Advertisement

Incidence of COVID-19 after vaccination in people with multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM

Published:August 11, 2022DOI:https://doi.org/10.1016/j.msard.2022.104104

      Highlights

      • Incidence of COVID-19 after vaccination in MS patients in Argentina was evaluated.
      • Cohort study conducted between May 2021 and December 2021.
      • twenty COVID-19 cases were observed for a total exposure time of 39557 days.
      • overall cumulative incidence for the observed period was 3.4% (SE 0.4%).
      • overall incidence density of 5 × 10.000 patients/day (95%CI 0.7–12).

      Abstract

      The objective of the study was to evaluate the incidence of COVID-19 after complete vaccination in people with multiple sclerosis (PwMS) included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177).

      Methods

      cohort study conducted between May 2021 and December 2021. The primary outcome was the appearance of infection during the follow-up time (at least three months after complete vaccination (second dose)). Data was collected through the contact between the treating physician and the patient. Specific information was requested (date, symptoms, need for hospitalization, ventilatory assistance, treatment, and evolution). The contact was made every 30 days during the period of 3 months after the full dose vaccination. A positive COVID-19 case was defined according to the definition established by the Ministry of Health in Argentina. Cumulative incidence was reported by Kaplan Meier survival curves as well as incidence density.

      Results

      A total of 576 PwMS were included, mean age 45.2 ± 13 years, 432 (75%) RRMS, 403 (70%) were female. The mean and median time of follow-up after the second dose was 91 ± 17 and 94 ± 21 days respectively. Most frequent first and second dose received was Astra-Zeneca vaccine, followed by Sputnik V vaccine. During follow-up a total of twenty COVID-19 cases were observed for a total exposure time of 39,557 days. The overall cumulative incidence for the observed period was 3.4% (SE 0.4%) with an overall incidence density of 5 × 10.000 patients/day (95%CI 0.7–12). We observed more cases in woman than men with an incidence density of 6 × 10.000 patients/day (95%CI 0.9–9) vs. 3 × 10.000 patients/day (95%CI 0.2–6) respectively, but not significantly different (IRR 1.7 95% CI 0.56–7.37 p = 0.15).

      Conclusion

      we found an incidence density of breakthrough COVID-19 infection of 5 × 10.000 patients/day (95%CI 0.7–12) after vaccination in Argentina.

