The unique presentation of SARS-CoV-2 Infection in patients with B-cell depletion: definition of ‘persistent inflammatory sero-negative COVID’

Belkin, Ana; Leibowitz, Avshalom; Shargian, Liat; Yahav, Dafna

doi:10.1016/j.cmi.2022.10.007

Cited by 27 publications

(34 citation statements)

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“…SARS-CoV-2 infection manifests with diverse clinical pictures, suggesting that the severity of symptoms might depend on the outcome of the SARS-CoV-2 immune system interaction within the patient (28)(29)(30). The prolonged shedding of virus and persistent symptomatic SARS-CoV-2 infection have been reported in the immunocompromised patients, mainly in hematological, after B-cell depletion with anti-CD20 antibodies (19,(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

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Case report: Sotrovimab, remdesivir and nirmatrelvir/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19

et al. 2023

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COVID-19 in immunocompromised patients is difficult to treat. SARS-CoV-2 interaction with the host immune system and the role of therapy still remains only partly understood. There are no data regarding the use of monoclonal antibodies and the combination of two antivirals in fighting viral replication and disease progression. We report the cases of two patients, both treated with rituximab for non-Hodgkin lymphoma and granulomatosis with polyangiitis, respectively, and both hospitalized for COVID-19 with positive SARS-CoV-2 RNAemia, who were successfully treated with a salvage combination therapy with sotrovimab, remdesivir and nirmatrelvir/ritonavir.

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Section: Discussionmentioning

confidence: 99%

“…The prolonged shedding of virus and persistent symptomatic SARS-CoV-2 infection have been reported in the immunocompromised patients, mainly in hematological, after B-cell depletion with anti-CD20 antibodies ( 19 , 31 – 33 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Sotrovimab, remdesivir and nirmatrelvir/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19

et al. 2023

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“…One patient had rheumatoid arthritis, treated with BCDT. Comorbidities associated with COVID-19 included hypertension (8 patients), diabetes mellitus (6), chronic renal failure (4), ischemic heart disease (3), congestive heart failure (3), chronic lung disease (3), obesity (2), and chronic liver disease in 1 patient. Nine patients had received 4 vaccine doses against COVID-19, a median of 146 (IQR 119,244) days before disease onset, which was considered adequate according to Israeli recommendations.…”

Section: Resultsmentioning

confidence: 99%

“…These patients commonly present with fever, cough, dyspnea, radiological signs of pneumonitis, and positive SARS-CoV-2 PCR tests, lasting for a prolonged period, sometimes in a remitting-relapsing pattern, while no serologic response develops. Definitions for persistent and seronegative COVID-19 were suggested by Belkin et al [2], to include symptom duration of 7-14 days and PCR positivity of >21 days. Most of our patients fulfilled these definitions, although some had a shorter disease duration.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, severely immunocompromised patients may have diminished vaccine efficacy and might be unable to clear severe-acute-respiratory-syndromecoronavirus-2 (SARS-CoV-2) infection [1]. Patients with hematological malignancies, recipients of B-cell depleting therapy (BCDT) and transplanted patients can develop persistent COVID-19, defined as prolonged symptomatic infection, with continuing SARS-CoV-2 replication, and lack of serologic responses [2]. Patients with this syndrome frequently relapse shortly after treatment, resulting in significant morbidity and mortality [3].…”

Section: Introductionmentioning

confidence: 99%

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Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmaltrevir/ritonavir and tixegavimab/cilgavimab

Brosh‐Nissimov

Ma'aravi²,

Leshin-Carmel³

et al. 2023

Preprint

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Background: Little data exists to guide the treatment of persistent COVID-19 in immunocompromised patients. We have employed a unique protocol combining tixegavimab/cilgavimab, and short-term combination antivirals including remdesivir. Methods: A retrospective single-center analysis of persistent COVID-19 in immunocompromised patients. Response was assessed by symptom resolution, declining C-reactive protein (CRP) levels and increasing SARS-CoV-2-PCR cycle-threshold (Ct) values. Results: Fourteen patients were included, including 2 kidney transplant recipients, 11 with B-cell lymphoproliferative disease, treated with anti-CD20 or ibrutinib, and 1 with rheumatoid arthritis, treated with anti-CD20. Median Ct-value was 27 (interquartile range (IQR):24-32). All patients received tixegavimab/cilgavimab and a 5-day course of remdesivir. Eleven also received nirmaltrevir/ritonavir and one received molnupiravir. Median follow-up was 45 days (IQR:12-89). Eleven patients had complete responses including symptom resolution, decrease in CRP, and increase in Ct values (all with either a negative PCR or Ct value>30 on day 4-16). Three patients had a partial response with relapses requiring re-admission. One had died, and two responded to prolonged antiviral treatments. Conclusions: A combination of monoclonal antibodies with antivirals has led to complete resolution of persistent COVID-19 in most severely-immunocompromised patients. Controlled studies will further direct the treatment of these patients, while more effective antivirals are urgently needed.

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An international multicenter study comparing COVID‐19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab

Shafat,

Grupel,

Porges

et al. 2024

Cancer Medicine

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ObjectivesHematological malignancy (HM) patients treated with anti‐CD20 monoclonal antibodies are at higher risk for severe COVID‐19. A previous single‐center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort.MethodsWe included HM patients from 15 centers, from five countries treated with anti‐CD20, comparing those treated with obinutuzumab (O‐G) to rituximab (R‐G) between December 2021 and June 2022, when Omicron lineage was dominant.ResultsWe collected data on 1048 patients. Within the R‐G (n = 762, 73%), 191 (25%) contracted COVID‐19 compared to 103 (36%) in the O‐G. COVID‐19 patients in the O‐G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID‐19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe‐critical COVID‐19 occurred in 31.1% of patients in the O‐G and 22.5% in the R‐G. In multivariable analysis, O‐G had a 2.08‐fold increased risk for severe‐critical COVID‐19 compared to R‐G (95% CI 1.13–3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T‐C) prophylaxis. Further analysis comparing O‐G to R‐G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID‐19‐related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293).ConclusionsDespite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID‐19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk–benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks.

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The unique presentation of SARS-CoV-2 Infection in patients with B-cell depletion: definition of ‘persistent inflammatory sero-negative COVID’

Cited by 27 publications

References 10 publications

Case report: Sotrovimab, remdesivir and nirmatrelvir/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19

Case report: Sotrovimab, remdesivir and nirmatrelvir/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19

Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmaltrevir/ritonavir and tixegavimab/cilgavimab

An international multicenter study comparing COVID‐19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab

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