ARTICLE OPEN ACCESS

COVID-19 Severity in Multiple SclerosisPutting Data Into Context

Maria Pia Sormani PhD Irene Schiavetti PhD Luca Carmisciano MD Cinzia Cordioli MD

Massimo Filippi MD Marta Radaelli MD Paolo Immovilli MD Marco Capobianco MD Nicola De Rossi MD

Giampaolo Brichetto PhD Eleonora Cocco MD Cinzia Scandellari MD Paola Cavalla MD Ilaria Pesci MD

Antonio Zito MD Paolo Confalonieri MD Girolama Alessandra Marfia MD Paola Perini MD

Matilde Inglese MD Maria Trojano MD Vincenzo Brescia Morra PhD Gioacchino Tedeschi MD

Giancarlo Comi MD Mario Alberto Battaglia MD Francesco Patti MD and Marco Salvetti MD on behalf of

the MuSC-19 Study Group

Neurol Neuroimmunol Neuroinflamm 20229e1105 doi101212NXI0000000000001105

Correspondence

Dr Salvetti

marcosalvettiuniroma1it

AbstractBackground and ObjectivesIt is unclear how multiple sclerosis (MS) affects the severity of COVID-19 The aim of thisstudy is to compare COVID-19ndashrelated outcomes collected in an Italian cohort of patients withMS with the outcomes expected in the age- and sex-matched Italian population

MethodsHospitalization intensive care unit (ICU) admission and death after COVID-19 diagnosis of1362 patients with MS were compared with the age- and sex-matched Italian population in aretrospective observational case-cohort study with population-based control The observed vsthe expected events were compared in the whole MS cohort and in different subgroups (higherrisk Expanded Disability Status Scale [EDSS] score gt 3 or at least 1 comorbidity lower riskEDSS score le 3 and no comorbidities) by the χ2 test and the risk excess was quantified by riskratios (RRs)

ResultsThe risk of severe events was about twice the risk in the age- and sex-matched Italian pop-ulation RR = 212 for hospitalization (p lt 0001) RR = 219 for ICU admission (p lt 0001)and RR = 243 for death (p lt 0001) The excess of risk was confined to the higher-risk group (n= 553) In lower-risk patients (n = 809) the rate of events was close to that of the Italian age-and sex-matched population (RR = 112 for hospitalization RR = 152 for ICU admission andRR = 119 for death) In the lower-risk group an increased hospitalization risk was detected inpatients on anti-CD20 (RR = 303 p = 0005) whereas a decrease was detected in patients oninterferon (0 observed vs 4 expected events p = 004)

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From the Department of Health Sciences (MPS IS LC) University of Genova IRCCS Ospedale Policlinico San Martino (MPS MI) Genoa Centro Sclerosi Multipla ASST SpedaliCivili di Brescia (CC NDR) Montichiari Neurology Unit (MF) Neurorehabilitation Unit (MF) and Neurophysiology Unit (MF) IRCCS San Raffaele Scientific Institute MilanNeuroimaging Research Unit (MF) Division of Neuroscience IRCCS San Raffaele Scientific Institute Milan Vita-Salute San Raffaele University (MF) Milan Department ofNeurology and Multiple Sclerosis Center (MR) ASST ldquoPapa Giovanni XXIIIrdquo Bergamo Multiple Sclerosis Center (PI) Ospedale Guglielmo da Saliceto Piacenza Regional ReferralMultiple Sclerosis Centre (MC) Department of Neurology University Hospital San Luigi Orbassano Torino AISM Rehabilitation Center (GB) Italian MS Society Genoa CentroSclerosi Multipla (EC) ATS Sardegna Dipartimento Scienze Mediche e Sanita Pubblica (EC) Universita di Cagliari IRCCS Istituto delle Scienze Neurologiche di Bologna (CS) UOSIRiabilitazione Sclerosi Multipla MS Center (P Cavalla) Department of Neuroscience City of Health and Science University Hospital of Turin Centro SM UOC Neurologia (I Pesci)Fidenza AUSL PR Multiple Sclerosis Research Center (AZ) IRCCS Mondino Foundation Pavia Multiple Sclerosis Centre (P Confalonieri) Neuroimmunology DepartmentmdashldquoCarloBestardquo Neurological Institute Milan Multiple Sclerosis Clinical and Research Unit (GAM) Department of Systems Medicine Tor Vergata University Rome Department of NeurologyMultiple Sclerosis Center (PP) University of Padua Department of Neurosciences Rehabilitation Ophthalmology Genetics Maternal and Child Health (DINOGMI) (MI) University ofGenoa Department of Basic Medical Sciences Neurosciences and Sense Organs (MT) University of Bari Federico II University of Naples (VBM) Department of Advanced Medicaland Surgical Sciences (GT) University of Campania Napoli Universita Vita Salute San Raffaele (GC) Casa di Cura Privata Del Policlinico Milan Research Department (MAB) ItalianMultiple Sclerosis Foundation Genoa Department of Life Sciences (MAB) University of Siena Department of Medical and Surgical Sciences and Advanced Technologies (FP) GFIngrassia University of Catania Centro Sclerosi Multipla (FP) Policlinico Catania University of Catania Department of Neuroscience Mental Health and Sensory Organs (MS)Sapienza University of Rome and Unit of Neurology (MS) IRCCS Neuromed Pozzilli Isernia Italy

Go to NeurologyorgNN for full disclosures Funding information is provided at the end of the article

The Article Processing Charge was funded by the authors

MuSC-19 Study Group coinvestigators are listed in the appendix at the end of the article

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 40 (CC BY-NC-ND) which permits downloadingand sharing the work provided it is properly cited The work cannot be changed in any way or used commercially without permission from the journal

Copyright copy 2021 The Author(s) Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology 1

DiscussionOverall the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population Thisexcess of risk is mainly explained by the EDSS score and comorbidities whereas a residual increase of hospitalization risk wasobserved in patients on anti-CD20 therapies and a decrease in people on interferon

Several studies have assessed the impact of COVID-19 inpatients with multiple sclerosis (MS) unanimously in-dicating older age male sex concomitant comorbiditiesand higher disability as risk factors for a more severe dis-ease course1-4 The possible association between immu-notherapies and COVID-19 severity was also investigatedmostly indicating an increased risk for patients with MSwho are on anti-CD20 therapies or who received meth-ylprednisolone just before the COVID-19 onset134 andsuggesting a protective role of interferon14 A recent meta-analysis of all the published studies on COVID-19 in pa-tients with MS suggested that MS did not significantlyincrease the mortality rate from COVID-195 but the au-thors pointed out that these data should be interpretedwith caution as patients with MS are more likely femaleand younger compared with the general population whereage and male sex are risk factors for worse disease out-come5 Therefore even if all the studies agree that dataavailable so far are overall reassuring excluding majorsafety issues1-4 comparisons with external control pop-ulations are lacking

It is unclear whether and how MS biologymdashapart fromtreatmentsmdashaffects the ability to cope with severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2) in-fection This is not trivial as immunocompetence in animmune-mediated disease such as MS may be reducedMoreover SARS-CoV-2 interacts in a way that is stillpoorly understood with the genetic background predis-posing to autoimmune diseases (including MS)6 and mis-directs host immune responses toward autoimmunity aspart of COVID-19 pathophysiology7-9 It is thereforeplausible that preexisting autoimmunity may exacerbateCOVID-19 severity Therefore to understand whetherpatients with MS with COVID-19 are exposed to higherrisks than the healthy population a comparison with anexternal cohort is needed The aim of this study is tocompare the outcomes collected in an Italian cohort ofpatients with MS with COVID-19 (within the MuSC-19project) with the outcomes expected in the age- and sex-matched Italian population using data provided by theItalian Istituto Superiore di Sanita (ISS)

MethodsData Sources MuSC-19 StudyData of patients with MS with suspected or confirmed COVID-19 were retrospectively collected at a national level in Italy fromFebruary 24 2020 to February 2 2021 Details on data collectionmethods and inclusion criteria were previously reported1 Brieflywe obtained clinician-reported demographic and clinical data onpatients with MS with a confirmed or suspected COVID-19 in-fection from 118 Italian MS centers (eAppendix 2 linkslwwcomNXGA493) We used a common web-based electronicCase Report Form to collect the data and a unified protocol toanalyze them Demographic MS history COVID-19 infectionand follow-up data were collected For this analysis we includedonly patients with confirmedCOVID-19 To be a confirmed casethe patient must have a positive reverse transcriptase-polymerasechain reaction (RT-PCR) nasopharynegal swab