      Keywords

      1. Introduction

      Different vaccines have been evaluated and implemented to achieve immunization against COVID-19 in the world (
      • Achiron A.
      • Dolev M.
      • Menascu S.
      • Zohar D.N.
      • Dreyer-Alster S.
      • Miron S.
      • Shirbint E.
      • Magalashvili D.
      • Flechter S.
      • Givon U.
      • Guber D.
      • Stern Y.
      • Polliack M.
      • Falb R.
      • Gurevich M.
      COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021.
      ;
      • Alonso R.
      • Chertcoff A.
      • Leguizamon F.D.V.
      • Galleguillos Goiry L.
      • Eizaguirre M.B.
      • Rodriguez R.
      • Sosa M.
      • Carballido S.
      • Cruchet V.
      • de Jong-Martis A.
      • Giachello S.
      • Henestroza P.
      • Ferrandina F.
      • Bauer J.
      • Carra A.
      • Silva B.A.
      Evaluation of short-term safety of COVID-19 vaccines in patients with multiple sclerosis from Latin America.
      ,
      • Alonso R.
      • Silva B.
      • Garcea O.
      • Diaz P.E.C.
      • Dos Passos G.R.
      • Navarro D.A.R.
      • Valle L.A.G.
      • Salinas L.C.R.
      • Negrotto L.
      • Luetic G.
      • Tkachuk V.A.
      • Miguez J.
      • de Bedoya F.H.D.
      • Goiry L.G.
      • Sanchez N.E.R.
      • Burgos M.
      • Steinberg J.
      • Balbuena M.E.
      • Alvarez P.M.
      • Lopez P.A.
      • Ysrraelit M.C.
      • Leon R.A.
      • Cohen A.B.
      • Gracia F.
      • Molina O.
      • Casas M.
      • Deri N.H.
      • Pappolla A.
      • Patrucco L.
      • Cristiano E.
      • Tavolini D.
      • Nadur D.
      • Granda A.M.T.
      • Weiser R.
      • Cassara F.P.
      • Sinay V.
      • Rodriguez C.C.
      • Lazaro L.G.
      • Menichini M.L.
      • Piedrabuena R.
      • Escobar G.O.
      • Carra A.
      • Chertcoff A.
      • Pujols B.S.
      • Vrech C.
      • Tarulla A.
      • Carvajal R.
      • Mainella C.
      • Becker J.
      • Peeters L.M.
      • Walton C.
      • Serena M.A.
      • Nunez S.
      • Rojas J.I.
      COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America: COVID-19 in MS and NMOSD patients in LATAM.
      ;
      • Belete T.M.
      Review on up-to-date status of candidate vaccines for COVID-19 disease.
      )
      In people with multiple sclerosis (PwMS), during the last months, several publications have demonstrated evidence about the effect of vaccination against COVID-19 mainly on serological responses and, to a minor extent, on T cell response (
      • Achiron A.
      • Dolev M.
      • Menascu S.
      • Zohar D.N.
      • Dreyer-Alster S.
      • Miron S.
      • Shirbint E.
      • Magalashvili D.
      • Flechter S.
      • Givon U.
      • Guber D.
      • Stern Y.
      • Polliack M.
      • Falb R.
      • Gurevich M.
      COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021.
      ;
      • Brill L.
      • Rechtman A.
      • Zveik O.
      • Haham N.
      • Oiknine-Djian E.
      • Wolf D.G.
      • Levin N.
      • Raposo C.
      • Vaknin-Dembinsky A.
      Humoral and T-cell response to SARS-CoV-2 vaccination in patients with multiple sclerosis treated with ocrelizumab.
      ;
      • Sahin U.
      • Muik A.
      • Derhovanessian E.
      • Vogler I.
      • Kranz L.M.
      • Vormehr M.
      • Baum A.
      • Pascal K.
      • Quandt J.
      • Maurus D.
      • Brachtendorf S.
      • Lorks V.
      • Sikorski J.
      • Hilker R.
      • Becker D.
      • Eller A.K.
      • Grutzner J.
      • Boesler C.
      • Rosenbaum C.
      • Kuhnle M.C.
      • Luxemburger U.
      • Kemmer-Bruck A.
      • Langer D.
      • Bexon M.
      • Bolte S.
      • Kariko K.
      • Palanche T.
      • Fischer B.
      • Schultz A.
      • Shi P.Y.
      • Fontes-Garfias C.
      • Perez J.L.
      • Swanson K.A.
      • Loschko J.
      • Scully I.L.
      • Cutler M.
      • Kalina W.
      • Kyratsous C.A.
      • Cooper D.
      • Dormitzer P.R.
      • Jansen K.U.
      • Tureci O.
      COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses.
      ;
      • Salter A.
      • Fox R.J.
      • Newsome S.D.
      • Halper J.
      • Li D.K.B.
      • Kanellis P.
      • Costello K.
      • Bebo B.
      • Rammohan K.
      • Cutter G.R.
      • Cross A.H.
      Outcomes and risk factors associated with SARS-CoV-2 infection in a North American registry of patients with multiple sclerosis.
      ). This was translated in a reduction in the frequency of PwMS infected post vaccination as well as a reduction in the severity of COVID-19 cases (
      • Achiron A.
      • Dolev M.
      • Menascu S.
      • Zohar D.N.
      • Dreyer-Alster S.
      • Miron S.
      • Shirbint E.
      • Magalashvili D.
      • Flechter S.
      • Givon U.
      • Guber D.
      • Stern Y.
      • Polliack M.
      • Falb R.
      • Gurevich M.
      COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021.
      ;
      • Brill L.
      • Rechtman A.
      • Zveik O.
      • Haham N.
      • Oiknine-Djian E.
      • Wolf D.G.
      • Levin N.
      • Raposo C.
      • Vaknin-Dembinsky A.
      Humoral and T-cell response to SARS-CoV-2 vaccination in patients with multiple sclerosis treated with ocrelizumab.
      ;
      • Sahin U.
      • Muik A.
      • Derhovanessian E.
      • Vogler I.
      • Kranz L.M.
      • Vormehr M.
      • Baum A.
      • Pascal K.
      • Quandt J.
      • Maurus D.
      • Brachtendorf S.
      • Lorks V.
      • Sikorski J.
      • Hilker R.
      • Becker D.
      • Eller A.K.
      • Grutzner J.
      • Boesler C.
      • Rosenbaum C.
      • Kuhnle M.C.
      • Luxemburger U.
      • Kemmer-Bruck A.
      • Langer D.
      • Bexon M.
      • Bolte S.
      • Kariko K.
      • Palanche T.
      • Fischer B.
      • Schultz A.
      • Shi P.Y.
      • Fontes-Garfias C.
      • Perez J.L.
      • Swanson K.A.
      • Loschko J.
      • Scully I.L.
      • Cutler M.
      • Kalina W.
      • Kyratsous C.A.
      • Cooper D.
      • Dormitzer P.R.
      • Jansen K.U.
      • Tureci O.
      COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses.
      ;
      • Salter A.
      • Fox R.J.
      • Newsome S.D.
      • Halper J.
      • Li D.K.B.
      • Kanellis P.
      • Costello K.
      • Bebo B.
      • Rammohan K.
      • Cutter G.R.
      • Cross A.H.
