardless of initial illness severity, COVID-19 survivors had longitudinal improvements in physical and mental health, and most returned to their original job within 2 years; however, the burden of symptomatic sequelae remained quite high.
COVID-19 survivors had markedly lower health status than the general population at 2 years. The study findings indicate that there is an urgent need to explore the pathogenesis of long COVID and develop effective interventions to reduce the risk of long COVID.
Comments
- Study of 1,192 participants hospitalized with COVID-19 in Wuhan, China, between January 7 and May 29, 2020, with follow-up at six months, 12 months, and two years after discharge.
- Physical and mental health improved over time, regardless of initial disease severity, with 55% reporting at least one symptom caused by initial COVID-19 infection at two years, compared to 68% at two years. six months.
- Overall, recovered COVID-19 patients tend to be in poorer health two years after initial infection compared to the general population, indicating that some patients need more time to fully recover.
- About half of the study participants had long COVID symptoms, such as fatigue and sleep difficulties, at two years, and experienced poorer quality of life and ability to exercise, more mental health problems, and greater use of healthcare services compared to those without long COVID symptoms.
Two years after COVID-19 infection, half of patients admitted to hospital still have at least one symptom, according to the longest follow-up study to date, published in The Lancet Respiratory Medicine . The study followed 1,192 participants in China infected with SARS-CoV-2 during the first phase of the pandemic in 2020.
While overall physical and mental health has improved over time, analysis suggests that COVID-19 patients still tend to have worse health and quality of life than the general population. This is especially the case for participants with long COVID, who typically still have at least one symptom including fatigue, shortness of breath, and difficulty sleeping two years after initially getting sick.
The long-term health impacts of COVID-19 have remained largely unknown, as the longest follow-up studies to date have spanned about a year. The lack of references to pre-COVID-19 health status and comparisons with the general population in most studies has also made it difficult to determine how well COVID-19 patients have recovered.
Lead author Professor Bin Cao, from China-Japan Friendship Hospital, China, says: "Our findings indicate that for a certain proportion of hospitalized COVID-19 survivors, although they may have cleared the initial infection, more are needed. two years to fully recover from COVID-19.
Continued monitoring of COVID-19 survivors, particularly those with long COVID symptoms, is essential to understanding the longer course of the disease, as is further exploration of the benefits of rehabilitation programs for recovery. “There is a clear need to provide continued support to a significant proportion of people who have had COVID-19 and to understand how vaccines, emerging treatments and variants affect long-term health outcomes.”
The authors of the new study sought to analyze the long-term health outcomes of hospitalized COVID-19 survivors, as well as the specific health impacts of long COVID. They assessed the health of 1,192 participants with acute COVID-19 treated at Jin Yin-tan Hospital in Wuhan, China, between January 7 and May 29, 2020, at six months, 12 months, and two years.
Assessments included a six-minute walk test, laboratory tests, and questionnaires about symptoms, mental health, health-related quality of life, whether they had returned to work, and health care use after discharge. The negative effects of long COVID on quality of life, exercise capacity, mental health, and healthcare use were determined by comparing participants with and without long COVID symptoms. Two-year health outcomes were determined using an age-, sex-, and comorbidity-matched control group of people in the general population with no history of COVID-19 infection.
The median age of participants at discharge was 57 years and 54% (n=641) were men. Six months after initially getting sick, 68% (777/1149) of participants reported at least one long COVID symptom. Two years after infection, symptom reports decreased to 55% (650/1190).
Fatigue or muscle weakness were the most common symptoms and decreased from 52% (593/1151) at six months to 30% (357/1190) at two years. Regardless of the severity of their initial illness, 89% (438/494) of participants had returned to their original job by two years.
Two years after initially becoming ill, COVID-19 patients are generally in poorer health than the general population, with 31% (351/1,127) reporting fatigue or muscle weakness and 31% (354/1,127) reporting difficulty sleeping. The proportion of participants without COVID-19 who reported these symptoms was 5% (55/1127) and 14% (153/1127), respectively.
COVID-19 patients were also more likely to report a number of other symptoms, such as joint pain, palpitations, dizziness and headaches.
In quality of life questionnaires, patients with COVID-19 also reported pain or discomfort more frequently (23% [254/1127]) and anxiety or depression (12% [131/1127]) than participants without COVID-19. 19 (5% [57/1,127] and 5% [61/1,127], respectively).
