Monitoring athletes in a COVID-19 environment: measuring inflammation with a point-of-care test.

Dr Nathan Lewis

July 22, 2020

Sports Hematology

The COVID-19 pandemic has caused sport scientists to rethink the way athletes are monitored and point of care blood testing has largely been put on hold because of social distancing and PPE requirements.  Here, Dr Nathan Lewis discusses the rationale for prioritizing inflammation as a key variable.

Monitoring athletes in a COVID-19 environment: measuring inflammation with a point-of-care test.

Illness (i.e. an infection) results in loss of training time, which is a major determinant of performance success or failure for elite international athletes competing in individual Olympic sports [1]. Athletes who are repeatedly ill and therefore lose training time due to illness are more likely to experience competition failure. Furthermore, illness and accumulating fatigue, which may persist post-infective episode, particularly in the athlete who continues to train with too much intensity too early, may result in the development of chronic underperformance [2]. Finally, complications can result from viral infections, such as those affecting the heart muscle (e.g. endocarditis), and knowing when to safely return to training, and progress the training load is essential to athlete health and well-being, which above all, is the priority [3]. The monitoring process (e.g. symptoms, wellness, biochemistry, load) plays a crucial role in managing the athlete’s health and performance potential. Here we give some discussion to the application and science behindthe incorporation of inflammation testing in the athlete monitoring process post COVID-19.  

Inflammation

Inflammation is a well-documented and well-characterised response to infection (see figure),trauma, and exercise; of which significant exercise induced skeletal muscle trauma (i.e. muscle damage, reflected in increased creatine kinase activity)may or may not be present. Increases in inflammation are consistently observed post-exercise. However, there are a number of factors dictating the inflammatory response to exercise, such as: the mode of exercise (e.g. cycling vs.running) and the degree of underlying muscle damage (e.g. eccentric vs concentric component; [4]; the intensity and duration of the exercise; the training status and nutritional status of the individual undertaking the exercise; sex [5]; age [6]; and the less well known: the environment (e.g. altitude vs. sea level). A 3-day period of functional overreaching in runners leads to significantly increased inflammation persisting into the recovery period (i.e.rise in high-sensitivity C-reactive protein (hs-CRP)[4]). Inadequate recovery for the athlete, for example from an intensified period of match play/games for the team sport player, results in an increasing systemic inflammatory response, captured through hs-CRP [7]. Point of care testing (POCT) for hs-CRP provides real-time on the ground objective data for the team scientists and coaches, which can be incorporated into the decision-making process around individual athlete and player training and competition/match day load, recovery strategies and planned rest.    

Outside of the sporting arena. In general practice, hs-CRP POCT is used to test for evidence of systemic inflammation in patients with suspected upper respiratory tract infections [8]. The majority of URTI’s are viral in origin, and POCT testing can assist in diagnosis and clinical decision making. Viral infections give rise to significant increases in hs-CRP, with the reported peak 3 days post-viral challenge with influenza A and rhinoviruses [9]. However, the response is by no means consistent, with hs-CRP values reported to show no relationship to the type of virus administered, the severity of the cold or the antibody response under controlled conditions of infection [9].  Certainly, systemic inflammation and a raised hs-CRP are among the most common abnormalities in COVID-19cases requiring hospital attention [10].However, the hs-CRP response to COVID-19 in mildly symptomatic (not requiring medical intervention and supportive treatment) or indeed asymptomatic individuals is not well understood at this time. The use of hs-CRP POCT in the training environment provides a valid, reliable test for inflammation, whether testing for the inflammatory response to training, or from an infective episode.  Both of these are undesirable states for an athlete to experience for sustained periods of time, and thus testing may assist the team physician in clinical decision making around athlete health, as well as being used by the sports science team to monitor the recovery fromtraining and match play.

 

Mental health

The mental health of the athlete cannot be separated from the physical health of the athlete [11]. Athletes are known to experience episodes of adverse mental health, including depression, with a prevalence reported to be comparable to the general population [12]. Athletes around the world have experienced significant curtailment of their normal training routines and cancellation of competition schedules; the impact of which on the mental health of athletes whether infected or not, is currently unknown. Inflammation may be deemed a risk factor for depression [13]; over half of patients with depression show mildly elevated(>1mg/L) CRP levels, and, low grade inflammation (i.e. CRP >3mg/L) is present in 1 in 4 patients, adjusting to 1 in 6 when infections are excluded [14]. A significant relationship between depressive symptoms and chronic low-grade inflammation has been reported by others; e.g. a meta-analytical review of community studies, excluding all chronic and inflammatory diseases [15]. Thus, there is a large body of research showing a relationship between inflammation and poor mental health.  

