Multiple Sclerosis and Related Disorders 57 (2022) 103359
Available online 1 November 2021
2211-0348/© 2021 Elsevier B.V. All rights reserved.
COVID-19 susceptibility and outcomes among patients with neuromyelitis
optica spectrum disorder (NMOSD): A systematic review and meta-analysis
Mahdi Barzegar
a, b
, Omid Mirmosayyeb
a, b
, Narges Ebrahimi
b
, Sara Bagherieh
b
, Alireza Afshari-
Safavi
b, c
, Ali Mahdi Hosseinabadi
b
, Vahid Shaygannejad
a, b
, Nasrin Asgari
d, *
a
Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
b
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
c
Department of Biostatistics and Epidemiology, Faculty of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
d
Department of Neurology, Slagelse Hospital & Institutes of Regional Health Research and Molecular Medicine, University of Southern Denmark, J.B. Winsloewsvej 25.2,
Odense 5000, Denmark
A R T I C L E INFO
Keywords:
Neuromyelitis optica spectrum disorder
Coronavirus
COVID-19
Infection
Prevalence
Outcome
ABSTRACT
Background: We conducted this systematic review and meta-analysis to assess the risk of coronavirus disease
(COVID-19), clinical features and outcome among patients with neuromyelitis optica spectrum disorder
(NMOSD).
Methods: We systematically searched PubMed, Scopus, Web of Science, and Embase from December 1, 2019, to
July 2, 2021. The gray literature including the references of original studies, review studies, conference abstracts,
and WHO COVID-19 database was also searched. We included any type of studies that reported NMOSD patients
with COVID-19, prevalence of COVID-19 among NMOSD patients or the infection outcome (hospitalization,
intensive care unit [ICU] admission, or mortality).
Results: Out of 540 records, a total of 23 studies (19 published articles and 4 conference abstracts) including 112
NMOSD patients with COVID-19 met the inclusion criteria. Nine studies reporting risk of COVID-19 and nine
studies on outcome were included in a quantitative synthesis. The pooled prevalence of COVID-19 was 1.2%
(95% CI: 0.001%–0.030%; I
2
= 92%, p< 0.001), with hospitalization of 33.7% (95% CI: 23.3–44.8%; I
2
= 9.1%,
p = 0.360) with 52.9% on rituximab treatment. ICU admission was 15.4% (95% CI: 7.6%-24.7%; I
2
= 20.7%, p =
0.272) and mortality was 3.3% (95% CI: 0–9.7%; I
2
= 21.3%, p = 0.253). Thirty-eight patients (48.7%) reported
at least one comorbidity. The mean age of the included patients was 40.8 (10.63) years, female/male ratio was
3.35:1. The most common COVID-19 symptom was fever (54.5%), followed by fatigue/asthenia (42.9%),
headache (41.6%), and cough (40.3%). Four patients developed neurological worsening. The Begg’s and Egger’s
tests showed no evidence of publication bias.
Conclusion: The analysis suggests that comorbidity and treatment with rituximab may be risk factors for COVID-
19 infection in NMOSD patients.
1. Introduction
The outbreak of Coronavirus Disease 2019 (COVID-19), which is
caused by Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-
CoV-2), has led to the tragic loss of over 4 million people as of June 23,
2021 with more than 18 million infected cases worldwide (World Health
Organization, 2021). From the early stages of the outbreak, it has been
suggested that patients with suppressed immune systems may be at an
elevated risk of contracting the virus, experiencing more severe forms of
the disease (World Health Organization, 2020).
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune
infammatory disease of the central nervous system (CNS) that mainly
presents with optic neuritis and myelitis (Wingerchuk et al., 2007). For
many years, NMOSD was considered as a variant of multiple sclerosis
(MS) (Wingerchuk et al., 2007). However, the discovery of
anti-aquaporin 4 antibody (AQP4 Ab) and further immunological and
pathological evidence characterised it a distinct entity different from
MS, and defned NMOSD as an autoimmune astrocytopathy (Lennon
* Corresponding author.
E-mail address: nasgari@health.sdu.dk (N. Asgari).
Contents lists available at ScienceDirect
Multiple Sclerosis and Related Disorders
journal homepage: www.elsevier.com/locate/msard
https://doi.org/10.1016/j.msard.2021.103359
Received 26 August 2021; Received in revised form 22 October 2021; Accepted 28 October 2021