About half of the study participants (650/1,190) had long COVID symptoms at two years and reported a lower quality of life than those without long COVID. On mental health questionnaires, 35% (228/650) reported pain or discomfort and 19% (123/650) reported anxiety or depression.
The proportion of COVID-19 patients without long COVID who reported these symptoms was 10% (55/540) and 4% (19/540) at two years, respectively. Participants with long COVID also more frequently reported problems with their mobility (5% [33/650]) or activity levels (4% [24/540]) than those without long COVID (1% [8/540] and 2% [10 /540], respectively).
Mental health assessments of participants with long COVID found that 13% (83/650) showed symptoms of anxiety and 11% (70/649) showed symptoms of depression .
Participants with long COVID more frequently used healthcare services after discharge, with 26% (169/648) reporting an outpatient clinic visit compared to 11% (57/538) of those participants with non-prolonged COVID. At 17% (107/648), hospitalization among participants with long COVID was higher than the 10% (52/538) reported by participants without long COVID.
The authors acknowledge the limitations of their study. Without a control group of hospital survivors unrelated to COVID-19 infection, it is difficult to determine whether the observed abnormalities are specific to COVID-19. Although the moderate response rate may introduce selection bias, most baseline characteristics were balanced between COVID-19 survivors who were included in the analysis and those who were not.
The slightly higher proportion of participants included in the analysis who received oxygen leads to the possibility that those who did not participate in the study had fewer symptoms than those who did. This may result in an overestimation of the prevalence of long COVID symptoms. As a single-center study from early in the pandemic, the findings may not directly extend to the long-term health outcomes of patients infected with later variants.
Like most COVID-19 tracking studies, there is also potential for information bias when analyzing self-reported health outcomes. Some outcome measures, including employment status and healthcare use after discharge, were not recorded at all visits, meaning that only partial analysis of long-term impacts on these outcomes was possible.
Discussion
To our knowledge, this is the longest longitudinal follow-up study of people who recovered from acute COVID-19 illness, and it systematically and comprehensively describes the longitudinal evolution of health and functional outcomes among COVID-19 survivors. 19 with different severity up to 2 years.
We found that HRQoL, exercise capacity, and mental health continued to improve over 2 years, regardless of initial disease severity, but about half still had symptomatic sequelae at 2 years. Long COVID symptoms at 2 years were associated with lower quality of life, lower exercise capacity, abnormal mental health, and higher healthcare use after discharge.
The physical health and HRQoL of participants with COVID-19 remained worse than the control population 2 years after acute infection. Critically ill patients had a significantly higher burden of impaired restrictive ventilation and impaired pulmonary diffusion than controls at 2 years of follow-up.
Added value of this study
To our knowledge, this is the longest longitudinal cohort study of people who survived hospitalization with COVID-19, including an age-, sex-, and comorbidity-matched control group of people who had never had COVID-19, to describe the dynamic recovery of health in the 2 years after the onset of symptoms.
The proportion of individuals with at least one sequelae symptom decreased significantly from 68% at 6 months to 55% at 2 years, with fatigue or muscle weakness being the most frequently reported symptom during follow-up.
Long COVID symptoms at 2-year follow-up were associated with decreased health-related quality of life (HRQoL) and exercise capacity, psychological abnormalities, and increased healthcare use after discharge. HRQOL continued to improve in almost all domains, especially in terms of anxiety or depression, and the proportion of participants reporting symptoms of anxiety or depression decreased significantly from 23% at 6 months to 12% at 2 years.
The proportion of people with reduced walking ability decreased continuously to 8% at 2 years. 89% of COVID-19 survivors who had a job before COVID-19 have returned to their original job, regardless of initial illness severity. However, COVID-19 survivors still had more symptoms and lower HRQoL than controls at 2 years.
Implications of all available evidence
Long COVID could persist persistently for up to 2 years after acute infection, indicating that continued longitudinal follow-up is urgently needed to better characterize the natural history of long COVID and establish when COVID-19 survivors will fully recover. .
Future studies should further explore the pathogenesis of long COVID and develop effective intervention strategies to reduce the risk of long COVID. Furthermore, the higher proportion of restrictive ventilatory failure during the late recovery period raises concern for pulmonary interstitial abnormalities, especially for COVID-19 survivors with acute respiratory distress syndrome. In this particular population, simultaneous pulmonary function testing and pulmonary imaging are required.
