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. Funding: Supported by FISM - Fondazione Italiana Sclerosi Multipla – cod. 2021/Special-Multi/001 and financed or co-financed with the ‘5 per mille’ public funding
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, M. P.; 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, M. L.; Cordioli, C.; Landi, D.; Clerico, M.; Signoriello, E.; Cocco, E.; Frau, J.; Ferro, M. T.; Di Sapio, A.; Pasquali, L.; Ulivelli, M.; Marinelli, F.; Pizzorno, M.; Callari, G.; Iodice, R.; Liberatore, G.; Caleri, F.; Repice, A. M.; Cordera, S.; Battaglia, M. A.; Salvetti, M.; Franciotta, D.; Uccelli, A.. - In: EBIOMEDICINE. - ISSN 2352-3964. - 80:(2022), p. 104042. [10.1016/j.ebiom.2022.104042]
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 M. P.;Inglese M.;Visconti V.;Perego G.;Landi D.;Battaglia M. A.;Salvetti M.;Uccelli A.
2022
Abstract
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. Funding: Supported by FISM - Fondazione Italiana Sclerosi Multipla – cod. 2021/Special-Multi/001 and financed or co-financed with the ‘5 per mille’ public fundingI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
