Obesity and Impaired Metabolic Health Increase Risk of COVID-19-Related Mortality in Young and Middle-Aged Adults to the Level Observed in Older People: The LEOSS Registry

Abstract

Advanced age, followed by male sex, by far poses the greatest risk for severe COVID-19. An unresolved question is the extent to which modifiable comorbidities increase the risk of COVID-19-related mortality among younger patients, in whom COVID-19-related hospitalization strongly increased in 2021. A total of 3,163 patients with SARS-COV-2 diagnosis in the Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort were studied. LEOSS is a European non-interventional multi-center cohort study established in March 2020 to investigate the epidemiology and clinical course of SARS-CoV-2 infection. Data from hospitalized patients and those who received ambulatory care, with a positive SARS-CoV-2 test, were included in the study. An additive effect of obesity, diabetes and hypertension on the risk of mortality was observed, which was particularly strong in young and middle-aged patients. Compared to young and middle-aged (18-55 years) patients without obesity, diabetes and hypertension (non-obese and metabolically healthy; n = 593), young and middle-aged adult patients with all three risk parameters (obese and metabolically unhealthy; n = 31) had a similar adjusted increased risk of mortality [OR 7.42 (95% CI 1.55-27.3)] as older (56-75 years) non-obese and metabolically healthy patients [n = 339; OR 8.21 (95% CI 4.10-18.3)]. Furthermore, increased CRP levels explained part of the elevated risk of COVID-19-related mortality with age, specifically in the absence of obesity and impaired metabolic health. In conclusion, the modifiable risk factors obesity, diabetes and hypertension increase the risk of COVID-19-related mortality in young and middle-aged patients to the level of risk observed in advanced age.

Keywords: COVID-19; diabetes; hypertension; impaired metabolic health; mortality; obesity.

Figure 1

Proportion of COVID-19 patients who recovered and died divided in three age groups based on the presence or absence of obesity, diabetes and hypertension. All COVID-19 patients who recovered and died (n = 3,163) were first divided in three age groups (young and middle aged, 18–55 years, n = 1,068; older age, 56–75 years; n = 1,220 and old age, >75 years; n = 875) and subsequently divided in four groups based on the presence or absence of obesity (BMI ≥ 30 kg·m⁻²), and impaired metabolic health (diabetes and hypertension).

Figure 2

Multivariable relationships of selected anthropometrics, comorbidities and laboratory parameters with COVID-19-related mortality in three age groups based on the presence (unhealthy) or absence (healthy) of obesity, diabetes and hypertension. All COVID-19 patients who recovered and died (n = 3,163) were first divided in three age groups (young and middle aged, 18–55 years, n = 1,068; older age, 56–75 years; n = 1,220 and old age, >75 years; n = 875) and subsequently divided in two groups (n = 1,357) based on the presence (unhealthy) or absence (healthy) of obesity (BMI ≥ 30 kg·m⁻²), and impaired metabolic health (diabetes and hypertension). All parameters shown were included in the multivariable regression analysis.

Figure 3

Kaplan-Meier survival comparing three age groups based on the presence (unhealthy) or absence (healthy) of obesity, diabetes and hypertension. All COVID-19 patients who recovered and died (n = 3,163) were first divided in three age groups (young and middle aged, 18–55 years, n = 1,068; older age, 56–75 years; n = 1,220 and old age, >75 years; n = 875) and subsequently divided in two groups (n = 1,357) based on the presence (unhealthy) or absence (healthy) of obesity (BMI ≥ 30 kg·m⁻²), and impaired metabolic health (diabetes and hypertension).