Low-dose rituximab regimen does not increase severe COVID-19 risk in patients with neuroimmune diseases during the pandemic: a cross-sectional study

Low-dose rituximab regimen does not increase severe COVID-19 risk in patients with neuroimmune diseases during the pandemic: a cross-sectional study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Low-dose rituximab regimen does not increase severe COVID-19 risk in patients with neuroimmune diseases during the pandemic: a cross-sectional study Lin Li, Dan Yao, Chuan Li, Yunfeng Hao, Chao Zhao, Qi Yan, Xuan Zhou, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4624675/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract A retrospective study was conducted to evaluate the impact of low-dose rituximab (RTX) regimen on the severity of coronavirus disease 2019 (Covid-19) in patients with neuroimmune diseases (PwNIDs) at Tangdu Hospital, Fourth Military Medical University from July 2017 to December 2022. A total of 70 PwNIDs were enrolled, of which 39 contracted COVID-19. The co-residents of these PwNIDs, serving as the control group, comprised 94 individuals, among whom 56 contracted COVID-19. However, there was no significant difference in the severity of COVID-19, including severe cases or death, between the two groups. Among PwNIDs, there were no notable differences observed in age, sex, underlying conditions, comorbidities, cumulative RTX dosages, or the duration since the last RTX infusion between the infected and uninfected groups. Among the PwNIDs who contracted COVID-19, 89.7% (35/39) stated that the virus had no influence on their existing conditions. Only 10.3% (4/39) reported worsened previous symptoms without requirement of hospitalization, and none developed new-onset neurological symptoms requiring acute-phase treatment. The administration of a low-dose RTX regimen does not increase the risk of COVID-19 or severe illness in PwNIDs, irrespective of the cumulative RTX dosages or the duration since the last RTX infusion. Moreover, COVID-19 does not seem to significantly exacerbate underlying neuroimmune disorders in these individuals. COVID-19 low-dose rituximab regimen neuroimmune diseases severity risk factors Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1.Introduction Over the past several years, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to global pandemic known as coronavirus disease 2019 (COVID-19). While most healthy individuals infected with COVID-19 experience favorable outcomes, those with immunodeficiencies, such as patients with neuroimmune diseases (PwNIDs), who frequently receive long-term corticosteroids or other immunosuppressive and immunomodulatory therapies, remain at a heightened risk developing severe COVID-19. Rituximab (RTX), which specifically targets the CD20 antigen on B-lymphocyte differentiation membranes, has been increasingly used in recent years for PwNIDs as a disease-modifying therapy (DMT). This treatment helps prevent relapses and sustain therapeutic effectiveness(Chen et al. 2022 ). Numerous retrospective studies and systemic reviews found that anti-CD20 drugs, particularly RTX, increase the risk of COVID-19 infection and severe disease in patients with multiple sclerosis (PwMS)(Inshasi et al. 2021 ;Sharifian-Dorche et al. 2021 ༛Simpson-Yap et al. 2021 ༛Sormani et al. 2021 ༛Barzegar et al. 2022 ༛Schiavetti et al. 2022 ). However, several prospective studies have found that anti-CD20 therapy does not affect innate and CD8 + T cell responses, which are crucial for the elimination of SARS-CoV-2, nor does it lead to severe morbidity(Baker et al. 2020 ༛Alonso et al. 2021 ༛Maghbooli et al. 2022 ). There remains controversy over whether RTX increases the risk of COVID-19 infection and severe disease in PwNIDs, leading to debates on whether RTX should be postponed or even avoided during the COVID-19 pandemic. In our former studies, a low-dose RTX individualized regimen (100mg/week, for 3 consecutive weeks, repeated every 3 to 6 months at 100mg) was used to treat autoimmune encephalitis (AE)(Du et al. 2022 ), myasthenia gravis (MG)(Du et al. 2022 ), and neuro-Behcet's disease (NBD)(Zhao et al. 2021 ), achieving significant efficacy and minimal adverse reactions with sparing-steroid used. This regimen has also been applied to MS, neuromyelitis optica spectrum disorders (NMOSD), and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) gaining similar efficacy. Relevant research results are awaiting publication. However, to date, no data has been reported on COVID-19 infection rates and severity in PwNIDs treated with a low-dose individualized RTX regimen during COVID-19 pandemic. In the study, we aimed to investigate the influence of a low-dose RTX regimen on COVID-19 infection rates and severity in PwNIDs by comparing them to their co-residents. 2.Methods 2.1 Standard protocol approvals This study was approved by the Ethical Committee of Tangdu Hospital, Fourth Military Medical University. Furthermore, we ensured that patients received detailed information about the disease, and obtained the written informed consent for repeated low-dose RTX treatment. 2.2 Study population PwNIDs (including MG, CIDP, MS, AE, and NMOSD), diagnosed and evaluated by three experienced neurologists, were recruited at Tangdu Hospital, Fourth Military Medical University from July 2017 to December 2022. Patients eligible for inclusion in this study, who received a low-dose individualized RTX regimen (100mg/week for 3 consecutive weeks, with repeat doses of 100 mg every 3 to 6 months) and demonstrated significant and sustained efficacy, must meet the following criteria: 1. Comprehensive demographic and clinical data must be accessible during the initial assessment; 2. The low-dose RTX individualized regimen should have been initiated before contracting COVID-19; 3. Patients must have been residing with at least one co-resident. Exclusion criteria for this study are as follows: 1. A single infusion of RTX exceeding 100 mg; 2. Concurrent use of other immunosuppressive medications, such as corticosteroids, azathioprine, mycophenolate, cyclophosphamide, mycophenolate mofetil, cyclosporine, tacrolimus, or methotrexate, among others; 3. Treatment with monoclonal antibody biological agents like tocilizumab, satralizumab excluding RTX; 4. Loss of follow-up before the completion of the questionnaire survey. Participants in the control group must be at least 10 years old and reside with PwNIDs who have received a low-dose individualized RTX regimen. 2.3 Study design This was a cross-sectional observational study. We collected data of PwNIDs and their co-residents in the form of electronic questionnaires from January 31 to February 16, 2023 (chinacdc. cn). We gathered demographic data that includes age and gender, as well as information on comorbidities such as hypertension, diabetes mellitus (DM), coronary heart disease (CHD), cirrhosis, kidney disease, chronic obstructive pulmonary disease (COPD), connective tissue disease (CTD), epilepsy, dementia, stroke, underlying disease. Additional data collected pertained to the date of suspected or confirmed COVID-19 infection, specific COVID-19 symptoms, methods used for COVID-19 diagnosis, chest computer tomography (CT) scans and their findings, treatment settings (home care, hospitalization, outpatient or emergency services, intensive care unit [ICU] or death), the types of medications used (oral, injectable or inhaled), and the duration of symptoms of COVID-19 infection. This information was collected via electronic questionnaires completed by PwNIDs or their caregivers. We also collected self-reported information from PwNIDs on how COVID-19 affected their pre-existing conditions. We counted the doses of RTX administered and identified the date of the most recent RTX infusion for PwNIDs using the electronic medical record system (EMRS). Total RTX dosages of 300 mg or less were categorized as the induction group, while dosages exceeding 300 mg were classified as the maintenance group. According to former studies, the specific symptoms of COVID-19 infection were divided into six groups(Kratzer et al. 2021 ;Ochani et al. 2021 ): ①Flu like symptoms (Group1, G1): fever, cough, expectoration, nasal congestion, pharyngalgia, etc.; ②Systemic symptoms (Group2, G2): muscle pain, weakness, etc.; ③Gastrointestinal symptoms (Group3, G3): diarrhea; ④Dysosmia and hypogeusia (Group4, G4); ⑤Neurological symptoms (Group5, G5): dizziness, headache, slow responses, etc.; ⑥Other symptoms (Group6, G6): rash, eyes discomfort like conjunctivitis. The severity of COVID-19 was defined by four levels: ①Mild disease: characterized by mild symptoms, not necessitating hospitalization; ②Moderate disease: involving hospitalization without the need for mechanical ventilation; ③Severe disease: requiring ICU admission and/or mechanical ventilation; and ④ Death. 2.4 Statistical Analysis Statistical analyses were conducted with IBM SPSS version 26.0 software (IBM Corp, Armonk, New York). Quantitative data with normal distribution was expressed as mean ± SD and analyzed by T test. Continuous variables with skew distribution were expressed as median (inter-quartile range, IQR) and analyzed by Mann-Whitney U test. Categorical variables were presented as frequency and percentages and analyzed using χ2 test or Fisher exact tests. Logistic regression analysis was used to evaluate the risk factors of COVID-19 infection. P value ˂ 0.05 was considered to indicate statistical significance. 