      Outcomes and risk factors associated with SARS-CoV-2 infection in a North American registry of patients with multiple sclerosis.
      )(
      • Belete T.M.
      Review on up-to-date status of candidate vaccines for COVID-19 disease.
      ;
      • Reyes S.
      • Cunningham A.L.
      • Kalincik T.
      • Havrdova E.K.
      • Isobe N.
      • Pakpoor J.
      • Airas L.
      • Bunyan R.F.
      • van der Walt A.
      • Oh J.
      • Mathews J.
      • Mateen F.J.
      • Giovannoni G.
      Update on the management of multiple sclerosis during the COVID-19 pandemic and post pandemic: an international consensus statement.
      ;
      • Sormani M.P.
      • Inglese M.
      • Schiavetti I.
      • Carmisciano L.
      • Laroni A.
      • Lapucci C.
      • Da Rin G.
      • 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.
      • Frau J.
      • Ferro M.T.
      • Di Sapio A.
      • Pasquali L.
      • Ulivelli M.
      • Marinelli F.
      • Callari G.
      • Iodice R.
      • Liberatore G.
      • Caleri F.
      • Repice A.M.
      • Cordera S.
      • Battaglia M.A.
      • Salvetti M.
      • Franciotta D.
      • Uccelli A.
      CovaXi, M.S.s.g.o.b.o.t.I.C.-A.i.M.S.
      Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.
      ;
      • Tortorella C.
      • Aiello A.
      • Gasperini C.
      • Agrati C.
      • Castilletti C.
      • Ruggieri S.
      • Meschi S.
      • Matusali G.
      • Colavita F.
      • Farroni C.
      • Cuzzi G.
      • Cimini E.
      • Tartaglia E.
      • Vanini V.
      • Prosperini L.
      • Haggiag S.
      • Galgani S.
      • Quartuccio M.E.
      • Salmi A.
      • Repele F.
      • Altera A.M.G.
      • Cristofanelli F.
      • D'Abramo A.
      • Bevilacqua N.
      • Corpolongo A.
      • Puro V.
      • Vaia F.
      • Capobianchi M.R.
      • Ippolito G.
      • Nicastri E.
      • Goletti D.
      Group, I.C.-V.S.
      Humoral- and T-cell-specific immune responses to SARS-CoV-2 mRNA vaccination in patients with MS using different disease-modifying therapies.
      ) . However, much of the information comes from studies done in Europe or North America and scarce studies were done to evaluate technologies like Sputnik, Astra-Zeneca or inactivated vaccines for COVID-19 in PwMS like Sinopharm as well as heterologous schemes of those vaccines (
      • Achiron A.
      • Dolev M.
      • Menascu S.
      • Zohar D.N.
      • Dreyer-Alster S.
      • Miron S.
      • Shirbint E.
      • Magalashvili D.
      • Flechter S.
      • Givon U.
      • Guber D.
      • Stern Y.
      • Polliack M.
      • Falb R.
      • Gurevich M.
      COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021.
      ;
      • Belete T.M.
      Review on up-to-date status of candidate vaccines for COVID-19 disease.
      ;
      • Brill L.
      • Rechtman A.
      • Zveik O.
      • Haham N.
      • Oiknine-Djian E.
      • Wolf D.G.
      • Levin N.
      • Raposo C.
      • Vaknin-Dembinsky A.
      Humoral and T-cell response to SARS-CoV-2 vaccination in patients with multiple sclerosis treated with ocrelizumab.
      ;
      • Reyes S.
      • Cunningham A.L.
      • Kalincik T.
      • Havrdova E.K.
      • Isobe N.
      • Pakpoor J.
      • Airas L.
      • Bunyan R.F.
      • van der Walt A.
      • Oh J.
      • Mathews J.
      • Mateen F.J.
      • Giovannoni G.
      Update on the management of multiple sclerosis during the COVID-19 pandemic and post pandemic: an international consensus statement.
      ;
      • Sahin U.
      • Muik A.
      • Derhovanessian E.
      • Vogler I.
      • Kranz L.M.
      • Vormehr M.
      • Baum A.
      • Pascal K.
      • Quandt J.
      • Maurus D.
      • Brachtendorf S.
      • Lorks V.
      • Sikorski J.
      • Hilker R.
      • Becker D.
      • Eller A.K.
      • Grutzner J.
      • Boesler C.
      • Rosenbaum C.
      • Kuhnle M.C.
      • Luxemburger U.
      • Kemmer-Bruck A.
      • Langer D.
      • Bexon M.
      • Bolte S.
      • Kariko K.
      • Palanche T.
      • Fischer B.
      • Schultz A.
      • Shi P.Y.
      • Fontes-Garfias C.
      • Perez J.L.
      • Swanson K.A.
      • Loschko J.
      • Scully I.L.
      • Cutler M.
      • Kalina W.
      • Kyratsous C.A.
      • Cooper D.
      • Dormitzer P.R.
      • Jansen K.U.
      • Tureci O.
      COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses.
      ;
      • Salter A.
      • Fox R.J.
      • Newsome S.D.
      • Halper J.
      • Li D.K.B.
      • Kanellis P.
      • Costello K.
      • Bebo B.
      • Rammohan K.
      • Cutter G.R.
      • Cross A.H.
      Outcomes and risk factors associated with SARS-CoV-2 infection in a North American registry of patients with multiple sclerosis.
      ;
      • Sormani M.P.
      • Inglese M.
      • Schiavetti I.
      • Carmisciano L.
      • Laroni A.
      • Lapucci C.
      • Da Rin G.
      • 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.
      • Frau J.
      • Ferro M.T.
      • Di Sapio A.
      • Pasquali L.
      • Ulivelli M.
      • Marinelli F.
      • Callari G.
      • Iodice R.
      • Liberatore G.
      • Caleri F.
      • Repice A.M.
      • Cordera S.
      • Battaglia M.A.
      • Salvetti M.
      • Franciotta D.
      • Uccelli A.
      CovaXi, M.S.s.g.o.b.o.t.I.C.-A.i.M.S.
      Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.
      ;
      • Tortorella C.
      • Aiello A.
      • Gasperini C.
      • Agrati C.
      • Castilletti C.
      • Ruggieri S.
      • Meschi S.
      • Matusali G.
      • Colavita F.
      • Farroni C.
      • Cuzzi G.
      • Cimini E.
      • Tartaglia E.
      • Vanini V.
      • Prosperini L.
      • Haggiag S.
      • Galgani S.
      • Quartuccio M.E.
      • Salmi A.
      • Repele F.
      • Altera A.M.G.
      • Cristofanelli F.
      • D'Abramo A.
      • Bevilacqua N.
      • Corpolongo A.
      • Puro V.
      • Vaia F.
      • Capobianchi M.R.
      • Ippolito G.
      • Nicastri E.
      • Goletti D.
      Group, I.C.-V.S.
      Humoral- and T-cell-specific immune responses to SARS-CoV-2 mRNA vaccination in patients with MS using different disease-modifying therapies.
      ).
      The objective of the study was to evaluate the incidence of COVID-19 infections after complete vaccination in PwMS in Argentina included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177).

