Is age the most important risk factor in COVID-19 patients? The relevance of comorbidity burden: A retrospective analysis of 10,090 hospitalizations
Authors: Valero-Bover Damià , Monterde David , Carot-Sans Gerard , Cainzos-Achirica Miguel , Comin-Colet Josep , Vela Emili , Clèries Montse , Abilleira Sònia , Arrufat Miquel , Lejardi Yolanda , Solans Òscar , Dedeu Toni , Coca Marc , Pérez-Sust Pol , Piera-Jiménez Jordi 
Published: June 2022

AbstractObjectivesTo investigate whether the effect of chronological age on the risk of developing critical illness in COVID-19 hospitalized individuals is attenuated, and to which extent, when adjusting for increasingly exhaustive measures of the comorbidity burden.DesignRetrospective assessment of electronic health records.SettingAll public hospitals of the Catalan Institute of Health (Catalonia; North-East Spain; 7.7 million inhabitants), which account for 30% of all hospital admissions in Catalonia.ParticipantsWe included all individuals admitted to the hospital with COVID-19 as the main diagnosis between March 1, 2020, and January 31, 2022. Vaccinated individuals and those admitted within the first of the six COVID-19 epidemic waves were excluded from the primary analysis but were included in secondary analyses.Main outcome measuresThe primary composite outcome was critical illness, defined as the need for invasive mechanical ventilation, transfer to the intensive care unit (ICU), or in-hospital death (any of them). Explanatory variables included age, sex, and four summary measures of comorbidity burden on admission: the Charlson index (17 diagnostic group codes), the Elixhauser index and count (31 diagnostic group codes), and the Queralt DxS index (3,145 diagnostic group codes). All models were adjusted by wave and center. The proportion of the effect of age attributable to comorbidity burden was assessed using a causal mediation analysis.ResultsThe primary analysis included 10,090 hospitalizations due to COVID-19; of them, 3,524 experienced a critical illness. The frequency of critical illness increased with age and comorbidity burden on admission, irrespective of the measure used. In multivariate analyses, the effect size of age decreased with the number of diagnoses considered to estimate comorbidity burden. When adjusting for the Queralt DxS index, age showed a minimal contribution to critical illness; according to the causal mediation analysis, comorbidity burden on admission explained the 95.3% (95% CI 82.1% −112.7%) of the observed effect of age on critical illness.ConclusionsWhen measured exhaustively, comorbidity burden rather than chronological age explains the increased risk of critical illness observed in patients hospitalized with COVID-19.Summary boxWhat is already known on this topicAge is broadly acknowledged as a critical risk factor for developing critical illness in individuals hospitalized due to COVID-19.When adjusting for other underlying factors, such as comorbidities, the effect size of age for predicting critical illness decreases; nevertheless, most studies have suggested that age remains independently associated with COVID-19 outcomes.What this study addsThe observed contribution of chronological age to the risk of critical illness in hospitalized COVID-19 patients decreases with the exhaustivity of the measure of comorbidity burden.When adjusting for a comprehensive comorbidity index that considers all possible clinical conditions from a weighted list of 3,145 possible diagnostic groups, age has little or no relevant effect on the risk of critical illness.Mediation analyses confirm that the effect of chronological age on COVID-19 outcomes can be explained by comorbidity burden.