Clinical experience of treatment of immunocompromised individuals with persistent SARS-CoV-2 infection based on drug resistance mutations determined by genomic analysis: a descriptive study.

BACKGROUND: The efficacy of antiviral drugs that neutralize antibody drugs and fight against SARS-COV-2 is reported to be attenuated by genetic mutations of the virus in vitro. When B-cell immunocompromised patients are infected with SARS-COV-2, the infection can be prolonged, and genetic mutations can occur during the course of treatment. Therefore, for refractory patients with persistent COVID-19 infection, genomic analysis was performed to obtain data on drug resistance mutations as a reference to determine which antiviral drugs and antibody therapies might be effective in their treatment. METHODS: This was a descriptive analysis with no controls. Patients were diagnosed as having COVID-19, examined, and treated in the Kansai Medical University General Medical Center between January 2022 and January 2023. The subjects of the study were B-cell immunocompromised patients in whom genome analysis of SARS-CoV-2 was performed. RESULTS: During the study period, 984 patients with COVID-19 were treated at our hospital. Of those, 17 refractory cases underwent genomic analysis. All 17 patients had factors related to immunodeficiency, such as malignant lymphoma or post-organ transplantation. Eleven patients started initial treatment for COVID-19 at our hospital, developed persistent infection, and underwent genomic analysis. Six patients who were initially treated for COVID-19 at other hospitals became persistently infected and were transferred to our hospital. Before COVID-19 treatment, genomic analysis showed no intrahost mutations in the NSP5, the NSP12, and the RBD regions. After COVID-19 treatment, mutations in these regions were found in 12 of 17 cases (71%). Sixteen patients survived the quarantine, but one died of sepsis. CONCLUSIONS: In genomic analysis, more mutations were found to be drug-resistant after COVID-19 treatment than before COVID-19 treatment. Although it was not possible to demonstrate the usefulness of genome analysis for clinical application, the change of the treatment drug with reference to drug resistance indicated by genomic analysis may lead to good outcome of immunocompromised COVID-19 patients.

Novel treatment combining antiviral and neutralizing antibody-based therapies with monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection.

Because prolonged viral replication of SARS-CoV-2 is increasingly being recognized among immunocompromised patients, subacute or chronic COVID-19 pneumonia can cause persistent lung damage and may lead to viral escape phenomena. Highly efficacious antiviral therapies in immunosuppressed hosts with COVID-19 are urgently needed. From February 2022, we introduced novel treatment combining antiviral therapies and neutralizing antibodies with frequent monitoring of spike-specific antibody and RT-PCR cycle threshold (Ct) values as indicators of viral load for immunocompromised patients with persistent COVID-19 infection. We applied this treatment to 10 immunosuppressed patients with COVID-19, and all completed treatment without relapse of infection. This may be a potentially successful treatment strategy that enables us to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation in immunocompromised patients with persistent COVID-19.