Regular Exercise Is Associated With Low Fatigue Levels and Good Functional Outcomes After COVID-19 A Prospective Observational Study

The lingering effects of COVID-19, often termed post-COVID syndrome or long COVID, have been widely documented, with fatigue being a particularly prevalent and concerning symptom affecting a significant portion of recovered patients. Studies have shown that these persistent symptoms can last for weeks or months, impacting return to pre-infection levels of function and quality of life. The prevalence rates for post-COVID conditions vary, partly due to the lack of consensus on a standardized definition. The Centers for Disease Control and Prevention defines post-COVID conditions as a wide range of new, returning, or ongoing health problems experienced four or more weeks after infection. While some research has explored associations between comorbidities, COVID-19 severity, and post-COVID manifestations, understanding the factors influencing long-term recovery remains limited. This study aims to address this gap by investigating the distribution of persistent symptoms and their impact on function and quality of life among a group of recovered COVID-19 patients. The research questions are: 1. What is the distribution of persistent symptoms and their impact on function and quality of life among a cross-sectional group of patients who have recovered from SARS-CoV-2 infection? 2. Do these patients have risk factors for these persistent symptoms? This study collected in-depth data on cognitive, clinical, and patient-reported outcomes of COVID-19 patients to assess the long-term consequences of the infection. The data from the first study visit are reported in this article.

Previous studies have consistently shown that a substantial percentage of recovered COVID-19 patients experience persistent symptoms, worsening comorbidities, or new symptoms after the acute infection resolves. Reports indicate that as few as 10% of recovered patients experience no symptoms beyond 20 days post-infection, with approximately 75% reporting fatigue. The symptom burden can significantly interfere with the return to pre-infection functional levels. Accumulating evidence suggests that these persistent symptoms are not limited to severely ill patients; they can be observed across all patient groups, including those who were not hospitalized. However, prevalence rates vary considerably, depending on the definition of post-COVID-19, which remains a challenge. Some research has suggested associations between comorbidities and COVID-19 severity and the severity of post-COVID manifestations. Only a limited number of studies have focused on factors affecting long-term recovery after the acute infection has subsided. One prospective observational study identified hypothyroidism and hypoxia during acute illness as risk factors for long COVID sequelae. Studies examining differences in post-COVID-19 sequelae between hospitalized and non-hospitalized patients found that a significant percentage (45%) of patients experienced at least one symptom at 30, 60, or 90 days post-infection, irrespective of hospitalization. Given the high prevalence of persistent symptoms and the potential for long-term health impacts, there is a growing need for improved understanding of the factors associated with long COVID and strategies to promote recovery.

This prospective observational study enrolled 218 patients who tested positive for COVID-19 between March 2020 and July 2022 at Inova Health System. Patients were included if they were at least 28 days post-diagnosis, aged 18 or older, and provided informed consent. Patients who received monoclonal antibody treatment were excluded. Data were collected through in-person or virtual visits. The study utilized the International Classification of Function, Disability, and Health (ICF) framework, which allowed for assessment of impairments, activity limitations, and participation restrictions. Participants answered questions about their social and medical history, COVID-19 illness details, exercise habits, and post-COVID changes in health behaviors. Post-COVID symptom burden was assessed by asking participants if they experienced any new symptoms not present before infection. The investigators categorized these symptoms based on common occurrences. To assess symptom burden and impact on function, the study employed objective physical assessment measures, patient-reported outcome (PRO) questionnaires, and cognitive assessments. Physical assessments for the in-person arm included a physical examination, vital signs, a 2-minute walk distance (TMWD) test, and grip strength measurements, which were normalized using age- and sex-adjusted population norms. PRO questionnaires included the FACIT-F (fatigue, physical, emotional, social, and functional well-being), PHQ-9 (depression), Post-COVID Cognitive Questionnaire, Edmonton Symptom Assessment System (ESAS), GAD-7 (anxiety), Stigma Questionnaire, NCCN Distress Thermometer, and EQ-5D-5L (quality of life). Cognitive assessments included subtests from the Delis-Kaplan Executive Function System and the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) to evaluate processing speed and executive function domains. Statistical analysis included descriptive statistics, χ2 tests, Kruskal-Wallis tests, and generalized linear or logistic regression models to identify factors associated with outcomes. Two-sided P-values less than 0.05 were considered statistically significant.

