Healthy lifestyle for the prevention of post-COVID-19 multisystem sequelae, hospitalization, and death: a prospective cohort study

{ 'institution': [{'name': 'medRxiv'}], 'indexed': {'date-parts': [[2024, 2, 3]], 'date-time': '2024-02-03T00:25:01Z', 'timestamp': 1706919901241}, 'posted': {'date-parts': [[2024, 1, 31]]}, 'group-title': 'Epidemiology', 'reference-count': 51, 'publisher': 'Cold Spring Harbor Laboratory', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2024, 1, 31]]}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Post-COVID ' 'complications are emerging as a global public health crisis. Effective prevention strategies ' 'are needed to inform patients, clinicians and policy makers, and to reduce their cumulative ' 'burden. We aimed to investigate whether a habitual healthy lifestyle predated pandemic is ' 'associated with lower risks of multisystem sequelae and other adverse outcomes of COVID-19, ' 'and whether the potential protective effects are independent of pre-existing ' 'comorbidities.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The ' 'prospective population-based cohort study enrolled participants with SARS-CoV-2 infection ' 'confirmed by a positive polymerase chain reaction test result between March 1, 2020, and ' 'March 1, 2022. Participants with no history of the related outcome one year before infection ' 'were included and followed up for 210 days. Exposures included ten modifiable healthy ' 'lifestyle factors including past or never smoking, moderate alcohol intake (≤4 times week), ' 'body mass index &lt;30 kg/m<jats:sup>2</jats:sup>, at least 150 minutes of moderate or 75 ' 'minutes of vigorous physical activity per week, less sedentary time (&lt;4 hours per day), ' 'healthy sleep duration (7-9 hours per day), adequate intake of fruit and vegetables (≥400 ' 'g/day), adequate oily fish intake (≥1 portion/week), moderate intake of red meat (≤4 portions ' 'week) and processed meat (≤4 portions week). Outcomes included multisystem COVID-19 sequelae ' '(consisting of 75 diseases/symptoms in 10 organ systems), death, and hospital admission ' 'following SARS-CoV-2 infection, confirmed by hospital inpatient and death records. Risk was ' 'reported in relative scale (hazard ratio [HR]) and absolute scale (absolute risk reduction ' '[ARR]) during both the acute (the first 30 days) and post-acute (30-210 days) phases of ' 'infection using Cox ' 'models.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>A total of ' '68,896 participants (mean [SD] age, 66.6 [8.4]; 32,098 women [46.6%]) with COVID-19 were ' 'included. A favorable lifestyle (6-10 healthy lifestyle factors; 46.4%) was associated with a ' '36% lower risk of multisystem sequelae of COVID-19 (HR, 0.64; 95% CI, 0.58-0.69; ARR, 7.08%; ' '95% CI, 5.98-8.09), compared with unfavorable lifestyle (0-4 factors; 12.3%). Risk reductions ' 'were observed across all 10 prespecified organ systems including cardiovascular, coagulation, ' 'metabolic and endocrine, gastrointestinal, kidney, mental health, musculoskeletal, ' 'neurologic, and respiratory disorders, and general symptoms of fatigue and malaise. This ' 'beneficial effect was largely attributable to direct effects of healthy lifestyle, with ' 'mediation proportion ranging from 44% to 93% across organ systems. A favorable lifestyle was ' 'also associated with lower risk of post-COVID death (HR, 0.59; 95% CI, 0.52-0.66; ARR, 1.99%; ' '95% CI, 1.61-2.32) and hospitalization (HR, 0.78; 95% CI, 0.73-0.84; ARR, 6.14%; 95% CI, ' '4.48-7.68). These associations were observed after accounting for potential misclassification ' 'of lifestyle factors, and during acute and post-acute infection, in those tested positive in ' 'the hospital and community setting, and independent of vaccination status or SARS-CoV-2 ' 'variant.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>Adherence ' 'to a healthy lifestyle predated pandemic was associated with substantially lower risk of ' 'complications across organ systems, death, and hospitalization following COVID-19, regardless ' 'of phases of infection, vaccination status, test setting, and SARS-CoV-2 variants, and ' 'independent of comorbidities. These findings illustrate the benefits of adhering to a healthy ' 'lifestyle to reduce the long-term adverse health consequences following SARS-CoV-2 ' 'infection.</jats:p></jats:sec><jats:sec><jats:title>Research in ' 'context</jats:title><jats:sec><jats:title>Evidence before this study</jats:title><jats:p>We ' 'searched PubMed and MEDLINE for articles published between March 1, 2020, and December 1, ' '2023, using the search terms “healthy lifestyle”, “risk factor”, “post-COVID condition”, ' '“long COVID”, “post-acute sequelae”, “prevention”, “management”, and “treatment”, with no ' 'language restrictions. Previous evidence on the prevention and management of long COVID has ' 'mainly focused on vaccination and pharmaceutical approaches, including antivirals (e.g., ' 'molnupiravir and nirmatrelvir) and other drugs (e.g., metformin). Vaccination before ' 'infection or use of antivirals in selected high-risk patients during acute infection only ' 'partially mediates the risk of COVID-19 sequelae. Evidence for the non-pharmaceutical ' 'prevention strategies are lacking. We identified only two publications on the association ' 'between healthy lifestyle and post-COVID condition, and one meta-analysis of the risk factors ' 'for long COVID symptoms. A cross-sectional study of 1981 women suggested an inverse ' 'association between healthy lifestyle factors and self-reported symptoms following infection ' 'of non-Omicron variants, which was mainly driven by BMI and sleep duration. Another study ' 'suggested an inverse prospective association between healthy lifestyle prior to infection and ' 'post-COVID cardiovascular events. High BMI and smoking are risk factors for long COVID mainly ' 'in hospitalized patients. We did not find any study that assessed the association between a ' 'composite healthy lifestyle and subsequent post-COVID complications or sequelae across organ ' 'systems, hospitalization, and death.