Emily
Editor, Senior Moderator
https://www.medrxiv.org/content/10.1101/2022.06.25.22276445v1.full-text
SARS-CoV-2 evolution and evasion from multiple antibody treatments in a cancer patient
Guy Shapira, Chen Weiner, Reut Sorek Abramovich, Odit Gutwein, Nir Rainy, Patricia Benveniste-Levkovitz, Ezra Gordon, Adina Bar Chaim, Noam Shomron
medRxiv 2022.06.25.22276445; doi: https://doi.org/10.1101/2022.06.25.22276445
This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients may lead to accelerated viral mutation rate, immune evasion and persistent viral shedding over many months. Here we report the case of a severely immunocompromised cancer patient infected with the Delta variant of SARS-CoV-2 for over 8 months. Genome sequencing of samples taken after repeated monoclonal antibody treatments reveal the emergence and accumulation of mutations enabling escape from neutralization by antibodies. Mutations emerging in accessory and non-structural viral proteins target specific residues of immunomodulatory domains, potentially leading to loss of some functions, while preserving others. The mutated virus managed to completely overcome neutralization by monoclonal antibodies while remaining viable and infective. Our results suggest that the loss of specific immunomodulatory viral functions might confer a selective advantage in immunocompromised hosts. We also compare between mutations emerging in the presence and absence of neutralizing antibodies.
Highlights
Clinical presentation of the chronically infected patient
A female patient aged 60-69 was treated starting in June 2021 at Shamir Medical Center hospital, Be’er Yaacov, Israel as an oncological, immunocompromised patient (complete clinical timeline in Table 1). Oncological findings included: Malignant melanoma, Diffuse large B-cell lymphoma (DLBCL) and Squamous Cell Carcinoma (SCC). Background diseases included: fibromyalgia, treated asthma and Chronic Obstructive Pulmonary Disease (COPD). The patient was identified as Covid-19 positive during a routine visit in September 2021, and since then has tested positive 15 times and borderline positive once. The patient mostly presented as asymptomatic. Three Nasopharyngeal samples were obtained over the duration of infection and sent to viral whole-genome sequencing (Table 1).
SARS-CoV-2 evolution and evasion from multiple antibody treatments in a cancer patient
Guy Shapira, Chen Weiner, Reut Sorek Abramovich, Odit Gutwein, Nir Rainy, Patricia Benveniste-Levkovitz, Ezra Gordon, Adina Bar Chaim, Noam Shomron
medRxiv 2022.06.25.22276445; doi: https://doi.org/10.1101/2022.06.25.22276445
This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients may lead to accelerated viral mutation rate, immune evasion and persistent viral shedding over many months. Here we report the case of a severely immunocompromised cancer patient infected with the Delta variant of SARS-CoV-2 for over 8 months. Genome sequencing of samples taken after repeated monoclonal antibody treatments reveal the emergence and accumulation of mutations enabling escape from neutralization by antibodies. Mutations emerging in accessory and non-structural viral proteins target specific residues of immunomodulatory domains, potentially leading to loss of some functions, while preserving others. The mutated virus managed to completely overcome neutralization by monoclonal antibodies while remaining viable and infective. Our results suggest that the loss of specific immunomodulatory viral functions might confer a selective advantage in immunocompromised hosts. We also compare between mutations emerging in the presence and absence of neutralizing antibodies.
Highlights
- SARS-CoV-2 undergoes rapid evolution in an immunocompromised, chronically infected cancer patient, overcoming neutralization by two monoclonal antibody cocktail treatments
- Receptor binding domain (RBD) mutations emerging after monoclonal antibody treatment enable effective escape from neutralization in the absence of adaptive immunity
- Some emerging mutations are predicted to disrupt immunomodulatory viral proteins, including prevention of ORF8 homodimerization, mis-localization of ORF3a in host cells and alteration of the host-suppressive function of NSP1
Clinical presentation of the chronically infected patient
A female patient aged 60-69 was treated starting in June 2021 at Shamir Medical Center hospital, Be’er Yaacov, Israel as an oncological, immunocompromised patient (complete clinical timeline in Table 1). Oncological findings included: Malignant melanoma, Diffuse large B-cell lymphoma (DLBCL) and Squamous Cell Carcinoma (SCC). Background diseases included: fibromyalgia, treated asthma and Chronic Obstructive Pulmonary Disease (COPD). The patient was identified as Covid-19 positive during a routine visit in September 2021, and since then has tested positive 15 times and borderline positive once. The patient mostly presented as asymptomatic. Three Nasopharyngeal samples were obtained over the duration of infection and sent to viral whole-genome sequencing (Table 1).