Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy
Mauro Turrini, Angelo Gardellini, Livia Beretta, Lucia Buzzi, Stefano Ferrario, Sabrina Vasile, Raffaella Clerici, Andrea Colzani, Luigi Liparulo, Giovanni Scognamiglio, Gianni Imperiali, Giovanni Corrado, Antonello Strada, Marco Galletti, Nunzio Castiglione, Claudio Zanon
Vaccines, doi:10.3390/vaccines9060640
The aim of this study is to explore risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies of 205 laboratory-confirmed cases infected with SARS-CoV-2 during the Lombardy outbreak. All patients received the best supportive care and specific interventions that included the main drugs being tested for repurposing to treat COVID-19, such as hydroxychloroquine, anticoagulation and antiviral drugs, steroids, and interleukin-6 pathway inhibitors. Clinical, laboratory, and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality. Univariate analyses showed prognostic significance for age greater than 70 years, the presence of two or more relevant comorbidities, a P/F ratio less than 200 at presentation, elevated LDH (lactate dehydrogenase) and CRP (C-reactive protein) values, intermediate-or therapeutic-dose anticoagulation, hydroxychloroquine, early antiviral therapy with lopinavir/ritonavir, short courses of steroids, and tocilizumab therapy. Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (OR 3.26) and a reduction in mortality for patients treated with anticoagulant (−0.37), antiviral lopinavir/ritonavir (−1.22), or steroid (−0.59) therapy. In contrast, hydroxychloroquine and tocilizumab have not been confirmed to have a significant effect in the treatment of SARS-CoV-2 pneumonia. Results from this real-life single-center experience are in agreement and confirm actual literature data on SARS-CoV-2 pneumonia in terms of both clinical risk factors for in-hospital mortality and the effectiveness of the different therapies proposed for the management of COVID19 disease.
Conflicts of Interest: The authors declare no conflict of interest; no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
References
Adhikari, Meng, Wu, Mao, Ye et al., Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of cornavirus disease (COVID-19) during early outbreak period: A scoping review, Infect. Dis. Poverty,
doi:10.1186/s40249-020-00646-xCao, Wang, Wen, Liu, Wang et al., A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19, N. Engl. J. Med,
doi:10.1056/NEJMoa2001282Chan, Lai, Chu, Tsui, Tam et al., Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: A multicentre retrospective matched cohort study, Hong Kong Med. J
Chen, Wu, Chen, Yan, Yang et al., Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study, BMJ,
doi:10.1136/bmj.m1091Chen, Zhou, Dong, Qu, Gong et al., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study, Lancet
Cheung, Hung, Chan, Lung, Tso et al., Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis, Gastroenterology,
doi:10.1053/j.gastro.2020.03.065Chow, Fleming-Dutra, Gierke, Ussery, Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019-United States, 12, MMWR Morb. Mortal Wkly Rep
Chu, Cheng, Hung, Wong, Chan et al., Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings, Thorax,
doi:10.1136/thorax.2003.012658De Wilde, Jochmans, Psothuma, Zevenhoven-Dobbe, Van Nieuwkoop et al., Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture, Antimicrob. Agents Chemother,
doi:10.1128/AAC.03011-14Driggin, Madhavan, Bikdeli, Chuich, Laracy et al., Cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease 2019 (COVID-19) pandemic, J. Am. Coll. Cardiol,
doi:10.1016/j.jacc.2020.03.031Fantini, Scala, Chahinian, Yahiu, Structural and molecular modeling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection, Int. J. Antimicrob. Agents,
doi:10.1016/j.ijantimicag.2020.105960Ferri, Giuggioli, Raimondo, L'andolina, Tavoni et al., COVID-19 and rheumatic autoimmune systemic diseases: Report of a large Italian patients series, Clin. Rheumatol,
