The role of metabolic comorbidity in COVID-19 mortality of middle-aged adults. The case of Mexico.

BackgroundIn contrast to developed countries, in Mexico more than half of COVID-19 deaths have occurred in adults <65-years-old, with at least a million years of life lost to premature mortality (YLL) in eight months. Mexico has a young population but a high prevalence of metabolic diseases like obesity and diabetes that contribute to COVID-19 adverse outcomes. COVID-19 could be particularly risky in population with specific comorbidity combinations that havent been analyzed. MethodsTo explore what contributes to the high COVID-19 mortality in Mexican middle-aged adults, we calculated age-stratified COVID-19 case fatality rates, YLL and relative risk (RR) of 9 comorbidities and 23 comorbidity combinations in a retrospective Mexican cohort with 905,579 PCR-confirmed COVID-19 cases/89,167 deaths, until Nov/2/2020. FindingsChronic kidney disease (CKD) had the highest RR for COVID-19 fatality, followed by diabetes and immunosuppression, that in turn had higher RR than obesity or hypertension as single comorbidities. The combination diabetes/hypertension with or without obesity had RR as high as CKD as a single comorbidity (>3 in <60-year-olds). Notably, the RR of comorbidities decreased with age, tending to values near 1 after age 60; suggesting that in Mexico, comorbidities increase COVID-19 fatality mostly in young and middle-aged adults. Our analysis suggests that advanced metabolic disease, marked by multimorbidity (more than one chronic disease per individual) or diabetes before age 60, contribute particularly to the younger age of COVID-19 fatalities in Mexico. Around 38% of YLL to COVID-19, were attributable to the synergy between COVID-19 and pre-existing diseases, mainly combinations between obesity, diabetes and hypertension. Yet, [1/4] of deaths and 1/3 of YLL have occurred in individuals without known comorbidities. ConclusionsThe Mexican COVID-19 outbreak illustrates that middle-aged adults 45-64-yo can have high COVID-19 mortality during large outbreaks, especially if they present chronic metabolic comorbidities, but also in their absence, making them an important group of concern after elders. COVID-19 mortality in middle-aged adults is likely proportional to the gradual decline in health that accompanies ageing, which presents earlier in poorer populations that also get more exposed to SARS-CoV-2 and have less access to specialized medical attention.