Clinical and Virological Outcome of Monoclonal Antibody Therapies Across SARS-CoV-2 Variants in 245 Immunocompromised Patients: A Multicenter Prospective Cohort Study

Author:

Huygens Sammy1ORCID,GeurtsvanKessel Corine2,Gharbharan Arvind1,Bogers Susanne2,Worp Nathalie2,Boter Marjan2,Bax Hannelore I1,Kampschreur Linda M3,Hassing Robert-Jan4,Fiets Roel B5,Levenga Henriette6,Afonso Pedro Miranda78,Koopmans Marion2ORCID,Rijnders Bart J A1ORCID,Oude Munnink Bas B2

Affiliation:

1. Department of Internal Medicine, Section of Infectious Diseases and Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center , Rotterdam , The Netherlands

2. Department of Viroscience, Erasmus MC, University Medical Center , Rotterdam , The Netherlands

3. Department of Internal Medicine, Medical Center Leeuwarden , Leeuwarden , The Netherlands

4. Department of Internal Medicine, Rijnstate Hospital, Arnhem , The Netherlands

5. Department of Internal Medicine, Amphia Hospital , Breda , The Netherlands

6. Department of Internal Medicine, Groene Hart Gouda , Gouda , The Netherlands

7. Department of Biostatistics, Erasmus MC, University Medical Center , Rotterdam , The Netherlands

8. Department of Epidemiology, Erasmus MC, University Medical Center , Rotterdam , The Netherlands

Abstract

Abstract Background Immunocompromised patients (ICPs) have an increased risk for a severe and prolonged COVID-19. SARS-CoV-2 monoclonal antibodies (mAbs) were extensively used in these patients, but data from randomized trials that focus on ICPs are lacking. We evaluated the clinical and virological outcome of COVID-19 in ICPs treated with mAbs across SARS-CoV-2 variants. Methods In this multicenter prospective cohort study, we enrolled B-cell– and/or T-cell–deficient patients treated with casirivimab/imdevimab, sotrovimab, or tixagevimab/cilgavimab. SARS-CoV-2 RNA was quantified and sequenced weekly, and time to viral clearance, viral genome mutations, hospitalization, and death rates were registered. Results Two hundred and forty five patients infected with the Delta (50%) or Omicron BA.1, 2, or 5 (50%) variant were enrolled. Sixty-seven percent were vaccinated; 78 treated as outpatients, of whom 2 required hospital admission, but both survived. Of the 159 patients hospitalized at time of treatment, 43 (27%) required mechanical ventilation or died. The median time to viral clearance was 14 days (interquartile range, 7–22); however, it took >30 days in 15%. Resistance-associated spike mutations emerged in 9 patients in whom the median time to viral clearance was 63 days (95% confidence interval, 57–69; P < .001). Spike mutations were observed in 1 of 42 (2.4%) patients after treatment with 2 active mAbs, in 5 of 34 (14.7%) treated with actual monotherapy (sotrovimab), and 3 of 20 (12%) treated with functional monotherapy (ie, tixagevimab/cilgavimab against tixagevimab-resistant variant). Conclusions Despite treatment with mAbs, morbidity and mortality of COVID-19 in ICPs remained substantial. Combination antiviral therapy should be further explored and may be preferred in severely ICPs.

Funder

Roche

European Union’s

Horizon 2020

Versatile Emerging Infectious Disease Observatory

Rapid European SARS-CoV-2 Emergency Research Response

ZorgOnderzoek Nederland en het gebied Medische wetenschappen

Publisher

Oxford University Press (OUP)

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