Treatment of chronic COVID-19 with convalescent/postvaccination plasma in patients with hematologic malignancies.

Immunocompromised patients are at high risk to fail clearance of SARS-CoV-2. Prolonged COVID-19 constitutes a health risk and a management problem as cancer treatments often have to be disrupted. As SARS-CoV-2 evolves, new variants of concern have emerged that evade available monoclonal antibodies. Moreover, antiviral therapy promotes SARS-CoV-2 escape mutations, particularly in immunocompromised patients. These patients frequently suffer from prolonged infection. No successful treatment has been established for persistent COVID-19 infection. Here, we report on a series of 21 immunocompromised patients with COVID-19-most of them hematologic malignancies-treated with plasma obtained from recently convalescent or vaccinated donors or a combination thereof. Repeated dosing of SARS-CoV-2-antibody-containing plasma could clear SARS-CoV-2 infection in 16 out of 21 immunocompromised patients even if COVID-19-specific treatments failed to induce sustained viral clearance or to improve clinical course of SARS-CoV-2 infection. Ten patients were major responders defined as an increase delta(d)Ct of > = 5 after the first administration of convalescent and/or vaccinated plasma (C/VP). On average, SARS-CoV-2 PCR Ct values increased from a median value of 22.55 (IQR = 19.10-24.25) to a median value of 29.57 (IQR = 27.55-34.63; p = <.0001) in the major response subgroup. Furthermore, when treated a second time with C/VP, even 4 out of 5 of the initial nonresponders showed an increase in Ct-values from a median value of 23.13 (IQR = 17.75-28.05) to a median value of 32.79 (IQR = 31.75-33.75; p = .013). Our results suggest that C/VP could be a feasible treatment of COVID-19 infection in patients with hematologic malignancies who did not respond to antiviral treatment.

Outcomes of COVID-19 in patients with obinutuzumab compared with patients with rituximab: a retrospective cohort study.

BACKGROUND: Patients treated with anti-CD20 monoclonal antibodies could have a higher risk of adverse outcomes of coronavirus disease 2019 (COVID-19). The novel anti-CD20 monoclonal antibody obinutuzumab has shown greater B-cell depletion and superior in vitro efficacy than rituximab. We aimed to assess whether obinutuzumab would result in worse COVID-19 outcomes than rituximab. METHODS: We retrospectively reviewed 124 patients with B-cell lymphoma, 106 of whom received rituximab treatment and 18 of whom received obinutuzumab treatment. The adverse outcomes of COVID-19 were compared between patients in the two cohorts. RESULTS: The proportions of patients who were hospitalized (55.6% vs. 20.8%, p = 0.005), experienced prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (38.9% vs. 2.9%, p < 0.001), and developed severe COVID-19 (33.3% vs. 4.7%, p < 0.001) were higher in patients with obinutuzumab than in those with rituximab. Multivariate analyses showed that obinuzumab treatment was associated with higher incidences of prolonged SARS-CoV-2 infection (OR 27.05, 95% CI 3.75-195.22, p = 0.001) and severe COVID-19(OR 15.07, 95% CI 2.58-91.72, p = 0.003). CONCLUSIONS: Our study suggested that patients treated with obinutuzumab had a higher risk of prolonged SARS-CoV-2 infection and severe COVID-19 than those treated with rituximab.

Radiologic Abnormalities in Prolonged SARS-CoV-2 Infection: A Systematic Review.

We systematically reviewed radiological abnormalities in patients with prolonged SARS-CoV-2 infection, defined as persistently positive polymerase chain reaction (PCR) results for SARS-CoV-2 for > 21 days, with either persistent or relapsed symptoms. We extracted data from 24 patients (median age, 54.5 [interquartile range, 44-64 years]) reported in the literature and analyzed their representative CT images based on the timing of the CT scan relative to the initial PCR positivity. Our analysis focused on the patterns and distribution of CT findings, severity scores of lung involvement on a scale of 0-4, and the presence of migration. All patients were immunocompromised, including 62.5% (15/24) with underlying lymphoma and 83.3% (20/24) who had received anti-CD20 therapy within one year. Median duration of infection was 90 days. Most patients exhibited typical CT appearance of coronavirus disease 19 (COVID-19), including ground-glass opacities with or without consolidation, throughout the follow-up period. Notably, CT severity scores were significantly lower during ≤ 21 days than during > 21 days (P < 0.001). Migration was observed on CT in 22.7% (5/22) of patients at ≤ 21 days and in 68.2% (15/22) to 87.5% (14/16) of patients at > 21 days, with rare instances of parenchymal bands in previously affected areas. Prolonged SARS-CoV-2 infection usually presents as migrating typical COVID-19 pneumonia in immunocompromised patients, especially those with impaired B-cell immunity.

Prolonged SARS-CoV-2 Infection and Organizing Pneumonia in a Patient with Follicular Lymphoma, Treated with Obinutuzumab-Challenging Recognition and Treatment.

A Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) led to a pandemic outbreak in 2019. COVID-19's course and its treatment in immunocompromised patients are uncertain. Furthermore, there is a possibility of protracted SARS-CoV-2 infection and the need for repeated antiviral treatment. Monoclonal antibodies against CD20, which are used, among other things, in the therapy of chronic lymphocytic leukaemia and follicular lymphoma, can induct immunosuppression. We present a case report of a patient with follicular lymphoma, treated with obinutuzumab, who was diagnosed with prolonged, ongoing SARS-CoV-2 infection and related organizing pneumonia. The recognition and the treatment were challenging which makes this case noteworthy. Antiviral therapy with several medications was administrated to our patient and their temporary, positive effect was observed. Moreover, high-dose intravenous immunoglobulin was applied, because slowly decreasing IgM and IgG levels were observed. The patient also received standard treatment of organizing pneumonia. We believe that such a complex approach can create an opportunity for recovery. Physicians should be conscious of the course and treatment possibilities facing similar cases.

Remdesivir-induced emergence of SARS-CoV2 variants in patients with prolonged infection.

We here investigate the impact of antiviral treatments such as remdesivir on intra-host genomic diversity and emergence of SARS-CoV2 variants in patients with a prolonged course of infection. Sequencing and variant analysis performed in 112 longitudinal respiratory samples from 14 SARS-CoV2-infected patients with severe disease progression show that major frequency variants do not generally arise during prolonged infection. However, remdesivir treatment can increase intra-host genomic diversity and result in the emergence of novel major variant species harboring fixed mutations. This is particularly evident in a patient with B cell depletion who rapidly developed mutations in the RNA-dependent RNA polymerase gene following remdesivir treatment. Remdesivir treatment-associated emergence of novel variants is of great interest in light of current treatment guidelines for hospitalized patients suffering from severe SARS-CoV2 disease, as well as the potential use of remdesivir to preventively treat non-hospitalized patients at high risk for severe disease progression.