4CPS-174 Adjustment to the protocol of nirmatrelvir/ritonavir and remdesivir treatment in immunocompromised patients at high-risk of persistent COVID at a second-level hospital

<h3>Background and Importance</h3> Immunocompromised patients are at a higher risk of developing persistent COVID (pCOVID). In October-2023, our hospital implemented a multidisciplinary protocol developed together the haematology department and the Antimicrobial Stewardship Programme (PROA) to manage haematologic patients at high-risk of pCOVID. <h3>Aim and Objectives</h3> To evaluate the adjustment to the protocol and the clinical outcomes of patients treated with the combination of nirmatrelvir/ritonavir (N/R) and remdesivir (RDV). <h3>Material and Methods</h3> A retrospective observational study of patients treated with N/R+RDV between October 2023 and September 2024 in a second-level hospital. Demographic (sex, age) and clinical variables were collected: haematologic status, prior disease, treatment, symptoms, severity, and COVID history. Clinical virological response variables were monitored by PCR at days+5,+10 and+30 and overall survival (OS) at 30 days. The protocol defines the duration of N/R+RDV treatment for asymptomatic (5–10 days) and symptomatic (10 days) patients and identifies three high-risk groups for pCOVID: Active disease (Non-Hodgkin Lymphoma(NHL)/Chronic Lymphocytic Leukaemia (CLL)) treated with anti-CD20+chemotherapy or BCL-2 (BCL2i) or BTK inhibitors (BTKi). Patients undergoing haematopoietic stem cell transplant (HSCT) or CAR T-cell therapy. Treatments with bispecific antibodies, antibody-drug conjugates, or anti-CD19 antibodies. <h3>Statistics analysed with SPSSv</h3> 20. <h3>Results</h3> Thirty-two cases were included (53,1% male; median age 74 years [IQR=64–79]). 90,6% were haematological (62,5% NHL; 9,4% CLL; 18,8% other haematologic diseases): 62% were receiving anti-CD20 therapy; 6,9% CAR-T; 6,9% BTKi; 6,9% HSCT; 6,9% other immunosuppressants and 10,4% were untreated. 9,4% were non-haematologic patients, all on anti-CD20 therapy and under PROA follow-up. At diagnosis, 90,6% were symptomatic, 65,6% had received prior antiviral treatment. 84,4% were mild-to-moderate and the median initial PCR cycle was 21 [IQR=16–24,75]. The median persistence time to PCR negativity was 10 days [95% CI 5–30], with 28,1% achieving it by day 5; 40,6% day 10; and 75% day 30. One death was recorded due to non-COVID-related causes, and the median OS was not reached during follow-up. Overall protocol adherence was 71,9%; 79,3% for haematologic patients (82,6% group1;17,4% group2), while the remaining 20,7% did not meet inclusion criteria (50/50% for treatment/diagnostic criteria). <h3>Conclusion and Relevance</h3> Adjustment to the N/R+RDV combination treatment protocol was satisfactory, with a high PCR negativity rate, demonstrating its effectiveness. However, study design limitations and case selection prevent definitive conclusions. The exclusion of non-haematologic patients suggests a need to review and expand the inclusion criteria to allow other immunocompromised patients to benefit from this combined therapy. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest