This study analyzed the evolution of the patients admitted to our center during the first wave of the SARS-CoV-2 pandemic with a diagnosis of COVID-19 infection. Patients were divided into two categories according to the level of physical activity: group 1 or sedentary patients, and group 2 or active patients. The main findings are as follows: (1) despite similar symptoms at admission, sedentary patients had poor in-hospital outcomes with increased SIRS, renal failure, and respiratory failure; (2) overall mortality was higher in sedentary patients; (3) sedentary lifestyle was an independent predictor of mortality on multivariate Cox regression analysis. In the following paragraphs we will discuss these findings in more detail.
In our study, sedentary patients had a higher median age and more comorbidities such as hypertension, renal failure, COPD, cerebrovascular, connective tissue, and liver disease. Physical dependence was also more common. As a result, group 1 represents a cohort of patients with an increased baseline risk of poor COVID-19 prognosis. However, no differences were found at admission in most of the symptoms and physical signs of COVID-19 between both groups except a higher frequency of tachypnea in group 1 and fever in group 2. Patients in group 2, who undertake regular moderate intensity physical activity, might have better respiratory capacity and reserve than group 1 as discussed below, which may result in a better compensatory ability during respiratory illness. The fact that group 2 more frequently presented with pyrexia most likely represents a selection bias regarding the criteria for admission which were set by the hospital at the time of the first wave. The lack of pyrexia as a presenting symptom in group 1 may be reflective of the older age (fever can be absent in 30–50% of older patients) and higher rate of connective tissue disorders in this group (often requiring treatment with immunosuppressive therapy) .
Although a higher incidence of pneumonia was expected in group 1, in our study the presence of both unilateral and bilateral pneumonia was similar in both groups. Again, this may be reflective of a selection bias with pneumonia diagnosed on chest X-ray being one of the main criteria to warrant admission in our hospital. However, SIRS and respiratory and renal failure were significantly more frequent in group 1, representing a poorer evolution during hospitalization. This could also explain why the use of corticosteroids was more frequent in group 1. During the first wave of the pandemic, treatment regimens were not standardized. In our center first-line therapy included lopinavir/ritonavir and hydroxychloroquine. Corticosteroids, tocilizumab, and interferon were reserved for patients with worse clinical status or with severe inflammatory component, as occurred more frequently in group 1.
Surprisingly, despite the increased respiratory failure and SIRS in group 1, no statistically significant differences were found between the two groups in terms of respiratory support and intensive care unit admissions. Probably group 1, with a higher burden of comorbidities and lower probability of recovering, may have been less likely to be selected for ICU admission.
Mortality analysis showed an eightfold higher risk of death in group 1 versus group 2. Multivariable analysis showed that sedentary lifestyle was an independent risk factor for mortality in those patients requiring hospitalization for COVID-19 in our center. Expressed in another way, a regular moderate to high intensity physical activity seems to reduce the mortality related to COVID-19 infection. To the best of our knowledge, this finding has not been previously demonstrated and represents a significant benefit of regular exercise in the prognosis of COVID-19. As such, recommending regular physical exercise might be a simple preventative measure, which could have a real impact on mortality during the coming waves of the pandemic. In the following paragraphs several possible mechanisms that have been proposed in the literature to explain the possible effect of physical exercise on the prognosis of coronavirus infection will be discussed.
Physiological Respiratory Adaptations in Physically Trained Patients
Exercise results in a decrease in basal minute ventilation to achieve a given oxygen uptake and an increased in the maximal oxygen uptake during exercise . This could have preconditioned group 2 to have a greater resistance to hypoxemia at comparable degrees of lung disease. This is supported by the fact that in our series, group 2 had a tendency to higher oxygen saturation at admission and less incidence of respiratory failure despite similar pneumonia severity in X-ray.
