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Modifiable risk factors of COVID-19 in patients with multiple sclerosis: a single-centre case–control study

Montini et al., Journal of Neurology, doi:10.1007/s00415-023-11618-0
Feb 2023  
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Case 7% Improvement Relative Risk Vitamin D for COVID-19  Montini et al.  Sufficiency Are vitamin D levels associated with COVID-19 outcomes? Retrospective study in Italy (March 2020 - March 2021) Fewer cases with higher vitamin D levels (p<0.000001) c19early.org Montini et al., J. Neurology, February 2023 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
Case control analysis with 149 multiple sclerosis patients and 292 matched controls in Italy, showing lower risk of COVID-19 cases with higher vitamin D levels.
risk of case, 7.0% lower, OR 0.93, p < 0.001, adjusted per study, case control OR, multivariable.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Montini et al., 16 Feb 2023, retrospective, Italy, peer-reviewed, 10 authors, study period March 2020 - March 2021. Contact: filippi.massimo@hsr.it.
This PaperVitamin DAll
Modifiable risk factors of COVID-19 in patients with multiple sclerosis: a single-centre case–control study
Federico Montini, Agostino Nozzolillo, Paola M V Rancoita, Chiara Zanetta, Lucia Moiola, Federica Cugnata, Federica Esposito, Maria A Rocca, Vittorio Martinelli, Massimo Filippi
Journal of Neurology, doi:10.1007/s00415-023-11618-0
Background Disease and treatment-associated immune system abnormalities may confer higher risk of Coronavirus disease 2019 (COVID-19) to people with multiple sclerosis (PwMS). We assessed modifiable risk factors associated with COVID-19 in PwMS. Methods Among patients referring to our MS Center, we retrospectively collected epidemiological, clinical and laboratory data of PwMS with confirmed COVID-19 between March 2020 and March 2021 (MS-COVID, n = 149). We pursued a 1:2 matching of a control group by collecting data of PwMS without history of previous COVID-19 (MS-NCOVID, n = 292). MS-COVID and MS-NCOVID were matched for age, expanded disability status scale (EDSS) and line of treatment. We compared neurological examination, premorbid vitamin D levels, anthropometric variables, life-style habits, working activity, and living environment between the two groups. Logistic regression and Bayesian network analyses were used to evaluate the association with COVID-19. Results MS-COVID and MS-NCOVID were similar in terms of age, sex, disease duration, EDSS, clinical phenotype and treatment. At multiple logistic regression, higher levels of vitamin D (OR 0.93, p < 0.0001) and active smoking status (OR 0.27, p < 0.0001) emerged as protective factors against COVID-19. In contrast, higher number of cohabitants (OR 1.26, p = 0.02) and works requiring direct external contact (OR 2.61, p = 0.0002) or in the healthcare sector (OR 3.73, p = 0.0019) resulted risk factors for COVID-19. Bayesian network analysis showed that patients working in the healthcare sector, and therefore exposed to increased risk of COVID-19, were usually non-smokers, possibly explaining the protective association between active smoking and COVID-19. Conclusions Higher Vitamin D levels and teleworking may prevent unnecessary risk of infection in PwMS.
Author contributions Concept and design: MR, MF. Acquisition, analysis, or interpretation of data: MN, RZ, MC, ER, MF. Drafting of the manuscript: MR, CR, MF. Statistical analysis: RC. Supervision: RMF. Declarations Conflict of interest Federico Montini has no potential conflicts of interest and reports no disclosures; Agostino Nozzolillo has no potential conflicts of interest and reports no disclosures; Paola M.V. Rancoita has no potential conflicts of interest and reports no disclosures; Chiara Zanetta has no potential conflicts of interest and reports no disclosures; Lucia Moiola received compensation for speaking activities, and/or consulting services from Merck, Biogen, Novartis, Roche, Sanofi, and TEVA; Federica Cugnata has no potential conflicts of interest and reports no disclosures; Federica Esposito received consulting and speaking fees from Novartis, Sanofi Genzyme; Maria A. Rocca received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche; and speaker honoraria from AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. She receives research support from the MS Society of Canada, the Italian Ministry of Health, and Fondazione Italiana Sclerosi Multipla. She is Associate Editor for Multiple Sclerosis and Related Disorders; Vittorio Martinelli received compensation for speaking and/or for consultancy and support for travel expenses and..