Data Sources Italian PopulationWe made a specific data request to the ISS who is the Italiangoverning body responsible for COVID-19 surveillance inItaly Data requested (reported in Table 1) were about thepercentage of patients who were hospitalized who accessedintensive care unit (ICU) or who died for each sex and ageclass (0ndash29 30ndash39 40ndash49 50ndash59 60ndash69 70ndash79 80ndash89 andgt90 years) among those with a positive RT-PCR during theobservation period (February 24 2020 to February 2 2021)

Statistical AnalysisThe probability to be hospitalized to be admitted to ICU andto die was extracted from ISS data (Table 1) for each patientenrolled in the MuSC-19 data set according to their age andsex Then the expected number of events (eg hospitaliza-tions ICU admissions or deaths) in the MuSC-19 populationand in specific subgroups of patients (detailed below) wasestimated by summing up the probabilities for each patient inthe group as an example if 2 patients have a probability to behospitalized of 05 the expected number of hospitalizations inthis 2-patient group is 1 The expected proportions of hos-pitalizations ICU admissions and deaths were compared withthe observed proportions by a χ2 test and the relative

GlossaryDMT = disease-modifying therapy EDSS = Expanded Disability Status Scale ICU = intensive care unit ISS = IstitutoSuperiore di Sanita MS = multiple sclerosis RR = risk ratio RT-PCR = reverse transcriptase-polymerase chain reactionSARS-CoV-2 = severe acute respiratory syndrome coronavirus 2

2 Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 NeurologyorgNN

difference expressed as risk ratios (RRs) Binomial 95 CIswere calculated for the observed proportion of events

After the comparison of the rate of hospitalization ICU ad-mission and death between the MuSC-19 cohort and the age-and sex-matched Italian population was run we tried to ex-plain the differences observed between patients with MS andthe general population by evaluating the role of MS relatedrisk factors that is Expanded Disability Status Scale (EDSS)score comorbidities and disease-modifying therapy (DMT)exposure as indicated by previous literature1-4 We focused thisadditional analysis on hospitalization rates only because thenumber of observed ICU admissions and deaths was too low tobe evaluated in separate subgroups of patients The same resultson observed and expected deaths and ICU admissions arereported in eTable 1 (linkslwwcomNXGA492)

The specific subgroups of patients were defined according to acutoff of EDSS score = 3 and the presence of at least 1comorbidity The EDSS score cutoffwas chosen based also onthe EDSS distribution of the MuSC-19 cohort to have 2balanced groups Therefore the lower-risk group included pa-tients with EDSS score le 3 and no comorbidities whereas thehigher-risk group included patients with EDSS score gt 3 or atleast 1 comorbidity DMTs were grouped according to previousliterature as no therapy interferon therapy anti-CD20 therapy(rituximab or ocrelizumab) and other DMTs A χ2 test forheterogeneity was used to compare the RR between groups

Standard Protocol Approvals Registrationsand Patient ConsentsThe study was approved by the Regional Ethics Committee ofLiguria (University of Genoa) (n 1302020mdashDB id 10433)and at a national level by Agenzia Italiana del Farmaco

Written informed consent was obtained from all participantsbefore starting any study procedures

Data AvailabilityMuSC-19 data that support the findings of this study areavailable on request from the first author (MPS) The dataare not publicly available due to information that couldcompromise the privacy of research participants

ResultsIn the MuSC-19 database 1362 patients with MS had apositive RT-PCR swab for COVID-19 over the observationperiod and were included in the analysis The characteristicsof the included patients are reported in Table 2 In this cohortwe observed 174 hospitalizations (128) 22 ICU admissions(162) and 22 deaths (162) (not mutually exclusive)The expected number of hospitalizations in an age- and sex-matched cohort extracted from the Italian population was 82(60) the expected number of ICU admissions was 10(073) and the expected number of deaths was 9 (066)

In Figure 1 the number of observed and expected events isreported As compared to an age- and sex-matched cohortextracted from the Italian population the MuSC-19 MS co-hort had an excess of hospitalizations (RR = 212 95 CI =183ndash244 p lt 0001) an excess of ICU admissions (RR =219 95 CI = 138ndash330 p = 0007) and an excess of deaths(RR = 243 95 CI = 153ndash366 p = 0007)

We tried to explain this excess of risk in 2 steps First we checkedthe MS related risk factors (EDSS score and comorbidities) bysplitting the cohort in 2 risk groups as previously described TheMS lower-risk patients were 809 (60) and the MS higher-risk

Table 1 COVID-19 Data From the Surveillance Program in Italy

Age

Females Males

Cases (N or n) Hospa () ICU () Deathb () Cases (N or n) Hospa () ICU () Deathb ()

0ndash29 305174 23 01 00 320343 19 01 00

30ndash39 160677 35 02 00 153394 34 03 01

40ndash49 216028 35 02 01 189326 64 08 03

50ndash59 235272 56 05 03 219320 113 19 10

60ndash69 135201 114 17 16 151381 205 46 41

70ndash79 103496 227 32 65 111032 341 67 13

80ndash89 109071 290 25 152 74091 436 46 267

gt90 53545 227 13 218 15884 406 26 376

Unkc 58 0 0 mdash 53 0 0 0

Total 1318522 1234824

Abbreviation ICU = intensive care unita Admission at hospitalb Data on deaths are relative to the January 29 reportc Unknown age

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 3

patients were 553 (40) In the higher-risk group 119 (22)had both EDSS score gt 3 and comorbidities 150 (27) hadcomorbidities and EDSS score le 3 and 283 (51) had EDSSscore gt 3 and no comorbidities The observed vs expectednumber of events in these 2 groups is reported in Figure 2 Theexcess of risk of the MS cohort is mainly confined in the MShigher-risk group the hospitalization RR was 285 (95 CI =244ndash329 p lt 0001) in the higher MS group whereas it was112 (95CI = 080ndash152 p = 044) in the lower-risk group (the2 RRs were significantly heterogeneous p lt 0001) The ICUadmission RR was 252 (95 CI = 148ndash400 p lt 0001) in theMShigher-risk group and 152 (95CI = 049ndash352 p= 027) inthe MS lower-risk group (heterogeneity test p = 011) Finallythe death RR was 271 (95 CI = 167ndash414 p lt 0001) in the

MShigher-risk group and 119 (95CI = 014ndash429 p= 068) inthe MS lower-risk group (heterogeneity test p = 017)

To try to understand the role of DMTs in explaining the smallresidual increase of risk in theMS lower-risk group we split theobserved and the expected hospitalization events in 4 groupsuntreated patients patients treated with interferon patientstreated with anti-CD20 and patients treated with other DMTsIn the lower-risk group (Figure 3A) the RRs were significantlyheterogeneous among DMT groups (p = 0048) there was noresidual risk in untreated patients (RR = 115 95 CI =031ndash292 p = 078) nor in patients treated with other DMTs(RR = 109 95 CI = 072ndash157 p = 061) as compared to theage- and sex-matched general population patients with MStreated with interferon had no hospitalization (RR = 0 95 CI= 0ndash37) whereas about 4 were expected and the differencewas statistically significant (p = 0042) Patients treated withanti-CD20 had a significantly higher risk of hospitalization (RR= 303 95 CI = 130ndash594 p = 0005) than the age- and sex-matched general population showing that the small increase ofrisk of patients with MS with EDSS score le 3 and no comor-bidities is confined to this class of patients

In the MS higher-risk group (Figure 3B) the RRs were alsosignificantly heterogeneous among DMTs groups (p =0050) the RR was 427 (95 CI = 291ndash618 p lt 0001) forpatients under anti-CD20 313 (95 CI = 240ndash404 p lt0001) for untreated patients 231 (95 CI = 174ndash304 p lt0001) for patients under other DMTs and 180 (95 CI =066ndash442 p = 050) for patients under interferon

The number of deaths and ICU admissions according toDMT use in the lower- and in the higher-risk groups isreported in table e-1 (linkslwwcomNXGA492) In thehigher-risk group the excess of death risk was mainly in the notherapy group (RR = 326 95 CI = 177ndash537) and in theanti-CD20 group (RR = 540 95 CI = 111ndash1525) even ifthe low number of events does not allow to conclude for anheterogeneity of mortality risk according to the DMT group

DiscussionSeveral registries reported the COVID-19 lethality rates of MScohorts with heterogeneous results ranging from estimates of16 in an Italian cohort and 17 in a French cohort4 to esti-mates of 36 in a US cohort3 Explaining these differences is notstraightforward and can be linked to the intrinsic limitation ofregistry data analyses they are based in fact on a voluntaryreporting by health care professionals that may bias collecteddata towardmore severe cases Thismay cause an overestimationof clinical severity with less effect on the internal comparisonsamong risk factors but challenging external comparisons

Moreover comparing the lethality rate of theMS cohorts withthe respective national lethality rates in the general populationis not meaningful without an adjustment for age and sex The