Considerations in the female athlete

The fluctuation in endogenous ovarian hormones throughout the menstrual cycle gives rise to alterations in concentrations of various inflammatory biomarkers (i.e.  IL-6, IL-1beta,hs-CRP, TNF-alpha). Specific symptoms reported in the premenstrual (FitWoman phase4) and/or menstrual phase (FitrWoman phase 1) have been observed to correlate with the increased inflammatory response [16, 17].  In addition, it is important to acknowledge that some forms of hormonal contraception have been shown to cause a systemic rise in inflammation [18],and the Depo-Provera injection compromises immune function [19]. Therefore, when longitudinally monitoring female athletes it is important to capture current menstrual status, menstrual cycle phase, and the use of hormonal contraception. Furthermore, there is evidence demonstrating differing susceptibility to bacterial, viral and fungal infections based on the hormonal ratio at different time points in the menstrual cycle. For example, susceptibility to infections is increased in the second half of the menstrual cycle when progesterone concentrations are elevated [20].

Practical challenges:

Many sports are beginning to emerge from COVID-19 lockdown with a gradual resumption of athlete training and sports science and medicine team activities, however, access to athletes for sampling might be limited or impossible at this time, given social distancing and PPE requirements.  Location and sport regulations and guidelines concerning these should of course be respected.  As restrictions are gradually lifted, monitoring inflammation appears to be a high priority for tracking athlete health.                        

 

Acute Inflammatory Responses to Viral Infections

References  

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2. Lewis,N.A., et al., Can clinicians and scientists explain and prevent unexplained underperformance syndrome in elite athletes: an interdisciplinary perspective and 2016 update. BMJ Open SportExerc Med, 2015. 1(1): p. e000063.

3. Baggish, A., et al., Resurgence of sport in the wake of COVID-19: cardiac considerations in competitive athletes. BritishJournal of Sports Medicine, 2020: p. bjsports-2020-102516.

4. Nieman, D.C., et al., Immune and inflammation responses to a 3-day period of intensified running versus cycling. BrainBehav Immun, 2014. 39: p. 180-5.

5. Stupka, N., et al., Gender differences in muscle inflammation after eccentric exercise. J Appl Physiol (1985), 2000. 89(6): p. 2325-32.

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7.  Leeder, J.D.C., et al., Cold water immersion improves recovery of sprint speed following a simulated tournament. Eur JSport Sci, 2019. 19(9): p.1166-1174.

8.  Melbye, H., et al., The course of C-reactive protein response in untreated upper respiratory tract infection. Br J GenPract, 2004. 54(506): p. 653-8.

9.  Whicher, J.T., et al., Acute phase response of serum amyloid A protein and C reactive protein to the common cold and influenza. Journal of Clinical Pathology, 1985. 38(3): p. 312-316.

10. Fu,L., et al., Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: A systematic review and meta-analysis. J Infect, 2020. 80(6):p. 656-665.

11.  Reardon, C.L., et al., Mental health in elite athletes: International Olympic Committee consensus statement (2019). Br JSports Med, 2019. 53(11): p.667-699.

12.  Rice,S.M., et al., The Mental Health of EliteAthletes: A Narrative Systematic Review. Sports Med, 2016. 46(9): p. 1333-53.

13.  Dantzer, R., et al., From inflammation to sickness and depression: when the immune system subjugates the brain. Nat RevNeurosci, 2008. 9(1): p. 46-56.

14.  Osimo, E.F., et al., Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels. Psychol Med, 2019. 49(12): p.1958-1970.

15.  Valkanova,V., K.P. Ebmeier, and C.L. Allan, CRP,IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J Affect Disord, 2013. 150(3):p. 736-44.

16.  Gold,E.B., C. Wells, and M.O. Rasor, The Association of Inflammation with Premenstrual Symptoms. J Womens Health(Larchmt), 2016. 25(9): p. 865-74.

17.   Puder, J.J., et al., Menstrual cycle symptoms are associated with changes in low-grade inflammation. Eur J Clin Invest,2006. 36(1): p. 58-64.

18.   Cauci, S., M.P. Francescato, and F. Curcio, Combined Oral Contraceptives Increase High-Sensitivity C-Reactive Protein but Not Haptoglobin in Female Athletes. Sports Med, 2017. 47(1): p. 175-185.

19.   Tasker, C., et al., Depot medroxyprogesterone acetate administration alters immune markers for HIV preference and increases susceptibility of peripheral CD4(+) T cells to HIV infection. Immunohorizons, 2017. 1(9): p.223-235.

20.   Klein, S.L. and C.W. Roberts, Sex hormones and immunity to infection. Vol. 382. 2010: Springer.

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