Protracted exercise tolerance post-coronavirus disease 2019 in endurance athletes: A survey

Background The global coronavirus disease 2019 (COVID-19) pandemic irrevocably influenced our lives, yet research in a diversity of countries is lacking. Cardiorespiratory fitness may be impaired for up to a year post-COVID-19 infection. Objectives Our study aimed to compare acute and exertional symptoms, fatigue, and exercise performance in masters-age endurance athletes according to their return-to-sport status. Method A cross-sectional survey-based observational study of long-distance runners and cyclists was conducted. Data were stratified into two groups: those who returned to their pre-illness level of sport and those who did not and were compared statistically. Results A total of 308 survey responses were included in the analysis. The mean age of the athletes was 44.9 + 10.2 years, with 55.2% being male. The group that did not return to their pre-illness level of sport (31.5%) had more post-COVID sequelae, worse illness severity, with a higher frequency of resting and exertional symptoms, notably fatigue and dyspnoea. Decreased exercise capacity was correlated with increased physical fatigue scores. Conclusion Almost one-third of endurance athletes suffered protracted exercise tolerance post-COVID-19. Long-term symptoms may be more consequential in this athlete population. Clinical Implications Symptoms that may indicate cardiopulmonary consequences in recreational athletes should be investigated in order to facilitate return to sport and the important mental and physical benefits thereof. This will augment outcomes after respiratory tract infections and management of return to sport and expectations of endurance athletes.


Introduction
The global coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has irrevocably influenced our lives.Extensive research has explored this disease and its devastating consequences on the world's population and concurrently enhanced global knowledge of respiratory illnesses (Burgstahler et al. 2023).Comorbid diseases and a lack of regular physical activity predispose individuals to a more severe expression of COVID-19 (Chen et al. 2020;Snyders et al. 2022).However, high-intensity exercise may lower immune function and increase susceptibility to upper respiratory tract infections (Agha-Alinejad et al. 2022).Cardiorespiratory fitness is now classed as a vital sign (Mihalick et al. 2021), thus lagging athlete health and the hinderance of persistent symptoms in resuming preillness level of sport is worth assessing (Schroeder et al. 2023).
Coronavirus disease 2019 is a multifaceted disease with manifestations like no other virus, such as blood clotting and long-standing fatigue and dyspnoea (Schwellnus et al. 2021).The cardiovascular consequences of COVID-19 are by far the most threatening and range from peri-myocarditis, arrhythmias, thromboembolism, myocardial infarction, to sudden death (Monosilio et al. 2023).However, according to the American College of Cardiology (ACC) 2022 expert consensus statement, there is fortunately a low prevalence (Gluckman et al. 2022).Long-term respiratory sequelae are more likely post-COVID-19 (Durstenfeld et al. 2022).Pulmonary limitations have been found to be responsible for low exercise tolerance up to 1-year post-COVID-19 infection (Braga et al. 2023), even after mild illness (Vollrath et al. 2022).
Acute COVID-19 symptoms are categorised as asymptomatic, mild, moderate, severe, and critical illness according to the National Institute of Health (COVID-19 Treatment Guidelines 2023).Mild illness symptoms include malaise and/or fatigue, headache, myalgia, ageusia and/or anosmia, cough, fever, and diarrhoea and/or vomiting.Symptoms associated with moderate illness include dyspnoea and clinical evidence of lower respiratory disease on imaging with normal oxygen saturation (≥ 94% on room air).Individuals with severe illness present with respiratory distress and dyspnoea with oxygen saturation of < 94%, and critical illness includes respiratory failure, septic shock and multiorgan failure.In our study, the term long-COVID is used for new or persistent symptoms after 4 weeks post onset of illness as defined by the National Institute for Health and Care Excellence (NICE 2021).Fatigue is a multidimensional and subjective symptom that may or may not relate to other physiological factors (Smets et al. 1995).
During the early phase of the pandemic, most studies explored symptom severity and duration in collegiate elite athletes.There remains a paucity of literature concerning the masters athlete (over the age of 35 years) (Juhász et al. 2022).Endurance athletes require the ability to resist fatigue; typically training high volumes and placing a huge demand on their cardiorespiratory system (Joyner & Coyle 2008).To define and classify athletes, it has been proposed that competitive athletes exercise for 6 h or more per week and recreational athletes for at least 3 h; although endurance runners and cyclists often train equal volumes to professional athletes ( pelliccia et al. 2021).Running is a highly accessible and affordable sport attracting longdistance adult athletes predominantly at a recreational level (DeJong, Fish & Hertel 2021).Unlike elite athletes, they may lack access to sports medicine professionals who disseminate return to sport (RTS) guidelines and screen for the risk of cardiac involvement (Elliott et al. 2020).Published RTS criteria are primarily based on the presence and severity of symptoms (Steinacker et al. 2022).This leads to concerns about adult recreational athletes exercising while potentially still feeling unwell (Ruuskanen et al. 2022).There is a need for prolonged observation and follow-up of athletes who had COVID-19, particularly with cardiovascular sequelae (Monosilio et al. 2023).
Our study aims to compare acute and exertional symptoms, fatigue, and exercise performance experienced by masters age group endurance athletes who had returned to their previous level of sport to those who had not.The results of our study may provide valuable insights for healthcare professionals, coaches, and athletes alike to understand variables associated with protracted RTS after COVID-19.This will facilitate better outcomes after respiratory tract infections and more effective management of RTS and expectations of competitive and recreational endurance athletes after respiratory tract infections.

