Nirmatrelvir/Ritonavir Reduces Infection Duration in Hospitalized Hematological Malignancies Patients with Mild-to-Moderate COVID-19: A Retrospective Study

Background

Since the COVID-19 outbreak in 2020, the virus has significantly impacted global health, particularly affecting patients with hematological malignancies (HM) due to their immunocompromised status. These patients experience higher infection rates, prolonged virus clearance, and more severe outcomes. Immunocompromised individuals with persistent infections may also serve as reservoirs for viral variants, posing public health risks due to the rapid evolution of SARS-CoV-2. Nirmatrelvir/ritonavir, an antiviral agent approved for treating COVID-19, has demonstrated efficacy in reducing severity and mortality in high-risk, non-hospitalized patients. While some reported cases support the potential benefits of nirmatrelvir/ritonavir for hospitalized patients with mild-to-moderate COVID-19 and HM, its effectiveness in this specific patient population remains undetermined. To address this knowledge gap, we conducted a single-center retrospective study to assess the efficacy of nirmatrelvir/ritonavir in hospitalized patients with mild-to-moderate COVID-19 and HM.

Methods

We conducted a single-center, retrospective, real-world cohort study at West China Hospital of Sichuan University to evaluate the outcomes of hospitalized patients with HM and SARS-CoV-2 infection treated with nirmatrelvir/ritonavir. Patients hospitalized for a minimum of five days in the Department of Hematology between December 1, 2022, and February 28, 2023, were included. Eligibility criteria included an active HM diagnosis within the preceding three years and SARS-CoV-2 antigen or nucleic acid positivity. Patients diagnosed with severe COVID-19, or treated with convalescent plasma, azvudine, or molnupiravir, or with unknown vaccination status, were excluded. The severity levels for COVID-19 infections in this study followed the definitions provided in the China Diagnosis and Treatment Protocol for COVID-19 Patients (Tentative 10th Version). The Institutional Review Board approved the study protocol. The study, registered with the Chinese Clinical Trial Registry (ChiCTR2300069374), was conducted following the Helsinki Declaration.

Results

A total of 130 HM patients hospitalized for a minimum of five days with mild-to-moderate COVID-19 between December 1, 2022, and February 28, 2023, were included in this study, corresponding to China's first COVID-19 wave. In this study, 50% (65/130) of the patients were male, predominantly under 65 years old (n = 107, 82.3%), with a median age of 51 (16-91) years. Acute myeloid leukemia and myelodysplastic syndromes were the most common malignancies (33.1%), followed by non-Hodgkin's lymphoma (23.8%). There was no difference in the 90-day mortality rate between HM patients treated with nirmatrelvir/ritonavir within five days of confirmed SARS-CoV-2 infection and the control group (4.8% vs 5.3%, P = 0.916). Regarding the infection duration, Cox regression multivariate analysis showed that patients receiving chemotherapy with antibodies had a significantly prolonged infection duration (HR=0.51, 95% CI 0.29-0.81). Other treatment regimens did not achieve a statistically significant difference in time to viral clearance. Nirmatrelvir/ritonavir use within five days reduced the time to viral clearance (HR=1.51, 95% CI 1.01-2.23).

Conclusions

Nirmatrelvir/ritonavir use within five days in hospitalized HM patients with mild-to-moderate COVID-19 does not reduce mortality but shortens infection duration.

No relevant conflicts of interest to declare.