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Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study

Chen et al., Journal of Translational Medicine, doi:10.1186/s12967-022-03407-6
May 2022  
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Exercise for COVID-19
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4,300+ studies for 77 treatments. c19early.org
UK Biobank Mendelian randomization study showing decreased risk of COVID-19 hospitalization with genetically predicted accelerometer-assessed physical activity, and increased risk with television watching.
Chen et al., 13 May 2022, United Kingdom, peer-reviewed, 7 authors. Contact: caijh6@mail2.sysu.edu.cn (corresponding author), starbless2003@126.com, huangyn68@mail.sysu.edu.cn.
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Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study
Xiong Chen, Xiaosi Hong, Wenjing Gao, Shulu Luo, Jiahao Cai, Guochang Liu, Yinong Huang
Journal of Translational Medicine, doi:10.1186/s12967-022-03407-6
Background: The 2019 coronavirus disease pandemic poses an enormous threat to public health worldwide, and the ensuing management of social isolation has greatly decreased opportunities for physical activity (PA) and increased opportunities for leisure sedentary behaviors (LSB). Given that both PA and LSB have been established as major influencing factors for obesity, diabetes and cardiometabolic syndrome, whether PA/LSB in turn affects the susceptibility to COVID-19 by disrupting metabolic homeostasis remains to be explored. In this study, we aimed to systematically evaluate the causal relationship between PA/LSB and COVID-19 susceptibility, hospitalization and severity using a Mendelian randomization study. Methods: Data were obtained from a large-scale PA dataset (N = 377,000), LSB dataset (N = 422,218) and COVID-19 Host Genetics Initiative (N = 2,586,691). The causal effects were estimated with inverse variance weighted, MR-Egger, weighted median and MR-PRESSO. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. Risk factor analyses were further conducted to investigate the potential mediators. Results: Genetically predicted accelerometer-assessed PA decreased the risk for COVID-19 hospitalization (OR = 0.93, 95% CI 0.88-0.97; P = 0.002), while leisure television watching significantly increased the risk of COVID-19 hospitalization (OR = 1.55, 95% CI 1.29-1.88; P = 4.68 × 10 -6 ) and disease severity (OR = 1.85, 95% CI 1.33-2.56; P = 0.0002) after Bonferroni correction. No causal effects of self-reported moderate to vigorous physical activity (MVPA), accelerometer fraction of accelerations > 425 milligravities, computer use or driving on COVID-19 progression were observed. Risk factor analyses indicated that the above causal associations might be mediated by several metabolic risk factors,
such as reducing leisure sedentary behaviors and encouraging proper exercise, to combat COVID-19. Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s12967-022-03407-6. Additional file 1: Supplementary tables. Table S1 . Instrument variables of MVPA. Table S2 . Instrument variables of accelerations assessed physical activity. Table S3 . Instrument variables of fraction accelerations > 425 milli-gravities. Table S4 . Instrument variables of television watching. Table S5 . Instrument variables of computer used. Table S6 . Instrument variables of driving. Table S7 .MR estimates of the causal association between physical activity and leisure sedentary behaviors and the risk of COVID-19. Declarations Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. • fast, convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Given that both PA and LSB have been established as major ' 'influencing factors for obesity, diabetes and cardiometabolic syndrome, whether PA/LSB in ' 'turn affects the susceptibility to COVID-19 by disrupting metabolic homeostasis remains to be ' 'explored. In this study, we aimed to systematically evaluate the causal relationship between ' 'PA/LSB and COVID-19 susceptibility, hospitalization and severity using a Mendelian ' 'randomization study.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>Data were obtained from a large-scale PA dataset (N\u2009=\u2009' '377,000), LSB dataset (N\u2009=\u2009422,218) and COVID-19 Host Genetics Initiative (N\u2009' '=\u20092,586,691). The causal effects were estimated with inverse variance weighted, ' 'MR-Egger, weighted median and MR-PRESSO. Sensitivity analyses were implemented with Cochran’s ' 'Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. Risk ' 'factor analyses were further conducted to investigate the potential mediators.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>Genetically predicted accelerometer-assessed PA decreased the risk ' 'for COVID-19 hospitalization (OR\u2009=\u20090.93, 95% CI 0.88–0.97; P\u2009=\u20090.002), ' 'while leisure television watching significantly increased the risk of COVID-19 ' 'hospitalization (OR\u2009=\u20091.55, 95% CI 1.29–1.88; P\u2009=\u20094.68\u2009×\u2009' '10<jats:sup>–6</jats:sup>) and disease severity (OR\u2009=\u20091.85, 95% CI 1.33–2.56; ' 'P\u2009=\u20090.0002) after Bonferroni correction. No causal effects of self-reported ' 'moderate to vigorous physical activity (MVPA), accelerometer fraction of accelerations\u2009' '&gt;\u2009425 milligravities, computer use or driving on COVID-19 progression were observed. ' 'Risk factor analyses indicated that the above causal associations might be mediated by ' 'several metabolic risk factors, including smoking, high body mass index, elevated serum ' 'triglyceride levels, insulin resistance and the occurrence of type 2 diabetes.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Conclusion</jats:title>\n' ' <jats:p>Our findings supported a causal effect of accelerometer-assessed PA ' 'on the reduced risk of COVID-19 hospitalization as well as television watching on the ' 'increased risk of COVID-19 hospitalization and severity, which was potentially mediated by ' 'smoking, obesity and type 2 diabetes-related phenotypes. 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Diabetes Care. 2022;45(3):701–9.', 'journal-title': 'Diabetes Care'}], 'container-title': 'Journal of Translational Medicine', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12967-022-03407-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1186/s12967-022-03407-6/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12967-022-03407-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 5, 13]], 'date-time': '2022-05-13T12:09:17Z', 'timestamp': 1652443757000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03407-6'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 5, 13]]}, 'references-count': 55, 'journal-issue': {'issue': '1', 'published-print': {'date-parts': [[2022, 12]]}}, 'alternative-id': ['3407'], 'URL': 'http://dx.doi.org/10.1186/s12967-022-03407-6', 'relation': {}, 'ISSN': ['1479-5876'], 'subject': ['General Biochemistry, Genetics and Molecular Biology', 'General Medicine'], 'container-title-short': 'J Transl Med', 'published': {'date-parts': [[2022, 5, 13]]}, 'assertion': [ { 'value': '21 January 2022', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '24 April 2022', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '13 May 2022', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'Not applicable.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'The authors declare that they have no competing interests.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '216'}
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