Dual combined antiviral treatment with remdesivir and nirmatrelvir/ritonavir in patients with impaired humoral immunity and persistent SARS‐CoV‐2 infection

Abstract

Despite global vaccination efforts, immunocompromized patients remain at high risk for COVID‐19‐associated morbidity. In particular, patients with impaired humoral immunity have shown a high risk of persistent infection. We report a case series of adult patients with B cell malignancies and/or undergoing B cell targeting therapies with persisting SARS‐CoV‐2 infection and treated with a combination antiviral therapy of remdesivir and nirmatrelvir/ritonavir, in three Italian tertiary academic hospitals. A total of 14 patients with impaired adaptive humoral immunity and prolonged SARS‐CoV‐2 infection were treated with the dual antiviral therapy. The median age was 60 (IQR 56–68) years, and 11 were male. Twelve patients had B cell lymphoma, one patient had chronic lymphocytic leukemia and one patient had multiple sclerosis. Thirteen out of 14 patients had received prior B cell‐targeting therapies, consisting of anti‐CD20 monoclonal antibodies in 11 patients, and chimeric antigen receptor T therapy in 2 patients. The median time between diagnosis and therapy start was 42.0 (IQR 35–46) days. Seven patients had mild, 6 moderate and one severe disease. Nine patients had signs of interstitial pneumonitis on chest computed tomography scans before treatment. The median duration of nirmatrelvir/ritonavir and remdesivir combination therapy was 10 days. All patients showed resolution of COVID‐19‐related symptoms after a median of 6 (IQR 4–11) days and viral clearance after 9 (IQR 5–11) days. Combination therapy with remdesivir and nirmatrelvir/ritonavir is a promising treatment option for persistent COVID‐19 in immunocompromized patients with humoral immunity impairment, worthy of prospective comparative trials.

Combined antiviral therapy as effective and feasible option in allogenic hematopoietic stem cell transplantation during SARS-COV-2 infection: a case report

“…Later, MoAb neutralization activity decreased against the newly VOC and new therapeutic strategies were proposed. A double antiviral regime based on extended course of nirmatrelvir/ritonavir and remdesevir, eventually associated with CCP has been found effective in IC patients ( 4 , 13 , 14 ).…”

Severe acute respiratory syndrome coronavirus 2 infection in patients with hematological malignancies in the Omicron era: Respiratory failure, need for mechanical ventilation and mortality in seronegative and seropositive patients

“…For this reason, it is necessary to focus on these patients to find a personalized approach for seronegative HM. On one hand, it should be a priority to continue vaccinating HM patients, in order to improve their immunological response; on the other hand, different research groups have started to perform off‐label treatments either combining more than one antiviral such as remdesivir plus nirmatrelvir/ritonavir [ 30 , 31 ] or prolonging the approved duration of label treatment [ 32 ].…”

Clinical efficacy of prophylactic intravenous immunoglobulin for elderly DLBCL patients with hypogammaglobulinemia in the COVID-19 pandemic era

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