Table 2 Characteristics of Patients With MS

Overall (N = 1362)

Age mean (SD) 44middot1 (126)

Female sex no () 936 (687)

Comorbidities no ()

Hypertension no () 147 (108)

Major depressive disorder no () 49 (36)

Hematologic disease no () 38 (28)

Diabetes no () 47 (35)

Cancer no () 23 (17)

Coronary heart disease no () 15 (11)

MS duration median (IQR) 89 (38ndash159)

EDSS score median (IQR) 20 (10ndash35)

MS treatment no ()

Dimethyl fumarate 239 (175)

Natalizumab 188 (138)

Fingolimod 166 (122)

Ocrelizumab 149 (109)

Interferon 133 (98)

Copaxone 101 (74)

Teriflunomide 79 (58)

Cladribine 27 (20)

Rituximab 27 (20)

Azathioprine 26 (19)

Alemtuzumab 24 (18)

Methotrexate 3 (02)

Other 11 (08)

None 189 (139)

Abbreviations EDSS = Expanded Disability Status Scale IQR = interquartilerange MS = multiple sclerosis

4 Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 NeurologyorgNN

MS population is in fact more likely female and youngercompared with the general population and age and male sexare well known risk factors for COVID-19

This study shows that overall the patients withMS have a risk ofdeveloping a severe COVID-19 that is twice the risk of the age-

and sex-matched Italian population This excess of risk could bein part explained by the abovementioned bias affecting collecteddata toward more severe cases However in patients with MSwith a low EDSS score (le3) and no comorbidities the risk ofsevere events is very close to the risk of the age- and sex-matchedItalian population in this lower-risk group only patients under

Figure 1 Observed Hospitalizations ICU Admissions and Deaths in the MuSC-19 Cohort and Age-SexndashMatched ItalianPopulation

Observed hospitalizations ICU admissions and deaths intheMuSC-19 cohort (n = 1362) as compared to the expectednumber of events in an age and matched cohort from theItalian population ICU = intensive care unit RR = risk ratio

Figure 2Observed and Expected Hospitalizations ICU Admissions and Deaths in Lower-Risk (A) and Higher-Risk (B) Patients

Observed hospitalizations ICU admissions and deaths in the lower-risk patients (A EDSS score le 3 and no comorbidities n = 809) and in the higher-riskpatients (B EDSS score gt 3 or comorbidities n = 553) as compared to the expected number of events in the age and matched cohort from the Italianpopulation EDSS = Expanded Disability Status Scale ICU = intensive care unit RR = risk ratio

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 5

anti-CD20 therapy show an increased risk of hospitalization thanthe age- and sex-matched Italian population Of interest theprotective role of interferon previously suggested134 is sup-ported here because patients with MS taking interferon show asignificantly lower number of hospitalization events than the age-and sex-atched Italian population In patients withMS the excessof risk of severe COVID-19 detected is confined to the group ofpatients with EDSS score gt 3 or with additional comorbiditieswere the RR ranges from 180 in patients treated with interferonto 427 in patients treated with anti-CD20

The association with disability and not with the disease itselfsuggests that the immunologic defects determining MS donot impair the immunocompetence against SARS-CoV-2 in-fection Furthermore this result is consistent with data fromthe largest health analytic platforms10 where neurologic dis-eases emerged as factors associated with COVID-19 severeoutcome independently of their immune-mediated patho-genesis However we cannot exclude that an increased at-tention to social distancing11 may have counterbalanced therisk of COVID-19 linked to a dysfunctional immune system

In conclusion this study shows that in Italy disability andcomorbidities are determinants of an increased risk of severeCOVID-19 in patients with MS Among DMTs a residual in-crease of hospitalization is associated with anti-CD20 whereaswith interferon the risk seems to be reduced These resultscannot be generalized because of possibly relevant differences in

heritable and nonheritable factors affecting the response toSARS-CoV-2 in different populations12 However the consis-tency of the results of previous studies on the impact DMTs onCOVID-19 severity in MS performed in different nationssupports the possibility that our results will be replicated also inother geographic areas and populations

AcknowledgmentThe MuSC-19 Study Group thanks Roche for donating theweb-based platform for data collection the Department ofInformatics Bioengineering Robotics and Systems EngineeringUniversity of Genoa for its help in installing the platform andDrPatrizio Pezzotti for extracting data from the ISS database

Study FundingNo targeted funding reported

DisclosureMP Sormani reports a grant from Roche to cover datamanagement of the MuSC-19 study Roche makes ocrelizu-mab which is one of the DMTs assessed in this study Go toNeurologyorgNN for full disclosures

Publication HistoryThis manuscript was prepublished in [Sormani Maria Pia andSchiavetti Irene and Carmisciano Luca and Cordioli Cinziaand Filippi Massimo and Radaelli Marta and ImmovilliPaolo and Capobianco Marco and De Rossi Nicola and

Figure 3 Observed and Expected Hospitalizations ICU Admissions and Deaths According to DMT and Lower-Risk (A)and Higher-Risk (B) Groups

Observed hospitalizations ICU admissions and deaths in the lower-risk patients (EDSS score le 3 and no comorbidities n = 809) and in the higher-risk patients(EDSS score gt 3 or comorbidities n = 553) according to the DMT taken as compared to the expected number of hospitalizations in the age- and sex-matchedsample from the Italian population In the interferon group the RR = 0 because there were no observed events DMT = disease-modifying therapy EDSS =Expanded Disability Status Scale ICU = intensive care unit IFN = interferon RR = risk ratio

6 Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 NeurologyorgNN

Brichetto Giampaolo and Cocco Eleonora and ScandellariCinzia and Cavalla Paola and Pesci Ilaria and Zito Antonioand Confalonieri Paolo and Marfia Girolama Alessandra andPerini Paola and Inglese Matilde and Trojano Maria andBrescia Morra Vincenzo and Tedeschi Gioacchino and ComiGiancarlo and Battaglia Mario Alberto and Patti Francescoand Salvetti Marco and Study Group MuSC-19 COVID-19Severity in Multiple Sclerosis Putting Data Into ContextAvailable at SSRN ssrncomabstract=3884934] Received byNeurology Neuroimmunology amp Neuroinflammation July 152021 Accepted in final form September 15 2021

Appendix 1 Authors

Name Location Contribution

Maria PiaSormani PhD

Department of HealthSciences University ofGenova Italy IRCCSOspedale Policlinico SanMartino Genoa Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent study concept ordesign and analysis orinterpretation of data

IreneSchiavettiPhD

Department of HealthSciences University ofGenova Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent major role in theacquisition of data studyconcept or design andanalysis or interpretation ofdata

LucaCarmiscianoMD

Department of HealthSciences University ofGenova Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent study concept ordesign and analysis orinterpretation of data

CinziaCordioli MD

Centro Sclerosi MultiplaASST Spedali Civili di BresciaMontichiari Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

MassimoFilippi MD

Neurology Unit IRCCS SanRaffaele Scientific InstituteMilan ItalyNeurorehabilitation UnitIRCCS San Raffaele ScientificInstitute Milan ItalyNeurophysiology Unit IRCCSSan Raffaele ScientificInstitute Milan ItalyNeuroimaging Research UnitDivision of NeuroscienceIRCCS San Raffaele ScientificInstitute Milan Italy Vita-Salute SanRaffaeleUniversityMilan Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

MartaRadaelli MD

Department of Neurologyand Multiple SclerosisCenter ASST Papa GiovanniXXIII Bergamo Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

PaoloImmovilliMD

Multiple Sclerosis CenterOspedale Guglielmo daSaliceto Piacenza Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

Appendix 1 (continued)

Name Location Contribution

MarcoCapobiancoMD

Regional Referral MultipleSclerosis Centre Dept ofNeurology UniversityHospital San LuigiOrbassano Torino Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

Nicola DeRossi MD

Centro Sclerosi MultiplaASST Spedali Civili di BresciaMontichiari Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

GiampaoloBrichettoPhD

AISM Rehabilitation CenterItalian MS Society GenoaItaly

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

EleonoraCocco MD

Centro Sclerosi Multipla ATSSardegna DipartimentoScienze Mediche e SanitaPubblica Universita diCagliari

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

CinziaScandellariMD

IRCCS Istituto delle ScienzeNeurologiche di BolognaUOSI Riabilitazione SclerosiMultipla

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

PaolaCavalla MD

MS Center Department ofNeuroscience City of Healthand Science UniversityHospital of Turin Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

Ilaria PesciMD

Centro SM UOC NeurologiaFidenza AUSL PR

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

Antonio ZitoMD

Multiple Sclerosis ResearchCenter IRCCS MondinoFoundation Pavia

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

PaoloConfalonieriMD

Multiple Sclerosis CentreNeuroimmunologyDepartmentmdashldquoCarlo BestardquoNeurological InstituteMilan Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