Exercise and Upper Respiratory Tract Infections
Randomized clinical trials consistently show that participants assigned to moderate exercise programs experienced reduced upper respiratory tract infections incidence and duration . In the study by Nieman et al. a group of 1002 adults were followed for 12 weeks during the winter and fall seasons. In their analysis, the number of days with upper respiratory tract infection was 43% lower in subjects engaging in an average of 5 or more days per week of aerobic exercise compared with those who were largely sedentary . Although there are no specific studies, this could be applicable to COVID-19 infection.
Exercise and Inflammation
There is evidence that lifelong training has an overall anti-inflammatory influence mediated through multiple pathways: enhanced innate immune function, release of muscle myokines that stimulate production of IL-1ra and IL-10, decrease in dysfunctional adipose tissue, and improved oxygenation . In adults with higher levels of physical activity and fitness, epidemiologic studies consistently show reduced white blood cell count, CRP, IL-6, IL-18, tumor necrosis factor alpha, and other inflammatory biomarkers [29,30,31]. This could have protected group 2 from presenting exuberant inflammatory responses that are frequent in critical forms of COVID-19. As previously commented, patients in the sedentary group had a significantly higher frequency of raised CRP and SIRS.
Exercise and Renin Angiotensin System (RAS)
The angiotensin-converting enzyme 2 has been proposed as the receptor for SARS-CoV-2 protein in the alveolar epithelial cells in the lungs, and pharmacological manipulation of the RAS has been discussed as a potential therapy for COVID-19 . It was reported that decreasing angiotensin II with pharmacological strategies can improve angiotensin 1–7 and attenuate inflammation, fibrosis, and lung injury  In the same way, regular physical exercise also induces a shift in the RAS towards angiotensin 1–7 which may possibly reduce the severity of clinical outcome of COVID-19 infection.
Other Predictors of Mortality
As a secondary finding our study also confirmed that age, smoking habit, and renal disease are independent risks factors for mortality as has been noted in previous studies. No statistically significant relationship was found for gender, hypertension, obesity, non-Caucasian races, diabetes, pulmonary, heart, cerebrovascular, liver, and connective tissue diseases, or malignancy, although the trends are consistent with the data previously published. This is in contrast to other series where these comorbidities have been strongly associated with the prognosis of COVID-19, specifically in a recent publication which analyzed almost 11,000 COVID-19 deaths . This difference may be explained by our inclusion criteria, which included patients between 18 and 70 years. Almost 20% of the patients included in the series by Williamson et al. were older than 70 years and in this study, patients over 80 years had a 20-fold higher rate of death than those under 60 years. The exclusion of patients older than 70 years in our series may have limited the ability to demonstrate a statistically significant relationship between mortality and the previously mentioned pathologies because they were not fully represented in this cohort. Furthermore, previous studies have stratified these comorbidities according to their severity, while in our cohort these comorbidities are presented as dichotomous variables (being present or absent). Therefore, the lack of association of previously demonstrated risk factors for mortality in our cohort may be more related to the design of our study rather than a lack of association.
This is a single-center retrospective study in which only patients who required hospital admission were included. Those patients who were managed on an outpatient basis were not included. Patients who died before obtaining medical attention or in whom the diagnosis of COVID-19 could not be confirmed by PCR were not included either. The importance of the BPAL in these groups might have been different and further work is required to confirm the impact in these cohorts. The effect of other potential confounding variables not included in the analysis cannot be quantified.
Assessment of BPAL was performed after hospital discharge through a self-evaluation questionnaire that could be highly influenced by the physical and emotional state of patients after overcoming the disease. Besides, in those patients who died during or after hospitalization (45 patients) the questionnaire was completed using information facilitated by relatives, which may have impacted the reporting of BPAL. However, in the context of the limitations imposed by the pandemic (isolation and confinement measures), the RAPA questionnaire provided a simple and easy to understand tool that could be administered by telephone. Nevertheless, prospective studies with a more exhaustive analysis of the BPAL are necessary to confirm the results of this study.