ABSTRACT
Background: An emergency use authorization was issued in March 2021 for two combinations of monoclonal antibodies (MAbs) for SARS-CoV-2 infected patients at high risk of severe COVID-19. We performed a cohort study of patients receiving early treatment with Bamlanivimab/Etesevimab (B/E) or Casirivimab/Imdevimab (C/I) in a Paris university hospital. Methods: All patients receiving a MAbs therapy from March to July 2021 were included. Prescriptions were systematically advised by a multidisciplinary team. Both MAbs dual therapies were used up to May 12th, then only C/I due to local emergence of Delta variant. Nasopharyngeal swabs (NPS) were performed at diagnosis and 7 days after infusion. Additional NPS were collected for hospitalized patients at day 3 and during follow-up until negative RT-PCR or patients discharge. Viral sequencing was carried out and viral mutations were retained if present at more than 20% of viral subpopulations. Results: Overall, 66 patients (19 ambulatory) received a MAbs dual therapy for a documented SARS-CoV-2 asymptomatic infection or within 5 days after symptoms onset. Patients had a median age of 67 years [IQR=41-75], 53% were male, 30 (45%) were receiving immunosuppressive treatment (17 being solid organ recipients), 8 (12%) had chronic respiratory insufficiency, and 6 (9%) were receiving chemotherapy. Regarding variants, 82% were Alpha, 5% Delta and 13% other variants. 8 patients (12%) died (6 treated with B/E and two with C/I). Five deaths were related to COVID-19 worsening and three were unrelated. Among the surviving patients, 42 (64%) did not require any oxygen and 16 (24%) required low-flow oxygen. No severe adverse event related to MAbs occurred. A slower viral decay was observed among patients receiving B/E than C/I, with 17/29 and 5/13 having <30 Ct at day 7 post-infusion (p=0.3), respectively, and 9/14 and 1/8 at day 14 (p=0.03). Different Spike mutations emergence were observed including Q493R in 7 patients and E484K in 2 patients, all infected with an Alpha variant, and detected from 6 to 18 days after MAbs infusion. Among the 9 mutations, 8 occurred after B/E infusion and one Q493R occurred after C/I infusions. Conclusion: We described safety and efficacy of early MAbs therapies administration in a cohort of 66 patients at risk of severe COVID-19. Emergence of mutations were observed under both therapies, with increased frequency under B/E. Further studies including patients infected by Delta variant and receiving C/I infusion are ongoing.