Cardiorespiratory fitness and lifestyle on severe COVID-19 risk in 279,455 adults: a case control study

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Abstract

Background

The impact of cardiorespiratory fitness (CRF) and other lifestyle-related factors on severe COVID-19 risk is understudied. The present study aims to investigate lifestyle-related and socioeconomic factors as possible predictors of COVID-19, with special focus on CRF, and to further study whether these factors may attenuate obesity- and hypertension-related risks, as well as mediate associations between socioeconomic factors and severe COVID-19 risk.

Methods

Out of initially 407,131 participants who participated in nationwide occupational health service screening between 1992 and 2020, n = 857 cases (70% men, mean age 49.9 years) of severe COVID-19 were identified. CRF was estimated using a sub-maximum cycle test, and other lifestyle variables were self-reported. Analyses were performed including both unmatched, n = 278,598, and sex-and age-matched, n = 3426, controls. Severe COVID-19 included hospitalization, intensive care or death due to COVID-19.

Results

Patients with more severe COVID-19 had significantly lower CRF, higher BMI, a greater presence of comorbidities and were more often daily smokers. In matched analyses, there was a graded decrease in odds for severe COVID-19 with each ml in CRF (OR = 0.98, 95% CI 0.970 to 0.998), and a two-fold increase in odds between the lowest and highest (< 32 vs. ≥ 46 ml·min ⁻¹·kg ⁻¹) CRF group. Higher BMI (per unit increase, OR = 1.09, 1.06 to 1.12), larger waist circumference (per cm, OR = 1.04, 1.02 to 1.06), daily smoking (OR = 0.60, 0.41 to 0.89) and high overall stress (OR = 1.36, 1.001 to 1.84) also remained significantly associated with severe COVID-19 risk. Obesity- and blood pressure-related risks were attenuated by adjustment for CRF and lifestyle variables. Mediation through CRF, BMI and smoking accounted for 9% to 54% of the associations between low education, low income and blue collar/low skilled occupations and severe COVID-19 risk. The results were consistent using either matched or unmatched controls.

Conclusions

Both lifestyle-related and socioeconomic factors were associated with risk of severe COVID-19. However, higher CRF attenuated the risk associated with obesity and high blood pressure, and mediated the risk associated with various socioeconomic factors. This emphasises the importance of interventions to maintain or increase CRF in the general population to strengthen the resilience to severe COVID-19, especially in high-risk individuals.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12966-021-01198-5.

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Most cited references 34

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COVID-19: consider cytokine storm syndromes and immunosuppression

Puja Mehta, Daniel McAuley, Michael Brown … (2020)

As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, 1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. 2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections 3 and occurs in 3·7–4·3% of sepsis cases. 4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients. 5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α. 6 Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p 39·4°C 49 Organomegaly None 0 Hepatomegaly or splenomegaly 23 Hepatomegaly and splenomegaly 38 Number of cytopenias * One lineage 0 Two lineages 24 Three lineages 34 Triglycerides (mmol/L) 4·0 mmol/L 64 Fibrinogen (g/L) >2·5 g/L 0 ≤2·5 g/L 30 Ferritin ng/ml 6000 ng/ml 50 Serum aspartate aminotransferase <30 IU/L 0 ≥30 IU/L 19 Haemophagocytosis on bone marrow aspirate No 0 Yes 35 Known immunosuppression † No 0 Yes 18 The Hscore 11 generates a probability for the presence of secondary HLH. HScores greater than 169 are 93% sensitive and 86% specific for HLH. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of HLH. HScores can be calculated using an online HScore calculator. 11 HLH=haemophagocytic lymphohistiocytosis. * Defined as either haemoglobin concentration of 9·2 g/dL or less (≤5·71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. † HIV positive or receiving longterm immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine).

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OpenSAFELY: factors associated with COVID-19 death in 17 million patients

Elizabeth J Williamson, Alex J Walker, Krishnan Bhaskaran … (2020)

COVID-19 has rapidly impacted on mortality worldwide. 1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths. COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively). We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.

