key: cord-0812484-gyjnt6gx
authors: Conte, WL
title: Attenuation of antibody response to SARS-CoV-2 in a patient on ocrelizumab with hypogammaglobulinemia.
date: 2020-06-20
journal: Mult Scler Relat Disord
DOI: 10.1016/j.msard.2020.102315
sha: 91d38f0ba10871de6228c39deb7eb458722f3f5b
doc_id: 812484
cord_uid: gyjnt6gx

nan

As the world faces the spread and aftermath of the novel coronavirus disease (COVID-19), we are expectantly looking forward to vaccine. Ocrelizumab, which is a monoclonal antibody directed against peripheral CD20+ B cells, is approved in multiple countries for both RRMS and PPMS 1,2 . There has been concern about differential effects on immunoglobulin production for ocrelizumab based on the rituximab literature. Rituximab decreased serum antibody levels compared to methotrexate in the pivotal trial for rheumatoid arthritis 3, 4 . In the VELOCE trial for ocrelizumab, humoral responses were attenuated but patients were still able to mount an immune response to vaccines 5 .

A 48-year-old female on ocrelizumab (last dose 1/24/2020) presented to a drive up COVID-19 testing site with two days of fever, upper respiratory symptoms, and malaise on March 30, 2020. She tested positive for the antigen to SARS-CoV-2. She was prescribed hydroxychloroquine and azithromycin by her primary care physician, but withheld the hydroxychloroquine due to concern about side effects. Due to worsening shortness of breath, one week later she presented to the emergency room and was admitted for supportive care.

Chest x-ray showed left upper lobe and left lung base pneumonia. She was started on ceftriaxone and hydroxychloroquine. Lymphocytes were normal at 1000/ul, IgG was 538 mg/dl, IgM was <25 mg/dl, and IgA was 161 mg/dl. She did not require oxygen and was discharged 3 days later after clinical improvement. She had a prolonged symptomatic period, requiring over 3 weeks from onset to recover from her shortness of breath and fever and 7 weeks to recover from her malaise. In early June 2020, she sought antibody testing and tested negative for SARS-CoV-2 IgG with the Abbott immunoassay. She had a second specimen tested several days later and it also tested negative with the same immunoassay.

This patient illustrates a growing concern about the immunogenicity of SARS-CoV-2 in patients on ocrelizumab. On the one hand, one could argue that perhaps she had a false negative result.

However, a study found the Abbott IgG immunoassay to be 100% sensitive and 99.9% specific 6 .

On the other hand, this could represent an example of an attenuation of humoral response in response to ocrelizumab, especially in the context of hypogammaglobulinemia. The question is whether exposure to a future vaccine will also result in an attenuation of humoral response.

However, as seen in the VELOCE trial, patients were still able to mount an immune response to vaccines despite the attenuated humoral response. Further studies should be conducted and a database should be formed regarding the humoral response to SARS-CoV-2.

Honorarium from: Allergan, Alexion, Bayer, Biogen, EMD Serono, Genentech, Novartis, Sanofi Genzyme.

Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Efficacy of B-Cell-Targeted Therapy with Rituximab in Patients with Rheumatoid Arthritis

Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials

A Phase III, open-label study to evaluate the effect of ocrelizumab on immune responses in patients with relapsing multiple sclerosis

Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in