Case report: Variant-specific pre-exposure prophylaxis of SARS-CoV-2 infection in multiple sclerosis patients lacking vaccination responses

Abstract

Sphingosine-1-phosphate receptor modulators and anti-CD20 treatment are widely used disease-modifying treatments for multiple sclerosis. Unfortunately, they may impair the patient’s ability to mount sufficient humoral and T-cellular responses to vaccination, which is of special relevance in the context of the SARS-CoV-2 pandemic. We present here a case series of six multiple sclerosis patients on treatment with sphingosine-1-phosphate receptor modulators who failed to develop SARS-CoV-2-specific antibodies and T-cells after three doses of vaccination. Due to their ongoing immunotherapy, lacking vaccination response, and additional risk factors, we offered them pre-exposure prophylactic treatment with monoclonal SARS-CoV-2-neutralizing antibodies. Initially, treatment was conducted with the antibody cocktail casirivimab/imdevimab. When the SARS-CoV-2 Omicron variant became predominant, we switched treatment to monoclonal antibody sotrovimab due to its sustained neutralizing ability also against the Omicron strain. Since sotrovimab was approved only for the treatment of COVID-19 infection and not for pre-exposure prophylaxis, we switched treatment to tixagevimab/cilgavimab as soon as it was granted marketing authorization in the European Union. This antibody cocktail has retained, albeit reduced, neutralizing activity against the Omicron variant and is approved for pre-exposure prophylaxis. No severe adverse events were recorded for our patients. One patient had a positive RT-PCR for SARS-CoV-2 under treatment with sotrovimab, but was asymptomatic. The other five patients did not develop symptoms of an upper respiratory tract infection or evidence of a SARS-CoV-2 infection during the time of treatment up until the finalization of this report. SARS-CoV-2-neutralizing antibody treatment should be considered individually for multiple sclerosis patients lacking adequate vaccination responses on account of their immunomodulatory treatment, especially in times of high incidences of SARS-CoV-2 infection.

Systematic review of the clinical effectiveness of Tixagevimab/Cilgavimab for prophylaxis of COVID-19 in immunocompromised patients

“…It included studies from the United States, France, Israel, Belgium, Spain and the United Kingdom. This review included ten retrospective cohort studies 12,[16][17][18][19][20][22][23][24][25] (including two preprints 16,20 ), six prospective, observational cohort studies [26][27][28][29][30][31] (also including one preprint…”

“…It is important to note that three studies Of the eleven cohort studies without controls, six were prospective [26][27][28][29][30][31] and five were retrospective 12,[22][23][24][25] .…”

“…8,12,[16][17][18][19][20][22][23][24][25][27][28][29][30][31] (RRR: relative risk ratio; HR: hazard ratio; IRR: incidence risk ratio; OR: odds ratio; IQR: interquartile range)Neutralising ability of patient seraThis systematic review included 17 large scale human studies, including a total of 24,773 immunocompromised participants, of whom 10,775 received Tixagevimab/Cilgavimab as a prophylactic antibody therapy. While our findings are generally positive, it should be acknowledged that the real-world studies differed in quality.…”

The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination

“…However, blocking the serological responses to infection and/or vaccination in immunosuppressed-individuals have supported the need for effective anti-viral treatments. Monoclonal antibodies often generated from COVID-19 convalescent individuals have shown promise in protecting individuals from infection ( Planas et al, 2022 , Wang et al, 2022 , Focosi et al, 2022 , Woopen et al, 2022 Jul 25 ). There, is limited expression of S1PR receptors, except for S1PR4, by polymorphonuclear neutrophils and neutropenia is not typically associated with S1PR modulation and may control egress from inflamed tissues ( Harris et al, 2020 , Sehr et al, 2020 , Mao-Draayer et al, 2017 ).…”

“…There is therefore limited reason to believe that S1PR would directly influence viral activity via antibodies or a direct effect on viral activity. However, poor viral elimination in SARS-CoV-2 neutralizing antibody-treated and immunosuppressed people can support the selection of immune escape variants that can render SARS-CoV-2-specific neutralizing antibodies such as casirivimab/imdevimab, tixagevimab/cilgavimab and sotrovimab to become rather ineffective as the SARS-CoV-2 virus evolves ( Shrestha et al, 2022 , Scherer et al, 2022 , Ohashi et al, 2022 , Planas et al, 2022 , Wang et al, 2022 , Woopen et al, 2022 Jul 25 , Magnè et al, 2022 ). Therefore, alternative strategies are needed.…”