A total of 218 participants (34% in-person visits) were included, with a mean age of 51 ± 16 years. 95% reported having COVID-19 symptoms, 57% received treatment, 46% were hospitalized, 34% required supplemental oxygen, and 6% needed mechanical ventilation. Patients reported a decline in health status from a mean pre-COVID score of 7.9 to a mean post-COVID score of 6.5. On average, patients reported 1.76 post-COVID symptoms, with fatigue, memory loss, and shortness of breath being the most common. Among patients with fatigue, 41% reported mild, 43% moderate, and 16% severe fatigue. Compared to age- and sex-adjusted norms, patients showed significantly lower grip strength (−14%), impaired fatigue scores (FACIT-F), PHQ-9 scores, and EQ-5D utility scores. Cognitive assessments revealed lower color naming and arithmetic scores compared to norms. Hospitalized patients were older, less likely to exercise regularly, and more likely to have congestive heart failure and hypertension. They also reported longer symptom duration, more healthcare resource utilization, and greater need for supportive care during their COVID-19 illness. No significant differences were found in self-assessed health scores or post-COVID habits between hospitalized and non-hospitalized patients. There were no differences in TMWD or grip strength between hospitalized and non-hospitalized patients. However, PRO scores were lower in the functional well-being domain for hospitalized patients. Among patients with severe fatigue (30%), those individuals were significantly younger, less often male, and had more comorbidities (anxiety, chronic kidney disease, depression), and less commonly reported regular exercise. No differences in COVID-19 illness course or hospitalization rates were observed between those with and without severe fatigue. Patients with severe fatigue had worse diet, weight, and sleep habits post-COVID. Severe fatigue was associated with substantial impairments in all PRO scores but not with TMWD or grip strength. Patients with severe fatigue reported a greater number of post-COVID symptoms. Multivariate analysis revealed that regular exercise was the most consistent predictor of superior PRO scores. Lower fatigue scores were associated with female gender, chronic kidney disease, depression, and a higher number of post-COVID symptoms. Severe fatigue was linked to younger age, anxiety, and symptom number, while the absence of fatigue was associated with regular exercise.

This prospective observational study provides valuable insights into the long-term consequences of COVID-19 infection. The findings confirm that COVID-19 infection is associated with significant functional deficits, including impaired grip strength, increased fatigue and depression, and reduced quality of life. The study's use of both objective measures (grip strength, TMWD) and PROs provides a comprehensive assessment of the impact of COVID-19. The lack of significant differences between hospitalized and non-hospitalized patients in some key outcome measures, like fatigue scores, suggests that COVID-19 severity as indicated by hospitalization is not the sole determinant of long-term symptom burden. The strong association between regular exercise and improved health outcomes highlights the potential importance of promoting physical activity in post-COVID recovery. Encouraging regular exercise may not only mitigate the development of post-COVID symptoms but also help alleviate fatigue and improve physical and cognitive performance. The observed link between fatigue and other factors, such as younger age, specific comorbidities, and dietary habits, points towards the complex interplay of factors influencing long COVID. Further investigation is needed to understand the underlying mechanisms driving fatigue and explore effective interventions to improve patient outcomes.

This prospective study shows that SARS-CoV-2 infection leads to impaired handgrip strength, elevated fatigue and depression levels, and decreased quality of life. Regular exercise strongly predicts better outcomes, including reduced fatigue, depression, and anxiety, improved quality of life and executive functions, and enhanced grip strength. Hospitalized patients tended to be older, unemployed, have more comorbidities, and less likely to exercise. They also reported higher depression levels and lower quality of life compared to norms. Managing comorbidities, encouraging exercise, and addressing fatigue and depression may improve long COVID symptoms, warranting further research for assessing long-term effects and developing targeted interventions.

The study's participants were recruited from a single health system and participation was voluntary; thus, the findings may not fully generalize to all patients with post-COVID sequelae. Pre-COVID health status was retrospectively evaluated, introducing potential recall bias. The time window between infection and enrollment varied, with potential differences in patient experiences and risks over time as variants emerged. This report presents data only from the first time point, limiting insight into the longitudinal course of recovery. Not all patients could have in-person visits, leading to missing data on certain outcome measures. Missing data on some study endpoints could result in biased analysis.