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471. In-Depth Characterization of SARS-CoV-2 Variants Causing Breakthrough COVID-19 Among Hospitalized Immunocompromised (IC) Patients with or without Prior Exposure to Tixagevimab-Cilgavimab (T/C) Pre-Exposure Prophylaxis (PrEP)

BACKGROUND: PrEP with T/C can prevent COVID-19 hospitalization and death in IC patients (pts) up to 6 months after injection. However, in the USA, authorization of T/C PrEP was paused in Jan 2023 due to loss of in vitro activity of T/C against dominant circulating SARS-CoV-2 variants, although loss...

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Autores principales: Haidar, Ghady, Jacobs, Jana L, Salese, Erin, Ludwig, Justin, Heaps, Amy, Parikh, Urvi, Sethi, Rahil, Caruso, Lori, Camacho, Haley, Chinakarn, Tina, Edick, Stacey, Fischer, Dawn, Kramer, Kailey Hughes, Lukanski, Amy, Marks, Kiersten, Saenz-Morales, Naomi, Sierra, Sara, Ferreira, Cátia, Glasser, Lisa, Heil, Kathleen, Talarico, Carla, Taylor, Sylvia, McCreary, Erin K, Mellors, John W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10678141/
http://dx.doi.org/10.1093/ofid/ofad500.541
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author Haidar, Ghady
Jacobs, Jana L
Salese, Erin
Ludwig, Justin
Heaps, Amy
Parikh, Urvi
Sethi, Rahil
Caruso, Lori
Camacho, Haley
Chinakarn, Tina
Edick, Stacey
Fischer, Dawn
Kramer, Kailey Hughes
Lukanski, Amy
Marks, Kiersten
Saenz-Morales, Naomi
Sierra, Sara
Ferreira, Cátia
Glasser, Lisa
Heil, Kathleen
Talarico, Carla
Taylor, Sylvia
McCreary, Erin K
Mellors, John W
author_facet Haidar, Ghady
Jacobs, Jana L
Salese, Erin
Ludwig, Justin
Heaps, Amy
Parikh, Urvi
Sethi, Rahil
Caruso, Lori
Camacho, Haley
Chinakarn, Tina
Edick, Stacey
Fischer, Dawn
Kramer, Kailey Hughes
Lukanski, Amy
Marks, Kiersten
Saenz-Morales, Naomi
Sierra, Sara
Ferreira, Cátia
Glasser, Lisa
Heil, Kathleen
Talarico, Carla
Taylor, Sylvia
McCreary, Erin K
Mellors, John W
author_sort Haidar, Ghady
collection PubMed
description BACKGROUND: PrEP with T/C can prevent COVID-19 hospitalization and death in IC patients (pts) up to 6 months after injection. However, in the USA, authorization of T/C PrEP was paused in Jan 2023 due to loss of in vitro activity of T/C against dominant circulating SARS-CoV-2 variants, although loss of clinical efficacy is unclear. We investigated in vivo mechanisms of viral breakthrough in hospitalized IC pts with vs without prior T/C exposure. METHODS: We analyzed remnant clinical SARS-CoV-2 PCR-positive swabs and sera from IC pts hospitalized at UPMC. SARS-CoV-2 variants and mutants were determined by whole genome sequencing and anti-RBD IgG levels by an enzyme immunoassay. RESULTS: From Mar 28, 2022, to Mar 3, 2023, 72% (174/243) of swabs were successfully sequenced from 170 pts (Table 1). Median age was 67 yrs; 49% were male. IC conditions included organ transplant (23%) and hematologic cancer (32%) (Table 2). In IC patients with sequenced swabs, 21% received T/C (Table 3). Variant frequency mirrored national trends (Table 3). BA.5, XBB.1, and BF.7 were less common in T/C vs non-T/C pts (28.57% vs 47.54%; 25.00% vs 32.43%; 2.86% vs 6.56%). BA.2 and BQ.1 were more common in T/C vs non-T/C pts (26.32% vs 16.36%; 50.00% vs 41.25%). The R346T and K444T/R/N mutations were more common in T/C vs non-T/C pts: 54% vs 41% and 37% vs 22% (Table 3). Anti-RBD IgG titers from 56% pts at the time of infection were higher in T/C vs non-T/C pts (median [U/mL, IQR] 1,524,000 [463,666–2,841,800] vs 433,380 [0–2,189,800], respectively). COVID-19 mortality was numerically lower in T/C vs non-T/C pts (11% [4/35] vs 21% [28/135], respectively, P=0.21). Mortality differences