      2. Methods

      This was an ambispective cohort study that started in May 2021 and finished in December 2021. The study was run on the current MS registry in Argentina, RelevarEM (
      • Rojas J.I.
      • Alonso Serena M.
      • Garcea O.
      • Patrucco L.
      • Carra A.
      • Correale J.
      • Vrech C.
      • Pappolla A.
      • Miguez J.
      • Doldan M.L.
      • Silveira F.
      • Alonso R.
      • Cohen L.
      • Pita C.
      • Silva B.A.
      • Fiol M.
      • Gaitan M.I.
      • Marrodan M.
      • Negrotto L.
      • Ysrraelit M.C.
      • Deri N.
      • Luetic G.
      • Caride A.
      • Carnero Contentti E.
      • Lopez P.A.
      • Pettinicchi J.P.
      • Curbelo C.
      • Martinez A.D.
      • Steinberg J.D.
      • Balbuena M.E.
      • Tkachuk V.
      • Burgos M.
      • Knorre E.
      • Leguizamon F.
      • Piedrabuena R.
      • Liwacki S.D.V.
      • Barboza A.G.
      • Nofal P.
      • Volman G.
      • Alvez Pinheiro A.
      • Hryb J.
      • Tavolini D.
      • Blaya P.A.
      • Silva E.
      • Blanche J.
      • Tizio S.
      • Caceres F.
      • Saladino M.L.
      • Zanga G.
      • Fracaro M.E.
      • Sgrilli G.
      • Pagani Cassara F.
      • Vazquez G.
      • Sinay V.
      • Menichini M.L.
      • Lazaro L.
      • Cabrera L.M.
      • Bestoso S.
      • Divi P.
      • Jacobo M.
      • Kohler E.
      • Kohler M.
      • Giunta D.
      • Mainella C.
      • Manzi R.
      • Parada Marcilla M.
      • Viglione J.P.
      • Martos I.
      • Reich E.
      • Jose G.
      • Cristiano E.
      • Fernandez Liguori N.
      on behalf Relevar, E.M.i.
      Multiple sclerosis and neuromyelitis optica spectrum disorders in Argentina: comparing baseline data from the Argentinean MS registry (RelevarEM).
      ,
      • Rojas J.I.
      • Carra A.
      • Correale J.
      • Cristiano E.
      • Fernandez Liguori N.
      • Alonso R.
      • Alvez Pinheiro A.
      • Balbuena M.E.
      • Barboza A.G.
      • Bestoso S.
      • Blaya P.A.
      • Burgos M.
      • Cabrera L.M.
      • Caride A.
      • Carnero Contentti E.
      • Cohen L.
      • Curbelo C.
      • Deri N.
      • Divi P.
      • Fiol M.
      • Fracaro M.E.
      • Gaitan M.I.
      • Hryb J.
      • Jacobo M.
      • Knorre E.
      • Leguizamon F.
      • Giunta D.
      • Alonso Serena M.
      • Doldan M.L.
      • De Lio G.F.
      • Liwacki S.D.V.
      • Lopez P.A.
      • Luetic G.
      • Mainella C.
      • Manzi R.
      • Marrodan M.
      • Martinez A.D.
      • Miguez J.
      • Negrotto L.
      • Nofal P.
      • Parada Marcilla M.
      • Pettinicchi J.P.
      • Silva B.A.
      • Silva E.
      • Silveira F.
      • Steinberg J.D.
      • Tavolini D.
      • Tizio S.
      • Tkachuk V.
      • Vazquez G.
      • Volman G.
      • Vrech C.
      • Ysrraelit M.C.
      • Zanga G.
      • Garcea O.
      • Patrucco L.
      The Argentinean multiple sclerosis registry (RelevarEM): methodological aspects and directions.
      ). RelevarEM is a longitudinal, strictly observational MS and neuromyeltis optica spectrum disorders (NMOSD) registry in Argentina (
      • Rojas J.I.
      • Alonso Serena M.
      • Garcea O.
      • Patrucco L.
      • Carra A.
      • Correale J.
      • Vrech C.
      • Pappolla A.
      • Miguez J.
      • Doldan M.L.
      • Silveira F.
      • Alonso R.
      • Cohen L.
      • Pita C.
      • Silva B.A.
      • Fiol M.
      • Gaitan M.I.
      • Marrodan M.
      • Negrotto L.
      • Ysrraelit M.C.
      • Deri N.
      • Luetic G.
      • Caride A.
      • Carnero Contentti E.
      • Lopez P.A.
      • Pettinicchi J.P.
      • Curbelo C.
      • Martinez A.D.
      • Steinberg J.D.
      • Balbuena M.E.
      • Tkachuk V.
      • Burgos M.
      • Knorre E.
      • Leguizamon F.
      • Piedrabuena R.
      • Liwacki S.D.V.
      • Barboza A.G.
      • Nofal P.
      • Volman G.
      • Alvez Pinheiro A.
      • Hryb J.
      • Tavolini D.
      • Blaya P.A.
      • Silva E.
      • Blanche J.
      • Tizio S.
      • Caceres F.
      • Saladino M.L.
      • Zanga G.
      • Fracaro M.E.
      • Sgrilli G.
      • Pagani Cassara F.
      • Vazquez G.
      • Sinay V.
      • Menichini M.L.
      • Lazaro L.
      • Cabrera L.M.
      • Bestoso S.
      • Divi P.
      • Jacobo M.
      • Kohler E.
      • Kohler M.
      • Giunta D.
      • Mainella C.
      • Manzi R.
      • Parada Marcilla M.
      • Viglione J.P.
      • Martos I.
      • Reich E.
      • Jose G.
      • Cristiano E.
      • Fernandez Liguori N.
      on behalf Relevar, E.M.i.
      Multiple sclerosis and neuromyelitis optica spectrum disorders in Argentina: comparing baseline data from the Argentinean MS registry (RelevarEM).
      ,
      • Rojas J.I.
      • Carra A.
      • Correale J.
      • Cristiano E.
      • Fernandez Liguori N.
      • Alonso R.
      • Alvez Pinheiro A.
      • Balbuena M.E.
      • Barboza A.G.
      • Bestoso S.
      • Blaya P.A.
      • Burgos M.
      • Cabrera L.M.
      • Caride A.
      • Carnero Contentti E.
      • Cohen L.
      • Curbelo C.
      • Deri N.
      • Divi P.
      • Fiol M.
      • Fracaro M.E.
      • Gaitan M.I.
      • Hryb J.
      • Jacobo M.
      • Knorre E.
      • Leguizamon F.
      • Giunta D.
      • Alonso Serena M.
      • Doldan M.L.
      • De Lio G.F.
      • Liwacki S.D.V.
      • Lopez P.A.
      • Luetic G.
      • Mainella C.
      • Manzi R.
      • Marrodan M.
      • Martinez A.D.
      • Miguez J.
      • Negrotto L.
      • Nofal P.
      • Parada Marcilla M.
      • Pettinicchi J.P.
      • Silva B.A.
      • Silva E.
      • Silveira F.
      • Steinberg J.D.
      • Tavolini D.
      • Tizio S.
      • Tkachuk V.
      • Vazquez G.
      • Volman G.
      • Vrech C.
      • Ysrraelit M.C.
      • Zanga G.
      • Garcea O.
      • Patrucco L.
      The Argentinean multiple sclerosis registry (RelevarEM): methodological aspects and directions.
      ). It is open to all practicing neurologists and MS specialists and their teams across the country. The registry tracks the outcomes of routine clinical practice of patients with MS and NMOSD in a web-based platform that allows researchers to register and follow up their patients. The primary objective of the registry was to create an MS physician network in Argentina that captures pragmatic and relevant information from MS patients in terms of clinical and demographic aspects (
      • Rojas J.I.
      • Alonso Serena M.
      • Garcea O.
      • Patrucco L.
      • Carra A.
      • Correale J.
      • Vrech C.
      • Pappolla A.
      • Miguez J.
      • Doldan M.L.
      • Silveira F.
      • Alonso R.
      • Cohen L.
      • Pita C.
      • Silva B.A.
      • Fiol M.
      • Gaitan M.I.
      • Marrodan M.
      • Negrotto L.
      • Ysrraelit M.C.
      • Deri N.
      • Luetic G.
      • Caride A.
      • Carnero Contentti E.
      • Lopez P.A.
      • Pettinicchi J.P.
      • Curbelo C.
      • Martinez A.D.
      • Steinberg J.D.
      • Balbuena M.E.
      • Tkachuk V.
      • Burgos M.
      • Knorre E.
      • Leguizamon F.
      • Piedrabuena R.
      • Liwacki S.D.V.
      • Barboza A.G.
      • Nofal P.
      • Volman G.
      • Alvez Pinheiro A.
      • Hryb J.
      • Tavolini D.
      • Blaya P.A.
      • Silva E.
      • Blanche J.
      • Tizio S.
      • Caceres F.
      • Saladino M.L.
      • Zanga G.
      • Fracaro M.E.
      • Sgrilli G.
      • Pagani Cassara F.
      • Vazquez G.
      • Sinay V.
      • Menichini M.L.
      • Lazaro L.
      • Cabrera L.M.
      • Bestoso S.
      • Divi P.
      • Jacobo M.
      • Kohler E.
      • Kohler M.
      • Giunta D.
      • Mainella C.
      • Manzi R.
      • Parada Marcilla M.
      • Viglione J.P.
      • Martos I.
      • Reich E.
      • Jose G.
      • Cristiano E.
      • Fernandez Liguori N.
      on behalf Relevar, E.M.i.
      Multiple sclerosis and neuromyelitis optica spectrum disorders in Argentina: comparing baseline data from the Argentinean MS registry (RelevarEM).
      ,
      • Rojas J.I.
      • Carra A.
      • Correale J.
      • Cristiano E.
      • Fernandez Liguori N.
      • Alonso R.
      • Alvez Pinheiro A.
      • Balbuena M.E.
      • Barboza A.G.
      • Bestoso S.
      • Blaya P.A.
      • Burgos M.
      • Cabrera L.M.
      • Caride A.
      • Carnero Contentti E.
      • Cohen L.
      • Curbelo C.
      • Deri N.
      • Divi P.
      • Fiol M.
      • Fracaro M.E.
      • Gaitan M.I.
      • Hryb J.
      • Jacobo M.
      • Knorre E.
      • Leguizamon F.
      • Giunta D.
      • Alonso Serena M.
      • Doldan M.L.
      • De Lio G.F.
      • Liwacki S.D.V.
      • Lopez P.A.
      • Luetic G.
      • Mainella C.
      • Manzi R.
      • Marrodan M.
      • Martinez A.D.
      • Miguez J.
      • Negrotto L.
      • Nofal P.
      • Parada Marcilla M.
      • Pettinicchi J.P.
      • Silva B.A.
      • Silva E.
      • Silveira F.
      • Steinberg J.D.
      • Tavolini D.
      • Tizio S.
      • Tkachuk V.
      • Vazquez G.
      • Volman G.
      • Vrech C.
      • Ysrraelit M.C.
      • Zanga G.
      • Garcea O.
      • Patrucco L.
      The Argentinean multiple sclerosis registry (RelevarEM): methodological aspects and directions.
      ). Eligible subjects were contacted by their neurologist. Once the patient was included data was collected about demographic and clinical data of the disease (age at vaccination, EDSS at study entry, ongoing treatment, MS phenotype, and comorbidities); vaccine received at first dose, second dose, dose, and dates; adverse events of vaccination and follow up time. Patients were actively followed during at least three months since the second dose of COVID-19 vaccine (complete suggested vaccine scheme).
      The primary outcome was the appearance of infection during the follow up time (at least three months after complete vaccination (second dose of vaccination)). This data was collected through the contact between the treating physician and the patient to assess whether they were infected in that period. If the answer was affirmative, specific information was requested from the treating physician regarding the infection (date, symptoms, need for hospitalization, ventilatory assistance, treatment, and evolution). The contact was made every 30 days during the period of 3 months after the full dose vaccination was done and the contact by the doctor was proactive, contacting the patient to obtain data on this result (
      • Sormani M.P.
      • Inglese M.
      • Schiavetti I.
      • Carmisciano L.
      • Laroni A.
      • Lapucci C.
      • Da Rin G.
      • 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.
      • Frau J.
      • Ferro M.T.
      • Di Sapio A.
      • Pasquali L.
      • Ulivelli M.
      • Marinelli F.
      • Callari G.
      • Iodice R.
      • Liberatore G.
      • Caleri F.
      • Repice A.M.
      • Cordera S.
      • Battaglia M.A.
      • Salvetti M.
      • Franciotta D.
      • Uccelli A.
      CovaXi, M.S.s.g.o.b.o.t.I.C.-A.i.M.S.
      Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.
      ). It was defined as a positive COVID-19 case according to the definition established by the Ministry of Health in Argentina. This implies performing a PCR or Antigen test at least as a microbiological confirmation, or in the absence of laboratory confirmation, a close contact with a COVID-19 case and compatible symptoms was considered a confirmed case.
      A specific form was developed to collect the data of the research project. The form was added to the RelevarEM registry as a vaccination sub form to follow every patient.

