Humoral and Cellular Responses to SARS-CoV-2 in Convalescent COVID-19 Patients With Multiple Sclerosis

Ana Zabalza; Georgina Arrambide; Paula Tagliani; Simón Cárdenas-Robledo; Susana Otero-Romero; Juliana Esperalba; Candela Fernandez-Naval; Jesus Trocoli Campuzano; Mónica Martínez Gallo; Mireia Castillo; Mercè Bonastre; Mireia Resina Sallés; Jordina Beltran; Pere Carbonell-Mirabent; Marta Rodríguez-Barranco; Samuel López-Maza; Pedro José Melgarejo Otálora; Mariano Ruiz-Ortiz; Agustin Pappolla; Breogán Rodríguez Acevedo; Luciana Midaglia; Angela Vidal-Jordana; Alvaro Cobo-Calvo; Carmen Tur; Ingrid Galán; Joaquín Castilló; Jordi Río; Carmen Espejo; Manuel Comabella; Carlos Nos; Jaume Sastre-Garriga; Mar Tintore; Xavier Montalban

doi:10.1212/NXI.0000000000001143

Humoral and Cellular Responses to SARS-CoV-2 in Convalescent COVID-19 Patients With Multiple Sclerosis

Neurol Neuroimmunol Neuroinflamm. 2022 Feb 1;9(2):e1143. doi: 10.1212/NXI.0000000000001143. Print 2022 Mar.

Authors

Ana Zabalza¹, Georgina Arrambide², Paula Tagliani², Simón Cárdenas-Robledo², Susana Otero-Romero², Juliana Esperalba², Candela Fernandez-Naval², Jesus Trocoli Campuzano², Mónica Martínez Gallo², Mireia Castillo², Mercè Bonastre², Mireia Resina Sallés², Jordina Beltran², Pere Carbonell-Mirabent², Marta Rodríguez-Barranco², Samuel López-Maza², Pedro José Melgarejo Otálora², Mariano Ruiz-Ortiz², Agustin Pappolla², Breogán Rodríguez Acevedo², Luciana Midaglia², Angela Vidal-Jordana², Alvaro Cobo-Calvo², Carmen Tur², Ingrid Galán², Joaquín Castilló², Jordi Río², Carmen Espejo², Manuel Comabella², Carlos Nos², Jaume Sastre-Garriga², Mar Tintore², Xavier Montalban²

Affiliations

¹ From the Servei de Neurologia-Neuroimmunologia (A.Z., G.A., P.T., S.C.-R., S.O.-R., M. Castillo, M.B., M.R.S., J.B., P.C.-M., M.R.-B., S.L.-M., A.P., B.R.A., L.M., A.V.-J., A.C.-C., C.T., I.G., J.C., J.R., C.E., M. Comabella, C.N., J.S.-G., M.T., X.M.), and Preventive Medicine and Epidemiology Department (S.O.-R.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Departament de Medicina, Universitat Autònoma de Barcelona; Microbiology Department (J.E., C.F.-N., J.T.C.), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona; Immunology Division (M.M.G.), Hospital Universitari Vall d'Hebron and Diagnostic Immunology Research Group, Vall d'Hebron Research Institute (VHIR), Barcelona; Department of Neurology (P.J.M.O.), Hospital General Universitario Gregorio Marañón, Madrid; and Department of Neurology (M.R.-O.), Hospital Universitario 12 de Octubre, Madrid, Spain. azabalza@cem-cat.org.
² From the Servei de Neurologia-Neuroimmunologia (A.Z., G.A., P.T., S.C.-R., S.O.-R., M. Castillo, M.B., M.R.S., J.B., P.C.-M., M.R.-B., S.L.-M., A.P., B.R.A., L.M., A.V.-J., A.C.-C., C.T., I.G., J.C., J.R., C.E., M. Comabella, C.N., J.S.-G., M.T., X.M.), and Preventive Medicine and Epidemiology Department (S.O.-R.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Departament de Medicina, Universitat Autònoma de Barcelona; Microbiology Department (J.E., C.F.-N., J.T.C.), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona; Immunology Division (M.M.G.), Hospital Universitari Vall d'Hebron and Diagnostic Immunology Research Group, Vall d'Hebron Research Institute (VHIR), Barcelona; Department of Neurology (P.J.M.O.), Hospital General Universitario Gregorio Marañón, Madrid; and Department of Neurology (M.R.-O.), Hospital Universitario 12 de Octubre, Madrid, Spain.

Abstract

Background and objectives: Information about humoral and cellular responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antibody persistence in convalescent (COVID-19) patients with multiple sclerosis (PwMS) is scarce. The objectives of this study were to investigate factors influencing humoral and cellular responses to SARS-CoV-2 and its persistence in convalescent COVID-19 PwMS.

Methods: This is a retrospective study of confirmed COVID-19 convalescent PwMS identified between February 2020 and May 2021 by SARS-CoV-2 antibody testing. We examined relationships between demographics, MS characteristics, disease-modifying therapy (DMT), and humoral (immunoglobulin G against spike and nucleocapsid proteins) and cellular (interferon-gamma [IFN-γ]) responses to SARS-CoV-2.

Results: A total of 121 (83.45%) of 145 PwMS were seropositive, and 25/42 (59.5%) presented a cellular response up to 13.1 months after COVID-19. Anti-CD20-treated patients had lower antibody titers than those under other DMTs (p < 0.001), but severe COVID-19 and a longer time from last infusion increased the likelihood of producing a humoral response. IFN-γ levels did not differ among DMT. Five of 7 (71.4%) anti--CD20-treated seronegative patients had a cellular response. The humoral response persisted for more than 6 months in 41/56(81.13%) PwMS. In multivariate analysis, seropositivity decreased due to anti-CD20 therapy (OR 0.08 [95% CI 0.01-0.55]) and increased in males (OR 3.59 [1.02-12.68]), whereas the cellular response decreased in those with progressive disease (OR 0.04 [0.001-0.88]). No factors were associated with antibody persistence.

Discussion: Humoral and cellular responses to SARS-CoV-2 are present in COVID-19 convalescent PwMS up to 13.10 months after COVID-19. The humoral response decreases under anti-CD20 treatment, although the cellular response can be detected in anti-CD20-treated patients, even in the absence of antibodies.

MeSH terms

Adult
Aged
Antibodies, Viral / analysis
Antigens, CD20 / immunology
COVID-19 / complications
COVID-19 / immunology*
Female
Humans
Immunity, Cellular*
Immunity, Humoral*
Immunoglobulin G / analysis
Interferon-gamma / biosynthesis
Interferon-gamma / immunology
Male
Middle Aged
Multiple Sclerosis / complications
Multiple Sclerosis / immunology*
Nucleocapsid / chemistry
Nucleocapsid / immunology
Retrospective Studies

Substances

Antibodies, Viral
Antigens, CD20
Immunoglobulin G
Interferon-gamma