GirolamaAlessandraMarfia MD

Multiple Sclerosis Clinicaland Research UnitDepartment of SystemsMedicine Tor VergataUniversity Rome Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

Paola PeriniMD

Department of NeurologyMultiple Sclerosis CenterUniversity of Padua Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

MatildeInglese MD

Department ofNeurosciencesRehabilitationOphthalmology GeneticsMaternal and Child Health(DINOGMI) University ofGenoa Italy IRCCSOspedale Policlinico SanMartino Genoa Italy

Draftingrevision of themanuscript for contentincludingmedical writing forcontent and major role inthe acquisition of data

Continued

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 7

Appendix 1 (continued)

Name Location Contribution

MariaTrojano MD

Department of BasicMedical SciencesNeurosciences and SenseOrgans University of BariItaly

Draftingrevision of themanuscript for contentincluding medical writing forcontent and major role inthe acquisition of data

VincenzoBresciaMorra PhD

Federico II University ofNaples Italy

Draftingrevision of themanuscript for contentincluding medical writing forcontent and major role inthe acquisition of data

GioacchinoTedeschi MD

Department of AdvancedMedical and SurgicalSciences University ofCampania Napoli Italy

Draftingrevision of themanuscript for contentincluding medical writing forcontent and major role inthe acquisition of data

GiancarloComi MD

Universita Vita Salute SanRaffaele Casa di CuraPrivata del Policlinico MilanItaly

Draftingrevision of themanuscript for contentincluding medical writing forcontent and major role inthe acquisition of data

MarioAlbertoBattaglia MD

Research DepartmentItalian Multiple SclerosisFoundation Genoa ItalyDepartment of Life SciencesUniversity of Siena Italy

Draftingrevision of themanuscript for contentincluding medical writing forcontent and major role inthe acquisition of data

FrancescoPatti MD

Department of Medical andSurgical Sciences andAdvanced Technologies GFIngrassia University ofCatania Centro SclerosiMultipla Policlinico CataniaUniversity of Catania

Draftingrevision of themanuscript for contentincluding medical writing forcontent and major role inthe acquisition of data

MarcoSalvetti MD

Department ofNeuroscience MentalHealth and Sensory OrgansSapienza University ofRome ItalyUnitofNeurologyIRCCS Neuromed PozzilliIsernia Italy

Draftingrevision of themanuscript for contentincluding medical writing forcontent and major role inthe acquisition of data

Appendix 2 Coinvestigators

Name Location Role Contribution

GianmarcoAbbadessa

Department of AdvancedMedical and SurgicalSciences University ofCampania LuigiVanvitelli 80138 NaplesItaly

SiteInvestigator

Datacollection

UmbertoAguglia

Department of medicaland surgical sciencesMagna GraeciaUniversity Catanzaro

SiteInvestigator

Datacollection

Lia Allegorico Multiple Sclerosis CentreA Cardarelli HospitalNaples Italy

SiteInvestigator

Datacollection

Beatrice MariaAllegri Rossi

Centro SM Fidenza (PR) SiteInvestigator

Datacollection

Appendix 2 (continued)

Name Location Role Contribution

Maria PiaAmato

Universita degli Studi diFirenze DipartimentoNEUROFARBA Firenze -IRCCS Fondazione DonCarlo Gnocchi Firenze

SiteInvestigator

Datacollection

PietroAnnovazzi

Centro Sclerosi MultiplaOspedale di GallarateASST della Valle Olona

SiteInvestigator

Datacollection

Carlo Antozzi Centro Sclerosi MultiplaUO Neurologia IVFondazione IRCCSIstituto NeurologicoCarlo Besta Milano

SiteInvestigator

Datacollection

LuciaAppendino

SCNeurologia1OspedaleMaria Vittoria- Torino

SiteInvestigator

Datacollection

SebastianoArena

Dipartimento ScienzeMediche e Chirurgiche eTecnologie Avanzate GFIngrassia Universita diCatania Centro SclerosiMultipla Policlinico GRodolico- San MarcoUniversita di Catania

SiteInvestigator

Datacollection

Viola Baione Department of HumanNeurosciences SapienzaUniversity of Rome

SiteInvestigator

Datacollection

RobertoBalgera

MS Center ASST Lecco SiteInvestigator

Datacollection

ValeriaBarcella

USS NeuroimmunologiaASST Papa Giovanni XXIII

SiteInvestigator

Datacollection

DamianoBaroncini

Centro Sclerosi MultiplaOspedale di GallarateASST della Valle Olona

SiteInvestigator

Datacollection

CaterinaBarrila

ASST Rhodense SiteInvestigator

Datacollection

AlessandraBellacosa

CentroSclerosiMultiplaUONeurologia Ospedale SanGiacomo Monopoli (Bari)

SiteInvestigator

Datacollection

GianmarcoBellucci

Department ofNeuroscience MentalHealth and SensoryOrgans SapienzaUniversity S AndreaHospital-site Rome

SiteInvestigator

Datacollection

RobertoBergamaschi

IRCCS MondinoFoundation Pavia

SiteInvestigator

Datacollection

ValeriaBergamaschi

AISM RehabilitationService Liguria

SiteInvestigator

Datacollection

Daiana Bezzini Department of LifeSciences University ofSiena Siena Italy

SiteInvestigator

Datacollection

Beatrice Biolzi Centro SM Fidenza (PR) SiteInvestigator

Datacollection

Alvino Bisecco Centro SM I ClinicaNeurologica AOU-Policlinico Universitadella Campania LuigiVanvitelli

SiteInvestigator

Datacollection

8 Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 NeurologyorgNN

Appendix 2 (continued)

Name Location Role Contribution

SimonaBonavita

Department of AdvancedMedical and SurgicalSciences University ofCampania Luigi Vanvitelli80138 Naples Italy

SiteInvestigator

Datacollection

GiovannaBorriello

NCL Isituto diNeuroscienze Roma

SiteInvestigator

Datacollection

Chiara Bosa MS Center Departmentof Neuroscience City ofHealth and ScienceUniversity Hospital ofTurin Turin Italy

SiteInvestigator

Datacollection

Antonio Bosco Neurology UnitDepartment of MedicalSurgical and HealthSciences CattinaraUniversity HospitalASUGI Trieste

SiteInvestigator

Datacollection

FrancescaBovis

Department of HealthSciences University ofGenoa Genoa Italy

Biostatistician Support instatisticalanalysis

Marco Bozzali Neurology II Dept ofNeuroscience Universityof Turin

SiteInvestigator

Datacollection

LauraBrambilla

Centro Sclerosi MultiplaUO Neurologia IVFondazione IRCCSIstituto NeurologicoCarlo Besta Milano

SiteInvestigator

Datacollection

MariaBuccafusca

Centro Sclerosi MultiplaUOC Neurologia e MalattieNeuromuscolari AOUPoliclinico G MartinoMessina

SiteInvestigator

Datacollection

ElisabettaBucciantini

Ospedale SaviglianoASLCN1

SiteInvestigator

Datacollection

SebastianoBucello

Centro SM OspedaleMuscatello Augusta(ASP8 SR)

SiteInvestigator

Datacollection

Maria ChiaraBuscarinu

Department ofNeuroscience MentalHealth and SensoryOrgans SapienzaUniversity S AndreaHospital-site Rome

SiteInvestigator

Datacollection

Maria PaolaCabboi

UOC Neurologia- centroSM- AUSL- IRCCS RE

SiteInvestigator

Datacollection

MassimilianoCalabrese

The Multiple SclerosisCenter of UniversityHospital of Verona Deptof NeuroscienceBiomedicine andMovements

SiteInvestigator

Datacollection

FrancescaCalabria

UO Neurologia A-AziendaOspedaliera UniversitariaIntegrata Verona

SiteInvestigator

Datacollection

FrancescaCaleri

Multiple Sclerosis CenterDepartment ofNeurology - FranzTappeiner HospitalMeran (BZ) Italy

SiteInvestigator

Datacollection

Appendix 2 (continued)

Name Location Role Contribution

FedericoCamilli

IRCCS Istituto delleScienze Neurologiche diBologna UOSIRiabilitazione SclerosiMultipla

SiteInvestigator

Datacollection

Luisa MariaCaniatti

Centro sclerosi Multiplaazienda ospedalierauniversitaria S AnnaFerrara

SiteInvestigator

Datacollection

RobertoCantello

Neurology UnitMaggiore della CaritaHospital Department ofTranslational MedicineUniversity of PiemonteOrientale Novara Italy