Study design
Our study is a cross-sectional survey-based observational to determine the difference in demographic and sport-specific characteristics, disease severity, duration, and symptoms, self-reported approach to RTS and exercise capacity, and fatigue score between athletes who had returned to their preillness level of sport and those who had not.The impetus for our study was the threat of COVID-19 consequences in athletes over the age of 35 years, doing a high volume of cardiovascular exercise.Participants were recruited by snowball sampling from athletic clubs in South Africa between December 2021 and July 2022.Emailers were sent to 64 athletic clubs containing the invitation to participate in the online survey and a request to forward it on to their members.The invitation was also disseminated via social media to 18 WhatsApp groups and 25 Facebook pages.Athletic clubs approved the post on their social media pages and chats.Invitations could then be forwarded by the recipients in a snowball fashion to fellow athletes.

Study population and sampling strategy
Eligible participants were adult (age 18+) endurance athletes of both sexes who ran for three or more hours per week or cycled for three or more hours per week (McKinney et al. 2019).Those who participated in additional sports over and above were also included and described as multisport athletes.The athletes had either been diagnosed with COVID-19 through a positive polymerase chain reaction (PCR) test or exhibited the known symptoms of COVID-19.Athletes who were admitted to the intensive care unit (ICU) were excluded as ICU-acquired weakness occurs from 15-29 days, and necessitates prolonged rehabilitation to return to normal function (Van Aerde et al. 2020).Other exclusion criteria for athletes were not being proficient in the English language, residing outside of South Africa, and a lack of informed consent.The sample size estimation equalled 178.This was based on the change in aerobic capacity of the athletic population infected with COVID-19 compared to a control group (10.0% vs. 3.5%) (Crameri et al. 2020), with an effect size of 0.63, a confidence interval (CI) of 0.05, power of 0.9, and adding 10% for each confounding variable that is age, sex, sport, stage of disease.To achieve this sample size, we assumed a 30% response rate and 50 members per athletics club.At the time, the prevalence of COVID-19 infections in the city was 5.4%, thus, the questionnaire needed to be accessed by 3200 athletes at 64 clubs.