3.Results 3.1 COVID-19 infection in PwNIDs and controls We totally enrolled 70 PwNIDs (MG[N = 19], CIDP[N = 11], AE[N = 19], MS[N = 5], NMOSD[N = 16]). Among these participants, 55.7% (39/70) contracted COVID-19. They lived with 94 people (serving as controls), of whom 59.5% (56/94) contracted COVID-19 (Figs. 1 and 2 ). There was no significant difference in gender (percentage of females: 66.7% vs 46.4%, p = 0.051) and age (mean [SD], years:47.02 [14.85] vs 44.48 [19.40], p = 0.672), medication treatment for COVID-19, or site of care between PwNIDs and controls who contracted COVID-19. Based on the defined severity of COVID-19, among PwNIDs, 94.9% (37/39) had mild infections, 5.1% (2/39) patients had moderate infection. In the control group, 96.4% (54/56) had mild infection, and 3.6% (2/56) people had moderate infections. There was no significant difference in severity of COVID-19 infection between PwNIDs and controls(p = 1.000). Furthermore, there were no cases of severe disease nor death in either group. We also detailed the symptoms of COVID-19 infection between PwNIDs and controls. Interestingly, there was no significant difference in symptom groups G1, G2, G5, but there was a significant difference in symptom groups G3, G4, G6(Table 1 , Fig. 3 ). Table 1 COVID-19 infection in PwNIDs and controls. Variables PwNIDs with COVID-19 infection n=39 Controls with COVID-19 infection n=56 P Value Sex, female, No. (%) 26(66.7) 26(46.4) 0.051 Age, years, mean (SD) 47.02(14.85) 44.48(19.40) 0.672 Medicine treatment of COVID-19, No. (%) 0.873 Treatment 14(35.9) 21(37.5) Not treatment 25(64.1) 35(62.5) Site of care,n(%) 0.287 Home 37(94.9) 50(89.3) Hospitalization 2(5.1) 2(3.6) Outpatient/Emergency 0(0.0) 4(7.1) Severity of COVID-19, No. (%) 1.000 Mild 37(94.9) 54(96.4) Moderate 2(5.1) 2(3.6) Severe 0(0.0) 0(0.0) Death 0(0.0) 0(0.0) Symptoms of COVID-19, No. (%) Group1(G1) Fever 29(74.4) 44(78.6) 0.632 Cough 10(25.6) 25(44.6) 0.059 Expectoration 8(20.5) 8(14.3) 0.425 Rhinobyon 9(23.1) 15(26.8) 0.682 Runny nose 5(12.8) 9(16.1) 0.660 Pharyngalgia 12(30.8) 17(30.4) 0.996 Group2(G2) Myalgia 12(30.8) 8(14.3) 0.053 Weakness 13(33.3) 21(37.5) 0.677 Group3(G3) Diarrhea 5(12.8) 0(0.0) 0.022 * Group4(G4) Dysosmia and hypogeusia 10(25.6) 5(8.9) 0.028 * Group5(G5) Dizziness 4(10.3) 7(12.5) 0.737 Headache 8(20.5) 11(19.6) 0.917 Unresponsive 0(0.0) 2(3.6) 0.641 Group6(G6) Eye discomfort 10(25.6) 1(1.8) 0.001 * Rash 4(10.3) 0(0.0) 0.054 Abbreviations: COVID-19,Coronavirus disease 2019; PwNIDs,Patients with neuroimmune diseases. *：Statistical significance (p < 0.05). 3.2 RTX treatment in PwNIDs To explore the risk factors for COVID-19 infection, we divided PwNIDs into two groups: the uninfected group (N = 31) and the infected group (N = 39), based on their COVID-19 infection status (Table 2 ). There were no significant difference observed in gender (percentage of females: 45.2% vs 66.7%, p = 0.071), age (mean [SD], years:52.29 [17.49] vs 47.03 [14.85], p = 0.178), or the presence of comorbidities including hypertension, diabetes, CHD, cirrhosis, kidney disease, COPD, CTD, epilepsy, dementia, stroke between the uninfected and the infected groups. Table 2 Basic characteristics and RTX in PwNIDs. Uninfected group (N = 31) Infected group (N = 39) P Value Sex, female, No. (%) 14(45.2) 26(66.7) 0.071 Age, mean (SD), y 52.29(17.49) 47.03(14.85) 0.178 Underlying disease, No. (%) 0.652 MG 9(29.0) 10(25.6) CIDP 4(12.9) 7(17.9) AE 10(32.3) 9(23.1) MS 3(9.7) 2(5.1) NMOSD 5(16.1) 11(28.2) Comorbidities, No. (%) Hypertension 5(16.1) 4(10.3) 0.712 Diabetes mellitus 3(9.7) 4(10.3) 1.000 CHD 1(3.2) 3(7.7) 0.778 Cirrhosis 1(3.2) 0(0.0) 0.908 Kidney disease 1(3.2) 0(0.0) 0.908 CODP 2(6.5) 1(2.6) 0.839 CTD 0(0.0) 2(5.1) 0.577 Epilepsy 0(0.0) 5(12.8) 0.109 Dementia 1(3.2) 0(0.0) 0.908 Stroke 3(9.7) 3(7.7) 1.000 Cumulative RTX dosages, median (IQR), mg 300(100) 300(100) 0.123 Total RTX doses, No. (%) 0.186 1 5(16.1) 5(12.8) 2 1(3.2) 3(7.7) 3 17(54.8) 12(30.8) 4 6(19.4) 12(30.8) 5 2(6.5) 3(7.7) 6 0(0) 2(5.1) 8 0(0) 2(5.1) Patients stratified by accumulative RTX dosages, No. (%) 0.050 Induction group (≤ 300mg) 23(74.2) 20(51.3) Maintenance group (>300mg) 8(25.8) 19(48.7) Time interval of the last RTX infusion, median (IQR), months 9.80(15) 6.83(19.73) 0.324 The duration since the last RTX infusion, No. (%), months 0.103 ≤ 6 9(29) 18(46.1) 6 12 15(48.4) 12(30.8) Patients stratified by disease entities, No. (%) 0.890 Peripheral diseases 13(41.9) 17(43.6) Central diseases 18(58.1) 22(56.4) Abbreviations: SD, Standard deviation; M, Median; IQR, Inter-quartile range; MG, Myasthenia gravis; CIDP, Chronic inflammatory demyelinating polyradiculoneuropathy; AE, Autoimmune encephalitis; MS, Multiple sclerosis; NMOSD, Neuromyelitis optica spectrum disorders; CHD, Coronary heart disease; COPD, Chronic obstructive pulmonary disease; CTD, Connective tissue disease; RTX, Rituximab. To assess the potential impact of RTX on COVID-19 infection, we tallied the cumulative RTX dosages and determined the time since the last RTX infusion. Our findings revealed that the median cumulative dosages of RTX in both groups were 300 mg with no significant difference observed between them (p = 0.123). Base on whether the cumulative RTX dosages exceeded 300 mg, we categorized patients into two groups: the induction group (uninfected group/infected group:23/20) and the maintenance group (uninfected group/infected group:8/19). However, we found no significant difference between these groups (p = 0.05). The median time interval, measured in months(m), since the last RTX infusion were 9.80 months in uninfected group and 6.83 months in infected group. However, there was no significant difference between these two groups (p = 0.324). We categorized the duration since the last RTX infusion into three levels (≤ 6m, 6˂m ≤ 12, ˃12) and found no significant difference between the uninfected and the infected group (p = 0.103). In our study, both univariable and multivariable logistic analysis failed to identify any risk factors for COVID-19 infection among the variables considered, which included age, sex, comorbidities, underlying disease, cumulative RTX dosages, and the duration since the last RTX infusion. 3.3 Impact of COVID-19 infection on the underlying disease in PwNIDs In the study, we enrolled 30 patients with peripheral neurological immune diseases (NIDs) including MG and CIDP, and 40 patients with central NIDs including MS, AE, and NMOSD. The two groups had no statistical difference in disease entities (p = 0.890). The infection status of various diseases in PwNIDs is as follows: (uninfected/infected: MG 9/10, CIDP 4/7, AE 10/9, MS 3/2, NMOSD 5/11) (Table 2 , Fig. 4 ). We assessed the impact of COVID-19 infection on the underlying disease in PwNIDs through self-reports. Among patients with COVID-19 infection, 89.7% (35/39) reported that COVID-19 did not affect their primary disease. 10.3% (4/39) experienced a worsening of their original symptoms due to COVID-19. However, they did not require hospitalization for intervention. None of them developed new-onset symptoms that necessitated hospitalization for acute-phase therapy (Fig. 5). 4.Discussion In contrast to other studies published during the COVID-19 pandemic (Esmaeili et al. 2021 ;Klineova et al. 2021 ༛Reder et al. 2021 ༛Longinetti et al. 2022 ༛Smith et al. 2022 ), we designed a cross-sectional observational study to assess the severity and risk factors associated with COVID-19 infection in PwNIDs treated with a low-dose RTX regimen. Our study yielded three principal findings. Firstly, it is worth noting that we observed no discernible difference in the severity of COVID-19 infections between PwNIDs and their co-residents. Neither group experienced severe infection or death. Secondly, we found that a shorter duration between the last RTX infusion and contracting COVID-19, as well as higher cumulative dosages of RTX, were not risk factors for COVID-19 infection. Lastly, our investigation revealed that COVID-19 infection did not have a significant impact on the underlying neuroimmune diseases in PwNIDs who had contracted COVID-19 and were undergoing low-dose RTX therapy. The severity of COVID-19 infection was comparable between PwNIDs and their co-residents, with no instances of severe disease or death observed among them. The observed outcomes may be attributed to the individualized low-dose RTX regimen we administered to PwNIDs. This regimen is rarely associated with reduced immunoglobulin levels and increase infection risk, yet it demonstrates comparable efficacy to higher dosages of RTX infusion. The dosages of RTX for autoimmune diseases (AIDs) were primarily derived from the regimen used for non-Hodgkin’s lymphoma (NHL). This includes an induction dose of 1 g per infusion (administered twice consecutively, with a 2-week interval) or 375 mg/m 2 per week based on body surface area (for 4 consecutive weeks). Maintenance therapy involves 1 g every 6 months or reinfusion only after recurrence. The efficacy of RTX in eliminating CD20 + B cells was found to have a dose accumulative effect. Higher doses of RTX resulted in a longer duration required for B cell remodeling and had a more pronounced impact in humoral immune function, increasing the risk of hypogammaglobulinemia and subsequent infections, even severe infections(Tieu et al. 2021 ;Kim et al. 2022 ). Steve Simpson-Yap(Simpson-Yap et al. 2022 ) updated data of PwMS from 27 countries revealed a significant association between anti-CD20 therapy and a more severe course of COVID-19. Thamer S Alhowaish(Alhowaish et al. 2023 ) analyzed 35 PwMS who were infected COVID-19 and had received RTX at a dose of 375 mg/m2 with a median frequency of 4 doses. It was found that more than a third of these individuals developed hypogammaglobulinemia and required hospitalization and treatment in the intensive care unit (ICU). They thought RTX was a potential risk factor for unfavorable outcomes in COVID-19 patients. Interestingly, D. Baker(Baker et al. 2020 ) hypothesized that anti-CD20 treatment did not predispose patients to severe COVID-19 due to the reduction in B cells and inflammatory storms following COVID-19 