| 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) |
| Authors: |
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 |
| Source: |
Open Forum Infectious Diseases ; volume 10, issue Supplement_2 ; ISSN 2328-8957 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2023 |
| 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). 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 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/ofid/ofad500.541 |
| Availability: |
https://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/ |
| Accession Number: |
edsbas.AFFCD7B8 |
| Database: |
BASE |