https://orcid.org/0000-0003-2995-6391
Figures
Abstract
Objectives
Previous studies suggested a higher rate of COVID-19 infection in patients with multiple sclerosis than in the general population, and limited studies addressed the impact of COVID-19 and its vaccination in patients with multiple sclerosis in Iran. We decided to investigate the factors associated with COVID-19 infection, the effects and side effects of the COVID-19 vaccination in patients with multiple sclerosis (MS).
Methods
We used the data of the patients with multiple sclerosis registered in a referral clinic in Kerman, one of the large cities in Iran (a population of 537,000 inhabitants), to explore the association between demographic variables, the history of COVID-19 vaccination, and the clinical outcomes.
Results
Of the 367 participants in this study, 88.3% received the COVID-19 vaccine, 35.4% were confirmed COVID-19 cases, and the incidence of COVID-19 was much higher before vaccination (24.5% before vaccination versus 10.1% after vaccination). The multivariable logistic regression model showed that male gender (OR = 2.64, 95% confidence interval: 1.21, 5.74) and current employment (OR = 3.04, 95% confidence interval: 1.59, 5.80) were associated with an increased risk of COVID-19. The only factor associated with the adverse effects of COVID-19 vaccination was the type of vaccine (AstraZeneca).
Conclusion
Our findings showed that the vaccination protected MS cases considerably against COVID-19. In addition, the side effects of the vaccines were not noticeably high in these cases as well. Among all COVID-19 vaccines, AstraZeneca had the most common side effects, so people must be aware of them before vaccination. The male gender and employment were the most important variables in the prevalence of COVID-19 in patients with multiple sclerosis in our study.
Citation: Sedighi B, Haghdoost A, Jangipour Afshar P, Abna Z, Bahmani S, Jafari S (2023) Multiple sclerosis and COVID-19: A retrospective study in Iran. PLoS ONE 18(3): e0283538. https://doi.org/10.1371/journal.pone.0283538
Editor: Anza Bilal Memon, Henry Ford Health System, UNITED STATES
Received: August 14, 2022; Accepted: March 10, 2023; Published: March 23, 2023
Copyright: © 2023 Sedighi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The author received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for COVID-19, which was first seen in Wuhan, China, in 2019 [1]. This disease is very contagious and manifests with fever, cough, myalgia, and dyspnea. The virus spread all over the world, resulting in a pandemic that killed 5.4 million people and infected more than 304 million people until January 9, 2022 [2]. COVID-19 posed a great challenge to all healthcare systems around the world, with the greatest impact on the health organizations of each country [3].
Multiple sclerosis (MS), one of the most disabling CNS diseases, is an autoimmune inflammatory demyelinating pathology that affects approximately 2.8 million people worldwide [4,5]. Many patients with multiple sclerosis have a suppressed immune system due to disease-modifying therapy (DMT), so they are more at risk for infectious diseases than the general population [6].
The COVID-19 outbreak has caused many issues for patients with multiple sclerosis in various aspects of their lives, including fragile mental health, poor treatment follow-up, and increased annual hospitalization [7,8]. The suppressive immune system due to DMT has also raised concerns about the facilitation of COVID-19 infection in patients with MS [9–11].
Fortunately, initiating vaccination against COVID-19 has controlled the spread of the disease and improved the medical status of patients with MS [12,13]. Previous studies showed that COVID-19 has a higher rate of infection and hospitalization in patients with MS than in the general population, while early vaccination may be effective in reducing these rates [14]. Numerous studies were conducted on the patients with MS in Iran during the COVID-19 pandemic [7,8,15]. However, limited studies investigated the factors affecting COVID-19 infection, the effectiveness of vaccination, and the complications of vaccination in patients with MS in Iran. Most of these studies were conducted at the beginning of the pandemic [14,16–18]. The current study investigated the factors associated with COVID-19 infection, the impact of vaccination, as well as factors affecting the side effects of vaccination in patients with MS in Kerman Province, Iran.
Materials and methods
Study design and participants
This retrospective study aimed to investigate the factors associated with the COVID-19 and the effectiveness and side effects of vaccination in patients with MS in a referral clinic in Kerman, one of the large cities in Iran, from March to December 2021.
We used the data of patients registered in the referral hospital in Kerman province. Out of 548 registered cases, we recruited 367 (66.9%) and excluded those who disagreed or had a major non-communicable disease, such as diabetes, hypertension, cardiovascular, cerebrovascular, and respiratory diseases. The final diagnosis of MS in this registry was confirmed by neurologists who are affiliated with the Shafa hospital and the Kerman University of Medical Sciences, based on the revised McDonald criteria (2017) [19].
Outcomes measurement
Data were collected using three questionnaires: 1. demographic information (age, gender, BMI, education level, employment status, number of children, place of residence (urban or rural), no common comorbidities (complications accompanying MS other than diabetes, hypertension, cardiovascular, cerebrovascular, and respiratory diseases), tobacco, alcohol, and substance abuse (opioids, heroin, methamphetamine, or other stimulants)); 2: COVID-19-related information (including vaccine injection, type, and side effects; confirmed COVID-19 that was based on physician judgment, which used lab tests including PCR and clinical signs and symptoms since the beginning of the pandemic; infection with COVID-19 before or after vaccination; and the time (days) to infection after vaccination); 3: Multiple sclerosis-related information (duration of illness and the Expanded Disability Status Scale).
The expanded disability status scale (EDSS) of MS patients was designed by John Kurtzke. It assesses the functioning of systems such as pyramidal, cerebellar, brainstem, sensory, bowel, and bladder, visual and cerebellar regions [20], The score varies from 0 (a normal neurological state) to 10 (MS-induced death): 0–2.5 refers to people with a mild degree of disability, 3–5 refers to people with a moderate degree of disability, and 5.5–10 refers to people with a severe degree of disability.
Statistical analysis
SPSS 26 was used to analyze the data. Descriptive statistics were used to describe qualitative (number and percentage) and quantitative variables (mean and standard deviation). A multivariable logistic regression model was used to determine the factors related to COVID-19 and its side effects in patients with MS. A significant level of 0.05 was considered.
Results
The study included 367 participants, of whom 305 (83.1%) were female and 62 (16.9%) were male. Participants were between 17 and 67 years old, with a mean age of 37.99±9.80. The mean duration of multiple sclerosis was 8.26 ± 5.60 years, and the mean EDSS score was 1.18±1.60 out of 10, which was categorized as a mild category. Most of the patients had 12–16 years of academic education (80.4%), were unemployed (67.8%), lived in urban areas (93.5%), did not use tobacco or other substances (89.4%), received a vaccine against COVID-19 (88.3%), did not acquire COVID-19 (64.6%), and had mild disease activity (84.2%). Tables 1 and 2 present other demographic characteristics.
The multivariable logistic regression model showed that gender (OR = 2.64, 95% confidence interval: 1.21, 5.74), and employment status (OR = 3.04, 95% confidence interval: 1.59, 5.80), were all associated with an increased risk of COVID-19 infection in the patients with MS. (Table 3).
According to a multivariable logistic regression model, only the type of vaccine (AstraZeneca) (OR = 23.578, 95% confidence interval: 3.041,182.80) was a risk factor for adverse effects of COVID-19 injection in the patients with MS (Table 4).
We compared the frequency of post-vaccination side effects among patients based on the types of vaccines. Our results showed that the patients with multiple sclerosis who received AstraZeneca and Sinopharm had significant adverse effects (Table 5). Also, our results showed that the patients had side effects such as injection site pain, tenderness, redness, fever, headache, fatigue, nausea, diarrhea, and muscle pain after vaccination. The most common adverse effect was pain at the injection site (31.3%) (Table 6).
Furthermore, we compared the prevalence of COVID-19 in patients with MS based on the type of DMT, and our results showed no significant difference in the prevalence of COVID-19 based on the kind of DMT taken by the patients. (Table 7).
Discussion
We investigated the factors associated with COVID-19 infection, the impacts and side effects of vaccination in patients with multiple sclerosis in Kerman Province, Iran.
We found that the male gender and employment status of the patients with MS played a significant role in evaluating factors associated with suspected or confirmed COVID-19, and the type of vaccine (AstraZeneca) was the only factor associated with the adverse effects of COVID-19 vaccination.
We revealed that the prevalence of COVID-19 in the patients with MS was approximately 35%, but Naghavi et al. indicated that the suspected rate of COVID-19 in the patients with MS was 20.4%, with 11.7% having PCR confirmation [21], and Zabalza et al. reported that COVID-19 was prevalent in 6.3 percent of the patients with MS. The difference between these studies and our study could be due to genetic and racial differences, disease-modifying therapies, and poor compliance with COVID-19 protection protocols [22–26].