infection. This treatment also may not interfere with the innate immune response and CD8 + T cell response. Based on these findings, some studies have indicated that patients undergoing anti-CD20 treatment did not experience severe COVID-19 infections and were able to recover rapidly after being infected with COVID-19(Kim et al. 2022 ;Longinetti et al. 2022 ༛Zabalza et al. 2022 ). Basic research also found that patients who received anti-C20 treatment experienced reduced COVID-19-specific-antibody production due to clearance of B cells. However, their COVID-19-specific T cell response remained robust. This provides a theoretical basis for the belief that anti-CD20 treatment dose not increase the severity of COVID-19 infection in patients(Madelon et al. 2022 ༛Wolf et al. 2023 ). Besides, we did not find any risk factors (including recent low-dose RTX infusion, higher cumulative RTX dosages and so on) for COVID-19 infection. Rajesh B Iyer(Iyer et al. 2022) enrolled 62 PwMS who received RTX infusion with an initial dose typically ranging from 1000 to 2000 mg, and subsequent doses averaging between 500 and 1000 mg. Their finding indicated that factors such as older age, secondary progressive MS(SPMS), a shorter duration between RTX infusion and COVID-19 onset, and receiving a higher dose at the last RTX infusion were associated with an increased risk of severe disease, which aligned with findings from other studies. Annette Langer-Gould(Langer-Gould et al. 2021 ) enrolled 1895 PwMS who were treated with RTX. Out of these, 24 patients contracted COVID-19. Compared to patients who either did not contract COVID-19 or experienced a mild of the disease, 8 out of 24 patients developed moderate disease. Among these patients, the median cumulative RTX dose was higher (3250 mg versus 2000 mg), and median time since last infusion was shorter (2.5 m versus 7.8 m). They also observed that the duration in months since the last infusion and receiving a dose of 1000 mg compared to lower doses at the last infusion were independent factors predicting the severity of COVID-19. This indicates that PwNIDs who have a shorter median time since their last infusion and a higher cumulative RTX dose remain vulnerable to COVID-19 and are at an increased risk of severe infection(Landtblom et al. 2021 ;Spelman et al. 2022 ). Our study found that low-dose RTX effectively cleared CD20 + B cell without causing a decrease in immunoglobulin levels and had minimal impact on adaptive immune responses. Numerous reviews have highlighted that the most prevalent symptom of COVID-19 infection is an upper respiratory tract infection, typically presenting with symptoms such as fever, followed by dry cough, fatigue, and so an(Furlan et al. 2021 ;Ochani et al. 2021 ༛Salter et al. 2021 ). Some patients with COVID-19 infection may be accompanied by muscle soreness, loss of smell and taste, nasal congestion, runny nose, diarrhea, conjunctivitis, etc. In our study, fever was the most common frequently reported symptom among PwNIDs who had COVID-19 infection. This was followed by systemic symptoms like myalgia, fatigue, as well as less uncommon symptoms such as rash and conjunctivitis, pharyngodynia, and decreased sense of smell and taste. In controls with COVID-19 infection, the most common symptom was also fever, followed by upper respiratory tract infections and systemic symptoms such as fatigue, dry cough, pharyngodynia, nasal congestion, headache, runny nose, and phlegm. There were statistically significant differences in systemic, gastrointestinal and less common symptoms between the two groups. We took into account that the immune system composition in PwNIDs receiving RTX might differ from that of the general population(Winkelmann et al. 2016 ). After COVID-19 infection, varying immune responses can occur, resulting in different symptom presentations or syndromes. It is widely recognized that virus infections can act as triggers for patients with AIDs. A cohort in Iranian focusing on MS reported that 17% of patients experienced a relapse after contracting COVID-19(Paybast et al. 2023 ). In order to clarify the impact of SARS CoV-2 on NIDs, we used the self-assessment questionnaire to investigate the underlying diseases in PwNIDs after COVID-19 infection. The results showed that the majority of PwNIDs who received a low-dose RTX regimen did not experience any significant impact on their primary diseases after COVID-19 infection. Fewer patients reported that their previous neurological symptoms and signs worsened, although this did not require hospitalization. The worsened clinical manifestations experienced by some individuals improved upon full recovery from COVID-19. Importantly, none of these patients developed new-onset neurological symptoms that required acute-phase treatment. Up to date, PwNIDs who have been followed up for more than one and a half years in our study have not reported any disease relapse. Furthermore, some of them are still undergoing regular low-dose RTX infusion as part of their treatment regimen. It appears that COVID-19 infection did not have any discernible impact on the underlying disease in PwNIDs who were receiving an individualized low-dose RTX regimen. The study has certain limitations: firstly, it is a single-center retrospective survey study with a small sample size. To reduce bias, we conducted a questionnaire survey on all patients with NIDs who received low-dose RTX treatment before the enrollment deadline. We also conducted a case-control study to investigate the infection status of co-residents and compare the infection status between groups. Secondly, this study used a questionnaire survey instead of face-to-face interviews. To minimize errors resulting from data entry, all completed questionnaires were cross-checked against EMRS. Any discrepancies or unclear responses were addressed through followed-up phone calls to ensure the accuracy of the data collected. 5.Conclusion Overall, our study found that recent low-dose RTX infusion and higher cumulative doses did not increase the risk of COVID-19 infection and severe disease in PwNIDs. This study offers a clinical foundation supporting the advantageous use of a low-dose RTX regimen for treating NIDs during the COVID-19 pandemic. Declarations ACKNOWLEDGMENTS We thank the patients and their co-residents for the collaboration. AUTHOR CONTRIBUTIONS LL, DY, CL: contributed equally to this study and are co-first authors. Prof. WZ and YD had full access to all the data in the study and take full responsibility for the integrity of the data and the accuracy of the data analysis. LL, DY, CL,YH, CZ, QY, XZ, YL, YD, LH, RZ, JL, WZ, SL, LG,YD,WZ：acquired, analyzed, or interpreted of data and critically revised of the manuscript for important intellectual content. LL, DY, CL：drafted of the manuscript. YD and WZ: performed final manuscript review and editing. All authors contributed to the article and approved the submitted. FUNDING This work was supported by research grants from the National Natural Science Foundation of China (82271457, 82171406, 81971003), Shaanxi Province Health Research and Innovation Team for Cognitive Dysfunction Disease (2023TD-06), Shaanxi Innovative Team for Science and Technology (2024RS-CXTD-87), Tangdu hospital innovation development foundation (2018QYTS010, 2019QYTS002), Tangdu hospital clinical research project (2021LCYJ040), Tangdu hospital foundation for social recruitment talent (2021SHRC011). DATA AVAILABILITY STATEMENT The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding authors. ETHICS STATEMENT We provided patients detailed information about the diseases, and obtained the consent of the patients to repeated low-dose rituximab treatment. We have also reported to the Ethical Committee of Tangdu Hospital, Fourth Military Medical University, and obtained the approval from the committee. CONFLICT OF INTEREST These authors declare that they have no competing interest. CONSENT FOR PUBLICATION We obtained written informed consent from both patients for publication of this report. A copy of the written consent is available for review by the Editor-in-Chief of this journal. References Alhowaish TS, Alhamadh MS, Mathkour A, Alamoudi M, Alqahtani HA, Alrashid A (2023) Clinical Course and Outcomes of COVID-19 Infection in Patients Treated with Rituximab: A Tertiary Care Center Experience. 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BMC Neurol 21(1):183. https://doi.org/10.1186/s12883-021-02218-4 Furlan A, Forner G, Cipriani L, Vian E, Rigoli R, Gherlinzoni F, Scotton P (2021) COVID-19 in B Cell-Depleted Patients After Rituximab: A Diagnostic and Therapeutic Challenge. Front Immunol 12:763412. https://doi.org/10.3389/fimmu.2021.763412 Inshasi J, Alroughani R, Al-Asmi A, Alkhaboury J, Alsalti A, Boshra A, Thakre M (2021) Expert Consensus and Narrative Review on the Management of Multiple Sclerosis in the Arabian Gulf in the COVID-19 Era: Focus on Disease-Modifying Therapies and Vaccination Against COVID-19. Neurol Therapy 10(2):539–555. https://doi.org/10.1007/s40120-021-00260-5 Iyer RB, R. S, J. N. M and J. R (2022) COVID-19 outcomes in persons with multiple sclerosis treated with rituximab. 