Metabolically Unhealthy Individuals at Increased Risk for Critical COVID-19: Epidemiological Findings

Previous observations revealed that patients with severe forms of COVID-19 were more obese than those with non-severe disease. Multiple studies have indicated that obesity, which is typically represented by a high body mass index (BMI), is associated with COVID-19 severity and mortality.

However, obesity is a condition that predisposes to metabolic disorders and cardiovascular diseases, which have also been recognized as important risk factors for adverse outcomes of COVID-19.

Therefore, the observed association between obesity and critical COVID-19 could be biased by the effects of comorbidities. Previous studies have attempted to resolve this issue by adjusting for comorbidities such as diabetes, hypertension, and dyslipidemia; however, this may be insufficient to identify a direct relationship between obesity and COVID-19 outcomes.

Many differences in the determining characteristics of metabolic phenotypes have been observed between East Asians and other ethnic groups. For example, a considerable number of East Asian patients with type 2 diabetes were reported to be non-obese , although the prevalence of type 2 diabetes was similar to that of Caucasians. This observation directed much interest to metabolically unhealthy phenotypes without obesity . However, metabolically healthy phenotypes have also been observed with obesity.

We hypothesize that metabolic health beyond obesity could be crucial in determining risk for COVID-19 outcomes. The aim of this large retrospective study was to investigate the relative contribution of obesity and metabolic health status to critical outcomes of COVID-19 patients in a national cohort in South Korea.

Goals

This study aimed to determine the relative and independent contributions of impaired metabolic health and obesity to coronavirus critical disease 2019 (COVID-19).

Methods

We analyzed 4069 COVID-19 patients between January and June 2020 in South Korea, classified into four groups based on metabolic health status and body mass index (BMI): metabolically healthy normal weight (MHNW), metabolically non-normal weight healthy weight (MUNW), metabolically healthy obesity weight (MHO) and metabolically unhealthy obesity (MUO).

The primary outcome was a composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), extracorporeal membrane oxygenation (ECMO), and death.

Multivariable Cox proportional hazard regression models were used to estimate the hazard ratio (HR) for the outcome.

Results

The incidence rate (per 100 person-months) of critical COVID-19 was the lowest in the MHNW group (0.90), followed by the MHO (1.64), MUNW (3.37), and MUO groups ( 3.37).

Compared with MHNW, a significantly higher risk of critical COVID-19 was observed in MUNW (HR, 1.41; 95% CI, 1.01–1.98) and MUO (HR, 1.77; 95% CI, 1.01–1.98). 1.39–2.44), but not in MHO (HR, 1.48; 95% CI, 0.98–2.23).

The risk of ICU or IMV/ECMO admission was increased only in MUO; however, the risk of death was significantly higher in MUNW and MUO.

The risk of critical COVID-19 increased insignificantly by 2% for each 1 kg/m2 increase in BMI, but significantly by 13% for each increase in a metabolically harmful component, even after mutually adjusting for BMI and the state of metabolic health.