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Evaluation of COVID-19 infection in patients with Neuromyelitis optica spectrum disorder (NMOSD): A report from Iran

      Since its inception in December 2019 in Wuhan, China, COVID-19 has spread rapidly around the world, killing and infecting a large number of people (
      • Wang LS
      • Wang YR
      • Ye DW
      • Liu QQ
      A review of the 2019 novel coronavirus (COVID-19) based on current evidence.
      ). The incidence of COVID-19 in normal people varies from 0.35% to 13.3% (
      • Signorelli C
      • Scognamiglio T
      • Odone A
      COVID-19 in Italy: impact of containment measures and prevalence estimates of infection in the general population.
      ). It has been warned that people with an underlying diseases or taking immunosuppressive drugs may be more likely to develop the disease or suffer from its complications (
      • Gavin Giovannoni
      • et al.
      The COVID-19 pandemic and the use of MS disease-modifying therapies.
      ). Patients with neuromyelitis optica spectrum disorder (NMOSD) are more prone to different types of infections due to use of immunosuppressive drugs to control the disease (
      • Sahraian MA
      • Moghadasi AN
      • Azimi AR
      • et al.
      Diagnosis and management of Neuromyelitis optica spectrum disorder (NMOSD) in Iran: a consensus guideline and recommendations.
      ;
      • Damato V
      • Evoli A
      • Iorio R
      Efficacy and safety of rituximab therapy in neuromyelitis optica spectrum disorders: a systematic review and meta-analysis.
      ). Therefore, it is crucial to determine the chance of developing COVID-19 in these patients and provide the necessary solutions. In this study, we investigated the prevalence of COVID-19 among patients with NMOSD, who referred to NMOSD Clinic at Sina Hospital, a referral center receiving patients from all over Iran.
      There are 149 patients in NMOSD Cohort Clinic of Sina Hospital. After the outbreak of Coronavirus in Iran, all these patients were contacted by phone from May 2 to May 9, 2020, and were asked about their infection with the Coronavirus or probable symptoms. Out of 149 patients, 130 answered the phone. Of these 130 patients, 112 were females and 18 were males. The mean age was 37.55 ± 11.57 years and their disease duration was 7.95 ± 4.71 years.
      The most commonly used drug (72.3%) was rituximab (Table 1). Five patients (3.8%) were infected with Coronavirus (Table 2). All five patients were treated with rituximab. The prevalence of COVID-19 was 5.1% in patients taking rituximab and 0% in patients taking other drugs.
      Table 1.Medications received by NMOSD patients
      VariablesCases (n=130)
      NMOSD medicationsAzathioprine22 (16.9%)
      Rituximab94 (72.3%)
      Mycophenolate Mofetil2 (1.5%)
      Prednisolone1 (0.8%)
      Mitoxantrone1 (0.8%)
      Azathioprine & Prednisolone2 (1.5%)
      Rituximab & Mycophenolate Mofetil1 (0.8%)
      Rituximab & Cyclophosphamide2 (1.5%)
      n: number of participants; NMOSD: Neuromyelitis Optica Spectrum Disorder
      Data are presented as n (%)
      Table 2.Demographics and clinical features of 5 cases with NMOSD
      Sex/ Age (years old)Duration of NMOSD (years)Clinical presentation of Covid-19RT-PCRNMOSD DrugInterval between Rituximab injection and Coronavirus infection (months)
      Woman/ 348Fever, Dyspnea, Myalgias, Gastrointestinal complications, Fatigue, VertigoNegativeRituximab6
      Woman/ 366Cough, Dyspnea, Gastrointestinal complications, Headache, FatigueNot performedRituximab0.1
      Woman/ 297Cough, Dyspnea, Odynophagia, Myalgias, Headache, FatiguePositiveRituximab1.5
      Man/ 2212Cough, FeverPositiveRituximab7
      Man/ 683Cough, FeverPositiveRituximab3
      Reverse transcription polymerase chain reaction: Spectrum Disorder; RT-PCR Optica Neuromyelitis: NMOSD
      Three patients were women and two patients were men. The mean age of these patients was 37.80 ± 17.72 years and the disease duration was 7.20 ± 3.27 years. There was not statistical difference between the mean age of infected patients and the rest of NMOSD population. The infected patients had not any other concomitant diseases such as hypertension, diabetes mellitus and obesity. The mean interval between rituximab injection and coronavirus infection was 3.52 ± 2.92 months. Unfortunately, B-cell numbers were not available.
      The onset of symptoms of COVID-19 was different in these five patients (Table 2). Two patients had gastrointestinal (GI) manifestation (40 %). Coronavirus polymerase chain reaction (PCR) testing was performed on four patients, with three positive and one negative outcomes. Lung computed tomography (CT) scans of patients showed bilateral pulmonary involvement with ground glass appearance. COVID-19 was diagnosed in all patients by an infectious disease specialist according to the symptoms and chest CT scans. Three patients (60% of patients with COVID-19) required hospitalization. One of the three patients had taken prednisolone orally two months before admission. These three patients were treated with drugs such as hydroxychloroquine, kaletra, and azithromycin. One patient was treated with 120 g intravenous immune globulin (IVIG) due to the progression of symptoms and increased dyspnea and bilateral consolidation in lung CT scan.
      Fortunately, all the patients recovered, and the neurological conditions of the patients did not change after the disease.
      Our study had limitations: our statistical population was small, which could be due to the rarity of NMOSD. Also, PCR test was not performed for one patient. However, this small study showed that the rate of infection in these patients is almost the same as the normal population despite the drugs taken to suppress the immune system (
      • Signorelli C
      • Scognamiglio T
      • Odone A
      COVID-19 in Italy: impact of containment measures and prevalence estimates of infection in the general population.
      ). This could be due to the greater health care of these patients and their greater sensitivity. However, despite the lower incidence of the disease, the severity of the disease in infected patients needing hospitalization was higher. According to statistics, only 20% of patients normally needed hospitalization (
      • Damato V
      • Evoli A
      • Iorio R
      Efficacy and safety of rituximab therapy in neuromyelitis optica spectrum disorders: a systematic review and meta-analysis.
      ), while in case of patients with NMOSD in the current study, this rate was 60%. On the other hand, all these patients received rituximab, and the rate of COVID-19 attributable to the taken drug was 5.1% in patients receiving rituximab. As mentioned above, the rate of GI manifestation was 40 % in these patients. According to the reports, the GI manifestation in general population infected by COVID-19 is 25% (
      • Nikpouraghdam M
      • Jalali Farahani A
      • Alishiri G
      • et al.
      Epidemiological characteristics of coronavirus disease 2019 (COVID-19) patients in Iran: a single center study.
      ;
      • Cheung KS
      • et al.
      Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from the Hong Kong cohort and systematic review and meta-analysis.
      ). This finding raise this question whether rituximab user is more prone to GI complications of COVID-19. This question should be investigated in further studies.
      Given that rituximab did not increase the incidence of infection in these patients, it may increase the severity of the disease. This requires to pay more attention to these patients. Following health related pieces of advice, doing telemedicine visits and frequent follow-up of patients in terms of possible symptoms of COVID-19 can contribute to the reduction of problems caused by COVID-19.

      Declaration of Competing Interests

      The authors declare there is no conflict of interest.

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