Effects of physical activity on the severity of illness and mortality in COVID-19 patients: A systematic review and meta-analysis
Nuttawut Sittichai, Nichapa Parasin, Surasak Saokaew, Sukrit Kanchanasurakit, Nuttawan Kayod, Ketnapa Praikaew, Pochamana Phisalprapa, Mujalin Prasannarong
Frontiers in Physiology, doi:10.3389/fphys.2022.1030568
Purpose: This systematic review and meta-analysis investigated the association between Physical activity (PA) before Coronavirus Disease 2019 (COVID-19) infection and the severity of illness and mortality in COVID-19 patients. Methods: A comprehensive search was undertaken to identify retrospective and nonrandomized controlled trial studies comparing the severity and mortality of COVID-19 infection among COVID-19 patients who had previously reported their participation in PA with those who had not. The databases searched were PubMed, Cochrane Library, Scopus, Science Direct, EMBASE, OPENGREY.EU, and ClinicalTrials.gov. The risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects model was used for determining pairwise meta-analyses. The protocol was registered with PROSPERO (CRD42021262548). Results: Eighteen studies met the inclusion criteria (5 cross-sectional, 12 cohort, and 1 case-control studies). All 1 618 680 subjects were adults. PA significantly decreased the risk of death in COVID-19 patients (odds ratio [OR] 0.34; 95% confidence interval [CI], 0.19-0.62; p < 0.001) and the risk of severe outcomes (OR 0.60; 95% CI, 0.48-0.76; p < 0.001). Subgroup analysis showed that PA for ≥150 min/wk at a moderate intensity or ≥75 min/wk at a vigorous intensity reduced the risks of severity and mortality. Vigorous PA reduced mortality risk, whereas moderate to vigorous PA reduced the risks of severity and mortality.
Conclusion: PA before infection might reduce severity and mortality in COVID-19 patients, especially PA ≥ 150 min/wk of moderate activity or ≥75 min/wk of
Author contributions NS, NP, SS, NK, KP, MP, and PP took part in designing the study, the selection process, and the writing of the first manuscript draft; NS, NP, SS, and MP took part in designing the study; NS, NP, SS, SK, NK, KP, and MP took part in the selection process and statistical analyses; NS, NP, NK, KP, MP, and PP wrote sections of the manuscript; all authors read and approved the final version of the manuscript and agreed with the order of presentation of the authors.
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphys. 2022.1030568/full#supplementary-material
SUPPLEMENTARY FIGURE S1 Assessing publication bias by funnel plot: (A) effects of physical activity on mortality; (B) effects of physical activity on severity.
SUPPLEMENTARY FIGURE S2 Assessing publication bias by Egger's test: (A) effects of physical activity..
References
Ad Hagiu, Moderate exercise may prevent the development of severe forms of COVID-19, whereas high-intensity exercise may result in the opposite, Med. Hypotheses,
doi:10.1016/j.mehy.2021.110705Agarwal, Welsch, Keller, Francis, Chronic exercise modulates RAS components and improves balance between pro-and antiinflammatory cytokines in the brain of SHR, Basic Res. Cardiol,
doi:10.1007/s00395-011-0231-7Ahmadi, Huang, Inan-Eroglu, Hamer, Stamatakis, None
Ahmed, COVID-19 -does exercise prescription and maximal oxygen uptake (VO2 max) have a role in risk-stratifying patients?, Clin. Med,
doi:10.7861/clinmed.2020-0111Baynouna Alketbi, Nagelkerke, Abdelbaqi, Alblooshi, Alsaedi et al., Risk factors for SARS-CoV-2 infection severity in Abu Dhabi, J. Epidemiol. Glob. Health,
doi:10.1007/s44197-021-00006-4Cai, Chen, Wang, Luo, Liu et al., Obesity and COVID-19 severity in a designated hospital in Shenzhen, China, Diabetes Care