Another finding of this study indicated that 70 percent of the COVID-19 infection occurred before vaccination, supporting the fact that vaccination against COVID-19 can reduce the infection rate of the coronavirus. Large-scale vaccination could be the only way to prevent COVID-19 [12,27,28].
We discovered, like Moss and Jehi et al., that the male gender and employment could increase the prevalence of COVID-19 in MS patients [6,29]. But Naghavi et al. reported no association between gender and COVID-19. They found the presence of comorbidity, EDSS scores, DMT, hospitalization rate due to COVID-19 infection could be associated with gender [21]. Rostami et al. reported that autoimmune diseases, DMT, age, gender, and high EDSS increased COVID-19 incidence and hospitalization in patients with multiple sclerosis [24]. The high incidence of COVID-19 in men and employed people could be due to strict self-protection, self-isolation, and social distancing in women more than men, and also high exposure to the coronavirus in employed people.
In this study, we did not find any significant difference in contracting COVID-19 between users and non-users of DMT. And also, no association was found between COVID-19 prevalence and the type of DMT, even in patients receiving anti CD20 therapies. These findings are in line with Alonso and Parrotta et al. [30,31], which found no association between DMT and the risk of COVID-19. It could be due to the small sample size in this study, the younger participants, or the lower EDSS. Recent large studies have shown that patients with MS treated with anti-CD20 DMTs (rituximab or ocrelizumab) were at higher risk of developing severe COVID-19 than other DMTs [32,33]; however, strict adherence to health protocols and self-isolation might be an important reason for the low prevalence and severity of COVID-19 infection among our patients.
Studies suggest that the COVID-19 pandemic has affected patients with multiple sclerosis, so the development of multiple vaccines against COVID-19 could be promising for the control and eradication of the disease. According to the current study, 88% of the patients received at least one dose of the vaccine, indicating their willingness to receive COVID-19 vaccines; Also, in the patients on the anti B cell therapies, vaccination was done one month before taking the next dose of the drug or three months after taking the drug (as a result of the previous studies on the efficacy of the vaccines in the patients treated with these drugs). Previous studies found that patients with multiple sclerosis were less reluctant to receive the COVID-19 vaccines after healthcare providers prepared adequate information for them [27].
Furthermore, we showed that 39 percent of the patients had side effects such as injection site pain, tenderness, redness, fever, headache, fatigue, nausea, diarrhea, and muscle pain after vaccination. Most of them received Sinopharm vaccines, and a few of them received Barekat, AstraZeneca, and Sputnik vaccines. We found a significant relationship between the type of vaccine and side effects after vaccination; all vaccines had side effects, but AstraZeneca had the most common side effects. Zare et al. supported this result [34], in contrast Babaee and Omeish et al. rejected it [35,36]. Previous studies reviewed the effect of other vaccines on patients with MS and found that those on immunosuppressive drugs experienced serious side effects and a relapse after vaccination; thus, patients with MS should seek medical advice before receiving vaccines [12,28].
Conclusion
We found that the prevalence of COVID-19 in the patients with MS was higher than in the other studies, which could be an alarm for patients with chronic and immunosuppressive diseases in the healthcare system in Iran.
In our study, men and employed people were more susceptible to COVID-19 infection, which could be due to their high exposure to SARS-CoV-2. The incidence of COVID-19 infection was much higher before vaccination, indicating an important role of vaccination in COVID-19 prevention. This study showed that a significant percentage of the patients with MS received at least one dose of vaccine, recalling the important role of vaccination in the control of COVID-19. The AstraZeneca vaccine caused the most common side effects among vaccines, so people should be aware of vaccine side effects before receiving vaccination. Future studies should address severe side effects to make more evidence-based decisions.
Acknowledgments
The researchers would like to thank all the patients with multiple sclerosis for participating in this study. This study was approved by the neurology research center of Kerman University of Medical Sciences.
References
- 1. Daniel J. Education and the COVID-19 pandemic. Prospects. 2020;49(1):91–6.
- 2.
Organization WH. COVID-19 weekly epidemiological update, edition 74, 11 January 2022. 2022.
