The incremental impact of comorbidities in COVID-19-related deaths compared to patients dying from cancer or cardiovascular disease

To the Editor,

Several lines of evidence attest that comorbidities may substantially influence the clinical course of coronavirus disease 2019 (COVID-19) [1]. Nevertheless, there is no evidence for a direct comparison between the impact of the total number of comorbidities and the less favorable outcome of COVID-19 compared to other common pathologies.

To this end, we performed an electronic search on the website of the Italian National Institute of Statistics (ISTAT), under the menu item “Number of pathologies for initial cause of death” [2], which compiles national statistics on deaths based on marital status and registry sources. The search focused on COVID-19 and on the two leading causes of death in Italy and the rest of the world (i.e., cardiovascular disease and cancer). The search was limited to the first two years of the pandemic (i.e., 2020 and 2021), using the European Short List for the causes of death “cardiovascular diseases”, “cancer” and “COVID-19”. The cumulative mortality for each of the three conditions was retrieved in absolute numbers, the mean number of deaths was calculated between the 2020 and 2021 values (i.e., [Mean deaths] = ([deaths in 2020] + [deaths in 2021)/2], and this mean value was then stratified by the number of comorbidities reported in the registry at the time of death (from 1 to 6 or more). We used the number of deaths of patients with a single comorbidity to standardize the number of deaths of patients with more than one comorbidity, as follows: [number of deaths with “x” comorbidities]/[number of deaths with 1 comorbidity], where “x” represents the number of comorbidities at death. The study was conducted in accordance with the Declaration of Helsinki and was exempt from Institutional Review Board review because ISAT is an anonymized and publicly available database.

The results of this study are summarized in Fig. 1. Although the proportion of deaths in patients with more than one comorbidity increased progressively for all three pathologies, the ratio ranged from 4.8 to 12.1 for cardiovascular disease, from 5.0 to 12.5 for cancer, while the ratio for COVID-19 increased exponentially from 9.3 in patients with two comorbidities up to 136.7 in patients with six or more comorbidities.

Fig. 1

Incremental risk of death from cardiovascular disease, cancer and coronavirus disease 2019 (COVID-19) in patients with more than one comorbidity compared to patients with a single comorbidity

The results of our analysis show that patients with cancer or cardiovascular disease have up to a 12-fold higher risk of dying from these pathologies when multiple comorbidities are present, but the risk of death with multiple comorbidities is much higher for COVID-19, increasing to over 130-fold for patients with six or more comorbidities. These findings imply that enhanced prevention against the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection needs to be planned especially in patients with comorbidities, while comprehensive clinical monitoring and more aggressive antiviral treatment may also be advisable in fragile patients who develop COVID-19.