Modifiable lifestyle factors and the risk of post-COVID-19 multisystem sequelae, hospitalization, and death

Abstract

Effective prevention strategies for post-COVID complications are crucial for patients, clinicians, and policy makers to mitigate their cumulative burden. This study evaluated the association of modifiable lifestyle factors (smoking, alcohol intake, BMI, physical activity, sedentary time, sleep duration, and dietary habits) with COVID-19 multisystem sequelae, death, and hospitalization in the UK Biobank cohort (n = 68,896). A favorable lifestyle (6-10 healthy factors; 46.4%) was associated with a 36% lower risk of multisystem sequelae (HR, 0.64; 95% CI, 0.58-0.69; ARR at 210 days, 7.08%; 95% CI, 5.98-8.09) compared to an unfavorable lifestyle (0-4 factors; 12.3%). Risk reductions spanned all 10 organ systems, including cardiovascular, coagulation, metabolic, gastrointestinal, kidney, mental health, musculoskeletal, respiratory disorders, and fatigue. This beneficial effect was largely attributable to direct lifestyle impacts independent of corresponding pre-infection comorbidities (71% for any sequelae). A favorable lifestyle was also related to the risk of post-COVID death (HR 0.59, 0.52-0.66) and hospitalization (HR 0.78, 0.73-0.84). These associations persisted across acute and post-acute infection phases, irrespective of hospitalization status, vaccination, or SARS-CoV-2 variant. These findings underscore the clinical and public health importance of adhering to a healthy lifestyle in mitigating long-term COVID-19 adverse impacts and enhancing future pandemic preparedness.

Fig. 1. Association of healthy lifestyle with multisystem sequelae of COVID-19, death, and hospital admissions, during overall phase of SARS-CoV-2 infection.

Healthy lifestyle (composite or number) and risk of multisystem sequelae (composite or by organ systems), death, and hospitalization during the overall phase (0–210 days) of SARS-CoV-2 infection. Adjusted HRs and 95% CI are presented for composite/individual multisystem sequelae, death, and hospitalization. Absolute risk reduction (ARR) per 100 persons at 210 days and 95% CIs were calculated. Solid squares represent HRs with the area inversely proportional to the variance of the log HR. Hollow square represents ARR. The horizontal lines indicate 95% CIs, with black line representing statistically significant results and gray line representing non-significant results. Intermediate lifestyle category are in orange, favorable lifestyle category in green.

Fig. 2. Association of healthy lifestyle with multisystem sequelae of COVID-19, death, and hospital admissions, during acute and post-acute phases of SARS-CoV-2 infection.

Composite healthy lifestyle and risk of multisystem sequelae, death, and hospitalization during the acute phase (first 30 days) and post-acute (30–210 days) phases of SARS-CoV-2 infection. Adjusted HRs and 95% CIs are presented for composite/individual multisystem sequelae, death, and hospitalization. Absolute risk reduction (ARR) per 100 persons at 30 days and 30–210 days and 95% CIs were calculated. Solid square represents HRs with the area inversely proportional to the variance of the log HR. Hollow square represents ARR. The horizontal lines indicate 95% CIs, with black line representing statistically significant results and gray line representing non-significant results. Intermediate lifestyle category are in orange, favorable lifestyle category in green.

Fig. 3. Direct and indirect effects of healthy lifestyle, and association of pre-infection medical conditions with multisystem sequelae of COVID-19.

a Proportion of the direct and indirect effect of a healthy lifestyle on multisystem sequelae (intermediate/favorable vs unfavorable lifestyle). Direct associations were accounted for pre-infection medical conditions (mediator), identified as any relevant event recorded between baseline measurement and infection date. b Association of corresponding pre-infection medical conditions with the risk of sequelae following SARS-CoV-2 infection. Outcomes were ascertained 0–210 days after SARS-CoV-2 infection. The horizontal bars indicate HR and lines indicate 95% CIs. The sample size was 68,892. 7975 incident events for any sequela, 354 for general fatigue, 923 for coagulation diseases, 1938 for neurologic diseases, 800 for pulmonary diseases, 2023 for Kidney diseases, 2064 for gastrointestinal diseases, 1739 for mental disorders, 1895 for musculoskeletal diseases, 2077 for cardiovascular diseases, and 2152 for diabetes.

Fig. 4. Association of individual healthy lifestyle with multisystem sequelae, death, and hospitalization.

Blue square represents risk estimates from models fully adjusted for age, sex, education level, ethnicity, IMD, and mutually for all lifestyle factors. The purple square represents risk estimates from models partially adjusted for age, sex, education level, ethnicity, and IMD. The horizontal lines indicate 95% CIs, with black line representing statistically significant results and the gray line representing non-significant results. The sample sizes were 60,561 for any sequela (4792 events), 55,106 for hospitalization (6958 events), and 68,887 for death (1203 events). The HR for each lifestyle factor was calculated by comparing the healthy category with the unhealthy category (e.g., past or never smoker versus current smoker).

Fig. 5. Cumulative incidence curves of composite multisystem sequelae, death, and hospitalization among participants with and without SARS-CoV-2 infection.

a Participants with SARS-CoV-2 infection. b Participants with no evidence of SARS-CoV-2 infection. Outcomes were ascertained 0–210 days after SARS-CoV-2 infection. Event rates are presented for the unfavorable lifestyle category (red), the intermediate lifestyle category (orange), and the favorable lifestyle category (green). The shadow of cumulative incidence curves represents 95% CIs.