SiteInvestigator

Datacollection

Ruggero Capra Centro Sclerosi MultiplaASST Spedali Civili diBrescia Ospedale diMontichiari

SiteInvestigator

Datacollection

RoccoCapuano

Centro SM I ClinicaNeurologica AOU-Policlinico Universitadella Campania LuigiVanvitelli

SiteInvestigator

Datacollection

Patrizia Carta Centro Sclerosi MultiplaOspedale di GallarateASST della Valle Olona

SiteInvestigator

Datacollection

Maria GraziaCelani

Azienda Ospedaliera diPerugia SC diNeurofisiopatologia

SiteInvestigator

Datacollection

MariaCellerino

DINOGMI Universitarsquo diGenova

SiteInvestigator

Datacollection

RaffaellaCerqua

Clinica NeurologicaOspedali Riuniti Ancona

SiteInvestigator

Datacollection

Clara Chisari Dipartimento ScienzeMediche e Chirurgichee Tecnologie AvanzateGF Ingrassia Universitadi Catania CentroSclerosi MultiplaPoliclinico G Rodolico-San Marco Universitadi Catania

SiteInvestigator

Datacollection

RaffaellaClerici

Centro Sclerosi MultiplaUO NeurologiaOspedale Valduce Como

SiteInvestigator

Datacollection

MarinellaClerico

Clinical and BiologicalSciences Dept Universityof Torino

SiteInvestigator

Datacollection

Gaia Cola Multiple Sclerosis Clinicaland Research UnitDepartment of SystemsMedicine Tor VergataUniversity Rome Italy

SiteInvestigator

Datacollection

AntonellaConte

1) Department of HumanNeurosciences SapienzaUniversity of Rome 2)IRCCS Neuromed Pozzilli(IS)

SiteInvestigator

Datacollection

Marta ZaffiraConti

USS NeuroimmunologiaASST Papa Giovanni XXIII

SiteInvestigator

Datacollection

Continued

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 9

Appendix 2 (continued)

Name Location Role Contribution

ChristianCordano

UCSF San Francisco USA SiteInvestigator

Datacollection

SusannaCordera

SC Neurologia Ausl ValleDrsquo Aosta

SiteInvestigator

Datacollection

FrancescoCorea

Neurologia OspedaleSan Giovanni Foligno

SiteInvestigator

Datacollection

ClaudioCorreale

AISM VicenzaRehabilitation Service

SiteInvestigator

Datacollection

SalvatoreCottone

Centro Sclerosi MultiplaUOC Neurologia conStroke Unit ARNASCivico (Palermo)

SiteInvestigator

Datacollection

FrancescoCrescenzo

The Multiple SclerosisCenter of UniversityHospital of Verona Deptof NeuroscienceBiomedicine andMovements

SiteInvestigator

Datacollection

Erica Curti Multiple Sclerosis CentreDepartment of GeneralMedicine ParmaUniversity HospitalParma

SiteInvestigator

Datacollection

AlessandrodrsquoAmbrosio

Centro SM I ClinicaNeurologica AOU-Policlinico Universitadella Campania LuigiVanvitelli

SiteInvestigator

Datacollection

EmanueleDrsquoAmico

Dipartimento ScienzeMediche e Chirurgiche eTecnologie Avanzate GFIngrassia Universita diCatania Centro SclerosiMultipla Policlinico GRodolico- San MarcoUniversita di Catania

SiteInvestigator

Datacollection

Maura ChiaraDanni

Clinica NeurologicaOspedali Riuniti Ancona

SiteInvestigator

Datacollection

Alessia drsquoArma IRCCS Fondazione DonCarlo Gnocchi ONLUSMilano

SiteInvestigator

Datacollection

VincenzoDattola

UOC Neurologia GrandeOspedale MetropolitanoBianchi MelacrinoMorelli Reggio diCalabria

SiteInvestigator

Datacollection

Stefano deBiase

Neurology UnitOspedale dellrsquoAngeloVenezia-Mestre Italy

SiteInvestigator

Datacollection

Giovanna DeLuca

MS Centre Departmentof Clinical Neurology SSAnnunziata UniversityHospital Chieti Italy

SiteInvestigator

Datacollection

StefaniaFederica DeMercanti

Clinical and BiologicalSciences Dept Universityof Torino

SiteInvestigator

Datacollection

Paolo De Mitri Emergency DepartmentGuglielmo da SalicetoHospital Piacenza Italy

SiteInvestigator

Datacollection

Appendix 2 (continued)

Name Location Role Contribution

Nicola DeStefano

Department of MedicineSurgery andNeuroscience Universityof Siena Italy

SiteInvestigator

Datacollection

Marco DellaCava

AISM PadovaRehabilitation Service

SiteInvestigator

Datacollection

Mario diNapoli

Centro Sclerosi MultiplaRieti (Rieti)

SiteInvestigator

Datacollection

Alessia DiSapio

Department ofNeurology ReginaMontis Regalis HospitalMondovı (CN)

SiteInvestigator

Datacollection

RenatoDocimo

Centro Sclerosi MultiplaPresidio Ospedaliero SanGiuseppe Moscati ASLCaserta Aversa (CE)

SiteInvestigator

Datacollection

Anna Dutto Ospedale SaviglianoAslcn1

SiteInvestigator

Datacollection

LuanaEvangelista

Demyelinating DiseaseCenter San SalvatoreHospital LrsquoAquila

SiteInvestigator

Datacollection

SalvatoreFanara

Department ofBiomedicineNeurosciences andAdvanced DiagnsoticsUniversity of Palermo

SiteInvestigator

Datacollection

Diana Ferraro Department ofBiomedical Metabolicand NeurosciencesUniversity of Modenaand Reggio EmiliaModena Italy

SiteInvestigator

Datacollection

Maria TeresaFerro

NeuroimmunologyCenter for MultipleSclerosis ASST CremaItaly

SiteInvestigator

Datacollection

CristinaFioretti

UO Neurologia Livorno SiteInvestigator

Datacollection

Mario Fratta II Clinica NeurologicaUniversita dellaCampania LuigiVanvitelli Naples

SiteInvestigator

Datacollection

Jessica Frau Centro Sclerosi MultiplaATS Sardegna DptScienze Mediche eSanita PublicaUniversita di CagliariCagliari

SiteInvestigator

Datacollection

Marzia Fronza Centro Sclerosi MultiplaATS Sardegna DptScienze Mediche e SanitaPublica Universita diCagliari Cagliari

SiteInvestigator

Datacollection

Roberto Furlan Institute of ExperimentalNeurology Division ofNeuroscience IRCCSOspedale San RaffaeleMilano Italy and ItalianNeuroimmunologyAssociation-AINI

SiteInvestigator

Datacollection

10 Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 NeurologyorgNN

Appendix 2 (continued)

Name Location Role Contribution

AlbertoGajofatto

Dipartimento diNeuroscienzeBiomedicina eMovimento Universita diVerona

SiteInvestigator

Datacollection

Antonio Gallo Centro SM I ClinicaNeurologica AOU-Policlinico Universitadella Campania LuigiVanvitelli

SiteInvestigator

Datacollection

Paolo Gallo Multiple Sclerosis Centre ofthe Veneto Region(CeSMuV) UniversityHospital of Padua Italy

SiteInvestigator

Datacollection

ClaudioGasperini

Dept Neurosciences SanCamillo ForlaniniHospital - Rome

SiteInvestigator

Datacollection

AnnaGhazaryan

UO Neurologia SiteInvestigator

Datacollection

BrunoGiometto

Ospedale Santa ChiaraTrento UO Neurologia(Trento)

SiteInvestigator

Datacollection

FrancescaGobbin

Dipartimento diNeuroscienzeBiomedicina eMovimento Universita diVerona

SiteInvestigator

Datacollection

Flora Govone Department of NeurologyRegina Montis RegalisHospital Mondovı (CN)

SiteInvestigator

Datacollection

FrancoGranella

Unit of NeurosciencesDepartment of Medicineand Surgery University ofParma Parma ampMultipleSclerosis CentreDepartment of GeneralMedicine Parma UniversityHospital Parma

SiteInvestigator

Datacollection

Erica Grange Dept of RehabilitationCRRF Mons LuigiNovarese MoncrivelloItaly

SiteInvestigator

Datacollection

Maria GraziaGrasso

IRCCS Fondazione SantaLucia

SiteInvestigator

Datacollection

AngelicaGuareschi

Centro SM Fidenza (PR) SiteInvestigator

Datacollection

ClaraGuaschino

Centro Sclerosi MultiplaOspedale di GallarateASST della Valle Olona

SiteInvestigator

Datacollection

SimoneGuerrieri

Neurology DepartmentMultiple Sclerosis CenterSan Raffaele HospitalMilan

SiteInvestigator

Datacollection

DonataGuidetti

Emergency DepartmentGuglielmo da SalicetoHospital Piacenza Italy

SiteInvestigator

Datacollection

PietroIaffaldano

Department of BasicMedical SciencesNeurosciences andSenseOrgans - Universityof Bari Aldo Moro