      3. Sample

      All patients diagnosed with MS included in RelevarEM who received the vaccine were invited to participate in the study. To reduce the possibility of selection bias, we seek to include all professionals in Argentina who oversee caring for patients with MS in Argentina and are active members of RelevarEM.
      Each center submitted the project for approval following the competent local regulations.
      An institutional ethics committee approved the registration or declare that it is exempt from the need for approval as well as its informed consent (IC).

      4. Statistical analysis

      Baseline characteristics of the cohort were reported in percentages for categorical data and in median and range or mean ± SD for continuous data. Only patients with a complete vaccination scheme (at least two doses) and at least three months follow up were included in the analysis. Cumulative incidence of COVID-19 infections was reported for the entire cohort by Kaplan Meier survival curves as well as incidence density. Sub-analysis of incidence of infection by gender, vaccine received and homologous or heterologous scheme during follow up was also done.

      5. Results

      A total of 576 PwMS were included during the study period that started in May 2021 and finished in December 2021. The mean age of included patients was 45.2 ± 13 years, mean disease duration 10.7 ± 6.4 years, 432 (75%) were RRMS, 403 (70%) were female, median EDSS 2.7 ± 2. The rest demographic and clinical variables are shown in Table 1.
      Table 1Baseline characteristics of included patients.
      N = 576
      Mean age at study entry, years (SD)45.2 (13)
      Mean disease duration, years (SD)10.7 (6.4)
      RRMS, n (%)432 (75)
      SPMS, n (%)67 (11.6)
      PPMS77 (13.4)
      Female gender, n (%)403 (70)
      Median EDSS, (SD)2.7 (2.0)
      Interferon beta, n (%)84 (14.58)
      Glatiramer acetate, n (%)43 (7.47)
      Teriflunomide, n (%)50 (8.68)
      Fingolimod, n (%)102 (17.71)
      Dimethylfumarate, n (%)25 (4.34)
      Natalizumab, n (%)48 (8.33)
      Alemtuzumab, n (%)25 (4.34)
      Ocrelizumab, n (%)33 (5.73)
      Rituximab, n (%)9 (1.56)
      Cladribine, n (%)37 (6.42)
      No treatment120 (20.83)
      Median Charlson score of comorbidities, (SD)0.23 (0.52)
      RRMS= relapsing remitting multiple sclerosis; SPMS= secondary progressive multiple sclerosis; PPMS= primary progressive multiple sclerosis; EDSS= expanded disability status scale; SD= standard deviation.
      The mean and median time of follow up after the second dose in included patients was 91 ± 17 and 94 ± 21 days and 55 (9.5%) patients reported to be infected by COVID-19 pre-vaccination (Table 2). Most frequent first and second dose received was Astra-Zeneca vaccine, followed by Sputnik vaccine (Table 2) and when homologous or heterologous scheme was described, 82.5% received a homologous scheme (Sputnik-Sputnik or Astra Zeneca-Astra Zeneca or Sinopharm-Sinopharm) vs. 17.5% that received and heterologous scheme of vaccination to complete the scheme (Table 2).
      Table 2Follow up time and vaccines received in included patients.
      N = 576
      Median follow up time after second dose, days (SD)94 ± 21
      Mean follow up time after second dose, days91 ± 17
      Previous covid infection, n (%)55 (9.54%)
      First dose vaccine received
      Sputnik V, n (%)172 (29.86%)
      Astra Zeneca, n (%)283(49.3%)
      Sinopharm106 (18.40%)
      Jansens15(2.6%)
      Second dose vaccine received
      Sputnik V, n (%)123(21.35%)
      Astra Zeneca, n (%)312(54.16%)
      Sinopharm94 (16.3%)
      Moderna26 (4.51)
      Pfizer21(3.64)
      Median time between first and second vaccine dose, (SD)55±18
      Homologous vaccine scheme, n (%)475 (82.5)
      Heterologous vaccine scheme, n (%)101 (17.5)
      SD= standard deviation.
      During follow up a total of twenty COVID-19 cases were observed for a total exposure time of 39,557 days (only one case of hospitalization due severe COVID-19 infection was reported in a patient treated with ocrelizumab) (Table 3). The overall cumulative incidence for the observed period was 3.4% (SE 0.4%) with an overall incidence density of 5 × 10.000 patients/day (95%CI 0.7–12) (Table 3). When we stratified the sample, we observed more cases in woman than men in the incidence density 6 × 10.000 patients/day (95%CI 0.9–9) vs. 3 × 10.000 patients/day (95%CI 0.2–6) respectively, but not significantly (IRR 1.7 95% CI 0.56–7.37 p = 0.15) as well as in the homologous scheme vs heterologous scheme (incidence density 5 × 10.000 patients per day (95%CI 0.8–8) vs. 1 × 10.000 patients per day (95%CI 0.02–3) respectively, IRR 3.77, 95%CI 0.59- 26, p = 0.15) Table 3).
      Table 3Incidence of COVID-19 after vaccination.
      Breakthrough COVID-19 infections during follow up (n)20
      Hospitalizations cases of COVID-19 infections, n1
      Total exposure time (days)39,557
      Overall cumulative incidence of infection3.4% (SE 0.4%)
      Overall incidence density of infection5 × 10.000 patients/day (95%CI 0.7–12)
      Cumulative incidence in men (4 cases) /women (16 cases)2.3% (SE 0.3%)3.9% (SE 0.5%)
      Incidence density in men (exposure time 12,364 days)/ women (exposure time 27,546 days)3 × 10.000 patients/day (95%CI 0.2–6)6 × 10.000 patients/day (95%CI 0.9–9)
      Frequency of infections per vaccines used
      Sputnik-Sputnik n (%)4 (20)
      Astra-Astra, n (%)10 (50)
      Sinopharm-Sinopharm n (%)5 (25)
      Heterologous vaccine scheme, n (%)1 (5)
      Frequency of infections per treatment used
      Interferon beta, n (%)2 (0.02)
      Glatiramer acetate, n (%)1 (0.02)
      Teriflunomide, n (%)2 (0.04)
      Fingolimod, n (%)3 (0.02)
      Dimethylfumarate, n (%)1 (0.04)
      Natalizumab, n (%)2 (0.04)
      Alemtuzumab, n (%)1 (0.04)
      Ocrelizumab, n (%)5 (0.15)
      Rituximab, n (%)1 (0.11)
      Cladribine, n (%)1 (0.02)
      No treatment1 (0.008)
      Cumulative incidence in homologous scheme (19 cases)3.3% (SE 0.4%)
      Incidence density in homologous scheme (exposure time 33,300 days)/ and heterologous scheme (1 cases, exposure time 6610 days)5 × 10.000 patients per day (95%CI 0.8–8)1 × 10.000 patients per day (95%CI 0.02–3)

