Since the outbreak of COVID-19, a large amount of research has quickly identified risk factors for severe COVID-19.
Some of these factors are older age, male sex, and underlying chronic conditions such as obesity, cardiovascular disease, lung disease, kidney disease, diabetes, and cancer.1
In addition, lower levels of fitness, as indexed by weaker muscle strength 2 or lower maximal exercise capacity are also risk factors for severe COVID-19.3
Physical activity has recently been suggested as a protective factor for severe COVID-19.4
There seems to be two pathways explaining the protective effect of physical activity:
Although there hasn’t been much attention to modifying a behavioral risk factor such as physical activity, recent evidence is clearly showing an association with physical activity, muscle strength and severity of COVID-19.
Below I will highlight 3 very recent studies that investigate the relationship between physical activity, muscle mass, strength and severity of COVID-19.
Aging and chronic conditions such as type-2 diabetes enhance the risk of developing severe forms of COVID-19. Nonetheless, apparently healthier, younger individuals may also require hospitalization and develop poor outcomes.8
This points to the possibility that there might be undiscovered clinical features associated with COVID-19 prognosis, with muscular parameters being potential candidates.
Skeletal muscle constitutes ~40% of total body mass and plays an essential role in different physiological processes such as immune response, regulation of glucose levels, protein synthesis, and basal metabolic rate.9
It has previously been shown that strength and muscle mass are predictive of clinical outcomes such as hospital length of stay and mortality.10
Cases of exacerbated cytokine production (i.e. ‘cytokine storm’) can lead to sepsis, which has been thought to be partially responsible for fatal cases of COVID-19.11
These conditions cause inflammation which leads to multi-organ damage, affecting mostly pulmonary, cardiac, hepatic, vascular, and renal systems.
Preservation of protein content in key tissues and organs, such as the brain, heart, and liver, is essential for survival. Protein content can be maintained relatively constant under acute stressful conditions, provided muscle mass is adequate to supply the required amino acids.12
In addition, skeletal muscle is also a major immunoregulatory organ, responsible for the production of a wide range of soluble factors with anti-inflammatory and immunoprotective effects, the so-called myokines, which could help ameliorate exacerbated inflammation in this disease.9
The potentially protective role of muscle tissue in COVID-19 allows the hypothesis that muscle health may be an important predictor of clinical outcomes in this disease.
A recent study investigated whether muscle strength and muscle mass assessed at hospital admission are predictive of length of stay in the hospital in patients with moderate to severe COVID-19.13
All patients were evaluated at the point of care within 48 hrs upon hospital admission for handgrip strength and vastus lateralis cross-sectional area.
Key findings and takeaways
This prospective observational study found that muscle strength and muscle mass are predictive of length of stay in hospitalized patients with moderate to severe COVID-19. This is the first study to demonstrate the prognostic value of these skeletal muscle parameters in this disease.
Findings from this study show that stronger patients admitted into the hospital with acute COVID-19 symptoms had lower length of stay than their weaker counterparts.13
Muscle mass is also considered as an indicator of general health status.
Previous research suggests that low muscle mass may predict mortality among elderly.14
During a critical illness, net breakdown of muscle proteins occurs to provide adequate amino acids to meet the increased tissue demands such as immune cells and liver.12
In this context, patients with limited muscle mass reserves would seemingly be more susceptible to stress factors, such as severe burn injuries and cancer. (26)
The current findings suggest this could also be the case with COVID-19.
Muscle tissue plays a crucial role in recovery from critical illness, whereas muscle strength and function are key to the recovery process.15
If there is a preexisting deficiency of muscle mass before the onset of an acute illness, it’s plausible that the expected loss of muscle mass and function associated with hospitalization may push the patient over a threshold that makes recovery of normal function unlikely to occur.15
The impact of this physiopathological mechanism on long-term effects of COVID-19 remains to be explored.
Summary of this research
This research demonstrates that muscle strength and mass assessed on hospital admission are predictors of length of stay in patients with COVID-19. Strength and muscle mass are both associated with better recovery from moderate to severe COVID-19.
This research paves the way for randomized controlled trials to test the utility of preventative or in-hospital interventions in shortening length of stay among these patients via improving muscle mass and/or function.
Another recent study utilized data from the Swedish military service conscription registry. This registry contains information about approximately 1.2 million Swedish individuals who enlisted for military service between late 1968 and 2005 giving between 15 and 52 years of follow-up until the outbreak of COVID-19.16
The main finding of this study is that lower cardiorespiratory fitness and lower muscle strength in young adulthood are predictive of severe illness and death due to COVID-19 15-52 years later.
As of this date, no other comparable study has been published on the link between fitness in young adulthood and later COVID-19.
Being consistently inactive is strongly associated with increased risk of severe COVID-19.17
A potential mechanism for associations between cardiorespiratory fitness and severe COVID-19 could be higher cardiovascular morbidity in the years after conscription examination among those with low cardiorespiratory fitness. Previous studies using the same data show an association between low fitness and higher risk of heart failure, type 2 diabetes, stroke, hypertension, ischemic heart disease and psychiatric disorders.18
As mentioned previously, another potential mechanism is that physical fitness could have a direct anti-inflammatory effect or modulation of the immune system.6
This research has clear clinical implications.
Physical fitness is a (largely) modifiable exposure and is therefore an important preventive measure both affecting later cardiovascular disease and severe COVID-19. The obvious public health implications should emphasize strengthening efforts concerning fitness in the young and retaining this throughout life.
Summary of this research
There is growing evidence of the importance of cardiorespiratory fitness on morbidity later in life, 19 whereas this research shows fitness at a young age may influence the severity level of COVID-19 many years later. The findings of the present study reinforce the need to promote regular physical activity early in life to enhance cardiorespiratory fitness and muscular strength.
