The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient-A Case Study.

BACKGROUND: Immunocompromised patients show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swabs. We report a case of prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of coronavirus disease 2019 (COVID-19) in a patient with mantle cell lymphoma who underwent treatment with rituximab, bendamustine, cytarabine with consequent lymphopenia and hypogammaglobulinemia. METHODS: Nasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR). On 5 positive nasopharyngeal swabs, we performed viral culture and next-generation sequencing. We analyzed the patient's adaptive and innate immunity to characterize T- and NK-cell subsets. RESULTS: SARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive for 268 days. All 5 performed viral cultures were positive, and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in 3 out of 4 COVID-19 clinical relapses and cleared each time after remdesivir treatment. The T- and NK-cell dynamic was different in aviremic and viremic samples, and no SARS-CoV-2-specific antibodies were detected throughout the disease course. CONCLUSIONS: In our patient, SARS-CoV-2 persisted with proven infectivity for >8 months. Viremia was associated with COVID-19 relapses, and remdesivir treatment was effective in viremia clearance and symptom remission, although it was unable to clear the virus from the upper respiratory airways. During the viremic phase, we observed a low frequency of terminal effector CD8+ T lymphocytes in peripheral blood; these are probably recruited in inflammatory tissue for viral eradication. In addition, we found a high level of NK-cell repertoire perturbation with relevant involvement during SARS-CoV-2 viremia.

Chemoimmunotherapy with oral low-dose fludarabine, cyclophosphamide and rituximab (old-FCR) as treatment for elderly patients with chronic lymphocytic leukaemia.

Median age at diagnosis for chronic lymphocytic leukaemia (CLL) patients is now 72 years, thus a consistent number of patients may not tolerate standard doses i.v. of fludarabine, cyclophosphamide and rituximab (FCR), the best available therapy, due to unacceptable myelotoxicity and risk of severe infections. We studied safety and efficacy of the addition of rituximab to the oral low-dose FC regimen (old-FCR) in a selected population of 30 elderly (median age 75, 15 untreated, 15 treated with 1 prior therapy) CLL patients. Complete remission (CR) rate was 80% in the untreated patients (overall response rate, ORR 93%), and 30% in pretreated patients (ORR 74%). Progression free survivals (PFS) were 45 months and 30 months in the untreated and treated patients, respectively. In patients achieving CR, old-FCR led to PFS of 67 months. Moreover, haematological toxicity was mild (grade 3-4: 15%) and patients were treated mostly in outpatient clinic. Old-FCR could be a good therapy option for elderly CLL patients outside clinical trials, larger studies are needed to confirm our findings.

Efficacy and safety of rituximab plus low-dose oral fludarabine and cyclophosphamide as first-line treatment of elderly patients with indolent non-Hodgkin lymphomas.

Indolent non-Hodgkin lymphomas (iNHLs) are B-cell neoplasms for which no consensus is available about optimal first-line therapy. Chemoimmunotherapy with fludarabine, cyclophospamide and rituximab is very effective, but may give severe hematological and non-hematological toxicity at standard doses, especially in elderly patients. In this phase II study, 25 untreated elderly patients with iNHL received rituximab (375 mg/m(2)) plus low-dose oral fludarabine (25 mg/m(2) for 4 consecutive days) and cyclophosphamide (150 mg/m(2) for 4 consecutive days) for four monthly cycles. Twenty-three patients were responsive (92%) and 12 patients achieved a complete remission (48%). Twenty-one patients (84%) were alive, median follow-up was 30 months and median event-free survival (EFS) was not reached. Patients who we previously treated with chemotherapy alone had a shorter EFS (median 20 months). Compliance was good, with mild toxicity. This regimen is effective for elderly patients with iNHL. The addition of rituximab results in long EFS without affecting toxicity.