The Italian Researchers have done some of the largest studies on COVID19.
We have seen that anti-CD20 antibodies and fingolimod inhibit antibody production and fingolimod inhibit T cell responses and you therefore would expect that break through infections in these groups would be a problem. When looking at delta infections there was a small increased risk but there were very few such breakthrough infections, with omicron it appears that ant-CD20 may be associated with breakthrough, but not fingolimod. Not sure how to explain this but something is odd about fingolimod and remember that early data showed no increase risk with fingolimod. So this data is consistent
Is is open source so have a read if interested.
Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy.Sormani MP, Schiavetti I, Inglese M, Carmisciano L, Laroni A, Lapucci C, Visconti V, Serrati C, Gandoglia I, Tassinari T, Perego G, Brichetto G, Gazzola P, Mannironi A, Stromillo ML, Cordioli C, Landi D, Clerico M, Signoriello E, Cocco E, Frau J, Ferrò MT, Di Sapio A, Pasquali L, Ulivelli M, Marinelli F, Pizzorno M, Callari G, Iodice R, Liberatore G, Caleri F, Repice AM, Cordera S, Battaglia MA, Salvetti M, Franciotta D, Uccelli A; CovaXiMS study group.EBioMedicine. 2022 May 5;80:104042. doi: 10.1016/j.ebiom.2022.104042.
Background: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection.
Methods: This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months. The cumulative incidence of breakthrough Covid-19 cases in pwMS was calculated before and after December 2021, to separate the Delta from the Omicron waves and to account for the advent of the third vaccine dose.
Findings: 1705 pwMS received 2 m-RNA vaccine doses, 21/28 days apart. Of them, 1508 (88.5%) had blood assessment 4 weeks after the second vaccine dose and 1154/1266 (92%) received the third dose after a mean interval of 210 days (range 90-342 days) after the second dose. During follow-up, 131 breakthrough Covid-19 infections (33 during the Delta and 98 during the Omicron wave) were observed. The probability to be infected during the Delta wave was associated with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.57, p < 0.001); the protective role of antibodies was preserved over the whole follow up (HR=0.57, 95%CI=0.43-0.75, p < 0.001), with a significant reduction (HR=1.40, 95%CI=1.01-1.94, p=0.04) for the Omicron cases. The third dose significantly reduced the risk of infection (HR=0.44, 95%CI=0.21-0.90,p=0.025) during the Omicron wave.
Interpretation: The risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response.
Online ahead of print.