ABSTRACT
Background: High-efficacy (HE) disease-modifying therapies (DMTs) for Multiple Sclerosis (MS), such as anti-CD20 monoclonal antibodies - i.e., Ocrelizumab (OCR) and Rituximab - may worsen COVID-19 course. Preliminary data suggest that two doses of mRNA COVID-19 vaccine (RNA-Vax) reduce the risk of breakthrough/severe COVID-19 in patients with MS (pwMS) under treatment with HE-DMTs. Little is known about the protective effect of a third booster dose of RNA-Vax in pwMS treated with most commonly used HE-DMTs, such as Natalizumab (NTZ), Fingolimod (FNG), and OCR. Aim(s): To compare COVID-19 course and outcomes in pwMS on NTZ, FNG, and OCR after receiving the third dose of RNA-Vax. Method(s): Inclusion criteria were: >18 years old, being treated with NTZ/OCR/FNG since the first vaccine dose, diagnosis of COVID-19 after a third booster dose of RNA-Vax, not being treated with steroids within the month prior to any vaccine dose or COVID-19. Result(s): 232 pwMS (63 NTZ, 106 OCR, 63 FNG) from 17 Italian MS centers were included in the analysis. pwMS on NTZ (37+/-9) were younger than those on OCR (42+/-10, p=0.026) and FNG (43+/-11, p=0.006);EDSS was higher in pwMS on OCR (3.0, IQR=1.5-5.5) than those on FNG (2.0, IQR=1.0-3.0, p=0.017). COVID-19 was diagnosed 65+/-41 days after receiving the third booster dose. PwMS on OCR compared with those on NTZ showed more frequently (p<0.02-0.001): fever >38degreeC (53.8% vs 20.6%), cough (67% vs 36.5%), dyspnea (18.9% vs 3.2%), longer symptoms duration (9.5+/-8.7 vs 6+/-4.6 days), use of NSAIDs (74.5% vs 52.4%), oxygen (7.5% vs 0%), antibiotics (45.3% vs 14.3%). PwMS on OCR compared with those on FNG needed more frequently the use of oxygen (7.5% vs 1.6%, p=0.002). PwMS on FNG compared with those on NTZ showed more frequently (p<0.03-0.002): fever >38degreeC (39.7% vs 20.6%), cough (65.1% vs 36.5%), dyspnea (15.9% vs 3.2%). There were no differences between the 3 groups of pwMS regarding: COVID-19 treatment with steroids or monoclonal antibodies, hospitalization, and full recovery or death (0%). Discussion and Conclusion(s): Breakthrough COVID-19 after a third booster dose of RNA-Vax was more symptomatic in pwMS on OCR and FNG than those on NTZ. Nevertheless, no deaths were reported and the Covid-19 course in terms of full recovery and hospitalization rates was not different across different HE-DMTs. These results support the efficacy of a third booster dose of RNA-Vax in preventing severe COVID-19 (with hospitalization/ death) in pwMS treated with most common HE-DMTs.