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Int J Infect Dis 105:15–20', 'journal-title': 'Int J Infect Dis'}, { 'issue': '1', 'key': '11618_CR28', 'doi-asserted-by': 'publisher', 'first-page': '252', 'DOI': '10.1186/s12879-022-07233-5', 'volume': '22', 'author': 'M Ellingjord-Dale', 'year': '2022', 'unstructured': 'Ellingjord-Dale M, Kalleberg KT, Istre MS, Nygaard AB, Brunvoll SH, ' 'Eggesbo LM et al (2022) The use of public transport and contraction of ' 'SARS-CoV-2 in a large prospective cohort in Norway. BMC Infect Dis ' '22(1):252', 'journal-title': 'BMC Infect Dis'}, { 'key': '11618_CR29', 'doi-asserted-by': 'crossref', 'unstructured': 'Hopkinson NS, Rossi N, El-Sayed Moustafa J, Laverty AA, Quint JK, ' 'Freidin M, et al. (2021) Current smoking and COVID-19 risk: results from ' 'a population symptom app in over 2.4 million people. Thorax ' '76(7):714–22.', 'DOI': '10.1136/thoraxjnl-2020-216422'}, { 'key': '11618_CR30', 'doi-asserted-by': 'publisher', 'first-page': '09', 'DOI': '10.18332/tid/132411', 'volume': '19', 'author': 'A Umnuaypornlert', 'year': '2021', 'unstructured': 'Umnuaypornlert A, Kanchanasurakit S, Lucero-Prisno DEI, Saokaew S (2021) ' 'Smoking and risk of negative outcomes among COVID-19 patients: a ' 'systematic review and meta-analysis. Tob Induc Dis 19:09', 'journal-title': 'Tob Induc Dis'}, { 'issue': '3', 'key': '11618_CR31', 'first-page': '431', 'volume': '50', 'author': 'Y He', 'year': '2021', 'unstructured': 'He Y, Sun J, Ding X, Wang Q (2021) Mechanisms in which smoking increases ' 'the risk of COVID-19 infection: a narrative review. Iran J Public Health ' '50(3):431–437', 'journal-title': 'Iran J Public Health'}, { 'key': '11618_CR32', 'doi-asserted-by': 'crossref', 'unstructured': 'Haddad C, Bou Malhab S, Sacre H, Salameh P (2021) Smoking and COVID-19: ' 'a scoping review. Tob Use Insights 14:1179173X21994612.', 'DOI': '10.1177/1179173X21994612'}, { 'issue': '1', 'key': '11618_CR33', 'doi-asserted-by': 'publisher', 'first-page': '1554', 'DOI': '10.1186/s12889-021-11579-x', 'volume': '21', 'author': 'R Patanavanich', 'year': '2021', 'unstructured': 'Patanavanich R, Glantz SA (2021) Smoking is associated with worse ' 'outcomes of COVID-19 particularly among younger adults: a systematic ' 'review and meta-analysis. BMC Public Health 21(1):1554', 'journal-title': 'BMC Public Health'}, { 'issue': '6', 'key': '11618_CR34', 'doi-asserted-by': 'publisher', 'first-page': '279', 'DOI': '10.1136/bmjebm-2020-111492', 'volume': '26', 'author': 'MS Usman', 'year': '2021', 'unstructured': 'Usman MS, Siddiqi TJ, Khan MS, Patel UK, Shahid I, Ahmed J et al (2021) ' 'Is there a smoker’s paradox in COVID-19? BMJ Evid Based Med ' '26(6):279–284', 'journal-title': 'BMJ Evid Based Med'}, { 'issue': '8', 'key': '11618_CR35', 'doi-asserted-by': 'publisher', 'first-page': '1398', 'DOI': '10.1093/ntr/ntab004', 'volume': '23', 'author': 'N Paleiron', 'year': '2021', 'unstructured': 'Paleiron N, Mayet A, Marbac V, Perisse A, Barazzutti H, Brocq FX et al ' '(2021) Impact of tobacco smoking on the risk of COVID-19: a large scale ' 'retrospective cohort study. Nicotine Tob Res 23(8):1398–1404', 'journal-title': 'Nicotine Tob Res'}, { 'key': '11618_CR36', 'unstructured': 'Wenzl T (2020) Smoking and COVID-19 A review of studies suggesting a ' 'protective effect of smoking against COVID-19. Pubblication office of ' 'the European Union'}, { 'issue': '1', 'key': '11618_CR37', 'doi-asserted-by': 'publisher', 'first-page': '10', 'DOI': '10.1038/s41533-021-00223-1', 'volume': '31', 'author': 'NA van Westen-Lagerweij', 'year': '2021', 'unstructured': 'van Westen-Lagerweij NA, Meijer E, Meeuwsen EG, Chavannes NH, Willemsen ' 'MC, Croes EA (2021) Are smokers protected against SARS-CoV-2 infection ' '(COVID-19)? The origins of the myth. NPJ Prim Care Respir Med 31(1):10', 'journal-title': 'NPJ Prim Care Respir Med'}, { 'key': '11618_CR38', 'doi-asserted-by': 'publisher', 'first-page': '335', 'DOI': '10.1016/j.ijid.2021.01.013', 'volume': '104', 'author': 'M Gholami', 'year': '2021', 'unstructured': 'Gholami M, Fawad I, Shadan S, Rowaiee R, Ghanem H, Hassan Khamis A et al ' '(2021) COVID-19 and healthcare workers: a systematic review and ' 'meta-analysis. Int J Infect Dis 104:335–346', 'journal-title': 'Int J Infect Dis'}, { 'issue': '5', 'key': '11618_CR39', 'doi-asserted-by': 'publisher', 'first-page': 'e200008', 'DOI': '10.1212/NXI.0000000000200008', 'volume': '9', 'author': 'IA Lie', 'year': '2022', 'unstructured': 'Lie IA, Wesnes K, Kvistad SS, Brouwer I, Wergeland S, Holmoy T et al ' '(2022) The effect of smoking on long-term gray matter