key: cord-328505-5fkpnbdb
authors: Thornton, Jeanine Rempe; Harel, Asaff
title: Negative SARS-CoV-2 antibody testing following COVID-19 infection in Two MS patients treated with ocrelizumab
date: 2020-06-26
journal: Mult Scler Relat Disord
DOI: 10.1016/j.msard.2020.102341
sha: 
doc_id: 328505
cord_uid: 5fkpnbdb

BACKGROUND: It is unknown whether MS disease modifying therapies impact ability to mount an antibody response to SARS-CoV-2. METHODS: Case series and literature review. We report a series of two MS patients who developed COVID-19 while on Ocrelizumab therapy and subsequently exhibited negative SARS-CoV-2 serology. RESULTS: A 42-year-old man and 39-year-old woman with MS developed COVID-19 while on Ocrelizumab therapy. Neither patient required hospitalization. The man exhibited negative serology at 7- and 9-weeks post-infection. The woman exhibited negative serology at 6- and 12-weeks post-infection. CONCLUSIONS: Large studies are essential to determine whether certain DMTs may blunt SARS-CoV-2 antibody production.

The emergence of SARS-CoV-2 has produced numerous questions surrounding immunomodulatory management of patients with autoimmune conditions like multiple sclerosis (MS) . Treatment of MS is complex, relying on a variety of disease modifying therapies (DMTs) with myriad mechanisms of action. Each DMT, therefore, may impact response to the virus in a different manner (Berger et al., 2020) .

As the majority of patients with coronavirus disease-19 (COVID-19) recover and the world moves to the next phase of the pandemic, COVID-19 antibody testing has emerged as a useful tool in determining prior infection and potential immunity. Several serological assays have been granted "Emergency Use Authorization" (EUA) by the FDA for this purpose. While the specificity of these assays is of concern with regards to false-positives, the sensitivity and negative predictive value are high (FDA.gov, "EUA Authorized Serology Test Performance").

The sensitivity may be diminished by inadequate timing of testing following an infection, but the most recent literature suggests that the vast majority of patients with symptomatic COVID-19 produce antibodies within the first two to three weeks after symptom onset (Long et al., 2020) .

In MS, a possible concern is the impact of certain DMTs, such as CD-20 monoclonal antibodies In this article, we report serology results from the first two patients at our center to have undergone SARS-CoV-2 antibody testing after developing COVID-19 while on Ocrelizumab therapy.

Case report, literature review.

A 42-year-old man with relapsing remitting (RR) MS treated with Ocrelizumab developed symptomatic COVID-19 infection. He was diagnosed with MS four years prior, had no comorbidities, and was a non-smoker. He began Ocrelizumab treatment nine months prior to infection, with the last infusion occurring two months prior contracting the disease. Initial symptoms of COVID-19 included fever, cough, and impaired taste. This progressed over several days to involve dyspnea on exertion. However, he did not exhibit shortness of breath at rest and did not require hospitalization. He underwent nasopharyngeal testing which confirmed SARS-CoV-2 infection. The patient's respiratory symptoms resolved after two weeks, while dysgeusia persisted >1 month. The patient underwent SARS-CoV-2 serology testing at 7-weeks postinfection (BioReference Laboratories, using either the DiaSorin Liaison Sars-CoV-2 S1/S2 assay) and again at 9-weeks post-infection (Northwell Health Laboratory, using the Roche Elecsys Anti-Sars-CoV-2 assay), both yielding a negative result (Table 1) IgG assay), both yielding a negative result (Table 1 ). At the time of the first negative result, absolute CD-19 count was 2 cells/uL (0.06%), ALC was 3900 cells/uL, and an immunoglobulin panel was within normal limits.

In this case series, we present negative results from the first two MS patients at our site who underwent SARS-CoV-2 antibody testing after developing PCR-confirmed COVID-19 while on Ocrelizumab. While accuracy of individual assays is a potential concern, the results are strengthened by the fact that each patient underwent two separate assays granted EUA by the FDA, performed at two separate labs, several weeks apart (Table 1) . Furthermore, negative testing over two timepoints greatly limits the possibility that timing was a significant factor. As most people infected with COVID-19 are expected to produce antibodies (Long et al., 2020) , we posit that Ocrelizumab played a role in dampening the antibody response.

Anti-CD20 monoclonal antibodies impair the humoral arm of Therefore, a functioning innate immune and an intact antigen-specific cytotoxic T-cell response may be sufficient for virus clearance.

Following COVID-19, short-term re-infection rates in the general population are low (Kirkcaldy et al., 2020) . It is thought that immunity is mediated by both the synthesis of neutralizing antibodies and formation of antigen-specific cytotoxic T-cells directed against the virus, but it is currently unknown whether either is essential or sufficient. Therefore, the failure of our patients to produce antibodies to SARS-CoV-2 may or may not indicate a higher risk of re-infection, and further research is necessary. Large studies are essential to conclusively determine whether certain DMTs may blunt SARS-CoV-2 antibody production, and whether this may increase reinfection risk in MS patients.

Jeanine Rempe Thornton reports no disclosures.

Asaff Harel has received research funding from the National Multiple Sclerosis Society and from the Consortium for Multiple Sclerosis Centers.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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