EBioMedicine (Jun 2022)

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

  • Maria Pia Sormani,
  • Irene Schiavetti,
  • Matilde Inglese,
  • Luca Carmisciano,
  • Alice Laroni,
  • Caterina Lapucci,
  • Valeria Visconti,
  • Carlo Serrati,
  • Ilaria Gandoglia,
  • Tiziana Tassinari,
  • Germana Perego,
  • Giampaolo Brichetto,
  • Paola Gazzola,
  • Antonio Mannironi,
  • Maria Laura Stromillo,
  • Cinzia Cordioli,
  • Doriana Landi,
  • Marinella Clerico,
  • Elisabetta Signoriello,
  • Eleonora Cocco,
  • Jessica Frau,
  • Maria Teresa Ferrò,
  • Alessia Di Sapio,
  • Livia Pasquali,
  • Monica Ulivelli,
  • Fabiana Marinelli,
  • Matteo Pizzorno,
  • Graziella Callari,
  • Rosa Iodice,
  • Giuseppe Liberatore,
  • Francesca Caleri,
  • Anna Maria Repice,
  • Susanna Cordera,
  • Mario Alberto Battaglia,
  • Marco Salvetti,
  • Diego Franciotta,
  • Antonio Uccelli,
  • Alessandro Maglione,
  • Alessia Di Sapio,
  • Alessio Signori,
  • Alice Laroni,
  • Aniello Iovino,
  • Anna Maria Repice,
  • Antonio Mannironi,
  • Antonio Uccelli,
  • Carlo Serrati,
  • Carolina Gabri Nicoletti,
  • Caterina Lapucci,
  • Chiara Rosa Mancinelli,
  • Cinzia Cordioli,
  • Daiana Bezzini,
  • Daniele Carmagnini,
  • Davide Brogi,
  • Diego Franciotta,
  • Doriana Landi,
  • Eduardo Nobile Orazio,
  • Eleonora Cocco,
  • Elisabetta Signoriello,
  • Enri Nako,
  • Ester Assandrir,
  • Fabiana Marinelli,
  • Federica Baldi,
  • Filippo Ansaldi,
  • Francesca Bovis,
  • Francesca Caleri,
  • Gabriele Siciliano,
  • Gaia Cola,
  • Germana Perego,
  • Giacomo Lus,
  • Giampaolo Brichetto,
  • Giancarlo Icardi,
  • Gianmarco Bellucci,
  • Giorgio Da Rin,
  • Girolama Alessandra Marfia,
  • Giulia Vazzoler,
  • Giuseppe Liberatore,
  • Giuseppe Trivelli,
  • Graziella Callari,
  • Ilaria Gandoglia,
  • Ilaria Maietta,
  • Irene Schiavetti,
  • Jessica Frau,
  • Laura Sticchi,
  • Livia Pasquali,
  • Lorena Lorefice,
  • Luca Carmisciano,
  • Lucia Ruggiero,
  • Marcello Manzino,
  • Marco Salvetti,
  • Margherita Monti Bragadin,
  • Maria Chiara Buscarinu,
  • Maria Gagliardi,
  • Maria Laura Stromillo,
  • Maria Pia Sormani,
  • Maria Teresa Ferrò,
  • Maria Teresa Rilla,
  • Marinella Clerico,
  • Mario Alberto Battaglia,
  • Marta Ponzano,
  • Marzia Fronza,
  • Massimo Del Sette,
  • Matilde Inglese,
  • Matteo Scialabba,
  • Michele Bedognetti,
  • Monica Ulivelli,
  • Nicola De Rossi,
  • Nicola De Stefano,
  • Paola Gazzola,
  • Rachele Bigi,
  • Raffaele Dubbioso,
  • Roberta Reniè,
  • Rosa Iodice,
  • Sabrina Fabbri,
  • Sarah Rasia,
  • Simona Rolla,
  • Stefan Platzgummer,
  • Susanna Cordera,
  • Tiziana Tassinari,
  • Valentina Carlini

Journal volume & issue
Vol. 80
p. 104042

Abstract

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Summary: 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

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