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Allergy 76(3):751–765. https://doi.org/10.1111/all.14647 Landtblom AM, Berntsson SG, Boström I, Iacobaeus E (2021) Multiple sclerosis and COVID-19: The Swedish experience. Acta Neurol Scand 144(3):229–235. https://doi.org/10.1111/ane.13453 Langer-Gould A, Smith JB, Li BH (2021) Multiple sclerosis, rituximab, and COVID-19. Ann Clin Transl Neurol 8(4):938–943. https://doi.org/10.1002/acn3.51342 Longinetti E, Bower H, McKay KA, Englund S, Burman J, Fink K, Frisell T (2022) COVID-19 clinical outcomes and DMT of MS patients and population‐based controls. Ann Clin Transl Neurol 9(9):1449–1458. https://doi.org/10.1002/acn3.51646 Madelon N, Lauper K, Breville G, Sabater Royo I, Goldstein R, Andrey DO, Eberhardt CS (2022) Robust T-Cell Responses in Anti-CD20-Treated Patients Following COVID-19 Vaccination: A Prospective Cohort Study. Clin Infect Dis 75(1):e1037–e1045. https://doi.org/10.1093/cid/ciab954 Maghbooli Z, Hosseinpour H, Fattahi MR, Varzandi T, Hamtaeigashi S, Mohammad-nabi S, Sahraian MA (2022) Association between disease-modifying therapies and adverse clinical outcomes in multiple sclerosis patients with COVID-19 infection. Multiple Scler Relat Disorders 67:104067. https://doi.org/10.1016/j.msard.2022.104067 Ochani R, Asad A, Yasmin F, Shaikh S, Khalid H, Batra S, Surani S (2021) COVID-19 pandemic: from origins to outcomes. A comprehensive review of viral pathogenesis, clinical manifestations, diagnostic evaluation, and management. Infez Med 29(1):20–36 Paybast S, Habibi MA, Naser Moghadasi A (2023) Characteristics and management of multiple sclerosis patients during the Omicron era: is there a concern about the MS course in the face of the new variant of COVID-19? Neurol Sci 44(2):659–665. https://doi.org/10.1007/s10072-022-06447-4 Reder AT, Centonze D, Naylor ML, Nagpal A, Rajbhandari R, Altincatal A, de Moor C (2021) COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies. CNS Drugs 35(3):317–330. https://doi.org/10.1007/s40263-021-00804-1 Salter A, Fox RJ, Newsome SD, Halper J, Li DKB, Kanellis P, Cross AH (2021) Outcomes and Risk Factors Associated With SARS-CoV-2 Infection in a North American Registry of Patients With Multiple Sclerosis. JAMA Neurol 78(6):699–708. https://doi.org/10.1001/jamaneurol.2021.0688 Schiavetti I, Cordioli C, Stromillo ML, Teresa Ferrò M, Laroni A, Cocco E, Sormani MP (2022) Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies. Multiple Scler J 28(13):2106–2111. https://doi.org/10.1177/13524585221102918 Sharifian-Dorche M, Sahraian MA, Fadda G, Osherov M, Sharifian-Dorche A, Karaminia M, Giacomini PS (2021) COVID-19 and disease-modifying therapies in patients with demyelinating diseases of the central nervous system: A systematic review. Multiple Scler Relat Disorders 50:102800. https://doi.org/10.1016/j.msard.2021.102800 Simpson-Yap S, De Brouwer E, Kalincik T, Rijke N, Hillert JA, Walton C, Peeters L (2021) Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis. Neurology 97(19):e1870–e1885. https://doi.org/10.1212/WNL.0000000000012753 Simpson-Yap S, Pirmani A, Kalincik T, De Brouwer E, Geys L, Parciak T, Peeters LM (2022) Updated Results of the COVID-19 in MS Global Data Sharing Initiative: Anti-CD20 and Other Risk Factors Associated With COVID-19 Severity. Neurol Neuroimmunol Neuroinflamm 9(6):e200021. https://doi.org/10.1212/NXI.0000000000200021 Smith JB, Gonzales EG, Li BH, Langer-Gould A (2022) Analysis of Rituximab Use, Time Between Rituximab and SARS-CoV-2 Vaccination, and COVID-19 Hospitalization or Death in Patients With Multiple Sclerosis. JAMA Netw Open 5(12):e2248664. https://doi.org/10.1001/jamanetworkopen.2022.48664 Sormani MP, De Rossi N, Schiavetti I, Carmisciano L, Cordioli C, Moiola L, Salvetti M (2021) Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis. Ann Neurol 89(4):780–789. https://doi.org/10.1002/ana.26028 Spelman T, Forsberg L, McKay K, Glaser A, Hillert J (2022) Increased rate of hospitalisation for COVID-19 among rituximab-treated multiple sclerosis patients: A study of the Swedish multiple sclerosis registry. Mult Scler 28(7):1051–1059. https://doi.org/10.1177/13524585211026272 Tieu J, Smith RM, Gopaluni S, Kumararatne DS, McClure M, Manson A, Jayne DRW (2021) Rituximab Associated Hypogammaglobulinemia in Autoimmune Disease. Front Immunol 12:671503. https://doi.org/10.3389/fimmu.2021.671503 Winkelmann A, Loebermann M, Reisinger EC, Hartung HP, Zettl UK (2016) Disease-modifying therapies and infectious risks in multiple sclerosis. Nat Rev Neurol 12(4):217–233. https://doi.org/10.1038/nrneurol.2016.21 Wolf AS, Ravussin A, König M, Øverås MH, Solum G, Kjønstad IF, Mjaaland S (2023) T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis. JCI Insight 8(12):e165111. https://doi.org/10.1172/jci.insight.165111 Zabalza A, Arrambide G, Otero-Romero S, Pappolla A, Tagliani P, López-Maza S, Montalban X (2022) Is humoral and cellular response to SARS-CoV-2 vaccine modified by DMT in patients with multiple sclerosis and other autoimmune diseases? Multiple Scler J 28(7):1138–1145. https://doi.org/10.1177/13524585221089540 Zhao C, Li C, Duan F-j, Yan Q, Zhang Z, Du Y, Zhang W (2021) Case Report: Repeated Low-Dose Rituximab Treatment Is Effective in Relapsing Neuro Behçet's Disease. Front Neurol 12:595984. https://doi.org/10.3389/fneur.2021.595984 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4624675","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":326781807,"identity":"08d54f07-16e6-4b5a-b156-f92c4009018c","order_by":0,"name":"Lin Li","email":"","orcid":"","institution":"Tangdu Hospital, Fourth Military Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Li","suffix":""},{"id":326781808,"identity":"941e8edb-58e8-4a22-8c71-3d295b657bdc","order_by":1,"name":"Dan Yao","email":"","orcid":"","institution":"Tangdu Hospital, Fourth Military Medical 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Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArUlEQVRIiWNgGAWjYFCCBAaGDzYQpgRRGniAWhhnpJGqhZmHJC327OnPpG0StkUbHGA+eJuHwS6PsC08D9KkcxJu5244wJZszcOQXExYi0TCsdu5P0BaeMykeRgOJDYQ1pLYdtsCbAv/N2K1JLPdZgBr4WEjUsuZZ+w/e4BaZh5mM7acY5BMWAt7e/pjgx9ALX3Hmx/eeFNhR1gLAjCDCAPi1Y+CUTAKRsEowAMAUEA7rqG2BzwAAAAASUVORK5CYII=","orcid":"","institution":"Tangdu Hospital, Fourth Military Medical University","correspondingAuthor":true,"prefix":"","firstName":"Wei","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-06-23 09:36:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4624675/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4624675/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":61348387,"identity":"e953d1a4-961d-4629-9a51-eb74b3a7b8a9","added_by":"auto","created_at":"2024-07-29 18:22:30","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":693899,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow chart illustrating recruitment and selection of the study cohort\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1Flowchartofthestudycohort.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4624675/v1/7dafcea18e12098150a7ffea.jpg"},{"id":61347007,"identity":"e5e541d1-6cb1-4bde-80a8-c799218fc233","added_by":"auto","created_at":"2024-07-29 18:14:30","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":577151,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCOVID-19 infection in PwNIDs and controls\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2COVID19infectioninPwNIDsandcontrols.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4624675/v1/0873912487c0014fabe3780f.jpg"},{"id":61349350,"identity":"d3b7bbb8-c353-4db9-8258-f9ae0034c726","added_by":"auto","created_at":"2024-07-29 18:30:30","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":614533,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSymptoms of COVID-19\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure3SymptomsofCOVID19.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4624675/v1/7c5259709c1523caf375882c.jpg"},{"id":61347012,"identity":"23693332-6b6b-46b9-9085-c709b9f05cf4","added_by":"auto","created_at":"2024-07-29 18:14:31","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":373150,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCOVID-19 infection in different diseases\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure4COVID19infectionindifferentdiseases.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4624675/v1/daa7880bb3a110b975a65d16.jpg"},{"id":61347010,"identity":"830de16f-8e1b-4863-9ca1-b2b88c86e836","added_by":"auto","created_at":"2024-07-29 18:14:30","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":342371,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImpact of COVID-19 on underlying disease\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure5ImpactofCOVID19onunderlyingdisease.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4624675/v1/982c580cea993f76e280c147.jpg"},{"id":62201568,"identity":"cdb57f05-e5f0-46c9-9a31-1c6f3c01a98e","added_by":"auto","created_at":"2024-08-10 20:16:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3412498,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4624675/v1/b216d62a-04bf-4f84-9561-8522cc6fba3b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Low-dose rituximab regimen does not increase severe COVID-19 risk in patients with neuroimmune diseases during the pandemic: a cross-sectional study","fulltext":[{"header":"1.Introduction","content":"\u003cp\u003eOver the past several years, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to global pandemic known as coronavirus disease 2019 (COVID-19). While most healthy individuals infected with COVID-19 experience favorable outcomes, those with immunodeficiencies, such as patients with neuroimmune diseases (PwNIDs), who frequently receive long-term corticosteroids or other immunosuppressive and immunomodulatory therapies, remain at a heightened risk developing severe COVID-19.