Atypical COVID-19 dynamics in a patient with mantle cell lymphoma exposed to rituximab

Abstract

Patients with non-hodgkin lymphomas (NHL) represent a population of special interest during the current Coronavirus disease-19 (COVID-19) pandemics. NHLs are associated with disease- and treatment-related immunodeficiencies which may generate unusual COVID-19 dynamics and pose unique management challenges. We report the unusual clinical course of COVID-19 in a patient with mantle cell lymphoma (MCL) exposed to nine doses of Rituximab shortly before infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). He had a prolonged asymptomatic phase, with negative molecular and antibody testing for SARS-CoV-2, followed by a rapidly progressive evolution to severe COVID-19. Despite detection of viral RNA overlapped with first symptoms occurrence, anti-SARS-CoV-2 antibodies displayed an asynchronous pattern, with IgG first appearing 2 days after RNA positivity and IgM never being detected throughout the entire clinical course. While disease-associated immune derangements and/or previous treatments involving anti-CD20 antibodies might have contributed to COVID-19 dynamics in our patient, data suggests that antibody testings, without concurrent molecular assessment for SARS-CoV-2, may turn inadequate for monitoring of MCL patients, and in general NHL patients heavily exposed to anti-CD20 antibodies, during the current pandemics. We suggest that repeated molecular testing of nasopharyngeal swab should be implemented in these subjects despite a negative serology and absence of symptoms of SARS-CoV-2 infection. For the same reasons, a customized strategy needs to be developed for patients exposed to anti-CD20 antibodies, based on different features and mechanism of action of available SARS-CoV-2 vaccines and novel vaccinomics developments.

Keywords: Anti-CD20 antibodies; COVID-19; Mantle cell lymphoma; Rituximab.

Fig. 1

Histopathologic, phenotypic and molecular features of a mantle cell lymphoma case developing COVID-19. a and b Haematoxylin and eosin stain of duodenal biopsy at restaging (March 11, 2020). c CD5, (d) CD20 and (e) cyclin D1 immunostainings. f FISH analysis documenting the presence in tumor cells at restaging of t (11;14) (q13;q32) translocation with IGH-CCND1 fusion. Tumor cells were were CD10 and SOX-11 negative and Kì67 staining was < 10% (not shown)

Fig. 2

Visual timeline including major clinical findings, treatments, virologic and laboratory data. a Clinical timeline and treatments in the context of results for SARS-CoV-2 RT-PCR and virus-specific IgG and IgM antibodies. ARDS severity was scored according to the Berlin definition. b, c Chest computed tomography scans (April 1, 2029) showing typical features of COVID-19 pneumonia with bilateral consolidative abnormalities, central and peripheral ground glass opacities. d RT-PCR results (Ct) vs. detection of anti SARS-CoV-2 IgG and IgM antibodies. RT-PCR data was obtained by using the Allplex™ 2019-nCoV multiplex Assay. IgG and IgM were evaluated by chemoluminiscence immunoassay (Shenzhen YHLO Biotech Co, Ltd) and results expressed in arbitrary units (AU)/mL. Cut off value for positivity as indicated by manufacturer was of 10 AU/mL both for IgM and IgG antibodies (e) Changes in serum levels of ferritin, IL-6 and ALC. Abbrevations used in the figures. FISH, fluorescence in situ hybridization; RT-PCR, reverse transcriptase-polymerase chain reaction (RT-PCR); BT, body temperature (°C); ARDS, acute respiratory distress syndrome; AU, arbitrary units; ALC, absolute lymphocyte counts; Ct, cycle threshold