SiteInvestigator

Datacollection

Appendix 2 (continued)

Name Location Role Contribution

AntonioIanniello

Centro SM SAndrea DipNeuroscienze UmaneSapienza Roma

SiteInvestigator

Datacollection

Luigi Iasevoli IRCCS Fondazione SantaLucia

SiteInvestigator

Datacollection

DanieleImperiale

SCNeurologia1OspedaleMaria Vittoria- Torino

SiteInvestigator

Datacollection

Maria TeresaInfante

Neurologia ASL 1imperiese

SiteInvestigator

Datacollection

Rosa Iodice Department ofNeuroscienceReproductive Sciencesand OdontostomatologyUniversity Federico II ofNaples Naples Italy

SiteInvestigator

Datacollection

Aniello Iovino Department of AdvancedBiomedical SciencesUniversity Federico IINaples Italy

SiteInvestigator

Datacollection

GiovannaKonrad

AISM AostaRehabilitation Service

SiteInvestigator

Datacollection

Doriana Landi Multiple Sclerosis Clinicaland Research UnitDepartment of SystemsMedicine Tor VergataUniversity Rome Italy

SiteInvestigator

Datacollection

RobertaLanzillo

Federico II University ofNaples

SiteInvestigator

Datacollection

CaterinaLapucci

DINOGMI Universitarsquo diGenova

SiteInvestigator

Datacollection

Luigi Lavorgna Department of AdvancedMedical and SurgicalSciences University ofCampania LuigiVanvitelli 80138 NaplesItaly

SiteInvestigator

Datacollection

Maria RitaLrsquoEpiscopo

Centro Sclerosi Multiplaospedale San Lazzaro(Alba CN)

SiteInvestigator

Datacollection

Serena Leva Centro Sclerosi MultiplaOspedale di LegnanoASST OVEST MI Italia

SiteInvestigator

Datacollection

GiuseppeLiberatore

Neuromuscular andNeuroimmunologyService IRCCSHumanitas Clinical andResearch InstituteRozzano Milan Italy

SiteInvestigator

Datacollection

Marianna LoRe

SCDO Neurologia eCentro di RiferimentoRegionale SclerosiMultipla AOU San Luigi -Orbassano (TO)

SiteInvestigator

Datacollection

Marco Longoni Local Health Agency ofRomagna MaurizioBufalini Hospital(Cesena) - Neurology Unit

SiteInvestigator

Datacollection

LeonardoLopiano

Neurology II Dept ofNeuroscience Universityof Turin

SiteInvestigator

Datacollection

Continued

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 11

Appendix 2 (continued)

Name Location Role Contribution

LorenaLorefice

Centro Sclerosi MultiplaATS Sardegna DptScienze Mediche eSanita PublicaUniversita di CagliariCagliari

SiteInvestigator

Datacollection

MatteoLucchini

Fondazione PoliclinicoUniversitario AgostinoGemelli IRCCS -Universita Cattolica delSacro Cuore

SiteInvestigator

Datacollection

Giacomo Lus II Clinica NeurologicaUniversita dellaCampania LuigiVanvitelli Naples

SiteInvestigator

Datacollection

DavideMaimone

Centro SM - UOCNeurologia - ARNASGaribaldi - Catania

SiteInvestigator

Datacollection

MariaMalentacchi

SCDO Neurologia eCentro di RiferimentoRegionale SclerosiMultipla AOU San Luigi -Orbassano (TO)

SiteInvestigator

Datacollection

Giulia Mallucci IRCCS MondinoFoundation Pavia

SiteInvestigator

Datacollection

SimonaMalucchi

SCDO Neurologia eCentro di RiferimentoRegionale SclerosiMultipla AOU San Luigi -Orbassano (TO)

SiteInvestigator

Datacollection

Chiara RosaMancinelli

Centro Sclerosi MultiplaASST Spedali Civili diBrescia Ospedale diMontichiari

SiteInvestigator

Datacollection

LucaMancinelli

Local Health Agency ofRomagna Maurizio BufaliniHospital (Cesena) -Neurology Unit

SiteInvestigator

Datacollection

PaoloManganotti

Neurology UnitDepartment of MedicalSurgical and HealthSciences CattinaraUniversity Hospital ASUGITrieste

SiteInvestigator

Datacollection

Giorgia TeresaManiscalco

Multiple Sclerosis CentreA Cardarelli HospitalNaples Italy

SiteInvestigator

Datacollection

Neurological Clinic andStroke Unit A CardarelliHospital Naples Italy

SiteInvestigator

Datacollection

VittorioMantero

MS Center ASST Lecco SiteInvestigator

Datacollection

SabrinaMarangoni

Ospedale Santa ChiaraTrento UO Neurologia(Trento)

SiteInvestigator

Datacollection

DamianoMarastoni

The Multiple SclerosisCenter of UniversityHospital of VeronaDept ofNeuroscienceBiomedicine andMovements

SiteInvestigator

Datacollection

Appendix 2 (continued)

Name Location Role Contribution

FabianaMarinelli

Ospedale FabrizioSpaziani Frosinone

SiteInvestigator

Datacollection

Asl Frosinone SiteInvestigator

Datacollection

AlessandroMarti

UOC Neurologia- centroSM Reggio Emilia- AUSL-IRCSS RE

SiteInvestigator

Datacollection

FilippoMartinelliBoneschi

1 IRCCS Fondazione CarsquoGranda OspedaleMaggiore PoliclinicoNeurology Unit MilanItaly Via Francesco Sforza35 20122

SiteInvestigator

Datacollection

2 Dino Ferrari CenterDepartment ofPathophysiology andTransplantationUniversity of MilanMilan Italy Via FrancescoSforza 35 20122

SiteInvestigator

Datacollection

FedercoMasserano Zoli

AISM PadovaRehabilitation Service

SiteInvestigator

Datacollection

FrancescaMatta

Centro SM - UOCNeurologia - ARNASGaribaldi - Catania

SiteInvestigator

Datacollection

LauraMendozzi

IRCCS Fondazione DonCarlo Gnocchi ONLUSMilano

SiteInvestigator

Datacollection

GiuseppeMeucci

UO Neurologia Livorno SiteInvestigator

Datacollection

Silvia Miante Multiple Sclerosis Centreof the Veneto Region(CeSMuV) UniversityHospital of Padua Italy

SiteInvestigator

Datacollection

GiuseppinaMiele

Department of AdvancedMedical and SurgicalSciences University ofCampania Luigi Vanvitelli80138 Naples Italy

SiteInvestigator

Datacollection

Eva Milano SCNeurologia1OspedaleMaria Vittoria- Torino

SiteInvestigator

Datacollection

MassimilianoMirabella

Fondazione PoliclinicoUniversitario AgostinoGemelli IRCCS -Universita Cattolica delSacro Cuore

SiteInvestigator

Datacollection

RosannaMissione

II Clinica NeurologicaUniversita dellaCampania LuigiVanvitelli Naples

SiteInvestigator

Datacollection

MarcelloMoccia

Federico II University ofNaples

SiteInvestigator

Datacollection

Lucia Moiola Neurology Unit IRCCSSan Raffaele ScientificInstitute Milan Italy

SiteInvestigator

Datacollection

SaraMontepietra

Responsabile del CentroSclerosi Multipla - ReggioEmilia- UOC Neurologia-AUSL-IRCSS RE

SiteInvestigator

Datacollection

12 Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 NeurologyorgNN

Appendix 2 (continued)

Name Location Role Contribution

MargheritaMontiBragadin

AISM RehabilitationService Liguria

SiteInvestigator

Datacollection

FedericoMontini

Neurology Unit IRCCSSan Raffaele ScientificInstitute Milan Italy

SiteInvestigator

Datacollection

Roberta Motta AISM RehabilitationService Liguria

SiteInvestigator

Datacollection

RaffaeleNardone

1 Paracelsus MedicalUniversity Department ofNeurology Salisburgo AU

SiteInvestigator

Datacollection

2 Department ofNeurology - FranzTappeiner HospitalMeran (BZ) Italy

SiteInvestigator

Datacollection

Carolina GabriNicoletti

Multiple Sclerosis Clinicaland Research UnitDepartment of SystemsMedicine Tor VergataUniversity Rome Italy

SiteInvestigator

Datacollection

EduardoNobile-Orazio

1)Neuromuscular andNeuroimmunologyService IRCCSHumanitas Clinical andResearch InstituteRozzano Milan Italy