- 3. Kaye AD, Okeagu CN, Pham AD, Silva RA, Hurley JJ, Arron BL, et al. Economic impact of COVID-19 pandemic on healthcare facilities and systems: International perspectives. Best Practice & Research Clinical Anaesthesiology. 2021;35(3):293–306. pmid:34511220
- 4. Jeanjean M, Bind M-A, Roux J, Ongagna J-C, De Sèze J, Bard D, et al. Ozone, NO2 and PM10 are associated with the occurrence of multiple sclerosis relapses. Evidence from seasonal multi-pollutant analyses. Environmental research. 2018;163:43–52. pmid:29426027
- 5. Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler. 2020;26(14):1816–21. Epub 2020/11/12. pmid:33174475; PubMed Central PMCID: PMC7720355.
- 6. Moss BP, Mahajan KR, Bermel RA, Hellisz K, Hua LH, Hudec T, et al. Multiple sclerosis management during the COVID-19 pandemic. Mult Scler. 2020;26(10):1163–71. Epub 2020/08/11. pmid:32772807; PubMed Central PMCID: PMC7424611.
- 7. Sahraian MA, Gheini MR, Rezaeimanesh N, Ghajarzadeh M, Moghadasi AN. Knowledge regarding COVID-19 pandemic in patients with multiple sclerosis (MS): A report from Iran. Multiple sclerosis and related disorders. 2020;42:102193. pmid:32420011
- 8. Moghadasi AN. Evaluation of the level of anxiety among Iranian multiple sclerosis fellowships during the outbreak of COVID-19. Archives of Iranian medicine. 2020;23(4):283. pmid:32271605
- 9. Ghajarzadeh M, Bonavita S. Are patients with multiple sclerosis (MS) at higher risk of COVID-19 infection? Neurological Sciences. 2020;41(9):2315–6. pmid:32638135
- 10. Crescenzo F, Marastoni D, Bovo C, Calabrese M. Frequency and severity of COVID-19 in multiple sclerosis: A short single-site report from northern Italy. Mult Scler Relat Disord. 2020;44:102372. Epub 2020/07/11. pmid:32650121; PubMed Central PMCID: PMC7335234.
- 11. Luna G, Alping P, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA neurology. 2020;77(2):184–91. pmid:31589278
- 12. Etemadifar M, Abhari AP, Nouri H, Sigari AA, Piran Daliyeh SM, Maracy MR, et al. Self-Reported safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among Iranian people with multiple sclerosis. Human vaccines & immunotherapeutics. 2022;18(1):2041945. Epub 2022/02/25. pmid:35201963; PubMed Central PMCID: PMC9009900.
- 13. Ghadiri F, Sahraian MA, Azimi A, Moghadasi AN. The study of COVID-19 infection following vaccination in patients with multiple sclerosis. Multiple Sclerosis and Related Disorders. 2021:103363. pmid:35158433
- 14. Safavi F, Nourbakhsh B, Azimi AR. B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran. Multiple sclerosis and related disorders. 2020;43:102195. pmid:32460086
- 15. Kwenandar F, Japar KV, Damay V, Hariyanto TI, Tanaka M, Lugito NPH, et al. Coronavirus disease 2019 and cardiovascular system: A narrative review. IJC Heart & Vasculature. 2020;29:100557. pmid:32550259
- 16. Barzegar M, Mirmosayyeb O, Gajarzadeh M, Afshari-Safavi A, Nehzat N, Vaheb S, et al. COVID-19 Among Patients With Multiple Sclerosis: A Systematic Review. Neurology-Neuroimmunology Neuroinflammation. 2021;8(4).
- 17. Rezaeimanesh N, Sahraian MA, Moghadasi AN. Evaluation of the opinion of patients with multiple sclerosis on the outcomes of catching COVID-19 and its effects on the MS symptoms. Basic and clinical neuroscience. 2020;11(2):201.
- 18. Möhn N, Konen FF, Pul R, Kleinschnitz C, Prüss H, Witte T, et al. Experience in multiple sclerosis patients with COVID-19 and disease-modifying therapies: a review of 873 published cases. Journal of clinical medicine. 2020;9(12):4067. pmid:33339436
- 19. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. 2018;17(2):162–73.
- 20. Kurtzke JFJN. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). 1983;33(11):1444–.