</jats:p></jats:sec><jats:sec><jats:title>Added value of ' 'this study</jats:title><jats:p>In a prospective, population-based cohort of 68,896 ' 'participants with COVID-19, adherence to a healthy lifestyle prior to infection was ' 'associated with a substantially lower risk of multisystem sequelae (by 20%-36%), death (by ' '26%-41%), and hospital admission (by 13%-22%) following COVID-19. The reduced risk of ' 'sequelae was evident across 10 prespecified organ systems, including cardiovascular, ' 'coagulation and hematologic, metabolic and endocrine, gastrointestinal, kidney, mental ' 'health, musculoskeletal, neurologic, and respiratory disorders, as well as general symptoms ' 'of fatigue and malaise. The reduced risk of multisystem sequelae, hospitalization, and death ' 'associated with a healthy lifestyle was consistently observed across participants, regardless ' 'of their vaccination status, disease severity, and major SARS-CoV-2 variants, and largely ' 'independent of relevant comorbidities. Adherence to a healthy lifestyle prior to infection ' 'was consistently and directly associated with reduced risk of sequelae and other adverse ' 'health outcomes following COVID-19.</jats:p></jats:sec><jats:sec><jats:title>Implications of ' 'all the available evidence</jats:title><jats:p>The inverse association of healthy lifestyle ' 'with multisystem sequelae was even larger than those observed in previous studies of ' 'pharmaceutical interventions in non-hospitalized patients. Considering the restricted scope ' 'of currently available therapies, such as antivirals (only selected patients at higher risk ' 'are qualified during the acute infection) and limited efficacy of vaccination in preventing ' 'long COVID, adherence to a healthy lifestyle, in combination with vaccination and, if ' 'necessary, potential medications, emerges as practical prevention and care strategies to ' 'mitigate the long-term health consequences of SARS-CoV-2 infection. These strategies are of ' 'significant clinical and public health importance in reducing the overall burden of ' 'post-COVID conditions and improving preparedness for future ' 'pandemics.</jats:p></jats:sec></jats:sec>', 'DOI': '10.1101/2024.01.30.24302040', 'type': 'posted-content', 'created': {'date-parts': [[2024, 2, 1]], 'date-time': '2024-02-01T04:35:10Z', 'timestamp': 1706762110000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Healthy lifestyle for the prevention of post-COVID-19 multisystem sequelae, hospitalization, and ' 'death: a prospective cohort study', 'prefix': '10.1101', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-0923-1441', 'authenticated-orcid': False, 'given': 'Yunhe', 'family': 'Wang', 'sequence': 'first', 'affiliation': []}, {'given': 'Binbin', 'family': 'Su', 'sequence': 'additional', 'affiliation': []}, {'given': 'Marta', 'family': 'Alcalde-Herraiz', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nicola L.', 'family': 'Barclay', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yaohua', 'family': 'Tian', 'sequence': 'additional', 'affiliation': []}, {'given': 'Chunxiao', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nicholas J.', 'family': 'Wareham', 'sequence': 'additional', 'affiliation': []}, {'given': 'Roger', 'family': 'Paredes', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-0040-0042', 'authenticated-orcid': False, 'given': 'Junqing', 'family': 'Xie', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-3950-6346', 'authenticated-orcid': False, 'given': 'Daniel', 'family': 'Prieto-Alhambra', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'reference': [ { 'key': '2024020211500666000_2024.01.30.24302040v1.1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/s2213-2600(23)00239-4'}, { 'key': '2024020211500666000_2024.01.30.24302040v1.2', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/s2213-2600(22)00169-2'}, { 'issue': '3', 'key': '2024020211500666000_2024.01.30.24302040v1.3', 'doi-asserted-by': 'crossref', 'first-page': '133', 'DOI': '10.1038/s41579-022-00846-2', 'article-title': 'Long COVID: major findings, mechanisms and recommendations', 'volume': '21', 'year': '2023', 'journal-title': 'Nature Reviews Microbiology'}, { 'issue': '1', 'key': '2024020211500666000_2024.01.30.24302040v1.4', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1038/s41581-022-00652-2', 'article-title': 'Long COVID: long-term health outcomes and implications for policy and ' 'research', 'volume': '19', 'year': '2023', 'journal-title': 'Nature Reviews Nephrology'}, { 'key': '2024020211500666000_2024.01.30.24302040v1.5', 'doi-asserted-by': 'crossref', 'unstructured': 'Bowe B , Xie Y , Al-Aly Z . 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