      6. Discussion

      This is the first study in the country and one of the first study in the region to evaluate the incidence of COVID-19 infection post vaccination in PwMS.
      In our Study we observed a cumulative incidence of 3.4% (SE 0.4%) with an overall incidence density of COVID-19 infection post vaccination of 5 × 10.000 patients/day (95%CI 0.7–12). The frequency observed by vaccines used and schemes (homologous vs. heterologous scheme) was quite similar and only one patient required hospitalization (Table 3).
      Our study is in line with previous studies performed in other regions. Sormani et al. in a long term clinical follow up of the CovaXiMS (Covid-19 vaccine in multiple sclerosis) evaluated the SARS-CoV-2 breakthrough infections incidence and the impact of DMTs on cumulative incidence of infections (
      • Sormani M.P.
      • Inglese M.
      • Schiavetti I.
      • Carmisciano L.
      • Laroni A.
      • Lapucci C.
      • Da Rin G.
      • 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.
      • Frau J.
      • Ferro M.T.
      • Di Sapio A.
      • Pasquali L.
      • Ulivelli M.
      • Marinelli F.
      • Callari G.
      • Iodice R.
      • Liberatore G.
      • Caleri F.
      • Repice A.M.
      • Cordera S.
      • Battaglia M.A.
      • Salvetti M.
      • Franciotta D.
      • Uccelli A.
      CovaXi, M.S.s.g.o.b.o.t.I.C.-A.i.M.S.
      Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.
      ). In that study, of a total of 1705 patients who had a full vaccination cycle (2 doses), 23 breakthrough infections were identified, displaying a cumulative incidence of 1.5% SE 0.3% after a mean 0f 108 days after the second dose (
      • Sormani M.P.
      • Inglese M.
      • Schiavetti I.
      • Carmisciano L.
      • Laroni A.
      • Lapucci C.
      • Da Rin G.
      • 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.
      • Frau J.
      • Ferro M.T.
      • Di Sapio A.
      • Pasquali L.
      • Ulivelli M.
      • Marinelli F.
      • Callari G.
      • Iodice R.
      • Liberatore G.
      • Caleri F.
      • Repice A.M.
      • Cordera S.
      • Battaglia M.A.
      • Salvetti M.
      • Franciotta D.
      • Uccelli A.
      CovaXi, M.S.s.g.o.b.o.t.I.C.-A.i.M.S.
      Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.
      ). Authors analyzed the role of treatments on the risk of infections and severity of infections and showed that the probability to be infected was associated with SARS-CoV2 antibody levels measured after the second vaccine dose (HR= 0.63, p = 0.007) and antibody levels of 660 U/mL as the cut-off (
      • Sormani M.P.
      • Inglese M.
      • Schiavetti I.
      • Carmisciano L.
      • Laroni A.
      • Lapucci C.
      • Da Rin G.
      • 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.
      • Frau J.
      • Ferro M.T.
      • Di Sapio A.
      • Pasquali L.
      • Ulivelli M.
      • Marinelli F.
      • Callari G.
      • Iodice R.
      • Liberatore G.
      • Caleri F.
      • Repice A.M.
      • Cordera S.
      • Battaglia M.A.
      • Salvetti M.
      • Franciotta D.
      • Uccelli A.
      CovaXi, M.S.s.g.o.b.o.t.I.C.-A.i.M.S.
      Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.
      ). In another study that followed 19,641 MS patients after complete vaccination for a median of 8 months, authors identified 137 breakthrough infections (cumulative incidence of 0.69%), and the sub analysis of risk between the incidences across DMTs showed an increased in patients treated with ocrelizumab and fingolimod (p<0.001) (

      Schiavetti, I., Cordioli, C., Stromillo, M.L., Ferrò, M.T., Laroni, A., Cocco, E., Cola, G., Pasquali, L., Rilla, M.T., Signoriello, E., Iodice, R., Sapio, A.D., Lanzillo, R., Caleri, F., Annovazzi, P., Conte, A., Liberatore, G., Ruscica, F., Docimo, R., Bonavita, S., Ulivelli, M., Cavalla, P., Patti, F., Ferraro, D., Clerico, M., Immovilli, P., Filippo, M.D., Salvetti, M., Sormani, M.P., group, t.B.i.i.M.s., 2022. Breakthrough SARS-CoV-2 infections in MS patients on disease modifying therapies. 2022.2001.2022.22269630.

      ). Rose et al. investigate breakthrough coronavirus disease 2019 (COVID-19) in vaccinated people with multiple sclerosis (PwMS) on DMT (
      • Rose D.R.
      • Mahadeen A.Z.
      • Carlson A.K.
      • Planchon S.M.
      • Sedlak J.
      • Husak S.
      • Bermel R.A.
      • Cohen J.A.
      • Moss B.P.
      Clinical features and outcomes of COVID-19 despite SARS-CoV-2 vaccination in people with multiple sclerosis.
      ). A total of 13 patients of 344 fully vaccinated people with multiple sclerosis on disease modifying therapies were diagnosed with COVID-19 after vaccination (cumulative incidence of 3.77%). No incidence density was described in the study (
      • Rose D.R.
      • Mahadeen A.Z.
      • Carlson A.K.
      • Planchon S.M.
      • Sedlak J.
      • Husak S.
      • Bermel R.A.
      • Cohen J.A.
      • Moss B.P.
      Clinical features and outcomes of COVID-19 despite SARS-CoV-2 vaccination in people with multiple sclerosis.
      ).
      It is important to comment that many of the included patients in our cohort were not receiving a specific treatment for MS (20.83%). This was mainly because we included PPMS (13.4%) and SPMS (11.6%) and many of those patients were untreated for the disease. It is also important to mention that when we developed the study, for the Argentine health system, the complete vaccination schedule consisted of having two doses of the COVID-19 vaccines available in our country. That is why from the design we proposed that methodological parameter in each MS patient and we did not consider extra doses of COVID −19 vaccines.
      Our study has many limitations that should be mentioned. First and probably the most relevant is that we were not able to perform a serological test to all the included patients, however, this was not the objective of the study. Second the observational design implemented and the possibility of information bias, however the strictest follow up possible was implemented to try to limit this possibility. Finally, we could not stratify the analysis by treatment received per patient to analyze the incidence risk by DMT. A future study is ongoing to answer this aspect with an increase sample.
      In conclusion, we found an incidence density of breakthrough COVID-19 infection of 5 × 10.000 patients/day (95%CI 0.7–12) after vaccination in Argentina mainly with Sputnik or Astra Zeneca vaccines.
      Despite increasing evidence is being collected and the gap of evidence is narrowing, still much is needed regarding the response to other vaccines and other factors like the ones we consider in our study.