Data collection
A self-administered web-based questionnaire was developed by the research team using the Research Electronic Data Capture (REDCap) platform and was based on current literature.Sociodemographic data including sex, age, and sport-specific data constituted the first 10 questions, followed by 10 questions on COVID-19 status, prevalence of comorbidities, and post-COVID sequelae.The third section included questions regarding the management of their acute illness based on the World Health Organization (WHO) Severity Scale (Marshall et al. 2020)  Fatigue was scored using the standardised Multidimensional Fatigue Inventory (MDFI) tool (Smets et al. 1995).The MDFI consists of 20 questions that assess five categories of fatigue, namely: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue.The scales used are freely available, thus no permissions were required.
The MDFI has good internal consistency (Cronbach's alpha = 0.84), and construct and convergent validity are reported (Smets et al. 1995).A professional panel in the field of sports medicine and respiratory health validated our study questionnaire.Construct validity of the questionnaire as a research tool was performed by sending a test questionnaire to 10 COVID-19 convalescent athletes, 4 of whom were medical professionals.Test-retest reliability was performed 2 weeks apart to avoid a learning effect.The null hypothesis of this study was that there was no difference in the effect of COVID-19 on the group that had returned to their pre-illness level of sports participation (y-RTS) versus those that had not (n-RTS).The primary outcome was a return to the pre-illness level of sport.Therefore, in the statistical analysis, we abbreviated the subgroup of athletes who selected the option 'still not returned to pre-illness level of sport' in the questionnaire as the n-RTS group.All others were combined into the y-RTS group.

Data analysis
A lack of consent, answering 'No' to contracting COVID-19, or incomplete symptom data resulted in exclusion from data analysis.There was minimal missing data as radio button questions were marked *required.

Ethical considerations
Unconditional ethical approval was provided by the University of the Witwatersrand's Human Research Ethics Committee (Medical) (Certificate no.M210657).Our study procedures adhered to the principles set forth in the Declaration of Helsinki and the South African Guidelines for Good Clinical Practice and the Medical Research Council.An information sheet explaining our study purpose and data sharing according to the FAIR principles (GO FAIR, FAIR principles 2016) was linked to the survey and ensured confidentiality and anonymity and permission to withdraw from our study at any point.The participants were asked if they consented to the anonymised data being used for research purposes.After electronic consent was obtained, the full questionnaire opened.The completion of the questions implied that consent was given throughout.Only the research team had access to the REDCap platform on which the information sheet and survey was developed and data were stored.The exported data were stored one password-protected computer and backed up to Apple iCloud Drive.

Demographic, sport-specific, and return to pre-illness level of sport characteristics of our study population
After the surveys were assessed for eligibility, 308 participants were included in data analysis (Figure 1).difference in the demographic and sport-specific characteristics of y-RTS versus n-RTS.
Most athletes did not have coexisting comorbidities (n = 253, 82.1%).However, comorbidities that were reported include asthma (n = 18, 5.8%), hypertension (n = 12, 3.8%), and cardiac disease (n = 4, 1.3%).The majority (94%) of athletes (n = 289) experienced one or more of the known COVID-19 symptoms.The only significant difference in COVID-19 characteristics of the y-RTS group compared to the n-RTS was the severity of the disease according to the WHO COVID-19 Severity Scale, indicating that more athletes consulted healthcare professionals and/or were admitted to hospital in the n-RTS group ( p = 0.032).

Acute and subacute symptoms
Table 2 summarises symptoms at the time of illness.There was no significant difference in asymptomatic disease experienced by the y-RTS versus n-RTS groups.A total of 21 participants (6.8%) tested negative, but their symptom presentation implied false negative tests.Fatigue was the only mild symptom more prevalent in the n-RTS group ( p = 0.044).We found a higher proportion of moderate disease in n-RTS group ( p = 0.006).
There were eight athletes in total with severe illness requiring supplemental oxygen, with no significant difference between the groups ( p = 0.710).No participants cited critical illness.

Factors associated with return to pre-illness level of sport
The time frame in which athletes in the whole group returned to pre-illness level of sport is displayed in Figure 2, with n = 97 (31.5% ) not yet at their previous level and constituted the n-RTS group.Table 3 displays the presence and severity of symptoms while exercising and other self-reported factors limiting their RTS.The athletes approached their resumption of training with similar consideration of most factors, with only pace being monitored more closely in the n-RTS group