Caspersen, Powell, Christenson, Physical activity, exercise, and physical fitness: Definitions and distinctions for health-related research,
doi:10.2307/20056429Chandrasekaran, Ganesan, Sedentarism and chronic disease risk in COVID 19 lockdown -A scoping review, Scott. Med. J,
doi:10.1177/0036933020946336Cho, Lee, Jae, Kim, Ha et al., Physical exercise as a tool to help the immune system against COVID-19: An integrative review of the current literature, Clin. Exp. Med,
doi:10.1007/s10238-020-00650-3Da Tavakol, Ghannadi, Tabesh, Halabchi, Noormohammadpour et al., Relationship between physical activity, healthy lifestyle and COVID-19 disease severity; a cross-sectional study, J. Public Health,
doi:10.1007/s10389-020-01468-9Ekblom-Bak, Väisänen, Ekblom, Blom, Kallings et al., Cardiorespiratory fitness and lifestyle on severe COVID-19 risk in 279, 455 adults: A case control study, Int. J. Behav. Nutr. Phys. Act,
doi:10.1186/s12966-021-01198-5Fahriani, Ilmawan, Fajar, Maliga, Frediansyah et al., Persistence of long COVID symptoms in COVID-19 survivors worldwide and its potential pathogenesis -a systematic review and metaanalysis, Narra J,
doi:10.52225/narraj.v1i2.36Fajar, Ilmawan, Mamada, Mutiawati, Husnah et al., Global prevalence of persistent neuromuscular symptoms and the possible pathomechanisms in COVID-19 recovered individuals: A systematic review and meta-analysis, Narra J,
doi:10.52225/narra.v1i3.48Foster, Ravikumar, Bellotto, Unger, Hsia, Fatty diabetic lung: Altered alveolar structure and surfactant protein expression, Am. J. Physiol. Lung Cell. Mol. Physiol,
doi:10.1152/ajplung.00041.2009Guyatt, Oxman, Vist, Kunz, Falck-Ytter et al., None
Halabchi, Mazaheri, Sabeti, Yunesian, Alizadeh et al., Regular sports participation as a potential predictor of better clinical outcome in adult patients with COVID-19: A large cross-sectional study, J. Phys. Act. Health,
doi:10.1123/jpah.2020-0392Halperin, Prevalence of asymptomatic SARS-CoV-2 infection
Hamer, Kivimäki, Gale, Batty, Lifestyle risk factors, inflammatory mechanisms, and COVID-19 hospitalization: A communitybased cohort study of 387, 109 adults in UK, Brain Behav. Immun,
doi:10.1016/j.bbi.2020.05.059Hamrouni, Roberts, Thackray, Stensel, Bishop, None
Kai, Kai, Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-Lessons from available evidence and insights into COVID-19, Hypertens. Res,
doi:10.1038/s41440-020-0455-8Lai, Shih, Ko, Tang, Hsueh, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges, Int. J. Antimicrob. Agents,
doi:10.1016/j.ijantimicag.2020.105924Latorre-Román, Guzmán-Guzmán, Delgado-Floody, Herrador, None
Lee, Lee, Moon, Jin, Yang et al., Physical activity and the risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related mortality in South Korea: A nationwide cohort study, Br. J. Sports Med,
doi:10.1136/bjsports-2021-104203Lowder, Padgett, Woods, Moderate exercise early after influenza virus infection reduces the Th1 inflammatory response in lungs of mice, Exerc. Immunol. Rev
Malisoux, Backes, Fischer, Aguayo, Ollert et al., Associations between physical activity prior to infection and COVID-19 disease severity and symptoms: Results from the prospective predi-COVID cohort study, BMJ Open,
doi:10.1136/bmjopen-2021-057863Maltagliati, Sieber, Sarrazin, Cullati, Chalabaev et al., Muscle strength explains the protective effect of physical activity against COVID-19 hospitalization among adults aged 50 Years and older, medRxiv,
doi:10.1101/2021.02.25.21252451Marino, Vargas, Skein, Hartmann, Mcfarlin et al., Metabolic and inflammatory health in SARS-CoV-2 and the potential role for habitual exercise in reducing disease severity, Inflamm. Res,