doi:10.1007/s10067-020-05334-7Gautret, Lagier, Parola, Meddeb, Mailhe et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial, Int. J. Antimicrob. Agents,
doi:10.1016/j.ijantimicag.2020.105949Geleris, Sun, Platt, Zucker, Baldwin et al., Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, N. Engl. J. Med
Giardini, Carrer, Casati, Contro, Vergani et al., Increased sFLT1/PlGF ratio in COVID-19: A novel link to Angiotensin II-mediated endothelial dysfunction, Am. J. Hematol,
doi:10.1002/ajh.25882Goyal, Choi, Pinheiro, Schenck, Chen et al., Clinical Characteristics of Covid-19 in New York City, N. Engl. J. Med,
doi:10.1056/NEJMc2010419Guan, Ni, Hu, Liang, Ou et al., Clinical Characteristics of Coronavirus Disease 2019 in China. China Medical Treatment Expert Group for Covid-19, N. Engl. J. Med,
doi:10.1056/NEJMoa2002032Helms, Tacquard, Severac, High risk of thrombosis in patients in severe SARS-CoV-2 infection: A multicenter prospective cohort study, Intensive Care Med,
doi:10.1007/s00134-020-06062-xHermine, Mariette, Tharaux, Corimuno-, 19 Collaborative Group. Effect of Tocilizumab vs Usual Care in Adults Hospitalized with COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial, JAMA Intern. Med,
doi:10.1001/jamainternmed.2020.6820Jin, Lian, Hu, Gao, Zheng et al., Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms, Gut,
doi:10.1136/gutjnl-2020-320926Klok, Kruip, Van Der Meer, Arbous, Gommers et al., Incidence of thrombotic complications in critically ill ICU patients with COVID-19, Thromb. Res,
doi:10.1016/j.thromres.2020.04.013Klopfenstein, Zayet, Lohse, Balblanc, Badie et al., Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients, Med. Mal. Infect,
doi:10.1016/j.medmal.2020.05.001Lauer, Grantz, Bi, Jones, Zheng et al., The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: Estimation and application, Ann. Int. Med,
doi:10.7326/M20-0504Lechien, Chiesa-Estomba, Hans, Barillari, Jouffe et al., Loss of Smell and Taste in 2013 European Patients with Mild to Moderate COVID-19, Ann. Intern. Med,
doi:10.7326/M20-2428Li, Yang, Zhao, Zhi, Wang et al., Prevalence and impact of cariovascular metabolic disease on COVID-19 in China, Clin. Res. Cardiol,
doi:10.1007/s00392-020-01626-9Lin, Lu, Cao, Li, Hypothesis for pothential pathogenesis of SARS-CoV-2 infection: A review of immune changes in patients with viral pneumonia, Emerg. Microbes Infect,
doi:10.1080/22221751.2020.1746199Lodigiani, Iapichino, Carenzo, Cecconi, Ferrazzi et al., Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy, Thromb. Res,
doi:10.1016/j.thromres.2020.04.024Luo, Liu, Qiu, Liu, Liu et al., Tocilizumab treatment in COVID-19: A single center experience, J. Med. Virol,
doi:10.1002/jmv.25801Mahevas, Tran, Roumier, Chabrol, Paule et al., Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: Observational comparative study using routine care data, BMJ,
doi:10.1136/bmj.m1844Mehta, Mcauley, Brown, Sanchez, Tattersall et al., HLH Across Speciality Collaboration, UK. COVID-19: Consider cytokine storm syndromes and immunosuppression, Lancet,
doi:10.1016/S0140-6736(20)30628-0Middeldorp, Coppens, Van Haaps, Incidence of venous thromboembolism in hospitalized patients with COVID-19, J. Thromb. Haemost,
doi:10.1111/jth.14888Onder, Rezza, Brusaferro, Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy, JAMA,
doi:10.1001/jama.2020.4683Paranjpe, Fuster, Lala, Russak, Glicksberg et al., Association of Treatment Dose Anticoagulation with In-Hospital Survival Among Hospitalized Patients with COVID-19, J. Am. Coll. Cardiol,
doi:10.1016/j.jacc.2020.05.001Passamonti, Cattaneo, Arcaini, Bruna, Cavo et al., Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: A retrospective, multicentre, cohort study, Lancet Haematol,
doi:10.1016/S2352-3026(20)30251-9Perrone, Piccirillo, Ascierto, Salvarani, Parrella et al., Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial, J. Transl. Med,
