Abstract

during 2020, Italy was one of the first nation hit by SARS-CoV-2, but it was not the hardest-hit country in terms of deaths. In absence of the death certificate, the burden of COVID-19 on mortality is usually calculated from overall deaths or from deaths of patients tested positive for COVID-19. However, these measures do not express the real burden of the disease on the population. identify deaths due to or involving COVID-19 in absence of the death certificates. deaths for all causes, cause-specific deaths, COVID-19 hospitalization and COVID-19 confirmed cases between 01.01.2020 and 31.12.2021 observed in subjects residing in the territory of the ATS of Milan. Potential deaths due to or involving COVID-19 as those occurring in an optimal time period between the date of death and the date of positive swab and/or COVID-19 hospitalization, were identified. Optimal time period was defined maximizing sensitivity and specificity, comparing potential COVID-19 deaths with 2020 cause-specific mortality as gold standard, stratifying results by time of deaths, age, and number of comorbidities. Then, this method was further validated using a time-series approach to estimate the excess mortality during the COVID-19 outbreak in comparison with the pre-outbreak period 2015-2019. Accuracy of predictions was evaluated with the Root Mean Square Error (RMSE) between observed and predicted values. 78,202 deaths for all causes, of which 8,815 due to or involving COVID-19 as classified by the Milan Register of Death Causes for 2020. all-cause mortality, cause-specific mortality. from the beginning of the epidemic, 30% (23,495) died in the first semester of 2020, 26% (19,988) in the second semester of 2020, 23% (18,189) in the first semester of 2021, and 21% (16,530) in the second semester of 2021. COVID-19 hospitalizations were 13.826 (17%), while confirmed COVID-19 cases were 17,548 (22%). The optimal time intervals capable to identify a potential death due to or involving COVID-19 were 0-61 between the date of death and the date of positive swab and 0-11 between the date of death and the date of COVID-19 hospitalization, with an overall sensitivity of 90%, a specificity of 95%, and a RMSE of 3.6. Comparing the method proposed with the time-series approach, a RMSE in 2021 of 15.8 was found. Results showed different optimal time intervals for 2021 vs 2020 and by years of age and comorbidities. this study found that deaths due to or involving COVID-19 could be sensitively identified from the date of positive swab and/or COVID-19 hospitalization. This method can be used for public health interventions which provided so far measures in terms of total deaths instead of real numbers of COVID-19 death, in particular those involving the effective reproduction number usually calculated from overall mortality.

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