SiteInvestigator

Datacollection

2)Department of MedicalBiotechnology andTranslational MedicineMilan University Milan

SiteInvestigator

Datacollection

Italy SiteInvestigator

Datacollection

AgostinoNozzolillo

Neurology Unit IRCCSSan Raffaele ScientificInstitute Milan Italy

SiteInvestigator

Datacollection

Marco Onofrj Department ofNeurosciences Imagingand Clinical SciencesUniversity G drsquoAnnunzioof Chieti-Pescara ChietiItaly

SiteInvestigator

Datacollection

RiccardoOrlandi

Dipartimento diNeuroscienzeBiomedicina eMovimento Universita diVerona

SiteInvestigator

Datacollection

Anna Palmieri UO Neurologia Treviso SiteInvestigator

Datacollection

DamianoPaolicelli

Department of BasicMedical SciencesNeurosciences andSenseOrgans - Universityof Bari Aldo Moro

SiteInvestigator

Datacollection

Livia Pasquali Department of Clinicaland ExperimentalMedicine NeurologyUnit University of PisaPisa Italy

SiteInvestigator

Datacollection

Luisa Pasto Azienda OspedalieroUniversitaria CareggiFirenze

SiteInvestigator

Datacollection

Appendix 2 (continued)

Name Location Role Contribution

ElisabettaPedrazzoli

AISM PadovaRehabilitation Service

SiteInvestigator

Datacollection

Maria Petracca Federico II University ofNaples

SiteInvestigator

Datacollection

AlfredoPetrone

Ospedale Annunziata(Cosenza)

SiteInvestigator

Datacollection

CarloPiantadosi

UOC Neurologia -Azienda OspedalieraSan Giovanni-Addolorata - Roma

SiteInvestigator

Datacollection

Anna MPietroboni

1 Fondazione IRCCS CarsquoGranda OspedaleMaggiore PoliclinicoMilan IT

SiteInvestigator

Datacollection

2 University of MilanDino Ferrari CenterMilan IT

SiteInvestigator

Datacollection

FedericaPinardi

IRCCS Istituto delleScienze Neurologiche diBologna UOSIRiabilitazione SclerosiMultipla

SiteInvestigator

Datacollection

MartaPonzano

Department of HealthSciences University ofGenoa Genoa Italy

Biostatistician Support instatisticalanalysis

EmilioPortaccio

Universita degli Studi diFirenze DipartimentoNEUROFARBA Firenze

SiteInvestigator

Datacollection

Mattia Pozzato 1 IRCCS Fondazione CarsquoGranda OspedaleMaggiore PoliclinicoNeurology UnitMilan Italy ViaFrancesco Sforza 3520122

SiteInvestigator

Datacollection

2 Dino Ferrari CenterDepartment ofPathophysiology andTransplantationUniversity of MilanMilan Italy Via FrancescoSforza 35 20122

SiteInvestigator

Datacollection

Carlo Pozzilli Centro SM SAndreaDipNeuroscienzeUmane Sapienza Roma

SiteInvestigator

Datacollection

LucaProsperini

Dept Neurosciences SanCamillo ForlaniniHospital - Rome

SiteInvestigator

Datacollection

AlessandraProtti

ASST GOM NIGUARDADIPARTIMENTONEUROSCIENZE

SiteInvestigator

Datacollection

PaoloRagonese

Department ofBiomedicineNeurosciences andAdvanced DiagnsoticsUniversity of Palermo

SiteInvestigator

Datacollection

Sarah Rasia Centro Sclerosi MultiplaASST Spedali Civili diBrescia Ospedale diMontichiari

SiteInvestigator

Datacollection

Continued

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 13

Appendix 2 (continued)

Name Location Role Contribution

SabrinaRealmuto

Centro Sclerosi MultiplaUOC di Neurologia eStroke Unit AOOR VillaSofia-Cervello Palermo

SiteInvestigator

Datacollection

Anna Repice Azienda OspedalieraUniversitaria CareggiFirenze

SiteInvestigator

Datacollection

EleonoraRigoni

IRCCS MondinoFoundation Pavia

SiteInvestigator

Datacollection

Maria TeresaRilla

Neurologia ASL 1imperiese

SiteInvestigator

Datacollection

FrancescaRinaldi

Multiple Sclerosis Centreof the Veneto Region(CeSMuV) UniversityHospital of Padua Italy

SiteInvestigator

Datacollection

CalogeroMarcelloRomano

Centro Sclerosi MultiplaUOC di Neurologia eStroke Unit AOOR VillaSofia-Cervello Palermo

SiteInvestigator

Datacollection

Marco Ronzoni ASST Rhodense SiteInvestigator

Datacollection

Marco Rovaris IRCCS Fondazione DonCarlo Gnocchi ONLUSMilano

SiteInvestigator

Datacollection

FrancescaRuscica

centro SM repartoneurologia Ospedale GGiglio Cefalu (PA)

SiteInvestigator

Datacollection

LoredanaSabattini

IRCCS Istituto delleScienze Neurologiche diBologna UOSIRiabilitazione SclerosiMultipla

SiteInvestigator

Datacollection

GiuseppeSalemi

Department ofBiomedicineNeurosciences andadvanced DiagnosticsUniversity of Palermo

SiteInvestigator

Datacollection

LorenzoSaraceno

ASST GOM NIGUARDADIPARTIMENTONEUROSCIENZE

SiteInvestigator

Datacollection

Alessia Sartori Department ofPharmacy OspedaleGuglielmo da SalicetoPiacenza Italy

SiteInvestigator

Datacollection

AriannaSartori

Neurology UnitDepartment of MedicalSurgical and HealthSciences CattinaraUniversity HospitalASUGI Trieste

SiteInvestigator

Datacollection

Elvira Sbragia DINOGMI Universitarsquo diGenova

SiteInvestigator

Datacollection

Giuditta IlariaScarano

1 Departement ofPsycology University ofMilano-Bicocca MilanItaly

SiteInvestigator

Datacollection

2 Departement ofPsychology FranzTappeiner HospitalMerano Italy

SiteInvestigator

Datacollection

Appendix 2 (continued)

Name Location Role Contribution

ValentinaScarano

UOC Neurologia e StrokeAORN San GiuseppeMoscati Avellino

SiteInvestigator

Datacollection

ValentinaSchillaci

MS Center Departmentof Neuroscience City ofHealth and ScienceUniversity Hospital ofTurin Turin Italy

SiteInvestigator

Datacollection

Maria Sessa UOC Neurologia USSNeuroimmunologiaASST Papa Giovanni XXIII

SiteInvestigator

Datacollection

CaterinaSgarito

AISM ComoRehabilitation Service

SiteInvestigator

Datacollection

Grazia Sibilia NEUROLOGY UNIT ANDMS CENTER ASL NAPOLI1 CENTRONAPLES ITALY

SiteInvestigator

Datacollection

GabrieleSiciliano

Department of Clinicaland ExperimentalMedicine NeurologyUnit University of PisaPisa Italy

SiteInvestigator

Datacollection

Alessio Signori Department of HealthSciences University ofGenoa Genoa Italy

Biostatistician Support instatisticalanalysis

ElisabettaSignoriello

II Clinica NeurologicaUniversita dellaCampania LuigiVanvitelli Naples

SiteInvestigator

Datacollection

LeonardoSinisi

NEUROLOGY UNIT ANDMS CENTER ASLNAPOLI 1 CENTRONAPLES ITALY

SiteInvestigator

Datacollection

FrancescaSireci

UOC Neurologia- centroSM Reggio Emilia- AUSL-IRCCS RE

SiteInvestigator

Datacollection

Patrizia Sola Neurology UnitOspedale Civile AziendaOspedaliero-Universitaria di ModenaModena Italy

SiteInvestigator

Datacollection

Claudio Solaro Dept of RehabilitationCRRF Mons LuigiNovarese MoncrivelloItaly

SiteInvestigator

Datacollection

Stefano Sotgiu Dipartimento di ScienzeMediche Chirurgiche eSperimentali - Universitadi Sassari

SiteInvestigator

Datacollection

MaddalenaSparaco

Department of AdvancedMedical and SurgicalSciences University ofCampania LuigiVanvitelli 80138 NaplesItaly

SiteInvestigator

Datacollection

Maria LauraStromillo

Department of MedicineSurgery andNeuroscience Universityof Siena Italy

SiteInvestigator

Datacollection

Silvia Strumia MS center NeurologyUnit Morgagni-Pierantoni Hospital Forlı

SiteInvestigator

Datacollection

14 Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 NeurologyorgNN

References1 Sormani MP De Rossi N Schiavetti I et al Disease-modifying therapies and coro-

navirus disease 2019 severity in multiple sclerosis Ann Neurol 202189(4)780-789doi 101002ana26028

