T cell responses to COVID-19 infection and vaccination in patients with multiple sclerosis receiving disease-modifying therapy

Abstract

Background: Multiple sclerosis (MS) is a neurological disorder marked by accumulating immune-mediated damage to the central nervous system. The dysregulated immune system in MS combined with immune effects of disease-modifying therapies (DMTs) used in MS treatment could alter responses to infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). Most of the literature on immune response to SARS-CoV-2 infection and COVID-19 vaccination, in both the general population and patients with MS on DMTs, has focused on humoral immunity. However, immune response to COVID-19 involves multiple lines of defense, including T cells.

Objective and methods: We review innate and adaptive immunity to COVID-19 and expand on the role of T cells in mediating protective immunity against SARS-CoV-2 infection and in responses to COVID-19 vaccination in MS.

Results: Innate, humoral, and T cell immune responses combat COVID-19 and generate protective immunity. Assays detecting cytokine expression by T cells show an association between SARS-CoV-2-specific T cell responses and milder/asymptomatic COVID-19 and protective immune memory.

Conclusion: Studies of COVID-19 immunity in people with MS on DMTs should ideally include comprehensive assessment of innate, humoral, and T cell responses.

Keywords: COVID-19; SARS-CoV-2; T cell; disease-modifying therapy; multiple sclerosis.

Figure 1.

SARS-CoV-2-specific humoral and T cell responses in patients with MS. *Other DMT refers to GA, IFN-β, teriflunomide, fumarates, cladribine, natalizumab, alemtuzumab, and S1P modulators. In patients with MS, humoral and cellular immune responses to SARS-CoV-2 infection and COVID-19 vaccination depend on the DMT. Patients with MS on RTX, OCR, OMB, or S1P receptor modulators exhibit decreased SARS-CoV-2-specific humoral responses compared with healthy controls. RTX-, OCR-, and OMB-treated patients still mount SARS-CoV-2-specific T cell responses, but S1P-treated patients may have reduced T cell responses. Patients with MS on other DMTs, including GA, IFN-β, teriflunomide, fumarates, cladribine, natalizumab, and alemtuzumab, also generate virus-specific T cell responses. Treatment with RTX, OCR, OMB, or non-S1P-modulating oral therapies was associated with enhanced T cell response after a two-dose vaccination with a mRNA COVID-19 vaccine. Ab: antibody; COVID-19: coronavirus disease 2019; DMT: disease-modifying therapy; GA: glatiramer acetate; HC: healthy control; IFN: interferon; OCR: ocrelizumab; OMB: ofatumumab; RTX: rituximab; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; S1P: sphingosine 1-phosphate.