\u003c/p\u003e \u003cp\u003eRituximab (RTX), which specifically targets the CD20 antigen on B-lymphocyte differentiation membranes, has been increasingly used in recent years for PwNIDs as a disease-modifying therapy (DMT). This treatment helps prevent relapses and sustain therapeutic effectiveness(Chen et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Numerous retrospective studies and systemic reviews found that anti-CD20 drugs, particularly RTX, increase the risk of COVID-19 infection and severe disease in patients with multiple sclerosis (PwMS)(Inshasi et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2021\u003c/span\u003e;Sharifian-Dorche et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2021\u003c/span\u003e༛Simpson-Yap et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2021\u003c/span\u003e༛Sormani et al. \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2021\u003c/span\u003e༛Barzegar et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2022\u003c/span\u003e༛Schiavetti et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). However, several prospective studies have found that anti-CD20 therapy does not affect innate and CD8\u003csup\u003e+\u003c/sup\u003e T cell responses, which are crucial for the elimination of SARS-CoV-2, nor does it lead to severe morbidity(Baker et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2020\u003c/span\u003e༛Alonso et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2021\u003c/span\u003e༛Maghbooli et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). There remains controversy over whether RTX increases the risk of COVID-19 infection and severe disease in PwNIDs, leading to debates on whether RTX should be postponed or even avoided during the COVID-19 pandemic.\u003c/p\u003e \u003cp\u003eIn our former studies, a low-dose RTX individualized regimen (100mg/week, for 3 consecutive weeks, repeated every 3 to 6 months at 100mg) was used to treat autoimmune encephalitis (AE)(Du et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), myasthenia gravis (MG)(Du et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), and neuro-Behcet's disease (NBD)(Zhao et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), achieving significant efficacy and minimal adverse reactions with sparing-steroid used. This regimen has also been applied to MS, neuromyelitis optica spectrum disorders (NMOSD), and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) gaining similar efficacy. Relevant research results are awaiting publication. However, to date, no data has been reported on COVID-19 infection rates and severity in PwNIDs treated with a low-dose individualized RTX regimen during COVID-19 pandemic.\u003c/p\u003e \u003cp\u003eIn the study, we aimed to investigate the influence of a low-dose RTX regimen on COVID-19 infection rates and severity in PwNIDs by comparing them to their co-residents.\u003c/p\u003e"},{"header":"2.Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Standard protocol approvals\u003c/h2\u003e \u003cp\u003e This study was approved by the Ethical Committee of Tangdu Hospital, Fourth Military Medical University. Furthermore, we ensured that patients received detailed information about the disease, and obtained the written informed consent for repeated low-dose RTX treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Study population\u003c/h2\u003e \u003cp\u003ePwNIDs (including MG, CIDP, MS, AE, and NMOSD), diagnosed and evaluated by three experienced neurologists, were recruited at Tangdu Hospital, Fourth Military Medical University from July 2017 to December 2022.\u003c/p\u003e \u003cp\u003ePatients eligible for inclusion in this study, who received a low-dose individualized RTX regimen (100mg/week for 3 consecutive weeks, with repeat doses of 100 mg every 3 to 6 months) and demonstrated significant and sustained efficacy, must meet the following criteria: 1. Comprehensive demographic and clinical data must be accessible during the initial assessment; 2. The low-dose RTX individualized regimen should have been initiated before contracting COVID-19; 3. Patients must have been residing with at least one co-resident.\u003c/p\u003e \u003cp\u003eExclusion criteria for this study are as follows: 1. A single infusion of RTX exceeding 100 mg; 2. Concurrent use of other immunosuppressive medications, such as corticosteroids, azathioprine, mycophenolate, cyclophosphamide, mycophenolate mofetil, cyclosporine, tacrolimus, or methotrexate, among others; 3. Treatment with monoclonal antibody biological agents like tocilizumab, satralizumab excluding RTX; 4. Loss of follow-up before the completion of the questionnaire survey.\u003c/p\u003e \u003cp\u003eParticipants in the control group must be at least 10 years old and reside with PwNIDs who have received a low-dose individualized RTX regimen.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Study design\u003c/h2\u003e \u003cp\u003eThis was a cross-sectional observational study. We collected data of PwNIDs and their co-residents in the form of electronic questionnaires from January 31 to February 16, 2023 (chinacdc. cn). We gathered demographic data that includes age and gender, as well as information on comorbidities such as hypertension, diabetes mellitus (DM), coronary heart disease (CHD), cirrhosis, kidney disease, chronic obstructive pulmonary disease (COPD), connective tissue disease (CTD), epilepsy, dementia, stroke, underlying disease. Additional data collected pertained to the date of suspected or confirmed COVID-19 infection, specific COVID-19 symptoms, methods used for COVID-19 diagnosis, chest computer tomography (CT) scans and their findings, treatment settings (home care, hospitalization, outpatient or emergency services, intensive care unit [ICU] or death), the types of medications used (oral, injectable or inhaled), and the duration of symptoms of COVID-19 infection. This information was collected via electronic questionnaires completed by PwNIDs or their caregivers. We also collected self-reported information from PwNIDs on how COVID-19 affected their pre-existing conditions. We counted the doses of RTX administered and identified the date of the most recent RTX infusion for PwNIDs using the electronic medical record system (EMRS). Total RTX dosages of 300 mg or less were categorized as the induction group, while dosages exceeding 300 mg were classified as the maintenance group.\u003c/p\u003e \u003cp\u003eAccording to former studies, the specific symptoms of COVID-19 infection were divided into six groups(Kratzer et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2021\u003c/span\u003e;Ochani et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2021\u003c/span\u003e): ①Flu like symptoms (Group1, G1): fever, cough, expectoration, nasal congestion, pharyngalgia, etc.; ②Systemic symptoms (Group2, G2): muscle pain, weakness, etc.; ③Gastrointestinal symptoms (Group3, G3): diarrhea; ④Dysosmia and hypogeusia (Group4, G4); ⑤Neurological symptoms (Group5, G5): dizziness, headache, slow responses, etc.; ⑥Other symptoms (Group6, G6): rash, eyes discomfort like conjunctivitis. The severity of COVID-19 was defined by four levels: ①Mild disease: characterized by mild symptoms, not necessitating hospitalization; ②Moderate disease: involving hospitalization without the need for mechanical ventilation; ③Severe disease: requiring ICU admission and/or mechanical ventilation; and ④ Death.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were conducted with IBM SPSS version 26.0 software (IBM Corp, Armonk, New York). Quantitative data with normal distribution was expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and analyzed by T test. Continuous variables with skew distribution were expressed as median (inter-quartile range, IQR) and analyzed by Mann-Whitney U test. Categorical variables were presented as frequency and percentages and analyzed using χ2 test or Fisher exact tests. Logistic regression analysis was used to evaluate the risk factors of COVID-19 infection. P value ˂ 0.05 was considered to indicate statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"3.Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1 COVID-19 infection in PwNIDs and controls\u003c/h2\u003e\n \u003cp\u003eWe totally enrolled 70 PwNIDs (MG[N\u0026thinsp;=\u0026thinsp;19], CIDP[N\u0026thinsp;=\u0026thinsp;11], AE[N\u0026thinsp;=\u0026thinsp;19], MS[N\u0026thinsp;=\u0026thinsp;5], NMOSD[N\u0026thinsp;=\u0026thinsp;16]). Among these participants, 55.7% (39/70) contracted COVID-19. They lived with 94 people (serving as controls), of whom 59.5% (56/94) contracted COVID-19 (Figs. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). There was no significant difference in gender (percentage of females: 66.7% vs 46.4%, p\u0026thinsp;=\u0026thinsp;0.051) and age (mean [SD], years:47.02 [14.85] vs 44.48 [19.40], p\u0026thinsp;=\u0026thinsp;0.672), medication treatment for COVID-19, or site of care between PwNIDs and controls who contracted COVID-19. Based on the defined severity of COVID-19, among PwNIDs, 94.9% (37/39) had mild infections, 5.1% (2/39) patients had moderate infection. In the control group, 96.4% (54/56) had mild infection, and 3.6% (2/56) people had moderate infections. There was no significant difference in severity of COVID-19 infection between PwNIDs and controls(p\u0026thinsp;=\u0026thinsp;1.000). Furthermore, there were no cases of severe disease nor death in either group. We also detailed the symptoms of COVID-19 infection between PwNIDs and controls. Interestingly, there was no significant difference in symptom groups G1, G2, G5, but there was a significant difference in symptom groups G3, G4, G6(Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1 COVID-19 infection in PwNIDs and controls.\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePwNIDs with\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCOVID-19 infection\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=39\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls with\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCOVID-19 infection\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=56\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eValue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex, female, No. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e26(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e26(46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, years, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e47.02(14.