doi:10.1007/s00011-021-01517-3Murphy, Davis, Carmichael, Gangemi, Ghaffar, None
Nieman, Nehlsen-Cannarella, Fagoaga, Henson, Shannonm et al., Immune function in female elite rowers and non-athletes, Br. J. Sports Med,
doi:10.1136/bjsm.34.3.181Nieman, Nehlsen-Cannarella, Markoff, Balk-Lamberton, Yang et al., The effects of moderate exercise training on natural killer cells and acute upper respiratory tract infections, Int. J. Sports Med
Page, Mckenzie, Bossuyt, Boutron, Hoffmann et al., The PRISMA 2020 statement: An updated guideline for reporting systematic reviews, Br. Med. J,
doi:10.1136/bmj.n71Pinto, Goessler, Fernandes, Murai, Sales et al., No independent associations between physical activity and clinical outcomes among hospitalized patients with moderate to severe COVID-19, J. Sport Health Sci,
doi:10.1016/j.jshs.2021.08.001Popkin, Du, Green, Beck, Algaith et al., Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships, Obes. Rev,
doi:10.1111/obr.13128Rahmati, Shamsi, Khoramipour, Malakoutinia, Woo et al., Baseline physical activity is associated with reduced mortality and disease outcomes in COVID-19: A systematic review and meta-analysis, Rev. Med. Virol,
doi:10.1002/rmv.2349Rowlands, Dempsey, Gillies, Kloecker, Razieh et al., Association between accelerometer-assessed physical activity and severity of COVID-19 in UK biobank, Mayo Clin. Proc. Innov. Qual. Outcomes,
doi:10.1016/j.mayocpiqo.2021.08.011Salgado-Aranda, Pérez-Castellano, Núñez-Gil, Orozco, Torres-Esquivel et al., Influence of baseline physical activity as a modifying factor on COVID-19 mortality: A single-center, retrospective study, Infect. Dis. Ther,
doi:10.1007/s40121-021-00418-6Sallis, Young, Tartof, Sallis, Sall et al., Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: A study in Frontiers in Physiology frontiersin
Sanchez, Aragón-Vela, García Pinillos, Protective role of physical activity patterns prior to COVID-19 confinement with the severity/ duration of respiratory pathologies consistent with COVID-19 symptoms in Spanish populations, Res. Sports Med,
doi:10.1080/15438627.2021.1937166Sim, Yu, Yoon, Loiacono, Kohut, Chronic exercise reduces illness severity, decreases viral load, and results in greater antiinflammatory effects than acute exercise during influenza infection, J. Infect. Dis,
doi:10.1086/606014Stang, Stockwell, Trott, Tully, Shin et al., Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses, Eur. J. Epidemiol,
doi:10.1007/s10654-010-9491-zStrath, Kaminsky, Ainsworth, Ekelund, Freedson et al., Guide to the assessment of physical activity: Clinical and research applications: A scientific statement from the American heart association, Circulation,
doi:10.1161/01.cir.0000435708.67487.daTimmons, Cieslak, Human natural killer cell subsets and acute exercise: A brief review, Exerc. Immunol. Rev
Toledo, Magalhaes, Hizume, Vieira, Biselli et al., Aerobic exercise attenuates pulmonary injury induced by exposure to cigarette smoke, Eur. Respir. J,
doi:10.1183/09031936.00003411Verity, Okell, Dorigatti, Winskill, Whittaker et al., Estimates of the severity of coronavirus disease 2019: A modelbased analysis, Lancet. Infect. Dis,
doi:10.1016/s1473-3099(20)30243-7Warren, Olson, Thompson, Cahill, Wyatt et al., None
Yan, Xiao, Lin, Angiotensin-converting enzyme 2 in severe acute respiratory syndrome coronavirus and SARS-CoV-2: A double-edged sword?, FASEB J,
doi:10.1096/fj.202000782Yuan, Huang, Chen, Chen, Zhang et al., Does pre-existent physical inactivity have a role in the severity of COVID-19?, Ther. Adv. Respir. Dis,
doi:10.1177/17534666211025221Zhang, Zhu, Cai, Lei, Qin et al., Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19, Circ. Res,
doi:10.1161/circresaha.120.317134