Fatigue and the endurance athlete
The MDFI (

Discussion
Our study provides insight into acute and exertional symptoms associated with protracted exercise tolerance in a masters-age athlete population that does a high volume of cardiovascular exercise yet has had little investigation.Following several studies earlier in the pandemic that focussed on elite team sport athletes (Petek et al. 2021) (Schwellnus et al. 2021).
The presence of exertional symptoms is widely documented, suggesting that athletes begin training while feeling unwell (Schroeder et al. 2023).Our study confirmed this, as 70% of the entire group experienced fatigue or elevated heart rate while exercising, 57% experienced dyspnoea, and 21% experienced chest pain.Hughes et al. (2022) proposed no exercise resumption until symptoms had abated or diminished.Whether the 35% of the n-RTS group who experienced chest pain followed RTS guidelines and thereby  reduced their training is unknown, as 14% of the y-RTS group also reported chest pain.Although the reasons why the athletes did not return to pre-illness level was not specifically investigated, the results suggest that persistent symptoms interfered with full athletic performance.
In our study, athletes with post-COVID-19 sequelae were less likely to return to their previous performance levels, consistent with Schroeder et al. (2023).Our study found a higher prevalence of cardiovascular sequelae (8.8%) compared to those reviewed by Monosilio et al. (2023), probably because of this study's higher average age.Herein lies an important finding.Myocarditis, arrythmias and other cardiopulmonary post-COVID-19 sequelae presented in our study, are a concern and may be underreported in masters age-group athletes.Ventricular arrhythmias were found to occur in asymptomatic or mild disease (Casasco et al. 2022), and these athletes, constituting the bulk of the field in marathons events, may not have undergone routine cardiac screening.Our findings imply that older athletes and those with post-COVID-19 sequelae require better management.These athletes should monitor resting and exertional heart rate, sleep quality, cardiopulmonary symptoms, and fatigue after resuming exercise (Steinacker et al. 2022).While the athletes in our study were adept at monitoring heart rate and pace facilitated by popular wearable devices, it is recommended that athletes be more aware of the symptoms they experience and the implications thereof on RTS.
A novel finding in our study was the significantly decreased odds of RTS in those with physical fatigue, while mental fatigue is strongly associated with increased odds of RTS.This may seem counterintuitive as fatigue and impaired neurocognitive ability can lead to protracted exercise tolerance (Steinacker et al. 2022).Mental fatigue often occurs because of a prolonged period of demanding cognitive tasks yet may also develop from the frustration of trying harder to resume fitness compared to other respiratory illnesses (Marcora et al. 2009).In a scoping review by Oswald et al. (2020), running has been unequivocally positively associated with improving mood, sense of well-being, self-efficacy, and decreased depression.Regular runners who were prevented from running for 2 weeks had increased anxiety and depression compared to the runners who continued (Oswald et al. 2020).Hence, an unexpected finding becomes expected.
This relationship may further explain the tendency for endurance athletes to resume training before recovering sufficiently.
Our study is one of the first to compare individuals who successfully rebuilt their pre-illness fitness level to those who were still struggling.

Strengths and limitations
The main strength of this study is the sample size and statistical power.Athletes were recruited throughout South Africa, which enhances generalisability to the South African athletic population, although generalisation may not be translated to other countries.The focus of our study was endurance athletes and therefore mostly older than 35 years of age, fulfilling a gap in the literature.Quantifying subjective descriptions of fatigue by using the MDFI is a strength of our study as to our knowledge, it has not been used in other studies on athletic populations.Future studies using the MDFI in athletes is recommended.This is one of few studies that has associated exertional symptoms with RTS status.
As is customary for surveys, certain limitations exist.Snowball sampling will not allow a response rate to be calculated and recorded, thus reducing the power of our study.The participant's responses rely on retrospective recall (recall bias) and the period from illness to the time of our study will vary between participants.The inclusion criteria did not specify the presence of COVID-19 symptoms, thus selection bias caused underrepresentation of the number of asymptomatic cases.Vaccine status was unknown; however, by deducing from the time of illness, most athletes would not have had the opportunity to be vaccinated.Athletes in our study would have been infected by a mix of viral strains.We did not ask whether home oxygen was used, which may have placed some participants not admitted to the hospital in the 'severe illness' category.These limitations were unavoidable with the current knowledge at the time of our study.No direct cause-effect relationship can be determined from our observational study.