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e44.48(19.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.672\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"89.8989898989899%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedicine treatment of COVID-19, No. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.873\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e14(35.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e21(37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eNot treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e25(64.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e35(62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"89.8989898989899%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite of care,n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.287\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eHome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e37(94.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e50(89.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eHospitalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2(5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2(3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eOutpatient/Emergency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e4(7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"89.8989898989899%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSeverity of COVID-19,\u003c/strong\u003e \u003cstrong\u003eNo. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e37(94.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e54(96.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eModerate\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2(5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2(3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eDeath\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSymptoms of COVID-19,\u003c/strong\u003e \u003cstrong\u003eNo. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup1(G1)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eFever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e29(74.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e44(78.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.632\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eCough\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e10(25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e25(44.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eExpectoration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e8(20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e8(14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.425\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eRhinobyon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e9(23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e15(26.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.682\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eRunny nose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e5(12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e9(16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.660\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003ePharyngalgia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e12(30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e17(30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup2(G2)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eMyalgia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e12(30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e8(14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eWeakness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e13(33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e21(37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.677\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup3(G3)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eDiarrhea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e5(12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.022\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup4(G4)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eDysosmia and hypogeusia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e10(25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e5(8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.028\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup5(G5)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eDizziness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e4(10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e7(12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.737\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eHeadache\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e8(20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e11(19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.917\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eUnresponsive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e2(3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.641\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup6(G6)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eEye discomfort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e10(25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e1(1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.45454545454545%\" valign=\"top\"\u003e\n \u003cp\u003eRash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e4(10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" valign=\"top\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAbbreviations: COVID-19,Coronavirus disease 2019; PwNIDs,Patients with neuroimmune diseases.\u003c/p\u003e\n\u003cp\u003e*：Statistical significance (p \u0026lt; 0.05).\u003c/p\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2 RTX treatment in PwNIDs\u003c/h2\u003e\n \u003cp\u003eTo explore the risk factors for COVID-19 infection, we divided PwNIDs into two groups: the uninfected group (N\u0026thinsp;=\u0026thinsp;31) and the infected group (N\u0026thinsp;=\u0026thinsp;39), based on their COVID-19 infection status (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). There were no significant difference observed in gender (percentage of females: 45.2% vs 66.7%, p\u0026thinsp;=\u0026thinsp;0.071), age (mean [SD], years:52.29 [17.49] vs 47.03 [14.85], p\u0026thinsp;=\u0026thinsp;0.178), or the presence of comorbidities including hypertension, diabetes, CHD, cirrhosis, kidney disease, COPD, CTD, epilepsy, dementia, stroke between the uninfected and the infected groups. \u0026nbsp;\u003c/p\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBasic characteristics and RTX in PwNIDs.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUninfected group\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInfected group\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex, female, No. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(45.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, mean (SD), y\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.29(17.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.03(14.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.178\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnderlying disease, No. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.652\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCIDP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(17.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(32.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNMOSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(28.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities, No. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.712\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.778\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.908\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKidney disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.908\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCODP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.839\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.577\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEpilepsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.109\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDementia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.908\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCumulative RTX dosages, median (IQR), mg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e300(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e300(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.123\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal RTX doses, No. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(54.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients stratified by accumulative RTX dosages, No. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInduction group (\u0026le;\u0026thinsp;300mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(74.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(51.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaintenance group (\u0026gt;300mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(48.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime interval of the last RTX\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003einfusion, median (IQR), months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.80(15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.83(19.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.324\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eThe duration since the last RTX infusion, No. (%), months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.103\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(46.