      Funding

      This study was possible due to an irrestrictive educational grant provided by Biogen.

      Credit author statement

      Juan I. Rojas1 and Sebastián Nuñez39 Conceptualization, Methodology, Data Curation Writing- Original draft preparation, riting- Reviewing and Editing and Formal analysis
      Geraldine G. Luetic3, Carlos Vrech4, Agustín Pappolla5, Liliana Patrucco1, Edgardo Cristiano1, Mariano Marrodan6, María C. Ysrraelit6, Marcela Fiol6, Jorge Correale6, Leila Cohen7, Ricardo Alonso7,8, Berenice Silva7, Magdalena Casas7, Orlando Garcea7, Norma Deri9, Marcos Burgos10, Susana Liwacki11, Verónica Tkachuk12, Andres Barboza13, Raúl Piedrabuena11,14, Patricio Blaya15, Judith Steinberg16, Alejandra Martínez17, Adriana Carra17,18, Darío Tavolini19, Pablo López20, Eduardo Knorre21, Pedro Nofal22, Edgar Carnero Contentti20, Amelia Alves Pinheiro23, Felisa Leguizamon21, Emanuel Silva24, Javier Hryb25, María Eugenia Balbuena12, Gisela Zanga26, Matías Kohler27, Luciana Lazaro8, Santiago Tizio28, Carolina Mainella29, Jorge Blanche30, Marcela Parada Marcilla31, María Eugenia Fracaro32, María Laura Menichini33, Gustavo Sgrilli34, Pablo Divi35, Miguel Jacobo35, Mariela Cabrera36, Jimena Míguez5, Nora Fernandez Liguori8, Juan Pablo Viglione37, Debora Nadur12,Marina Alonso Serena38, Writing – Review, Data Curation

      Author declaration

      We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property

      Declaration of Competing Interest

      Authors declare no potential conflicts of interest regarding this research, authorship and/or publication of this article.
      We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome

      References

        • Achiron A.
        • Dolev M.
        • Menascu S.
        • Zohar D.N.
        • Dreyer-Alster S.
        • Miron S.
        • Shirbint E.
        • Magalashvili D.
        • Flechter S.
        • Givon U.
        • Guber D.
        • Stern Y.
        • Polliack M.
        • Falb R.
        • Gurevich M.
        COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021.
        Mult. Scler. 2021; 27: 864-870
        • Alonso R.
        • Chertcoff A.
        • Leguizamon F.D.V.
        • Galleguillos Goiry L.
        • Eizaguirre M.B.
        • Rodriguez R.
        • Sosa M.
        • Carballido S.
        • Cruchet V.
        • de Jong-Martis A.
        • Giachello S.
        • Henestroza P.
        • Ferrandina F.
        • Bauer J.
        • Carra A.
        • Silva B.A.
        Evaluation of short-term safety of COVID-19 vaccines in patients with multiple sclerosis from Latin America.
        Mult. Scler. J. Exp. Transl. Clin. 2021; 7 (20552173211061543)
        • Alonso R.
        • Silva B.
        • Garcea O.
        • Diaz P.E.C.
        • Dos Passos G.R.
        • Navarro D.A.R.
        • Valle L.A.G.
        • Salinas L.C.R.
        • Negrotto L.
        • Luetic G.
        • Tkachuk V.A.
        • Miguez J.
        • de Bedoya F.H.D.
        • Goiry L.G.
        • Sanchez N.E.R.
        • Burgos M.
        • Steinberg J.
        • Balbuena M.E.
        • Alvarez P.M.
        • Lopez P.A.
        • Ysrraelit M.C.
        • Leon R.A.
        • Cohen A.B.
        • Gracia F.
        • Molina O.
        • Casas M.
        • Deri N.H.
        • Pappolla A.
        • Patrucco L.
        • Cristiano E.
        • Tavolini D.
        • Nadur D.
        • Granda A.M.T.
        • Weiser R.
        • Cassara F.P.
        • Sinay V.
        • Rodriguez C.C.
        • Lazaro L.G.
        • Menichini M.L.
        • Piedrabuena R.
        • Escobar G.O.
        • Carra A.
        • Chertcoff A.
        • Pujols B.S.
        • Vrech C.
        • Tarulla A.
        • Carvajal R.
        • Mainella C.
        • Becker J.
        • Peeters L.M.
        • Walton C.
        • Serena M.A.
        • Nunez S.
        • Rojas J.I.
        COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America: COVID-19 in MS and NMOSD patients in LATAM.
        Mult. Scler. Relat. Disord. 2021; 51102886
        • Belete T.M.
        Review on up-to-date status of candidate vaccines for COVID-19 disease.
        Infect. Drug Resist. 2021; 14: 151-161
        • Brill L.
        • Rechtman A.
        • Zveik O.
        • Haham N.
        • Oiknine-Djian E.
        • Wolf D.G.
        • Levin N.
        • Raposo C.
        • Vaknin-Dembinsky A.
        Humoral and T-cell response to SARS-CoV-2 vaccination in patients with multiple sclerosis treated with ocrelizumab.
        JAMA Neurol. 2021; 78: 1510-1514
        • Reyes S.
        • Cunningham A.L.
        • Kalincik T.
        • Havrdova E.K.
        • Isobe N.
        • Pakpoor J.
        • Airas L.
        • Bunyan R.F.
        • van der Walt A.
        • Oh J.
        • Mathews J.
        • Mateen F.J.
        • Giovannoni G.
        Update on the management of multiple sclerosis during the COVID-19 pandemic and post pandemic: an international consensus statement.
        J. Neuroimmunol. 2021; 357577627
        • Rojas J.I.
        • Alonso Serena M.
        • Garcea O.
        • Patrucco L.
        • Carra A.
        • Correale J.
        • Vrech C.
        • Pappolla A.
        • Miguez J.
        • Doldan M.L.
        • Silveira F.
        • Alonso R.
        • Cohen L.
        • Pita C.
        • Silva B.A.
        • Fiol M.
        • Gaitan M.I.
        • Marrodan M.
        • Negrotto L.
        • Ysrraelit M.C.
        • Deri N.
        • Luetic G.
        • Caride A.
        • Carnero Contentti E.
        • Lopez P.A.
        • Pettinicchi J.P.
        • Curbelo C.
        • Martinez A.D.
        • Steinberg J.D.
        • Balbuena M.E.
        • Tkachuk V.
        • Burgos M.
        • Knorre E.
        • Leguizamon F.
        • Piedrabuena R.
        • Liwacki S.D.V.
        • Barboza A.G.
        • Nofal P.
        • Volman G.
        • Alvez Pinheiro A.
        • Hryb J.
        • Tavolini D.
        • Blaya P.A.
        • Silva E.
        • Blanche J.
        • Tizio S.
        • Caceres F.
        • Saladino M.L.
        • Zanga G.
        • Fracaro M.E.
        • Sgrilli G.
        • Pagani Cassara F.
        • Vazquez G.
        • Sinay V.
        • Menichini M.L.
        • Lazaro L.
        • Cabrera L.M.
        • Bestoso S.
        • Divi P.
        • Jacobo M.
        • Kohler E.
        • Kohler M.
        • Giunta D.
        • Mainella C.
        • Manzi R.
        • Parada Marcilla M.
        • Viglione J.P.
        • Martos I.
        • Reich E.
        • Jose G.
        • Cristiano E.
        • Fernandez Liguori N.
        • on behalf Relevar, E.M.i.
        Multiple sclerosis and neuromyelitis optica spectrum disorders in Argentina: comparing baseline data from the Argentinean MS registry (RelevarEM).
        Neurol. Sci. 2020; 41: 1513-1519
        • Rojas J.I.
        • Carra A.
        • Correale J.
        • Cristiano E.
        • Fernandez Liguori N.
        • Alonso R.
        • Alvez Pinheiro A.
        • Balbuena M.E.
        • Barboza A.G.
        • Bestoso S.
        • Blaya P.A.
        • Burgos M.
        • Cabrera L.M.
        • Caride A.
        • Carnero Contentti E.
        • Cohen L.
        • Curbelo C.
        • Deri N.
        • Divi P.
        • Fiol M.
        • Fracaro M.E.
        • Gaitan M.I.
        • Hryb J.
        • Jacobo M.
        • Knorre E.
        • Leguizamon F.
        • Giunta D.
        • Alonso Serena M.
        • Doldan M.L.
        • De Lio G.F.
        • Liwacki S.D.V.
        • Lopez P.A.
        • Luetic G.
        • Mainella C.
        • Manzi R.
        • Marrodan M.
        • Martinez A.D.
        • Miguez J.
        • Negrotto L.
        • Nofal P.
        • Parada Marcilla M.
        • Pettinicchi J.P.
        • Silva B.A.
        • Silva E.
        • Silveira F.
        • Steinberg J.D.
        • Tavolini D.
        • Tizio S.
        • Tkachuk V.
        • Vazquez G.
        • Volman G.
        • Vrech C.
        • Ysrraelit M.C.
        • Zanga G.
        • Garcea O.
        • Patrucco L.
        The Argentinean multiple sclerosis registry (RelevarEM): methodological aspects and directions.
        Mult. Scler. Relat. Disord. 2019; 32: 133-137
        • Rose D.R.
        • Mahadeen A.Z.
        • Carlson A.K.
        • Planchon S.M.
        • Sedlak J.
        • Husak S.
        • Bermel R.A.
        • Cohen J.A.
        • Moss B.P.
        Clinical features and outcomes of COVID-19 despite SARS-CoV-2 vaccination in people with multiple sclerosis.
        Mult. Scler. J. Exp. Transl. Clin. 2021; 7 (20552173211057110)
        • Sahin U.
        • Muik A.
        • Derhovanessian E.
        • Vogler I.
        • Kranz L.M.
        • Vormehr M.
        • Baum A.
        • Pascal K.
        • Quandt J.
        • Maurus D.
        • Brachtendorf S.
        • Lorks V.
        • Sikorski J.
        • Hilker R.
        • Becker D.
        • Eller A.K.
        • Grutzner J.
        • Boesler C.
        • Rosenbaum C.
        • Kuhnle M.C.
        • Luxemburger U.
        • Kemmer-Bruck A.
        • Langer D.
        • Bexon M.
        • Bolte S.
        • Kariko K.
        • Palanche T.
        • Fischer B.
        • Schultz A.
        • Shi P.Y.
        • Fontes-Garfias C.
        • Perez J.L.
        • Swanson K.A.
        • Loschko J.
        • Scully I.L.
        • Cutler M.
        • Kalina W.
        • Kyratsous C.A.
        • Cooper D.
        • Dormitzer P.R.
        • Jansen K.U.
        • Tureci O.
        COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses.
        Nature. 2020; 586: 594-599
        • Salter A.
        • Fox R.J.
        • Newsome S.D.
        • Halper J.
        • Li D.K.B.
        • Kanellis P.
        • Costello K.
        • Bebo B.
        • Rammohan K.
        • Cutter G.R.
        • Cross A.H.
        Outcomes and risk factors associated with SARS-CoV-2 infection in a North American registry of patients with multiple sclerosis.
        JAMA Neurol. 2021; 78: 699-708
      1. Schiavetti, I., Cordioli, C., Stromillo, M.L., Ferrò, M.T., Laroni, A., Cocco, E., Cola, G., Pasquali, L., Rilla, M.T., Signoriello, E., Iodice, R., Sapio, A.D., Lanzillo, R., Caleri, F., Annovazzi, P., Conte, A., Liberatore, G., Ruscica, F., Docimo, R., Bonavita, S., Ulivelli, M., Cavalla, P., Patti, F., Ferraro, D., Clerico, M., Immovilli, P., Filippo, M.D., Salvetti, M., Sormani, M.P., group, t.B.i.i.M.s., 2022. Breakthrough SARS-CoV-2 infections in MS patients on disease modifying therapies. 2022.2001.2022.22269630.

        • Sormani M.P.
        • Inglese M.
        • Schiavetti I.
        • Carmisciano L.
        • Laroni A.
        • Lapucci C.
        • Da Rin G.
        • 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.
        • Frau J.
        • Ferro M.T.
        • Di Sapio A.
        • Pasquali L.
        • Ulivelli M.
        • Marinelli F.
        • Callari G.
        • Iodice R.
        • Liberatore G.
        • Caleri F.
        • Repice A.M.
        • Cordera S.
        • Battaglia M.A.
        • Salvetti M.
        • Franciotta D.
        • Uccelli A.
        • CovaXi, M.S.s.g.o.b.o.t.I.C.-A.i.M.S.
        Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.
        EBioMedicine. 2021; 72103581
        • Tortorella C.
        • Aiello A.
        • Gasperini C.
        • Agrati C.
        • Castilletti C.
        • Ruggieri S.
        • Meschi S.
        • Matusali G.
        • Colavita F.
        • Farroni C.
        • Cuzzi G.
        • Cimini E.
        • Tartaglia E.
        • Vanini V.
        • Prosperini L.
        • Haggiag S.
        • Galgani S.
        • Quartuccio M.E.
        • Salmi A.
        • Repele F.
        • Altera A.M.G.
        • Cristofanelli F.
        • D'Abramo A.
        • Bevilacqua N.
        • Corpolongo A.
        • Puro V.
        • Vaia F.
        • Capobianchi M.R.
        • Ippolito G.
        • Nicastri E.
        • Goletti D.
        • Group, I.C.-V.S.
        Humoral- and T-cell-specific immune responses to SARS-CoV-2 mRNA vaccination in patients with MS using different disease-modifying therapies.
        Neurology. 2022; 98: e541-e554