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Antonella Potalivo,1,* Jonathan Montomoli,1,* Francesca Facondini,1 Gianfranco Sanson,2 Luigi Arcangelo Lazzari Agli,3,4 Tiziana Perin,5 Francesco Cristini,6 Enrico Cavagna,7 Raffaella De Giovanni,8 Carlo Biagetti,6 Ilaria Panzini,9 Cinzia Ravaioli,10 Maria Maddalena Bitondo,1 Daniela Guerra,1 Giovanni Giuliani,1 Elena Mosconi,1 Sonia Guarino,1 Elisa Marchionni,6 Gianfilippo Gangitano,5 Ilaria Valentini,3,4 Luca Giampaolo,8 Francesco Muratore,7 Giuseppe Nardi1 1Department of Anaesthesia and Intensive Care, Infermi Hospital, AUSL della Romagna, Rimini, Italy; 2Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; 3Department of Pneumology, Infermi Hospital, Rimini, Italy; 4Ceccarini Hospital, AUSL della Romagna, Riccione, Italy; 5Department of Emergency Medicine, Infermi Hospital, AUSL Della Romagna, Rimini, Italy; 6Department of Infectious Diseases, Infermi Hospital, AUSL della Romagna, Rimini,Italy; 7Department of Radiology, Infermi Hospital, AUSL della Romagna, Rimini, Italy; 8Department of Internal Medicine, Cervesi Hospital, AUSL della Romagna, Cattolica, Italy; 9Department of Clinical Research, AUSL della Romagna, Ravenna, Italy; 10Ausl della Romagna Health Care Service Direction, Ravenna, Italy*These authors contributed equally to this workCorrespondence: Giuseppe NardiDepartment of Anaesthesia and Intensive Care, Infermi Hospital, AUSL della Romagna, Viale Settembrini 2, Rimini 47921, ItalyTel +39 0541-705254Fax +39 0541 705886Email 4doctornardi@gmail.comPurpose: Although the decision of which ventilation strategy to adopt in COVID-19 patients is crucial, yet the most appropriate means of carrying out this undertaking is not supported by strong evidence. We therefore described the organization of a province-level healthcare system during the occurrence of the COVID-19 epidemic and the 60-day outcomes of the hospitalized COVID-19 patients according to the respiratory strategy adopted given the limited available resources.Patients and Methods: All COVID-19 patients (26/02/2020– 18/04/2020) in the Rimini Province of Italy were included in this population-based cohort study. The hospitalized patients were classified according to the maximum level of respiratory support: oxygen supplementation (Oxygen group), non-invasive ventilation (NIV-only group), invasive mechanical ventilation (IMV-only group), and IMV after an NIV trial (IMV-after-NIV group). Sixty-day mortality risk was estimated with a Cox proportional hazard analysis adjusted by age, sex, and administration of steroids, canakinumab, and tocilizumab.Results: We identified a total of 1,424 symptomatic patients: 520 (36.5%) were hospitalized, while 904 (63.5%) were treated at home with no 60-day deaths. Based on the respiratory support, 408 (78.5%) were assigned to the Oxygen group, 46 (8.8%) to the NIV-only group, 25 (4.8%) to the IMV-after-NIV group, and 41 (7.9%) to the IMV-only group. There was no significant difference in the PaO2/FiO2 at IMV inception in the IMV-after-NIV and IMV-only groups (p=0.9). Overall 60-day mortality was 24.2% (Oxygen: 23.0%; NIV-only: 19.6%; IMV-after-NIV: 32.0%; IMV-only: 36.6%; p=0.165). Compared with the Oxygen group, the adjusted 60-day mortality risk significantly increased in the IMV-after-NIV (HR 2.776; p=0.024) and IMV-only groups (HR 2.966; p=0.001).Conclusion: This study provided a population-based estimate of the impact of the COVID-19 outbreak in a severely affected Italian province. A similar 60-day mortality risk was found for patients undergoing immediate IMV and those intubated after an NIV trial with favorable outcomes after prolonged IMV.Keywords: COVID-19, mechanical ventilation, mortality, noninvasive ventilation, multidisciplinary team approach, ARDS