- 21. Naghavi S, Kavosh A, Adibi I, Shaygannejad V, Arabi S, Rahimi M, et al. COVID-19 infection and hospitalization rate in Iranian multiple sclerosis patients: what we know by May 2021. Multiple Sclerosis and Related Disorders. 2022;57:103335. pmid:35158427
- 22. Patsopoulos NA. Genetics of multiple sclerosis: an overview and new directions. Cold Spring Harbor perspectives in medicine. 2018;8(7):a028951. pmid:29440325
- 23. Tirupathi R, Muradova V, Shekhar R, Salim SA, Al-Tawfiq JA, Palabindala V. COVID-19 disparity among racial and ethnic minorities in the US: a cross sectional analysis. Travel medicine and infectious disease. 2020;38:101904. pmid:33137491
- 24. Rostami Mansoor S, Ghasemi‐Kasman M. Impact of disease‐modifying drugs on the severity of COVID‐19 infection in multiple sclerosis patients. Journal of Medical Virology. 2021;93(3):1314–9.
- 25. Moore L, Ghannam M, Manousakis G. A first presentation of multiple sclerosis with concurrent COVID-19 infection. Eneurologicalsci. 2021;22:100299. pmid:33313429
- 26. Zabalza A, Cárdenas-Robledo S, Tagliani P, Arrambide G, Otero-Romero S, Carbonell-Mirabent P, et al. COVID-19 in multiple sclerosis patients: susceptibility, severity risk factors and serological response. European journal of neurology. 2021;28(10):3384–95. Epub 2020/12/20. pmid:33340215.
- 27. Ehde DM, Roberts MK, Humbert AT, Herring TE, Alschuler KN. COVID-19 vaccine hesitancy in adults with multiple sclerosis in the United States: a follow up survey during the initial vaccine rollout in 2021. Multiple Sclerosis and Related Disorders. 2021;54:103163. pmid:34325399
- 28. Tallantyre EC, Vickaryous N, Anderson V, Asardag AN, Baker D, Bestwick J, et al. Covid‐19 vaccine response in people with multiple sclerosis. Annals of neurology. 2022;91(1):89–100. pmid:34687063
- 29. Jehi L, Ji X, Milinovich A, Erzurum S, Rubin BP, Gordon S, et al. Individualizing Risk Prediction for Positive Coronavirus Disease 2019 Testing: Results From 11,672 Patients. Chest. 2020;158(4):1364–75. Epub 2020/06/14. pmid:32533957; PubMed Central PMCID: PMC7286244.
- 30. Parrotta E, Kister I, Charvet L, Sammarco C, Saha V, Charlson RE, et al. COVID-19 outcomes in MS: Observational study of early experience from NYU Multiple Sclerosis Comprehensive Care Center. 2020;7(5).
- 31. Alonso R, Silva B, Garcea O, Diaz PEC, Dos Passos GR, Navarro DAR, et al. COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America: COVID-19 in MS and NMOSD patients in LATAM. 2021;51:102886.
- 32. Sormani MPJTLN. An Italian programme for COVID-19 infection in multiple sclerosis. 2020;19(6):481–2.
- 33. Simpson-Yap S, Brouwer ED, Kalincik T, Rijke N, Hillert J, Walton C, et al. Associations of DMT Therapies with COVID-19 Severity in Multiple Sclerosis: An International Cohort Study. 2020.
- 34. Zare H, Rezapour H, Mahmoodzadeh S, Fereidouni M. Prevalence of COVID-19 vaccines (Sputnik V, AZD-1222, and Covaxin) side effects among healthcare workers in Birjand city, Iran. International immunopharmacology. 2021;101(Pt B):108351. Epub 2021/11/22. pmid:34801416; PubMed Central PMCID: PMC8577998.
- 35. Babaee E, Amirkafi A, Tehrani-Banihashemi A, SoleimanvandiAzar N, Eshrati B, Rampisheh Z, et al. Adverse effects following COVID-19 vaccination in Iran. BMC Infectious Diseases. 2022;22(1):476. pmid:35585518
- 36. Omeish H, Najadat A, Al-Azzam S, Tarabin N, Abu Hameed A, Al-Gallab N, et al. Reported COVID-19 vaccines side effects among Jordanian population: a cross sectional study. Human vaccines & immunotherapeutics. 2022;18(1):1981086. Epub 2021/10/07. pmid:34614383; PubMed Central PMCID: PMC8920252.