2 Louapre C Collongues N Stankoff B et al Clinical characteristics and outcomes inpatients with coronavirus disease 2019 and multiple sclerosis JAMA Neurol 202077(9)1079-1088 doi 101001jamaneurol20202581

Appendix 2 (continued)

Name Location Role Contribution

EmanuelaLaura Susani

ASST GOM NIGUARDADIPARTIMENTONEUROSCIENZE

SiteInvestigator

Datacollection

GiuliettaTabiadon

Multiple SclerosisOutptClinic ClinicalNeurology and StrokeUnit Dep CentralCountry HospitalBolzano Italy

SiteInvestigator

Datacollection

FrancescoTeatini

Multiple SclerosisOutptClinic ClinicalNeurology and StrokeUnit Dep CentralCountry HospitalBolzano Italy

SiteInvestigator

Datacollection

ValentinaTomassini

1 Institute for AdvancedBiomedicalTechnologies (ITAB)Department ofNeurosciences Imagingand Clinical SciencesUniversity G drsquoAnnunzioof Chieti-Pescara ChietiItaly

SiteInvestigator

Datacollection

2 MS CentreDepartment of ClinicalNeurology SSAnnunziata UniversityHospital Chieti Italy

SiteInvestigator

Datacollection

SimoneTonietti

Centro Sclerosi MultiplaOspedale San CarloBorromeo (Milano)

SiteInvestigator

Datacollection

Valentina TorriClerici

Centro Sclerosi MultiplaUO Neurologia IVFondazione IRCCSIstituto NeurologicoCarlo Besta Milano

SiteInvestigator

Datacollection

CarlaTortorella

Dept Neurosciences SanCamillo ForlaniniHospital - Rome

SiteInvestigator

Datacollection

SimonaToscano

Dipartimento ScienzeMediche e Chirurgiche eTecnologie Avanzate GFIngrassia Universita diCatania Centro SclerosiMultipla Policlinico GRodolico- San MarcoUniversita di Catania

SiteInvestigator

Datacollection

Rocco Totaro Demyelinating DiseaseCenter San SalvatoreHospital LrsquoAquila

SiteInvestigator

Datacollection

Maria Trotta Ospedale Annunziata(Cosenza)

SiteInvestigator

Datacollection

GabriellaTurano

Department ofNeurology ReginaMontis Regalis HospitalMondovı (CN)

SiteInvestigator

Datacollection

Monica Ulivelli Department of MedicineSurgery andNeuroscience Universityof Siena Siena Italy

SiteInvestigator

Datacollection

Appendix 2 (continued)

Name Location Role Contribution

ManzoValentino

Neurological Clinic andStroke Unit A CardarelliHospital Naples Italy

SiteInvestigator

Datacollection

GiovannaVaula

Neurology IIAOU Citta dellaSalute e della Scienza-Turin

SiteInvestigator

Datacollection

DomiziaVecchio

Neurology UnitMaggiore della CaritaHospital Departmentof TranslationalMedicine University ofPiemonte OrientaleNovara Italy

SiteInvestigator

Datacollection

MarcoVercellino

MS Center Departmentof Neuroscience City ofHealth and ScienceUniversity Hospital ofTurin Turin Italy

SiteInvestigator

Datacollection

Elena PinucciaVerrengia

Centro Sclerosi MultiplaOspedale di LegnanoASST OVEST MI Italia

SiteInvestigator

Datacollection

MarikaVianello

UO Neurologia Treviso SiteInvestigator

Datacollection

EleonoraVirgilio

Neurology UnitMaggiore della CaritaHospital Department ofTranslational MedicineUniversity of PiemonteOrientale Novara Italy

SiteInvestigator

Datacollection

FrancescaVitetta

Neurology UnitOspedale Civile AziendaOspedaliero-Universitaria di ModenaModena Italy

SiteInvestigator

Datacollection

StefanoVollaro

Emergency DepartmentGuglielmo da SalicetoHospital Piacenza Italy

SiteInvestigator

Datacollection

MauroZaffaroni

Centro Sclerosi MultiplaOspedale di GallarateASST della Valle Olona

SiteInvestigator

Datacollection

MauroZampolini

Neurologia OspedaleSan Giovanni Foligno

SiteInvestigator

Datacollection

IgnazioRoberto Zarbo

Dipartimento di ScienzeMediche Chirurgiche eSperimentali - Universitadi Sassari

SiteInvestigator

Datacollection

Luigi Zuliani Department ofNeurology - OspedaleSan Bortolo - AULSS8Berica Vicenza

Datacollection

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 15

3 Salter A Fox RJ Newsome SD et al Outcomes and risk factors associated withSARS-CoV-2 infection in a North American registry of patients with multiplesclerosis JAMA Neurol 202178(6)699-708 doi 101001jamaneurol20210688

4 Sormani MP Salvetti M Labauge P et al DMTs and Covid-19 severity in MS apooled analysis from Italy and France Ann Clin Transl Neurol 20218(8)1738-1744doi 101002acn351408

5 Barzegar M Mirmosayyeb O Gajarzadeh M et al COVID-19 among patients withmultiple sclerosis a systematic review Neurol Neuroimmunol Neuroinflammation20218(4)e1001 doi 101212NXI0000000000001001

6 Salvetti M Bellucci G Ballerini C et al SARS-CoV-2 meta-interactome suggestsdisease-specific autoimmune pathophysiologies and therapeutic targets F1000Res20209992 doi 1012688f1000research255931

7 Wang EY Mao T Klein J et al Diverse functional autoantibodies in patients withCOVID-19 Nature 2021595(7866)283-288 doi 101038s41586-021-03631-y

8 Bastard P Orlova E Sozaeva L et al Preexisting autoantibodies to type I IFNsunderlie critical COVID-19 pneumonia in patients with APS-1 J Exp Med 2021218(7)e20210554 doi 101084jem20210554

9 Bastard P Rosen LB ZhangQ et al Autoantibodies against type I IFNs in patients with life-threatening COVID-19 Science 2020370(6515)eabd4585 doi 101126scienceabd4585

10 Williamson EJ Walker AJ Bhaskaran K et al Factors associated with COVID-19-related death using OpenSAFELY Nature 2020584(7821)430-436 doi 101038s41586-020-2521-4

11 Stockmaier S Stroeymeyt N Shattuck EC Hawley DM Meyers LA Bolnick DIInfectious diseases and social distancing in nature Science 2021371(6533)eabc8881doi 101126scienceabc8881

12 Mathur R Rentsch CT Morton CE et al Ethnic differences in SARS-CoV-2 infection andCOVID-19-related hospitalisation intensive care unit admission and death in 17 millionadults in England an observational cohort study using theOpenSAFELY platform Lancet2021397(10286)1711-1724 doi 101016S0140-6736(21)00634-6

16 Neurology Neuroimmunology amp Neuroinflammation | Volume 9 Number 1 | January 2022 NeurologyorgNN

DOI 101212NXI000000000000110520229 Neurol Neuroimmunol Neuroinflamm

Maria Pia Sormani Irene Schiavetti Luca Carmisciano et al COVID-19 Severity in Multiple Sclerosis Putting Data Into Context

This information is current as of November 9 2021

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Academy of Neurology All rights reserved Online ISSN 2332-7812Copyright copy 2021 The Author(s) Published by Wolters Kluwer Health Inc on behalf of the AmericanPublished since April 2014 it is an open-access online-only continuous publication journal Copyright

is an official journal of the American Academy of NeurologyNeurol Neuroimmunol Neuroinflamm

ServicesUpdated Information amp

httpnnneurologyorgcontent91e1105fullhtmlincluding high resolution figures can be found at

References httpnnneurologyorgcontent91e1105fullhtmlref-list-1

This article cites 12 articles 2 of which you can access for free at

Citations httpnnneurologyorgcontent91e1105fullhtmlotherarticles

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Subspecialty Collections

httpnnneurologyorgcgicollectionrisk_factors_in_epidemiologyRisk factors in epidemiology

httpnnneurologyorgcgicollectionmultiple_sclerosisMultiple sclerosis

httpnnneurologyorgcgicollectionincidence_studiesIncidence studies

httpnnneurologyorgcgicollectioncovid_19COVID-19following collection(s) This article along with others on similar topics appears in the

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httpnnneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in

Reprints

httpnnneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online

Academy of Neurology All rights reserved Online ISSN 2332-7812Copyright copy 2021 The Author(s) Published by Wolters Kluwer Health Inc on behalf of the AmericanPublished since April 2014 it is an open-access online-only continuous publication journal Copyright

is an official journal of the American Academy of NeurologyNeurol Neuroimmunol Neuroinflamm