Interpretation
These findings may provide valuable insights into the acute and long-term manifestations of this disease in a mastersage athlete population.Symptoms that may indicate cardiopulmonary consequences in an athlete population that does a high volume of cardiovascular exercise should be investigated.An interdisciplinary approach to management is vital to facilitate return to sport and the important mental and physical benefits thereof.This will augment outcomes after respiratory tract infections in endurance athletes.

Conclusion
Our findings suggest that acute fatigue, longer symptom duration, post-COVID sequelae, the presence of exertional symptoms particularly dyspnoea, and chronic physical fatigue are associated with protracted RTS in endurance athletes.These symptoms still abound albeit less frequently after infection by the current Omicron variant.Such symptoms should continue to be flagged and managed to prevent protracted RTS, with further investigations if cardiopulmonary consequences are suspected.Consideration of the mental gains of physical activity ought to be given high regard while building the endurance athlete's training load to return to their pre-illness level.
i l l n e s s l e v e l Time to RTS at pre-illness level RTS, return to sport.

FIGURE 2 :
FIGURE 2: Time to return to pre-illness sport for our study population (n = 308).

TABLE 1 :
Demographic, sport-specific and coronavirus disease 2019 characteristics of our study population.
COVID-19, coronavirus disease 2019; n-RTS, not returned to pre-illness level of sport; WHO, World Health Organization; y-RTS, returned to pre-illness level of sport.†, type of sport was divided into 'running' = running only, 'cycling' = cycling only, and 'multisport' = additional sports including running or cycling.‡, we assume variant based on the elapsed time since onset of illness: omicron < 8 weeks, beta 3-6 months, delta > 7 months.§, World Health Organization COVID-19 Severity Scale: 0-2 = No treatment or did not consult a healthcare professional, 3 = Consulted a healthcare professional or admitted to hospital.p < 0.001), and cycling threshold power ( p = 0.024) were lower in the n-RTS group compared to the y-RTS group.

Table 4
) assesses five categories of fatigue (general fatigue, physical fatigue, reduced activity, reduced motivation and mental fatigue).Athletes who had not yet returned to pre-illness level scored higher in all fatigue categories, indicating considerably worse overall fatigue compared to the y-RTS group ( p < 0.001).The results of the univariate regression analysis in Table5suggest all variables excluding age and sex are associated with RTS.The multivariate regression analysis adjusted for dyspnoea and general fatigue, showed that an increase in physical fatigue is associated with decreased odds of return to sport (OR 0.673, p < 0.001).An increase in mental fatigue is associated with increased odds of return to sport (OR 1.0361, p = 0.047).

TABLE 2 :
Coronavirus disease 2019 symptoms experienced at the time of illness.
COVID-19, coronavirus disease 2019; n-RTS, not returned to pre-illness level of sport; WHO, World Health Organization; y-RTS, returned to pre-illness level of sport.†, Multiple responses were allowed in the survey, resulting in cumulative percentages exceeding 100%.Symptoms are classified as mild, moderate, or severe illness according to the National Institute of Health (COVID-19 Treatment Guidelines).dyspnoea, and chronic physical fatigue are associated with protracted RTS in endurance athletes.Nearly one third of the athletes had not yet returned to preillness levels at the time of data collection.Many (27.8%) were still experiencing symptoms at rest, potentially explaining the less than 6-h per week training volume typical of recreational endurance athletes (McKinney et al. 2019).

TABLE 3 :
The athlete's approach to return to sport, the presence of exertional symptoms, challenges, and exercise capacity.Multiple responses were allowed in the survey, resulting in cumulative percentages exceeding 100%.Symptoms are classified as mild, moderate, or severe illness according to the National Institute of Health (COVID-19 Treatment Guidelines).‡, Data can fall in more than one category.§, Pre-post: Pre-COVID-19 minus post-COVID-19.

TABLE 5 :
Univariate and multivariate logistic regression analysis to determine the likelihood of variables explaining the variation in return to sport.Hosmer and Lemershow goodness-of-fit test p = 0.495.