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u0026thinsp;\u0026lt;\u0026thinsp;m\u0026thinsp;\u0026le;\u0026thinsp;12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(22.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients stratified by disease entities, No. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.890\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeripheral diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(43.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCentral diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(58.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(56.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eAbbreviations: SD, Standard deviation; M, Median; IQR, Inter-quartile range; MG, Myasthenia gravis; CIDP, Chronic inflammatory demyelinating polyradiculoneuropathy; AE, Autoimmune encephalitis; MS, Multiple sclerosis; NMOSD, Neuromyelitis optica spectrum disorders; CHD, Coronary heart disease; COPD, Chronic obstructive pulmonary disease; CTD, Connective tissue disease; RTX, Rituximab.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eTo assess the potential impact of RTX on COVID-19 infection, we tallied the cumulative RTX dosages and determined the time since the last RTX infusion. Our findings revealed that the median cumulative dosages of RTX in both groups were 300 mg with no significant difference observed between them (p\u0026thinsp;=\u0026thinsp;0.123). Base on whether the cumulative RTX dosages exceeded 300 mg, we categorized patients into two groups: the induction group (uninfected group/infected group:23/20) and the maintenance group (uninfected group/infected group:8/19). However, we found no significant difference between these groups (p\u0026thinsp;=\u0026thinsp;0.05). The median time interval, measured in months(m), since the last RTX infusion were 9.80 months in uninfected group and 6.83 months in infected group. However, there was no significant difference between these two groups (p\u0026thinsp;=\u0026thinsp;0.324). We categorized the duration since the last RTX infusion into three levels (\u0026le;\u0026thinsp;6m, 6˂m\u0026thinsp;\u0026le;\u0026thinsp;12, ˃12) and found no significant difference between the uninfected and the infected group (p\u0026thinsp;=\u0026thinsp;0.103). In our study, both univariable and multivariable logistic analysis failed to identify any risk factors for COVID-19 infection among the variables considered, which included age, sex, comorbidities, underlying disease, cumulative RTX dosages, and the duration since the last RTX infusion.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3 Impact of COVID-19 infection on the underlying disease in PwNIDs\u003c/h2\u003e\n \u003cp\u003eIn the study, we enrolled 30 patients with peripheral neurological immune diseases (NIDs) including MG and CIDP, and 40 patients with central NIDs including MS, AE, and NMOSD. The two groups had no statistical difference in disease entities (p\u0026thinsp;=\u0026thinsp;0.890). The infection status of various diseases in PwNIDs is as follows: (uninfected/infected: MG 9/10, CIDP 4/7, AE 10/9, MS 3/2, NMOSD 5/11) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eWe assessed the impact of COVID-19 infection on the underlying disease in PwNIDs through self-reports. Among patients with COVID-19 infection, 89.7% (35/39) reported that COVID-19 did not affect their primary disease. 10.3% (4/39) experienced a worsening of their original symptoms due to COVID-19. However, they did not require hospitalization for intervention. None of them developed new-onset symptoms that necessitated hospitalization for acute-phase therapy (Fig.\u0026nbsp;5).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4.Discussion","content":"\u003cp\u003eIn contrast to other studies published during the COVID-19 pandemic (Esmaeili et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2021\u003c/span\u003e;Klineova et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2021\u003c/span\u003e༛Reder et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2021\u003c/span\u003e༛Longinetti et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2022\u003c/span\u003e༛Smith et al. \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), we designed a cross-sectional observational study to assess the severity and risk factors associated with COVID-19 infection in PwNIDs treated with a low-dose RTX regimen. Our study yielded three principal findings. Firstly, it is worth noting that we observed no discernible difference in the severity of COVID-19 infections between PwNIDs and their co-residents. Neither group experienced severe infection or death. Secondly, we found that a shorter duration between the last RTX infusion and contracting COVID-19, as well as higher cumulative dosages of RTX, were not risk factors for COVID-19 infection. Lastly, our investigation revealed that COVID-19 infection did not have a significant impact on the underlying neuroimmune diseases in PwNIDs who had contracted COVID-19 and were undergoing low-dose RTX therapy.\u003c/p\u003e \u003cp\u003eThe severity of COVID-19 infection was comparable between PwNIDs and their co-residents, with no instances of severe disease or death observed among them. The observed outcomes may be attributed to the individualized low-dose RTX regimen we administered to PwNIDs. This regimen is rarely associated with reduced immunoglobulin levels and increase infection risk, yet it demonstrates comparable efficacy to higher dosages of RTX infusion. The dosages of RTX for autoimmune diseases (AIDs) were primarily derived from the regimen used for non-Hodgkin\u0026rsquo;s lymphoma (NHL). This includes an induction dose of 1 g per infusion (administered twice consecutively, with a 2-week interval) or 375 mg/m\u003csup\u003e2\u003c/sup\u003e per week based on body surface area (for 4 consecutive weeks). Maintenance therapy involves 1 g every 6 months or reinfusion only after recurrence. The efficacy of RTX in eliminating CD20\u003csup\u003e+\u003c/sup\u003e B cells was found to have a dose accumulative effect. Higher doses of RTX resulted in a longer duration required for B cell remodeling and had a more pronounced impact in humoral immune function, increasing the risk of hypogammaglobulinemia and subsequent infections, even severe infections(Tieu et al. \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2021\u003c/span\u003e;Kim et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Steve Simpson-Yap(Simpson-Yap et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) updated data of PwMS from 27 countries revealed a significant association between anti-CD20 therapy and a more severe course of COVID-19. Thamer S Alhowaish(Alhowaish et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) analyzed 35 PwMS who were infected COVID-19 and had received RTX at a dose of 375 mg/m2 with a median frequency of 4 doses. It was found that more than a third of these individuals developed hypogammaglobulinemia and required hospitalization and treatment in the intensive care unit (ICU). They thought RTX was a potential risk factor for unfavorable outcomes in COVID-19 patients.\u003c/p\u003e \u003cp\u003eInterestingly, D. Baker(Baker et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) hypothesized that anti-CD20 treatment did not predispose patients to severe COVID-19 due to the reduction in B cells and inflammatory storms following COVID-19 infection. This treatment also may not interfere with the innate immune response and CD8\u003csup\u003e+\u003c/sup\u003eT cell response. Based on these findings, some studies have indicated that patients undergoing anti-CD20 treatment did not experience severe COVID-19 infections and were able to recover rapidly after being infected with COVID-19(Kim et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2022\u003c/span\u003e;Longinetti et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2022\u003c/span\u003e༛Zabalza et al. \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Basic research also found that patients who received anti-C20 treatment experienced reduced COVID-19-specific-antibody production due to clearance of B cells. However, their COVID-19-specific T cell response remained robust. This provides a theoretical basis for the belief that anti-CD20 treatment dose not increase the severity of COVID-19 infection in patients(Madelon et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e༛Wolf et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBesides, we did not find any risk factors (including recent low-dose RTX infusion, higher cumulative RTX dosages and so on) for COVID-19 infection. Rajesh B Iyer(Iyer et al. 2022) enrolled 62 PwMS who received RTX infusion with an initial dose typically ranging from 1000 to 2000 mg, and subsequent doses averaging between 500 and 1000 mg. Their finding indicated that factors such as older age, secondary progressive MS(SPMS), a shorter duration between RTX infusion and COVID-19 onset, and receiving a higher dose at the last RTX infusion were associated with an increased risk of severe disease, which aligned with findings from other studies. Annette Langer-Gould(Langer-Gould et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) enrolled 1895 PwMS who were treated with RTX. Out of these, 24 patients contracted COVID-19. Compared to patients who either did not contract COVID-19 or experienced a mild of the disease, 8 out of 24 patients developed moderate disease. Among these patients, the median cumulative RTX dose was higher (3250 mg versus 2000 mg), and median time since last infusion was shorter (2.5 m versus 7.8 m). They also observed that the duration in months since the last infusion and receiving a dose of 1000 mg compared to lower doses at the last infusion were independent factors predicting the severity of COVID-19. This indicates that PwNIDs who have a shorter median time since their last infusion and a higher cumulative RTX dose remain vulnerable to COVID-19 and are at an increased risk of severe infection(Landtblom et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2021\u003c/span\u003e;Spelman et al. \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Our study found that low-dose RTX effectively cleared CD20\u003csup\u003e+\u003c/sup\u003e B cell without causing a decrease in immunoglobulin levels and had minimal impact on adaptive immune responses.