ArticlePNAS nexus2025
Clinical and molecular landscape of prolonged SARS-CoV-2 infection with resistance to remdesivir in immunocompromised patients.
Article in PNAS nexus, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Cross-resistance patterns in SARS-CoV-2 against 3CL protease inhibitors.Nature communications · 2026Article
- Strategies for mitigating severe COVID-19 in patients with haematological malignancy during the omicron era.The Journal of antimicrobial chemotherapy · 2026Review
- Development of RNA Aptamers That Inhibit the RNA-Dependent RNA Polymerase Activity of SARS-CoV-2 Strains In Vitro.International journal of molecular sciences · 2025Article
- Intra-Host Evolution of SARS-CoV-2 During Persistent Infection of Pediatric COVID-19 Patients.Viruses · 2025Article
- The Emergence of Escape Mutations in COVID-19 Following Anti-Spike Monoclonal Antibody Treatment: How Do We Tackle It?Infection and drug resistance · 2025Review
- Severe and/or prolonged COVID-19 in hematologic diseases: clinical implications before and during the omicron era.Frontiers in oncology · 2025Article
Corrections and comments
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Authors and funding
30 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with hematologic diseases have experienced coronavirus disease 2019 (COVID-19) with a prolonged, progressive course. Here, we present clinical, pathological, and virological analyses of three cases of prolonged COVID-19 among patients undergoing treatment for B-cell lymphoma. These patients had all been treated with anti-CD20 antibody and bendamustine. Despite various antiviral treatments, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels persisted for >4 weeks, and two of them succumbed to COVID-19. The autopsy showed bronchopneumonia, interstitial pneumonia, alveolar hemorrhage, and fibrosis. Overlapping cytomegalovirus, fungal and/or bacterial infections were also confirmed. Sequencing of SARS-CoV-2 showed accumulation of mutations and changes in variant allele frequencies over time. NSP12 mutations V792I and M794I appeared independently in two cases as COVID-19 progressed. In vitro drug susceptibility analysis and an animal experiment using recombinant SARS-CoV-2 demonstrated that each mutation, V792 and M794I, was independently responsible for remdesivir resistance and attenuated pathogenicity. E340A, E340D, and F342INS mutations in the spike protein were found in one case, which may account for the sotrovimab resistance. Analysis of autopsy specimens indicated heterogeneous distribution of these mutations. In summary, we demonstrated temporal and spatial diversity in SARS-CoV-2 that evolved resistance to various antiviral agents in malignant lymphoma patients under immunodeficient conditions caused by certain types of immunochemotherapies. Strategies may be necessary to prevent the acquisition of drug resistance and improve outcomes, such as the selection of appropriate treatment strategies for lymphoma considering patients' immune status and the institution of early intensive antiviral therapy.
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