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Epidemiology of COVID‐19: A Systematic Review and Meta‐analysis of Clinical Characteristics, Risk factors and Outcomes

Jie Li, Daniel Q. Huang, Biyao Zou … (2020)

Abstract Background COVID‐19 has become a pandemic, but its reported characteristics and outcomes vary greatly amongst studies. Objectives We determined pooled estimates for clinical characteristics and outcomes in COVID‐19 patients including subgroups by disease severity (based on WHO Interim Guidance Report or IDSA/ATS criteria) and by country/region. Methods We searched Pubmed, Embase, Scopus, Cochrane, Chinese Medical Journal, and preprint databases from January 1, 2020 to April 6, 2020. Studies of laboratory confirmed COVID‐19 patients with relevant data were included. Two reviewers independently performed study selection and data extraction. Results From 6,007 articles, 212 studies from 11 countries/regions involving 281,461 individuals were analyzed. Overall, mean age was 46.7 years, 51.8% were male, 22.9% had severe disease, and mortality was 5.6%. Underlying immunosuppression, diabetes, and malignancy were most strongly associated with severe COVID‐19 (coefficient=53.9, 23.4, 23.4, respectively, all p<0.0007), while older age, male gender, diabetes, and hypertension were also associated with higher mortality (coefficient=0.05 per year, 5.1, 8.2, 6.99, respectively, p=0.006 to 0.0002). Gastrointestinal (nausea, vomiting, abdominal pain) and respiratory symptoms (shortness of breath, chest pain) were associated with severe COVID‐19, while pneumonia and end organ failure were associated with mortality. Conclusion COVID‐19 is associated with a severe disease course in about 23% and mortality in about 6% of infected persons. Individuals with comorbidities and clinical features associated with severity should be monitored closely, and preventive efforts should especially target those with diabetes, malignancy and immunosuppression. This article is protected by copyright. All rights reserved.

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Author and article information

Contributors

Elin Ekblom-Bak:

ORCID: http://orcid.org/0000-0002-3901-7833

Elin.Ekblom@gih.se

Journal

Journal ID (nlm-ta): Int J Behav Nutr Phys Act

Journal ID (iso-abbrev): Int J Behav Nutr Phys Act

Title: The International Journal of Behavioral Nutrition and Physical Activity

Publisher: BioMed Central (London )

ISSN (Electronic): 1479-5868

Publication date (Electronic): 19 October 2021

Publication date PMC-release: 19 October 2021

Publication date Collection: 2021

Volume: 18

Electronic Location Identifier: 135

Affiliations

[1 ]GRID grid.416784.8, ISNI 0000 0001 0694 3737, Department of Physical Activity and Health, The Swedish School of Sport and Health Sciences, ; PO Box 5626, 114 86 Stockholm, Sweden

[2 ]Research Department, HPI Health Profile Institute, PO Box 35, 182 11, Danderyd, Sweden

[3 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, , Karolinska Institute, ; 141 83 Stockholm, Sweden

[4 ]GRID grid.8761.8, ISNI 0000 0000 9919 9582, Department of Psychology, , University of Gothenburg, ; 405 30 Gothenburg, Sweden

[5 ]GRID grid.12650.30, ISNI 0000 0001 1034 3451, Department of Psychology, , Umeå University, ; 901 87 Umeå, Sweden

[6 ]GRID grid.23048.3d, ISNI 0000 0004 0417 6230, Department of Sport Science and Physical Education, , University of Agder, ; 4630 Kristiansand, Norway

[7 ]Women’s Health and Allied Health Professionals Theme Medical Unit Occupational Therapy and Physiotherapy, Stockholm, Sweden

Author information

Elin Ekblom-Bak http://orcid.org/0000-0002-3901-7833

Article

Publisher ID: 1198

DOI: 10.1186/s12966-021-01198-5

PMC ID: 8524225

PubMed ID: 34666788

SO-VID: 453f617c-cb71-4ddf-bc21-5f6cb5b7b5ad

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 1 June 2021

Date accepted : 2 September 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100003793, Hjärt-Lungfonden;

Award ID: 20200564

Award Recipient : Elin Ekblom-Bak

Funded by: FundRef http://dx.doi.org/10.13039/501100009238, Försvarsmakten;

Award ID: AF9220915

Award Recipient : Björn Ekblom

Funded by: FundRef http://dx.doi.org/10.13039/501100004359, Vetenskapsrådet;

Award ID: 2017-00273

Award Recipient : Andreas Stenling

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ScienceOpen disciplines: Nutrition & Dietetics

Keywords: cardiorespiratory fitness,lifestyle,obesity,socioeconomics,severe acute respiratory syndrome coronavirus 2

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ScienceOpen disciplines: Nutrition & Dietetics

Keywords: cardiorespiratory fitness, lifestyle, obesity, socioeconomics, severe acute respiratory syndrome coronavirus 2

Cardiorespiratory fitness and lifestyle on severe COVID-19 risk in 279,455 adults: a case control study

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Abstract

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Supplementary Information

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Novel Coronavirus Disease COVID-19

Most cited references 34

COVID-19: consider cytokine storm syndromes and immunosuppression

OpenSAFELY: factors associated with COVID-19 death in 17 million patients

Epidemiology of COVID‐19: A Systematic Review and Meta‐analysis of Clinical Characteristics, Risk factors and Outcomes

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