In addition, regular physical activity early in life will decrease the risk of future cardiovascular events and offer protection against potential consequences of future viral pandemics.
The third study aimed to test the association physical activity and the odds of COVID-19 hospitalization, and investigate whether this association is explained by established risk factors for COVID-19 hospitalization.2
This study included longitudinal and cross-national information on socioeconomic circumstances and health from 136,000 individuals aged 50 or older living in 27 European countries. Data was collected between 2004 and 2017.
In 2020, a special COVID-19 questionnaire was disseminated which assessed social, health, and economic data on 52,000 individuals. This study combines data from these two datasets.
Higher physical activity was associated with lower odds of COVID-19 hospitalization. Individuals who typically participated in physical activity more than once a week had lower odds to be hospitalized due to COVID-19 than those who hardly ever or never engaged in physical activity.
After adjusting for a wide range of established risk factors, muscle strength was the only factor explaining this association. It seems that muscle strength is potentially the underlying mechanism that can provide a protective association between physical activity and severe forms of COVID-19.
This was the first study to test and demonstrate that the link between physical activity and COVID-19 hospitalization was explained by muscle strength.
Summary of this Research
Physical activity and especially muscle strength is associated with lower odds of COVID-19 hospitalization in adults aged 50 years and older.
These findings highlight the need to encourage older adults to participate in exercise regularly, especially due to the inactivity in this population in general, especially during the COVID-19 pandemic.20
References:
1 Jordan, R. E., Adab, P. & Cheng, K. K. Covid-19: risk factors for severe disease and death. BMJ 368, m1198, doi:10.1136/bmj.m1198 (2020).
2 Maltagliati, S. et al. Muscle Strength Explains the Protective Effect of Physical Activity against COVID-19 Hospitalization among Adults aged 50 Years and Older. medRxiv, doi:10.1101/2021.02.25.21252451 (2021).
3 Brawner, C. A. et al. Inverse Relationship of Maximal Exercise Capacity to Hospitalization Secondary to Coronavirus Disease 2019. Mayo Clin Proc 96, 32-39, doi:10.1016/j.mayocp.2020.10.003 (2021).
4 Burtscher, J., Millet, G. P. & Burtscher, M. Low cardiorespiratory and mitochondrial fitness as risk factors in viral infections: implications for COVID-19. Br J Sports Med 55, 413-415, doi:10.1136/bjsports-2020-103572 (2021).
5 Nieman, D. C. & Wentz, L. M. The compelling link between physical activity and the body's defense system. J Sport Health Sci 8, 201-217, doi:10.1016/j.jshs.2018.09.009 (2019).
6 Gleeson, M. et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol 11, 607-615, doi:10.1038/nri3041 (2011).
7 Warburton, D. E., Nicol, C. W. & Bredin, S. S. Health benefits of physical activity: the evidence. CMAJ 174, 801-809, doi:10.1503/cmaj.051351 (2006).
8 Guan, W. J. et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med 382, 1708-1720, doi:10.1056/NEJMoa2002032 (2020).
9 Egan, B. & Zierath, J. R. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 17, 162-184, doi:10.1016/j.cmet.2012.12.012 (2013).
10 Burtin, C. et al. Handgrip weakness, low fat-free mass, and overall survival in non-small cell lung cancer treated with curative-intent radiotherapy. J Cachexia Sarcopenia Muscle 11, 424-431, doi:10.1002/jcsm.12526 (2020).
11 Fajgenbaum, D. C. & June, C. H. Cytokine Storm. N Engl J Med 383, 2255-2273, doi:10.1056/NEJMra2026131 (2020).
12 Wolfe, R. R. & Martini, W. Z. Changes in intermediary metabolism in severe surgical illness. World J Surg 24, 639-647, doi:10.1007/s002689910105 (2000).
13 Gil, S. et al. Muscle strength and muscle mass as predictors of hospital length of stay in patients with moderate to severe COVID-19: a prospective observational study. J Cachexia Sarcopenia Muscle, doi:10.1002/jcsm.12789 (2021).
14 Weng, C. H. et al. Mid-upper arm circumference, calf circumference and mortality in Chinese long-term care facility residents: a prospective cohort study. BMJ Open 8, e020485, doi:10.1136/bmjopen-2017-020485 (2018).
15 Wolfe, R. R. The underappreciated role of muscle in health and disease. Am J Clin Nutr 84, 475-482, doi:10.1093/ajcn/84.3.475 (2006).
16 Af Geijerstam, A. et al. Fitness, strength and severity of COVID-19: a prospective register study of 1 559 187 Swedish conscripts. BMJ Open 11, e051316, doi:10.1136/bmjopen-2021-051316 (2021).
17 Sallis, R. et al. Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: a study in 48 440 adult patients. Br J Sports Med 55, 1099-1105, doi:10.1136/bjsports-2021-104080 (2021).
18 Aberg, N. D. et al. Influence of Cardiovascular Fitness and Muscle Strength in Early Adulthood on Long-Term Risk of Stroke in Swedish Men. Stroke 46, 1769-1776, doi:10.1161/STROKEAHA.115.009008 (2015).
19 Ekblom-Bak, E. et al. Sex- and age-specific associations between cardiorespiratory fitness, CVD morbidity and all-cause mortality in 266.109 adults. Prev Med 127, 105799, doi:10.1016/j.ypmed.2019.105799 (2019).
20 Burtscher, J., Burtscher, M. & Millet, G. P. (Indoor) isolation, stress, and physical inactivity: Vicious circles accelerated by COVID-19? Scand J Med Sci Sports 30, 1544-1545, doi:10.1111/sms.13706 (2020).