\u003c/p\u003e \u003cp\u003eNumerous reviews have highlighted that the most prevalent symptom of COVID-19 infection is an upper respiratory tract infection, typically presenting with symptoms such as fever, followed by dry cough, fatigue, and so an(Furlan et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2021\u003c/span\u003e;Ochani et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2021\u003c/span\u003e༛Salter et al. \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Some patients with COVID-19 infection may be accompanied by muscle soreness, loss of smell and taste, nasal congestion, runny nose, diarrhea, conjunctivitis, etc. In our study, fever was the most common frequently reported symptom among PwNIDs who had COVID-19 infection. This was followed by systemic symptoms like myalgia, fatigue, as well as less uncommon symptoms such as rash and conjunctivitis, pharyngodynia, and decreased sense of smell and taste. In controls with COVID-19 infection, the most common symptom was also fever, followed by upper respiratory tract infections and systemic symptoms such as fatigue, dry cough, pharyngodynia, nasal congestion, headache, runny nose, and phlegm. There were statistically significant differences in systemic, gastrointestinal and less common symptoms between the two groups. We took into account that the immune system composition in PwNIDs receiving RTX might differ from that of the general population(Winkelmann et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). After COVID-19 infection, varying immune responses can occur, resulting in different symptom presentations or syndromes.\u003c/p\u003e \u003cp\u003eIt is widely recognized that virus infections can act as triggers for patients with AIDs. A cohort in Iranian focusing on MS reported that 17% of patients experienced a relapse after contracting COVID-19(Paybast et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). In order to clarify the impact of SARS CoV-2 on NIDs, we used the self-assessment questionnaire to investigate the underlying diseases in PwNIDs after COVID-19 infection. The results showed that the majority of PwNIDs who received a low-dose RTX regimen did not experience any significant impact on their primary diseases after COVID-19 infection. Fewer patients reported that their previous neurological symptoms and signs worsened, although this did not require hospitalization. The worsened clinical manifestations experienced by some individuals improved upon full recovery from COVID-19. Importantly, none of these patients developed new-onset neurological symptoms that required acute-phase treatment. Up to date, PwNIDs who have been followed up for more than one and a half years in our study have not reported any disease relapse. Furthermore, some of them are still undergoing regular low-dose RTX infusion as part of their treatment regimen. It appears that COVID-19 infection did not have any discernible impact on the underlying disease in PwNIDs who were receiving an individualized low-dose RTX regimen.\u003c/p\u003e \u003cp\u003eThe study has certain limitations: firstly, it is a single-center retrospective survey study with a small sample size. To reduce bias, we conducted a questionnaire survey on all patients with NIDs who received low-dose RTX treatment before the enrollment deadline. We also conducted a case-control study to investigate the infection status of co-residents and compare the infection status between groups. Secondly, this study used a questionnaire survey instead of face-to-face interviews. To minimize errors resulting from data entry, all completed questionnaires were cross-checked against EMRS. Any discrepancies or unclear responses were addressed through followed-up phone calls to ensure the accuracy of the data collected.\u003c/p\u003e"},{"header":"5.Conclusion","content":"\u003cp\u003eOverall, our study found that recent low-dose RTX infusion and higher cumulative doses did not increase the risk of COVID-19 infection and severe disease in PwNIDs. This study offers a clinical foundation supporting the advantageous use of a low-dose RTX regimen for treating NIDs during the COVID-19 pandemic.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u0026nbsp;\u003c/strong\u003eWe thank the patients and their co-residents for the collaboration.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u0026nbsp;\u003c/strong\u003eLL, DY, CL: contributed equally to this study and are co-first authors. Prof. WZ and YD had full access to all the data in the study and take full responsibility for the integrity of the data and the accuracy of the data analysis. LL, DY, CL,YH, CZ, QY, XZ, YL, YD, LH, RZ, JL, WZ, SL, LG,YD,WZ：acquired, analyzed, or interpreted of data and critically revised of the manuscript for important intellectual content. LL, DY, CL：drafted of the manuscript. YD and WZ: performed final manuscript review and editing. All authors contributed to the article and approved the submitted.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e This work was supported by research grants from the National Natural Science Foundation of China (82271457, 82171406, 81971003), Shaanxi Province Health Research and Innovation Team for Cognitive Dysfunction Disease (2023TD-06), Shaanxi Innovative Team for Science and Technology (2024RS-CXTD-87), Tangdu hospital innovation development foundation (2018QYTS010, 2019QYTS002), Tangdu hospital clinical research project (2021LCYJ040), Tangdu hospital foundation for social recruitment talent (2021SHRC011).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY STATEMENT\u003c/strong\u003e The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS STATEMENT\u0026nbsp;\u003c/strong\u003eWe provided patients detailed information about the diseases, and obtained the consent of the patients to repeated low-dose rituximab treatment. We have also reported to the Ethical Committee of Tangdu Hospital, Fourth Military Medical University, and obtained the approval from the committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST\u0026nbsp;\u003c/strong\u003eThese authors declare that they have no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT FOR PUBLICATION\u0026nbsp;\u003c/strong\u003eWe obtained written informed consent from both patients for publication of this report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAlhowaish TS, Alhamadh MS, Mathkour A, Alamoudi M, Alqahtani HA, Alrashid A (2023) Clinical Course and Outcomes of COVID-19 Infection in Patients Treated with Rituximab: A Tertiary Care Center Experience. 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Front Neurol 12:595984. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fneur.2021.595984\u003c/span\u003e\u003cspan address=\"10.3389/fneur.2021.595984\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, low-dose rituximab regimen, neuroimmune diseases, severity, risk factors","lastPublishedDoi":"10.21203/rs.3.rs-4624675/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4624675/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA retrospective study was conducted to evaluate the impact of low-dose rituximab (RTX) regimen on the severity of coronavirus disease 2019 (Covid-19) in patients with neuroimmune diseases (PwNIDs) at Tangdu Hospital, Fourth Military Medical University from July 2017 to December 2022. A total of 70 PwNIDs were enrolled, of which 39 contracted COVID-19. The co-residents of these PwNIDs, serving as the control group, comprised 94 individuals, among whom 56 contracted COVID-19. However, there was no significant difference in the severity of COVID-19, including severe cases or death, between the two groups. Among PwNIDs, there were no notable differences observed in age, sex, underlying conditions, comorbidities, cumulative RTX dosages, or the duration since the last RTX infusion between the infected and uninfected groups. Among the PwNIDs who contracted COVID-19, 89.7% (35/39) stated that the virus had no influence on their existing conditions. Only 10.3% (4/39) reported worsened previous symptoms without requirement of hospitalization, and none developed new-onset neurological symptoms requiring acute-phase treatment. The administration of a low-dose RTX regimen does not increase the risk of COVID-19 or severe illness in PwNIDs, irrespective of the cumulative RTX dosages or the duration since the last RTX infusion. Moreover, COVID-19 does not seem to significantly exacerbate underlying neuroimmune disorders in these individuals.\u003c/p\u003e","manuscriptTitle":"Low-dose rituximab regimen does not increase severe COVID-19 risk in patients with neuroimmune diseases during the pandemic: a cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-29 18:14:25","doi":"10.21203/rs.3.rs-4624675/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0970161f-6f44-44e1-a21d-dbccbe5decbb","owner":[],"postedDate":"July 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-10T20:08:23+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-29 18:14:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4624675","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4624675","identity":"rs-4624675","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}