Cardiorespiratory Fitness Attenuates the Impact of Risk Factors Associated With COVID-19 Hospitalization.

To the Editor:

As highlighted in the editorial “Fit Is It in COVID-19, Future Pandemics, and Overall Healthy Living,” published in the January 2021 issue of the Mayo Clinic Proceedings, it is important to bring more awareness to cardiorespiratory fitness (CRF) as an independent predictor of morbidity and mortality. To that end, we present additional data regarding the interaction of CRF with the traditional risk factors often associated with increased illness severity from coronavirus disease 2019 (COVID-19). Details regarding the methods and data extraction can be found in Brawner et al. Briefly, 246 patients who tested positive for severe acute respiratory syndrome coronavirus 2 and completed a clinically indicated stress test between January 2016 and February 2020 were retrospectively identified. Hospitalization for COVID-19 was identified through July 2020.

Using logistic regression, in univariate analyses we found that 8 of 13 previously identified risk factors were associated with an increased likelihood of hospitalization due to COVID-19 (Table ). However, when adjusted for CRF (ie, peak metabolic equivalents of task) in a multivariable analysis, only age (≥65 years), male sex, and chronic kidney disease remained as significant predictors (Table).

Table

Effect of Fitness on the Relationship Between Select Variables and Likelihood of Complications Due to COVID-19a

Variable	Univariate analyses			Adjusted for peak METs
	Wald X2	P	OR (95% CI)	Wald X2	P	OR (95% CI)
Age ≥65 years	18.3	<.001	3.31 (1.91 to 5.73)	10.8	.001	2.65 (1.48 to 4.74)
Male	3.9	.048	1.70 (1.00 to 2.88)	8.1	.004	2.29 (1.30 to 4.05)
Asthma	0.5	.49	1.28 (0.64 to 2.57)	0.6	.43	1.34 (0.74 to 0.92)
Obesityb	2.2	.13	0.67 (0.39 to 1.13)	3.9	.048	0.57 (0.33 to 0.995)
CKD	7.9	.005	5.39 (1.66 to 17.5)	4.6	.03	3.76 (1.12 to 12.7)
DM	4.8	.03	1.83 (1.06 to 3.13)	2.6	.11	1.57 (0.90 to 2.75)
COPD	1.4	.23	2.28 (0.60 to 8.71)	0.7	.41	1.78 (0.46 to 6.95)
CHD	4.5	.03	2.48 (1.07 to 5.72)	3.6	.06	2.31 (0.98 to 5.47)
Cancer	3.8	.05	2.26 (0.99 to 5.12)	2.6	.11	2.00 (0.87 to 4.62)
HTN	5.0	.03	1.95 (1.09 to 3.50)	1.9	.16	1.55 (0.84 to 2.85)
Stroke	0.04	.83	0.88 (0.26 to 3.00)	0.3	.59	0.70 (0.20 to 2.49)
Smoking	0.15	.70	0.86 (0.41 to 1.82)	0.1	.79	0.90 (0.42 to 1.94)
HF	4.6	.03	3.42 (1.11 to 10.55)	1.9	.16	2.29 (0.71 to 7.35)

CHD, coronary heart disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; DM, diabetes mellitus; HF, heart failure; HTN, hypertension; MET, metabolic equivalents of task; OR, odds ratio.

BMI≥30 kg/m2.

These results show how CRF improves the risk profile of higher-risk individuals and builds upon other studies that have reported similar findings.3, 4, 5 Although our limited sample size may have contributed to the large confidence intervals in the adjusted analysis, it is important to note that fitness attenuated the point estimate for all of the comorbidities that were significant in univariate analyses.

Surprisingly, in the univariate analysis, obesity was not associated with increased hospital risk and when CRF was introduced as a covariate it showed a paradoxical protective effect. This finding may simply be due to the nature of the cohort in this study, which consisted of individuals who were able to perform an exercise stress test on a treadmill. With respect to obesity showing a paradoxical protective effect, this has been reported previously and may again speak to the interaction between CRF and body mass index, with more fit individuals potentially having greater muscle mass, which body mass index does not differentiate.

In conclusion, our study shows the value of including CRF as an additional health indicator and adds to the importance of the public health message of the benefits of fitness and exercise, particularly for attenuating the risk associated with other health disorders. When performing risk stratification for research or clinical purposes, efforts should be made to include a measure of CRF.