tetano
Editor, Senior Moderator
Clin Infect Dis
. 2024 Mar 6:ciae026.
doi: 10.1093/cid/ciae026. Online ahead of print. Clinical and Virological Outcome of Monoclonal Antibody Therapies Across Severe Acute Respiratory Syndrome Coronavirus 2 Variants in 245 Immunocompromised Patients: A Multicenter Prospective Cohort Study
Sammy Huygens[SUP] 1 [/SUP], Corine GeurtsvanKessel[SUP] 2 [/SUP], Arvind Gharbharan[SUP] 1 [/SUP], Susanne Bogers[SUP] 2 [/SUP], Nathalie Worp[SUP] 2 [/SUP], Marjan Boter[SUP] 2 [/SUP], Hannelore I Bax[SUP] 1 [/SUP], Linda M Kampschreur[SUP] 3 [/SUP], Robert-Jan Hassing[SUP] 4 [/SUP], Roel B Fiets[SUP] 5 [/SUP], Henriette Levenga[SUP] 6 [/SUP], Pedro Miranda Afonso[SUP] 7 8 [/SUP], Marion Koopmans[SUP] 2 [/SUP], Bart J A Rijnders[SUP] 1 [/SUP], Bas B Oude Munnink[SUP] 2 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; immunocompromised; monoclonal antibodies; spike mutations.
. 2024 Mar 6:ciae026.
doi: 10.1093/cid/ciae026. Online ahead of print. Clinical and Virological Outcome of Monoclonal Antibody Therapies Across Severe Acute Respiratory Syndrome Coronavirus 2 Variants in 245 Immunocompromised Patients: A Multicenter Prospective Cohort Study
Sammy Huygens[SUP] 1 [/SUP], Corine GeurtsvanKessel[SUP] 2 [/SUP], Arvind Gharbharan[SUP] 1 [/SUP], Susanne Bogers[SUP] 2 [/SUP], Nathalie Worp[SUP] 2 [/SUP], Marjan Boter[SUP] 2 [/SUP], Hannelore I Bax[SUP] 1 [/SUP], Linda M Kampschreur[SUP] 3 [/SUP], Robert-Jan Hassing[SUP] 4 [/SUP], Roel B Fiets[SUP] 5 [/SUP], Henriette Levenga[SUP] 6 [/SUP], Pedro Miranda Afonso[SUP] 7 8 [/SUP], Marion Koopmans[SUP] 2 [/SUP], Bart J A Rijnders[SUP] 1 [/SUP], Bas B Oude Munnink[SUP] 2 [/SUP]
Affiliations
- PMID: 38445721
- DOI: 10.1093/cid/ciae026
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.
Keywords: SARS-CoV-2; immunocompromised; monoclonal antibodies; spike mutations.