Different disease modifying therapies can increase or decrease Covid-19 severity in Multiple Sclerosis
Maria Pia Sormani1, Nicola De Rossi2, Irene Schiavetti1, Luca Carmisciano1, Cinzia Cordioli2, Lucia Moiola3, Marta Radaelli4, Paolo Immovilli5, Marco Capobianco6, Maria Trojano7, Paola Zaratin8, Gioacchino Tedeschi9, Giancarlo Comi10, Mario Alberto Battaglia8, Francesco Patti11, Marco Salvetti12
1Department of Health Sciences, University of Genoa, 2Centro Sclerosi Multipla, ASST Spedali Civili di Brescia, 3Department of Neurology, Multiple Sclerosis Center, IRCCS Ospedale San Raffaele, Milan, 4Department of Neurology and Multiple Sclerosis Center, ASST “Papa Giovanni XXIII, Bergamo, 5Multiple Sclerosis Center, Ospedale Guglielmo da Saliceto, Piacenza, 6Regional Referral Multiple Sclerosis Centre, Dept. of Neurology, University Hospital San Luigi, Orbassano, 7Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, 8Research Department, Italian Multiple Sclerosis Foundation, Genoa, 9Department of Advanced Medical and Surgical Sciences, University of Campania, Napoli, 10Institute of Experimental Neurology, IRCCS Ospedale San Raffaele, Milan, 11Centro Sclerosi Multipla, Policlinico Catania, University of Catania, 12Department of Neuroscience, Mental Health and Sensory Organs, Sapienza University of Rome
Objective:
To describe the effect of disease modifying therapies (DMT) on Covid-19 severity in a large cohort of Italian patients with Covid-19 and multiple sclerosis (MS).  
Background:

We previously presented data from a nationwide study of persons with MS with suspected or confirmed Covid-19, collected from March 2020. In June we started collecting also asymptomatic patients, when serological tests started to be routinely done.

Design/Methods:

This was a retrospective multi-center observational study. We defined Covid-19 severity as a 4-level variable: level1=asymptomatic, level2=symptomatic without signs of pneumonia, level3=radiologically defined pneumonia or hospitalization, level4=intensive care unit (ICU) or death. We analysed the impact of baseline variables on this outcome by a multivariable ordinal logistic model quantifying the association by Odds Ratio (OR).

Results:
On October 12, we enrolled 902 MS patients, 298 (33%) with confirmed and 604 (67%) with suspected Covid-19; 37 (4%) were asymptomatic. The number of ICU/deaths were 8/95 (8%) among those treated with anti-CD20 therapies (mean age=41 years), 0/84 (0%) among those treated with Interferon (mean age=47 years) and 37/723 (5%) among those treated with other drugs (mean age=43 years). Among the 37 asymptomatic patients, 7/84 (8.3%) were in Interferon, 1/95 (1.1%) was on anti-CD20 and 29/723 (4%) were on other drugs. At multivariable analysis, independent risk factors for a severe Covid-19 were age (OR=1.05,p<0.001), EDSS(OR=1.13,p=0.02), Male sex(OR=1.44,p=0.057) and DMT used: treatment with anti-CD20 (Ocrelizumab or Rituximab) increased the risk (OR=1.99,p=0.035) and treatment with Interferon reduced the risk (OR=0.48, p=0.05) of severe Covid-19 as compared to treatment with DMF, used as the reference DMT. 
Conclusions:

This analysis confirms on a larger population the increase of risk of severe Covid-19 of anti-CD20 therapies and highlights the protective role of Interferon. Data on asymptomatic patients are rapidly accumulating and will provide useful information about this specific subgroup of subjects.