atrophy and ' 'clinical disability in patients with relapsing-remitting multiple ' 'sclerosis. Neurol Neuroimmunol Neuroinflamm 9(5):e200008', 'journal-title': 'Neurol Neuroimmunol Neuroinflamm'}, { 'key': '11618_CR40', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ebiom.2021.103581', 'volume': '72', 'author': 'MP Sormani', 'year': '2021', 'unstructured': 'Sormani MP, Inglese M, Schiavetti I, Carmisciano L, Laroni A, Lapucci C ' 'et al (2021) Effect of SARS-CoV-2 mRNA vaccination in MS patients ' 'treated with disease modifying therapies. EBioMedicine 72:103581', 'journal-title': 'EBioMedicine'}], 'container-title': 'Journal of Neurology', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s00415-023-11618-0.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s00415-023-11618-0/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s00415-023-11618-0.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 2, 16]], 'date-time': '2023-02-16T13:04:41Z', 'timestamp': 1676552681000}, 'score': 1, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s00415-023-11618-0'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 2, 16]]}, 'references-count': 40, 'alternative-id': ['11618'], 'URL': 'http://dx.doi.org/10.1007/s00415-023-11618-0', 'relation': {}, 'ISSN': ['0340-5354', '1432-1459'], 'subject': ['Neurology (clinical)', 'Neurology'], 'container-title-short': 'J Neurol', 'published': {'date-parts': [[2023, 2, 16]]}, 'assertion': [ { 'value': '21 December 2022', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '8 February 2023', 'order': 2, 'name': 'revised', 'label': 'Revised', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '8 February 2023', 'order': 3, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '16 February 2023', 'order': 4, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'Federico Montini has no potential conflicts of interest\xa0and reports no ' 'disclosures; Agostino Nozzolillo has no potential conflicts of interest\xa0and ' 'reports no disclosures; Paola M.V. Rancoita has no potential conflicts of ' 'interest\xa0and reports no disclosures; Chiara Zanetta has no potential ' 'conflicts of interest\xa0and reports no disclosures; Lucia Moiola received ' 'compensation for speaking activities, and/or consulting services from Merck, ' 'Biogen, Novartis, Roche, Sanofi, and TEVA; Federica Cugnata has no potential ' 'conflicts of interest\xa0and reports no disclosures; Federica Esposito received ' 'consulting and speaking fees from Novartis, Sanofi Genzyme; Maria A. Rocca ' 'received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, ' 'Roche; and speaker honoraria from AstraZaneca, Biogen, Bristol Myers Squibb, ' 'Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, ' 'Novartis, Roche, Sanofi and Teva. She receives research support from the MS ' 'Society of Canada, the Italian Ministry of Health, and Fondazione Italiana ' 'Sclerosi Multipla. She is Associate Editor for <i>Multiple Sclerosis and ' 'Related Disorders</i>; Vittorio Martinelli received compensation for speaking ' 'and/or for consultancy and support for travel expenses and participation in ' 'Congresses from Biogen, Merck-Serono, Novartis, Genzyme and Teva Pharmaceutical ' 'Industries; Massimo Filippi is Editor-in-Chief of the <i>Journal of ' 'Neurology</i>, Associate Editor of <i>Human Brain Mapping</i>, <i>Neurological ' 'Sciences,</i> and <i>Radiology</i>; received compensation for consulting ' 'services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; ' 'speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, ' 'Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, ' 'Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, ' 'Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, ' 'Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, ' 'Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; ' 'he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, ' 'Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA ' '(Fondazione Italiana di Ricerca per la SLA).', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Conflict of interest'}}, { 'value': 'Approval was received from the local ethical standards committee on human ' 'experimentation (Ethical committee approval no. 101/INT/2020), and written ' 'informed consent was obtained from all participants prior to study enrolment, ' 'according to the declaration of Helsinki.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethical standards'}}, { 'value': 'This content has been made available to all.', 'name': 'free', 'label': 'Free to read'}]}
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