key: cord-0912054-ppqq8ck5
authors: Bandera, Alessandra; Nobili, Alessandro; Tettamanti, Mauro; Harari, Sergio; Bosari, Silvano; Mannucci, Pier Mannuccio
title: Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: comment
date: 2021-08-18
journal: Intern Emerg Med
DOI: 10.1007/s11739-021-02797-7
sha: 117766ff34c07129f90f3d9b397f014597bf0cf2
doc_id: 912054
cord_uid: ppqq8ck5

nan

admission were positively or negatively associated with mortality. First and importantly, age was independently associated with in-hospital death (OR 2.46). The authors also evaluated the association of death with the main symptoms on admission and found that the presence of productive cough was positively associated, this symptom being a plausible proxy of bacterial superinfection, whereas fever was negatively associated with death, perhaps a proxy of a useful inflammation response. Then the authors evaluated the association with deaths of a number of pre-existing or current comorbidities recorded at admission. The strongest signals of positive associations were for dementia (OR 1.90), chronic heart failure (OR 1.58), atrial fibrillation (OR 1.51), chronic obstructive pulmonary disease (OR 1.23) and chronic renal failure (OR 1.30). Other variables recorded at admission with a positive association with mortality were the number of pre-existing comorbidities (OR 1.36) and domiciliary polypharmacy (OR 1.20) [1] , in broad agreement with a previous nationwide observational study [2] .

With these results as background, we elected to compare them with those obtained in the frame of another registry conducted in the same period of the first burst of SARS-CoV-2 infection under the initiative and coordination of a research hospital that acted as a hub for COVID-19 in the metropolitan area of Milan, the capital city of the Northern Italian Region Lombardy [3] . This most populated Italian region (approximately 10 million, 16% of the country population) had the peculiar feature of being the first to be heavily hit from the pandemic from February to May 2020. The registry was also promoted by the Mario Negri Institute of Pharmacological Research that, besides preparing the protocol and case report form together with the hub hospital, did the data analysis. A few hospitals, mainly from Lombardy but also Veneto, Abruzzo and Emilia Romagna, chose to join the registry, but 80% of patients were enrolled in the two research and teaching hospitals in Milan, i.e., IRCCS The members of "COVID-19 Network Working Group" are presented in the Acknowledgements section.

Maggiore Policlinico (who contributed for 61% of the study population) and San Giuseppe Multimedica (15%).

At variance with the patients reported by Corradini et al. [1] admitted upfront to medical wards, 1018 patients with COVID-19 (mean age 65 ± 16) enrolled in this registry were first screened at the emergency room and found to be positive for SARS-CoV2 RNA by RT-PCR. Then those who, owing to their moderately severe pulmonary involvement, did not need admission to intensive care units were preferentially admitted to pneumology wards, where continuous positive airway pressure (CPAP) non-invasive ventilation (NIV) or high flow-nasal cannula (HFNC) was initiated [4] . When lung involvement was relatively mild patients were preferentially admitted to infectious disease and internal medicine wards, where they were mainly handled by means of conventional oxygen supplementation (i.e., nasal cannula, oral nasal face mask, ventimask, reservoir) and more seldom with CPAP/NIV. This triage strategy was quite effective, because only a minority of patients admitted to these hospital wards needed transfer to intensive care units (3.1%). All admitted patients were evaluated and data collected until discharge or death.

To offer a comparison with the results obtained by Corradini et al. [1] in internal medicine wards, we chose like them to compare the patients who died (n = 220) with those who survived (n = 798) (mortality rate 21.6%), by means of logistic regression analysis adjusted for age and sex and multivariable logistic regression adjusted also for the comorbidities ascertained at admission, in order to assess the association between a number of variables and death. Table 1 reports the results, with particular but not exclusive emphasis on the variables analyzed and reported by Corradini et al. [1] . Our findings in the frame of the first and most heavily affected Italian region are largely confirmatory of those of the nationwide SIMI cohort. On statistical analysis fully adjusted for all comorbidities, there was a positive association of age with in-hospital mortality (OR 1.07, CI 1.05-1.09), particularly strong for the quintiles above 75 years [OR for 75-84 years, 7.78 (2.26-26.8); for 85 or more OR 11.8 (3.27-42.5)]. We also found that respiratory and heart rate measured at hospital entry were positively associated with mortality, as well as body temperature. Systolic and diastolic blood pressure were negatively associated, perhaps as a proxy of a greater cardiovascular reserve. We also confirm the findings of Corradini et al. that the number of comorbidities and chronic polypharmacy were associated with mortality, and that dementia and chronic heart failure were the pre-existing comorbidities recorded at admission more strongly associated. This was also true but with lower strength for cancer and diabetes, with a definite trend of positive association for a history of myocardial infarction and atrial fibrillation but only in the frame of the univariate analysis. At variance with Corradini et al. [1] , COPD was not associated with the mortality risk but this difference may be explained by the size of our cohort that was one third smaller than that based on the whole country. Regarding oxygen supplementation, similarly to the findings from the SIMI-COVID-19 cohort, 69.6% of patients enrolled in our registry was treated with oxygen support during hospitalization and 20.5% received non-invasive ventilation (CPAP, NIV or HFNC). At multivariable analysis, when compared to subjects without oxygen support, patients who needed non-invasive ventilation had a significantly higher risk of in-hospital mortality (OR 4.31, 2.69-6.89), while the need for low-flow oxygen support was not associated with the risk of death (OR 0.84, 0.57-1.25). All in all, the combined perusal of registry data obtained from these Italian cohorts is justified because, even though the criteria chosen for admission to hospital wards were different, age and total mortality rates were quasi identical in patients hospitalized during the first bout of the SARS-CoV-2 pandemic. Both data broadly confirm the primary role of aging and pre-existing chronic diseases in causing the similarly high mortality rate observed in both cohorts. Like Corradini et al. [1] , we chose to evaluate the potency of the association with death of variables recorded at admission because a more focused therapeutic approach on the basis of these symptoms and comorbidities may help to better plan and tailor the therapeutic strategies, at a time when specific antiviral agents were not available for COVID-19.

Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI)

Comorbidities, cardiovascular therapies, and COVID-19 mortality: a nationwide, Italian observational study (ItaliCO). Front Cardiovasc Med

COVID-19 Network: the response of an Italian Reference Institute to research challenges about a new pandemia

Early consensus management for non-ICU acute respiratory failure SARS-CoV-2 emergency in Italy: from ward to trenches

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

The authors declare that they have no conflict of interest.

This article does not contain any studies with humans and participants or animals performed by any of the authors.Informed consent For this type of study, formal consent is not required.