were consistent across variant epochs (Table 1). [Figure: see text] [Figure: see text] [Figure: see text] CONCLUSION: Breakthrough COVID-19 caused by SARS-CoV-2 variants with R346T or K444T/R/N mutations is more common in IC pts who received T/C PrEP vs those who did not. Though authorization of T/C was paused due to increased prevalence of non-neutralized variants, such variants were not consistently more common in hospitalized IC pts with breakthrough COVID-19 who had received T/C. Anti-RBD IgG titers were higher and mortality was lower for T/C vs non-T/C pts. Longer follow-up is needed to further delineate the mechanisms of breakthrough infection by T/C status. DISCLOSURES: Ghady Haidar, MD, Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|NIH: Grant/Research Support Cátia Ferreira, PhD, AstraZeneca: Employee Lisa Glasser, MD, AstraZeneca: Stocks/Bonds Kathleen Heil, RN, BSN, AstraZeneca: Employee Carla Talarico, PhD, MPH, AstraZeneca: Stocks/Bonds Sylvia Taylor, PhD, MPH, MBA, AstraZeneca: Stocks/Bonds Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Honoraria|La Jolla (Entasis): Advisor/Consultant|LabSimply: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria John W. Mellors, MD, AstraZeneca: Grant/Research Support|Gilead Sciences: Grant/Research Support
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spelling pubmed-106781412023-11-27 471. In-Depth Characterization of SARS-CoV-2 Variants Causing Breakthrough COVID-19 Among Hospitalized Immunocompromised (IC) Patients with or without Prior Exposure to Tixagevimab-Cilgavimab (T/C) Pre-Exposure Prophylaxis (PrEP) Haidar, Ghady Jacobs, Jana L Salese, Erin Ludwig, Justin Heaps, Amy Parikh, Urvi Sethi, Rahil Caruso, Lori Camacho, Haley Chinakarn, Tina Edick, Stacey Fischer, Dawn Kramer, Kailey Hughes Lukanski, Amy Marks, Kiersten Saenz-Morales, Naomi Sierra, Sara Ferreira, Cátia Glasser, Lisa Heil, Kathleen Talarico, Carla Taylor, Sylvia McCreary, Erin K Mellors, John W Open Forum Infect Dis Abstract BACKGROUND: PrEP with T/C can prevent COVID-19 hospitalization and death in IC patients (pts) up to 6 months after injection. However, in the USA, authorization of T/C PrEP was paused in Jan 2023 due to loss of in vitro activity of T/C against dominant circulating SARS-CoV-2 variants, although loss of clinical efficacy is unclear. We investigated in vivo mechanisms of viral breakthrough in hospitalized IC pts with vs without prior T/C exposure. METHODS: We analyzed remnant clinical SARS-CoV-2 PCR-positive swabs and sera from IC pts hospitalized at UPMC. SARS-CoV-2 variants and mutants were determined by whole genome sequencing and anti-RBD IgG levels by an enzyme immunoassay. RESULTS: From Mar 28, 2022, to Mar 3, 2023, 72% (174/243) of swabs were successfully sequenced from 170 pts (Table 1). Median age was 67 yrs; 49% were male. IC conditions included organ transplant (23%) and hematologic cancer (32%) (Table 2). In IC patients with sequenced swabs, 21% received T/C (Table 3). Variant frequency mirrored national trends (Table 3). BA.5, XBB.1, and BF.7 were less common in T/C vs non-T/C pts (28.57% vs 47.54%; 25.00% vs 32.43%; 2.86% vs 6.56%). BA.2 and BQ.1 were more common in T/C vs non-T/C pts (26.32% vs 16.36%; 50.00% vs 41.25%). The R346T and K444T/R/N mutations were more common in T/C vs non-T/C pts: 54% vs 41% and 37% vs 22% (Table 3). Anti-RBD IgG titers from 56% pts at the time of infection were higher in T/C vs non-T/C pts (median [U/mL, IQR] 1,524,000 [463,666–2,841,800] vs 433,380 [0–2,189,800], respectively). COVID-19 mortality was numerically lower in T/C vs non-T/C pts (11% [4/35] vs 21% [28/135], respectively, P=0.21). Mortality