TY - JOUR
T1 - Anti-SARS-CoV-2 T-stem cell memory persists in ocrelizumab-treated MS patients
AU - Guerrera, Gisella
AU - Mandelli, Alessandra
AU - Finardi, Annamaria
AU - Orrico, Mario
AU - D’Orso, Silvia
AU - Picozza, Mario
AU - Noviello, Maddalena
AU - Beretta, Valeria
AU - Bonetti, Bruno
AU - Calabrese, Massimiliano
AU - Marastoni, Damiano
AU - De Rossi, Nicola
AU - Capra, Ruggero
AU - Salvetti, Marco
AU - Buscarinu, Maria Chiara
AU - Inglese, Matilde
AU - Uccelli, Antonio
AU - Moiola, Lucia
AU - Raposo, Catarina
AU - Muros-Le Rouzic, Erwan
AU - Pedotti, Rosetta
AU - Filippi, Massimo
AU - Bonini, Chiara
AU - Battistini, Luca
AU - Borsellino, Giovanna
AU - Furlan, Roberto
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research has been supported by a dedicated grant from Hoffman-La Roche to the Italian COVID-19 Alliance in MS. C.B. received funding from COVID-19 program project grant from the IRCCS San Raffaele Hospital (grant no. COVID-2020-12371617 from the Italian Ministero della Salute, Cellnex (ACT4Covid) and the EHA grant on COVID-19. L.B. received funding from the Italian Ministero della Salute (grant nos. COVID-2020-12371735 and RF-2018-12366111) and from the Italian Multiple Sclerosis Foundation (Fism Progetto Speciale 2018/S/5). MP is supported by a research fellowship FISM - Fondazione Italiana Sclerosi Multipla – cod. 2020/BR/012 and financed or co-financed with the ‘5 per mille’ public funding.
Funding Information:
The authors thank the pwMS who have donated their blood for this study. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research has been supported by a dedicated grant from Hoffman-La Roche to the Italian COVID-19 Alliance in MS. C.B. received funding from COVID-19 program project grant from the IRCCS San Raffaele Hospital (grant no. COVID-2020-12371617 from the Italian Ministero della Salute, Cellnex (ACT4Covid) and the EHA grant on COVID-19. L.B. received funding from the Italian Ministero della Salute (grant nos. COVID-2020-12371735 and RF-2018-12366111) and from the Italian Multiple Sclerosis Foundation (Fism Progetto Speciale 2018/S/5). MP is supported by a research fellowship FISM - Fondazione Italiana Sclerosi Multipla – cod. 2020/BR/012 and financed or co-financed with the ‘5 per mille’ public funding.
Publisher Copyright:
© The Author(s), 2022.
PY - 2022/10
Y1 - 2022/10
N2 - Background: Development of long-lasting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) T-cell responses in persons with multiple sclerosis (pwMS) treated with ocrelizumab is questioned. Objective: Investigate antiviral T-cell responses after infection with SARS-CoV-2 in ocrelizumab-treated pwMS. Control groups included ocrelizumab-treated pwMS without SARS-CoV-2 infection, and non-MS individuals with and without SARS-CoV-2 infection. Methods: Peripheral blood mononuclear cells were stimulated with SARS-CoV-2 peptide pools and T-cell reactivity was assessed by ELISPOT for interferon (IFN)-γ detection, and by multiparametric fluorescence-activated cell sorting (FACS) analyses for assessment and characterization of T-cell activation. Results: ELISPOT assay against the spike and the N protein of SARS-CoV-2 displayed specific T-cell reactivity in 28/29 (96%) pwMS treated with ocrelizumab and infected by SARS-CoV-2, similar to infected persons without MS. This reactivity was present 1 year after infection and independent from the time of ocrelizumab infusion. FACS analysis following stimulation with SARS-CoV-2 peptide pools showed the presence of activation-induced markers (AIMs) in both CD4+ and CD8+ T-cell subsets in 96% and 92% of these individuals, respectively. Within naïve AIM+ CD4+ and CD8+ T-cells, we detected T memory stem cells, suggesting the acquisition of long-term memory. Conclusions: B-cell depletion using ocrelizumab does not impair the development of long-lasting anti-SARS-CoV-2 T-cell responses.
AB - Background: Development of long-lasting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) T-cell responses in persons with multiple sclerosis (pwMS) treated with ocrelizumab is questioned. Objective: Investigate antiviral T-cell responses after infection with SARS-CoV-2 in ocrelizumab-treated pwMS. Control groups included ocrelizumab-treated pwMS without SARS-CoV-2 infection, and non-MS individuals with and without SARS-CoV-2 infection. Methods: Peripheral blood mononuclear cells were stimulated with SARS-CoV-2 peptide pools and T-cell reactivity was assessed by ELISPOT for interferon (IFN)-γ detection, and by multiparametric fluorescence-activated cell sorting (FACS) analyses for assessment and characterization of T-cell activation. Results: ELISPOT assay against the spike and the N protein of SARS-CoV-2 displayed specific T-cell reactivity in 28/29 (96%) pwMS treated with ocrelizumab and infected by SARS-CoV-2, similar to infected persons without MS. This reactivity was present 1 year after infection and independent from the time of ocrelizumab infusion. FACS analysis following stimulation with SARS-CoV-2 peptide pools showed the presence of activation-induced markers (AIMs) in both CD4+ and CD8+ T-cell subsets in 96% and 92% of these individuals, respectively. Within naïve AIM+ CD4+ and CD8+ T-cells, we detected T memory stem cells, suggesting the acquisition of long-term memory. Conclusions: B-cell depletion using ocrelizumab does not impair the development of long-lasting anti-SARS-CoV-2 T-cell responses.
KW - COVID-19
KW - SARS-CoV-2
KW - anti-CD20
KW - cellular immune response
KW - multiple sclerosis
KW - ocrelizumab
UR - http://www.scopus.com/inward/record.url?scp=85138418521&partnerID=8YFLogxK
U2 - 10.1177/13524585221102158
DO - 10.1177/13524585221102158
M3 - Article
C2 - 35723265
AN - SCOPUS:85138418521
SN - 1352-4585
VL - 28
SP - 1937
EP - 1943
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 12
ER -