Host immunological responses facilitate development of SARS-CoV-2 mutations in patients receiving monoclonal antibody treatments

Abstract

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

XAV-19 a Glyco-Humanized polyclonal antibody targeting SARS-CoV-2 accelerates the recovery of mild to moderate COVID-19 patients and keeps its neutralizing activity against Omicron and its subvariants

“…Secondary endpoints were proportion of patients with an aggravation of COVID-19 within 8 days after treatment (defined as a worsening of the score of at least 2 points on the WHO clinical progression 7-point ordinal scale compared to the score at randomization); proportion of patients with an aggravation/improvement of COVID-19 between day 8 and day 15 (defined as a worsening/improvement of the score of at least 1 point on the WHO 7-point ordinal scale); time to aggravation/improvement measured by the proportion of patients with an aggravation/improvement at each measurement days (3, 5, 8, 15) after randomization. Safety outcomes included the cumulative incidence of any Adverse Event (AE).…”

SARS-CoV-2 evolution during persistent infection in a CAR-T recipient shows an escape to both sotrovimab and T-cell responses

“…Whole viral genome sequencing revealed Spike mutations (L5F, Y145D, E340A, L582F, F855L, and L938F) after receiving sotrovimab, as shown in Supplementary Table 2 (GISAID accession EPI_ISL_16849243, EPI_ISL_16849243, EPI_ISL_16849245). Notably, S:E340A confers immune escape to sotrovimab [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] . We also observed an overall reduction in the number of S epitopes that could be presented by the patient's HLA alleles, as depicted in Supplementary Materials.…”

SARS-CoV-2 variants resistant to monoclonal antibodies in immunocompromised patients constitute a public health concern

“…Escape variants can emerge during mAb therapy of RSV experimental infection in Cotton rats (6), or through prophylactic mAb pre-exposure in humans (7). Hence, the findings of Gupta et al (1) are not surprising, but they are of great importance given the implications for immunocompromised patients with COVID-19 and for potential directions of the pandemic.…”

“…the immediate clinical importance of the findings by Gupta et al (1) has been dulled by the withdrawal of all anti-Spike mAb therapies due to the emergence of resistant Omicron sublineages, their experience has valuable implications for other and future antiviral mAbs. mAb treatment-emergent resistance in immunocompromised patients could have been anticipated given what we know from the history of antibody-based therapies, the mechanism of action of mAbs, and the mutation-prone nature of SARS-CoV-2.…”

“…Resistance to neutralization can be either basal or develop after treatment. Gupta et al (1) show that the majority of such mutations were treatment specific and conferred specific treatment resistance. These findings closely parallel and confirm previous case reports and small case series reporting that mAb therapy, such as sotrovimab (2), can select for treatment-resistant variants in immunosuppressed patients.…”