differences were consistent across variant epochs (Table 1). [Figure: see text] [Figure: see text] [Figure: see text] CONCLUSION: Breakthrough COVID-19 caused by SARS-CoV-2 variants with R346T or K444T/R/N mutations is more common in IC pts who received T/C PrEP vs those who did not. Though authorization of T/C was paused due to increased prevalence of non-neutralized variants, such variants were not consistently more common in hospitalized IC pts with breakthrough COVID-19 who had received T/C. Anti-RBD IgG titers were higher and mortality was lower for T/C vs non-T/C pts. Longer follow-up is needed to further delineate the mechanisms of breakthrough infection by T/C status. DISCLOSURES: Ghady Haidar, MD, Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|NIH: Grant/Research Support Cátia Ferreira, PhD, AstraZeneca: Employee Lisa Glasser, MD, AstraZeneca: Stocks/Bonds Kathleen Heil, RN, BSN, AstraZeneca: Employee Carla Talarico, PhD, MPH, AstraZeneca: Stocks/Bonds Sylvia Taylor, PhD, MPH, MBA, AstraZeneca: Stocks/Bonds Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Honoraria|La Jolla (Entasis): Advisor/Consultant|LabSimply: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria John W. Mellors, MD, AstraZeneca: Grant/Research Support|Gilead Sciences: Grant/Research Support Oxford University Press 2023-11-27 /pmc/articles/PMC10678141/ http://dx.doi.org/10.1093/ofid/ofad500.541 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstract
Haidar, Ghady
Jacobs, Jana L
Salese, Erin
Ludwig, Justin
Heaps, Amy
Parikh, Urvi
Sethi, Rahil
Caruso, Lori
Camacho, Haley
Chinakarn, Tina
Edick, Stacey
Fischer, Dawn
Kramer, Kailey Hughes
Lukanski, Amy
Marks, Kiersten
Saenz-Morales, Naomi
Sierra, Sara
Ferreira, Cátia
Glasser, Lisa
Heil, Kathleen
Talarico, Carla
Taylor, Sylvia
McCreary, Erin K
Mellors, John W
471. In-Depth Characterization of SARS-CoV-2 Variants Causing Breakthrough COVID-19 Among Hospitalized Immunocompromised (IC) Patients with or without Prior Exposure to Tixagevimab-Cilgavimab (T/C) Pre-Exposure Prophylaxis (PrEP)
title 471. In-Depth Characterization of SARS-CoV-2 Variants Causing Breakthrough COVID-19 Among Hospitalized Immunocompromised (IC) Patients with or without Prior Exposure to Tixagevimab-Cilgavimab (T/C) Pre-Exposure Prophylaxis (PrEP)
title_full 471. In-Depth Characterization of SARS-CoV-2 Variants Causing Breakthrough COVID-19 Among Hospitalized Immunocompromised (IC) Patients with or without Prior Exposure to Tixagevimab-Cilgavimab (T/C) Pre-Exposure Prophylaxis (PrEP)
title_fullStr 471. In-Depth Characterization of SARS-CoV-2 Variants Causing Breakthrough COVID-19 Among Hospitalized Immunocompromised (IC) Patients with or without Prior Exposure to Tixagevimab-Cilgavimab (T/C) Pre-Exposure Prophylaxis (PrEP)
title_full_unstemmed 471. In-Depth Characterization of SARS-CoV-2 Variants Causing Breakthrough COVID-19 Among Hospitalized Immunocompromised (IC) Patients with or without Prior Exposure to Tixagevimab-Cilgavimab (T/C) Pre-Exposure Prophylaxis (PrEP)
title_short 471. In-Depth Characterization of SARS-CoV-2 Variants Causing Breakthrough COVID-19 Among Hospitalized Immunocompromised (IC) Patients with or without Prior Exposure to Tixagevimab-Cilgavimab (T/C) Pre-Exposure Prophylaxis (PrEP)
title_sort 471. in-depth characterization of sars-cov-2 variants causing breakthrough covid-19 among hospitalized immunocompromised (ic) patients with or without prior exposure to tixagevimab-cilgavimab (t/c) pre-exposure prophylaxis (prep)
topic Abstract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10678141/
http://dx.doi.org/10.1093/ofid/ofad500.541
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