REGEN-COV antibody cocktail (casirivimab/imdevimab) for the treatment of inpatients with early hospital-acquired COVID-19: a single center experience
Antonio Faraone, Francesca Fabbrizzi, Tommaso Picchioni, Elena Lovicu, Lorenzo Tofani, Giulia Scocchera, Aldo Lo Forte, Andrea Crociani, Paolo Carrai, Serena Sbaragli, Michael Bettucchi, Alberto Fortini
doi:10.21203/rs.3.rs-1170976/v1
Inpatients with hospital-acquired (HA) COVID-19 have mortality rates above 30%. Subjects with early diagnosis of COVID-19 and risk factors for disease progression are suitable for treatment with anti-SARS-CoV-2 neutralizing monoclonal antibodies (mAbs). We retrospectively assessed the outcome of a cohort of hospitalized patients with laboratory con rmed SARS-CoV-2 nosocomial infection who were admitted to the COVID-19 general ward of an acute-care Italian hospital between October 25, 2020 and April 30, 2021. Patients receiving the REGEN-COV mAb cocktail (casirivimab/imdevimab) were compared with those receiving standard care. Of 34 patients, 11 (mean age, 73.1; 9 males) underwent treatment with REGEN-COV and 23 received standard care. The 2 study groups were well balanced regarding age, sex, comorbidities, acute illness severity at diagnosis of SARS-CoV-2 infection, and all participants had at least 2 risk factors for disease progression. Five of 11 patients in the REGEN-COV group and 16 of 23 in the standard care group were asymptomatic at diagnosis; the remaining had symptoms of mild COVID-19. All patients received REGEN-COV within 3 days of infection con rmation. Treatment with REGEN-COV was inversely associated with oxygen requirement for COVID-19 during hospital stay (OR 0.02, CI 0-0.52, p=0.0174). No 28-day deaths were registered in the REGEN-COV group, compared to 8 (34.8%) in the standard care group (p=0.0339). Kaplan-Meier analysis con rmed the survival advantage of REGEN-COV group (log-rank p=0.00324). No serious adverse events related to REGEN-COV administration were recorded. Based on these ndings, REGEN-COV appears safe and might prevent disease progression in high-risk inpatients with early diagnosis of HA-COVID-19.
Author contributions All authors contributed to the study conception and design. Material preparation and data collection were performed by T Picchioni, E Lovicu, G Scocchera, A Lo Forte, A Crociani, P Carrai, S Sbaragli, M Bettucchi. Data analysis was conducted by A Faraone and L Tofani. The rst draft of the manuscript was written by A Faraone, F Fabbrizzi and A Fortini and all authors commented on previous versions of the manuscript. All authors read and approved the nal manuscript. Ethical standards The study was approved by the institutional review board of the Department of Medicine of the "Azienda USL Toscana Centro", Florence, Italy. All procedures were performed in accordance with the 1964 Helsinki declaration and its later amendments. Due to the retrospective nature of the study, informed consent was weaved according to the applicable local law. Data were de-identi ed to preserve the anonymity of participants.
References
Abbas, Nunes, Martischang, Nosocomial transmission and outbreaks of coronavirus disease 2019: the need to protect both patients and healthcare workers, Antimicrob Resist Infect Control,
doi:10.1186/s13756-020-00875-7Aifa, Determina, De nizione delle modalita' e delle condizioni di impiego dell'anticorpo monoclonale casirivimab-imdevimab ai sensi del decreto 6
Arnold, Bishop, Oppy, Scott, Stevenson, Surveillance testing reveals a signi cant proportion of hospitalized patients with SARS-CoV-2 are asymptomatic, Am J Infect Control,
doi:10.1016/j.ajic.2021.01.005Barranco, Bernucci, Tremoul, Ventura, Hospital-Acquired SARS-Cov-2 Infections in Patients: Inevitable Conditions or Medical Malpractice?, Int J Environ Res Public Health,
doi:10.3390/ijerph18020489Bierle, Ganesh, Tulledge-Scheitel, Monoclonal Antibody Treatment of Breakthrough COVID-19 in Fully Vaccinated Individuals with High-Risk Comorbidities, J Infect Dis,
doi:10.1093/infdis/jiab570Chen, Nirula, Heller, SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2029849Copin, Baum, Wloga, The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies, Cell,
doi:10.1016/j.cell.2021.06.002Curry, Salgado, When Hospitals Harm: Multimodal Entry of SARS-CoV-2 into Inpatient Healthcare, Clin Infect Dis,
doi:10.1093/cid/ciaa957Dougan, Nirula, Azizad, Blaze-, 1 Investigators et al (2021) Bamlanivimab plus Etesevimab in Mild or Moderate COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2102685Fda, Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Monoclonal Antibody Bamlanivimab
Fda, Letter of Authorization for Emergency Use of REGEN-COV (casirivimab with imdevimab
Gottlieb, Nirula, Chen, Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial, JAMA,
doi:10.1001/jama.2021.0202Hansen, Baum, Pascal, Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail, Science,
doi:10.1126/science.abd0827Khan, Reed-Embleton, Lewis, Saldanha, Does nosocomial COVID-19 result in increased 30-day mortality? A multi-centre observational study to identify risk factors for worse outcomes in patients with COVID-19, J Hosp Infect,
doi:10.1016/j.jhin.2020.09.017Khonyongwa, Taori, Soares, Incidence and outcomes of healthcare-associated COVID-19 infections: signi cance of delayed diagnosis and correlation with staff absence, J Hosp Infect,
doi:10.1016/j.jhin.2020.10.006Koehler, Ritzer, Weidlich, Use of monoclonal antibody therapy for nosocomial SARS-CoV-2 infection in patients at high risk for severe COVID-19: experience from a tertiary-care hospital in Germany, Infection,
doi:10.1007/s15010-021-01657-yLy-Cov555 Study, Group, Lundgren, Grund, A Neutralizing Monoclonal Antibody for Hospitalized Patients with COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2033130Rhee, Baker, Vaidya, CDC Prevention Epicenters Program. Incidence of Nosocomial COVID-19 in Patients Hospitalized at a Large US Academic Medical Center, JAMA Netw Open,
doi:10.1001/jamanetworkopen.2020.20498Rickman, Rampling, Shaw, Nosocomial Transmission of Coronavirus Disease 2019: A Retrospective Study of 66 Hospital-acquired Cases in a London Teaching Hospital, Clin Infect Dis,
doi:10.1093/cid/ciaa816Shiwani, Bilal, Shahzad, A comparison of characteristics and outcomes of patients with community-acquired and hospital-acquired COVID-19 in the United Kingdom: An observational study, Respir Med,
doi:10.1016/j.rmed.2021.106314Tani, Sawano, Kawamoto, Ozaki, Tanimoto, Nosocomial SARS-CoV-2 Infections in Japan: A Cross-sectional Newspaper Database Survey, Int J Health Policy Manag,
doi:10.34172/ijhpm.2020.75Taylor, Adams, Hufford, De La Torre, Winthrop et al., Neutralizing monoclonal antibodies for treatment of COVID-19, Nat Rev Immunol,
doi:10.1038/s41577-021-00542-xWake, Morgan, Choi, Winn, Reducing nosocomial transmission of COVID-19: implementation of a COVID-19 triage system, Clin Med (Lond),
doi:10.7861/clinmed.2020-0411Wang, Hu, Hu, Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China, JAMA,
doi:10.1001/jama.2020.1585Weinreich, Sivapalasingam, Norton, REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2108163