doi:10.1186/s12967-020-02573-9Petrilli, Jones, Yang, Rajagopalan, O'donnell et al., Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: Prospective cohort study, BMJ,
doi:10.1136/bmj.m1966Rawson, Moore, Zhu, Ranganathan, Skolimowska et al., Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing, Clin. Infect. Dis,
doi:10.1093/cid/ciaa530Richardson, Hirsch, Narasimhan, Crawford, Mcginn et al., Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area, JAMA,
doi:10.1001/jama.2020.6775Rosenberg, Dufort, Udo, Wilberschied, Kumar et al., Association of Treatment with Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State, Vaccines,
doi:10.1001/jama.2020.8630Salvarani, Dolci, Massari, Merlo, Cavuto et al., -COVID-19 Study Group. Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial, JAMA Intern Med,
doi:10.1001/jamainternmed.2020.6615Sciascia, Aprà, Baffa, Baldovino, Boaro et al., Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19, Clin. Exp. Rheumatol
Shi, Han, Jiang, Cao, Alwalid et al., Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: A descriptive study, Lancet Infect. Dis,
doi:10.1016/S1473-3099(20)30086-4Siemieniuk, Bartoszko, Ge, Zeraatkar, Izcovich et al., Drug treatments for covid-19: Living systematic review and network meta-analysis, BMJ,
doi:10.1136/bmj.m2980Stone, Frigault, Serling-Boyd, Fernandes, Harvey et al., Efficacy of Tocilizumab in Patients Hospitalized with Covid-19, N. Engl. J. Med,
doi:10.1056/NEJMoa2028836Tang, Bai, Chen, Gong, Li et al., Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy, J. Thromb. Haemost,
doi:10.1111/jth.14817Tang, Cao, Han, Wang, Chen et al., Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: Open label, randomised controlled trial, BMJ,
doi:10.1136/bmj.m1849Toniati, Piva, Cattalini, Garrafa, Regola et al., Tocilizumab for treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy, Autoimmun. Rev,
doi:10.1016/j.autrev.2020.102568Verity, Okell, Dorigatti, Winskill, Whittaker et al., Estimates of the severity of coronavirus disease 2019: A model-based analysis, Lancet Infect. Dis
Wang, Hu, Hu, Zhu, Liu et al., Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China, JAMA
Wong, Lam, Fong, Leung, Chin et al., Frequency and Distribution of Chest Radiographic Findings in COVID-19 Positive Patients, Radiology,
doi:10.1148/radiol.2020201160Wu, Chen, Cai, Zhou, Xu et al., Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China, JAMA Intern. Med,
doi:10.1001/jamainternmed.2020.0994Wu, Mcgoogan, Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases from the Chinese Center for Disease Control and Prevention, JAMA,
doi:10.1001/jama.2020.2648Yang, Zheng, Gou, Pu, Chen et al., Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: A systematic review and meta-analysis, Int. J. Infect. Dis. IJID
Yao, Qian, Zhu, Wang, Wang, A systematic review of lopinavir therapy fo SARS coronavirus and MERS coronavirus. A possible reference for coronavirus disease-19 treatment option, J. Med. Virol,
doi:10.1002/jmv.25729Yao, Ye, Zhang, Cui, Huang et al., In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin. Infect. Dis,
doi:10.1093/cid/ciaa237Young, Ong, Kalimuddin, Low, Tan et al., Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in singapore, JAMA,
doi:10.1001/jama.2020.3204Zhang, Du, Li, Zheng, Yang et al., Molecular and serological investigation of 109-nCoV infected patients: Implicationof multiple shedding routes, Emer. Microb. Infect,
doi:10.1080/22221751.2020.1729071Zhang, Wu, Li, Zhao, Wang, Cytokine release syndrome in severe COVID-19: Interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality, Int. J. Antimicrob. Agents,
doi:10.1016/j.ijantimicag.2020.105954Zhao, Zhong, Xie, Yu, Liu, Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A Multicenter Study, AJR Am. J. Roentgenol,
doi:10.2214/AJR.20.22976Zhou, Yang, Wang, Hu, Zhang et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature,
doi:10.1038/s41586-020-2012-7Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study, Lancet
