SARS-CoV-2 evolution and immune escape in immunocompromised patients treated with exogenous antibodies

Scherer, Erin M.; Babiker, Ahmed; Adelman, Max W.; Allman, Brent E.; Key, Autum; Kleinhenz, Jennifer M.; Langsjoen, Rose M.; Nguyen, Phuong-Vi; Onyechi, Ivy; Sherman, Jacob D.; Simon, Trevor W.; Soloff, Hannah; Tarabay, Jessica; Varkey, Jay B.; Webster, Andrew; Weiskopf, Daniela; Weissman, Daniel B.; Xu, Yongxian; Waggoner, Jesse J.; Koelle, Katia; Rouphael, Nadine; Pouch, Stephanie M.; Piantadosi, Anne

doi:10.1101/2022.04.12.22273675

Cited by 5 publications

(3 citation statements)

References 52 publications

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“…The COVID-19 disease risk in the general population has improved with the development of highly effective vaccines. However, many individuals with immunodeficiency are still at risk of developing severe and refractory COVID-19 infection, potentially leading to the development of SARS-CoV-2 variants of concern (27). This study aimed to evaluate the vaccine response and COVID-19 disease severity of a group of 71 individuals with immunodeficiency.…”

Section: Discussionmentioning

confidence: 99%

Cellular and humoral immunogenicity of the COVID-19 vaccine and COVID-19 disease severity in individuals with immunodeficiency

et al. 2023

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BackgroundA well-coordinated adaptive immune response is crucial for limiting COVID-19 disease. Some individuals with immunodeficiency are at a high risk of developing severe COVID-19. Therefore, the development of standardized methods for measuring different arms of the vaccine response in the setting of immunodeficiency is of particular interest. In this study, we compared the vaccine response of individuals living with immunodeficiency with healthy controls in terms of interferon gamma (IFN-γ) production and spike protein-specific antibody level post primary COVID-19 vaccination and booster vaccines. Additionally, the disease severity of those individuals who contracted COVID-19 was assessed.MethodsWhole blood was stimulated overnight from 71 participants and 99 healthy controls. Commercially available PepTivator® peptide pool and trimeric spike protein stimulation were used. ELISA was used to analyze IFN-γ levels. The total SARS-CoV-2 spike protein antibody titre was measured using a Roche Elecsys® S total antibody assay. Patient characteristics, COVID-19 infection status and IDDA 2.1 ‘Kaleidoscope’ scores were recorded. Vaccine responses were scored from zero to three.Results99% of healthy controls, 89% of individuals with IEI and 76% with secondary immunodeficiency (SID) had an IFN-γ level above the validated reference range after peptide mix stimulation following primary vaccination. There was an increase in IFN-γ levels in patients with inborn errors of immunity (IEI) following the booster vaccine (p = 0.0156). 100% of healthy controls, 70% of individuals living with IEI and 64% of individuals living with SID had detectable spike protein-specific antibody levels following the primary vaccination. 55% of immunodeficiency patients who had mild COVID-19 and 10% with moderate/severe COVID-19 had detectable antibody and IFN-γ levels post vaccine. The mean pre-infection IDDA 2.1 scores were higher in individuals who developed moderate/severe COVID-19 (25.2 compared to 9.41).ConclusionsCovid whole-blood IGRA is a highly accurate, straightforward and robust assay and can be easily adapted to measure cellular response to COVID-19. A complete evaluation of the vaccine response may be particularly important for individuals living with immunodeficiency. A clinical immunodeficiency score and a validated vaccine response score may be valuable tools in estimating COVID-19 disease risk and identifying individuals living with immunodeficiency who may benefit from enhanced vaccination schedules.

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Section: Discussionmentioning

confidence: 99%

Cellular and humoral immunogenicity of the COVID-19 vaccine and COVID-19 disease severity in individuals with immunodeficiency

et al. 2023

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“…The synthetic variant sequences share similar mutations with the chronic SARS-COV-2 infections. A reverse mutation, R493Q, for example, was found in a persistently infected, immunocompromised individual 44 . Other mutations found by our model, like E340K 45 , E484T 33 , G485R 46 , and F490L/E484G 47 , are also found in immunocompromised patients treated with monoclonal antibodies.…”

Section: Resultsmentioning

confidence: 99%

Predicting the antigenic evolution of SARS-COV-2 with deep learning

Han¹,

Chen²,

Wang³

et al. 2022

Preprint

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The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) antigenic profile evolves in response to the vaccine and natural infection-derived immune pressure, resulting in immune escape and threatening public health. Exploring the possible antigenic evolutionary potentials improves public health preparedness, but it is limited by the lack of experimental assays as the sequence space is exponentially large. Here we introduce the Machine Learning-guided Antigenic Evolution Prediction (MLAEP), which combines structure modeling, multi-task learning, and genetic algorithm to model the viral fitness landscape and explore the antigenic evolution via in silico directed evolution. As demonstrated by existing SARS-COV-2 variants, MLEAP can infer the order of variants along antigenic evolutionary trajectories, which is also strongly correlated with their sampling time. The novel mutations predicted by MLEAP are also found in immunocompromised covid patients and newly emerging variants, like BA. 4/5. In sum, our approach enables profiling existing variants and forecasting prospective antigenic variants, thus may help guide the development of vaccines and increase preparedness against future variants.

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“…Time courses demonstrate that sequential samples can be conveniently collected for the study of viral dynamics and monitoring within-host virus evolution. This may be particularly useful for identifying mutations in immunocompromised patients or following antiviral treatment (22).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 molecular testing and whole genome sequencing following RNA recovery from used BinaxNOW COVID-19 Antigen Self Tests

Nguyen

Carmola

Wang

et al. 2023

Preprint

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Widespread use of over-the-counter rapid diagnostic tests for SARS-CoV-2 has led to a decrease in availability of clinical samples for viral genomic surveillance. As an alternative sample source, we evaluated RNA isolated from BinaxNOW swabs stored at ambient temperature for SARS-CoV-2 rRT-PCR and full viral genome sequencing. 81 of 103 samples (78.6%) yielded detectable RNA, and 46 of 57 samples (80.7 %) yielded complete genome sequences. Our results illustrate that SARS-CoV-2 RNA extracted from used Binax test swabs provides an important opportunity for improving SARS-CoV-2 genomic surveillance, evaluating transmission clusters, and monitoring within-patient evolution.

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SARS-CoV-2 evolution and immune escape in immunocompromised patients treated with exogenous antibodies

Cited by 5 publications

References 52 publications

Cellular and humoral immunogenicity of the COVID-19 vaccine and COVID-19 disease severity in individuals with immunodeficiency

Cellular and humoral immunogenicity of the COVID-19 vaccine and COVID-19 disease severity in individuals with immunodeficiency

Predicting the antigenic evolution of SARS-COV-2 with deep learning

SARS-CoV-2 molecular testing and whole genome sequencing following RNA recovery from used BinaxNOW COVID-19 Antigen Self Tests

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