Death in COVID-19. A Non-ICU Spanish Series: The SADDEN DEATH Study

Background: The current worldwide pandemic, coronavirus disease 2019 (COVID-19) is a novel infection with serious clinical manifestations, including death. However, autopsy reports are scarce, and little is known about the causes of death. Here we report the results of the largest series investigating exclusively deceased patients with COVID-19 in Spain. Methods: In this single-centre retrospective study, we consecutively included all deceased inpatients with laboratory-confirmed COVID-19 from Hospital Clinico San Carlos (Madrid, Spain) who had died from March 4 to April 16, 2020 for screening due to unexpected death. Demographic, clinical, treatment, and serial laboratory data, were extracted from electronic medical records and patient files and compared between unexpected and non-unexpected deaths. We used univariable and multivariable logistic regression methods to identify those factors associated with unexpected death. Findings: In total, 324 deceased patients were included. Median age, 82 years (IQR 76-87); 55.9.% males. The most common cardiovascular risk factors were hypertension (78.4%), hyperlipidemia (57.7%), and diabetes (34.3%). Other common comorbidities were chronic kidney disease (40.1%), chronic pulmonary disease (30.3%), active cancer (13%), and immunosuppression (13%). The CURB-65 score at admission was >2 in only 40.7% of patients. During hospitalization, 77.8% of patients received antivirals, 43.3% systemic corticosteroids, and 22.2% full anticoagulation. One hundred and five (32.4%) patients had an increased level of troponin I during hospitalization. The rate of any bacterial co-infection was 5.5%. The median time from initiation of therapy to death was 5 days (IQR 3.0-8.0). SARS-CoV-2 infection contributed to the patient´s death in 92.3% of patients. Progressive respiratory failure was the most frequent cause of death (92.0%). Twenty-five patients (7.7%) had an unexpected death. In 45 patients (13.9%), the death was exclusively attributed to COVID-19, and in 254 patients (78.4%) both, COVID-19 and the patient´s clinical situation before admission contributed to death. Factors independently associated with unexpected death were male sex, chronic renal failure, insulin-treated diabetes, and functional independence. Interpretation: This case series provides in-depth characterization of hospitalized non-ICU deceased patients with confirmed COVID-19 in the city of Madrid. Insulin-dependent diabetic males with chronic renal failure and independent for activities of daily living are at risk of unexpected death. Funding Statement: None. Declaration of Interests: None. Ethics Approval Statement: This study was approved by the local ethical committee and the study protocol has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki).