Severe breakthrough COVID-19 in vaccinated patients with multiple sclerosis

A 50-year-old multiple-sclerosis patient fails to mount a humoral response after the first, second and third Moderna vaccination and even after COVID-19.

A 50-year-old female with relapsing remitting multiple sclerosis since 2013, treated with ocrelizumab since 2018, was vaccinated with Spikevax (Moderna) in April and May 2021 and received the booster vaccination in October. One to two weeks prior to the ocrelizumab infusions in March and September 2021 the patient was B-cell depleted. Eleven days after the booster vaccination the patient was tested positive for SARS-CoV-2 by PCR. She experienced symptoms of dyspnea and fever and was admitted to the hospital for eleven days where she was treated with oxygen and dexamethasone. After each vaccination and even 28 days after third vaccination and 17 days after positive SARS-CoV-2 PCR, the patient remained negative for anti-RBD as well as anti-nucleocapsid protein antibodies. The patient fully recovered from COVID-19, however two months after the breakthrough infection (December 2021) she still complained of increased cognitive deficit.


pooled analysis of cohort studies on COVID-19 in patients with MS published until July 31, 2021, suggests a 24%-increased risk of death from COVID-19 in patients with MS. Of 126 MS patients with COVID-19 (mean age 43.2 years [SD 13.4], 71% female), 86.5% had a mild course, 9.5% a severe course and 3.2% (4) died from COVID-19. These 4 people were 64- and 59-year-old females, 61- and 79-year-old males. 

MS patients have a higher risk of a breakthrough infection - especially if they are on ocrelizumab or fingolimod, but there are no estimates for its severity yet. History of severe allergic reactions in this population was related to severe COVID-19 after vaccination. 

In a small study of 13 patients, only 2 patients (15.4%), both on anti-CD20 therapy, required hospitalization and steroid treatment. Neither required Intensive Care Unit admission. one patient on fingolimod died from breakthrough COVID-19. In another study of 114 vaccinated individuals, 7 cases - all among those receiving fingolimod or anti-CD20 therapies (aCD20) - required hospitalization due to Coronavirus disease, one person died, and the rest recovered without complications. 

American TV News anchor Neil Cavuto is a notable example of a vaccinated and boosted MS patient who experienced COVID-19 twice, 2nd time during Omicron wave in severe form.

12/27/2022 Edit: A recent paper suggested that SARS-COV-2 omicron breakthrough infections were more prevalent in patients with MS on anti-CD20 therapies and S1PR modulators compared with other patients with MS, which correlates with decreased humoral responses after vaccination. Humoral responses after infection were higher in S1PR modulator-treated patients in comparison to patients on anti-CD20 therapies, suggesting that immunological protection from contracting infection or repeated exposures may differ between these therapies.


van Kempen ZL, Kummer LY, Wieske L, Rispens T, Eftimov F, Killestein J. Severe breakthrough COVID-19 after SARS-CoV-2 booster vaccination in an MS patient on ocrelizumab. Neuroimmunology Reports. 2022 Jan 30:100072.

Bsteh G, Assar H, Hegen H, Heschl B, Leutmezer F, Di Pauli F, Gradl C, Traxler G, Zulehner G, Rommer P, Wipfler P. COVID-19 severity and mortality in multiple sclerosis are not associated with immunotherapy: Insights from a nation-wide Austrian registry. PloS one. 2021 Jul 27;16(7):e0255316.

Prosperini L, Tortorella C, Haggiag S, Ruggieri S, Galgani S, Gasperini C. Increased risk of death from COVID-19 in multiple sclerosis: a pooled analysis of observational studies. Journal of Neurology. 2021 Sep 17:1-7.

Rose DR, Mahadeen AZ, Carlson AK, Planchon SM, Sedlak J, Husak S, Bermel RA, Cohen JA, Moss BP. Clinical features and outcomes of COVID-19 despite SARS-CoV-2 vaccination in people with multiple sclerosis. Multiple Sclerosis Journal–Experimental, Translational and Clinical. 2021 Oct;7(4):20552173211057110. 

Etemadifar M, Abhari AP, Nouri H, Eighani N, Salari M, Sedaghat N. Effect of Disease-Modifying Therapies on Clinical Efficacy of COVID-19 Inactivated Vaccination among People with Multiple Sclerosis. Available at SSRN 3998537. 2022.


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