Academic Journal
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)
| العنوان: | 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) |
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| المؤلفون: | 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 |
| المصدر: | Open Forum Infectious Diseases ; volume 10, issue Supplement_2 ; ISSN 2328-8957 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Infectious Diseases, Oncology |
| الوصف: | 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). 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/ofid/ofad500.541 |
| الاتاحة: | http://dx.doi.org/10.1093/ofid/ofad500.541 https://academic.oup.com/ofid/article-pdf/10/Supplement_2/ofad500.541/53778345/ofad500.541.pdf |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.AFFCD7B8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/ofid/ofad500.541 |
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