Investigation of Clinical Characteristics of COVID-19 Infection in Rheumatoid Patients on Immunosuppressive Drugs: A Cross-sectional Study

Investigation of Clinical Characteristics of COVID-19 Infection in Rheumatoid Patients on Immunosuppressive Drugs: 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 Investigation of Clinical Characteristics of COVID-19 Infection in Rheumatoid Patients on Immunosuppressive Drugs: A Cross-sectional Study Faezeh Sehatpour, Elham Aflaki This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6547229/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Backgrounds : Cytokine storm has been considered as the main pathogenesis in COVID-19 patients with severe disease. Inflammatory cytokines, such as interleukin-6(IL-6), IL-1, and tumor necrosis factor alpha (TNF-α) released from the lung epithelium in COVID-19 infection are very similar to cytokines which are released in inflammatory rheumatic diseases. Immunosuppressive drugs are the cornerstone of treatment in many rheumatologic diseases. Prolonged use of these agents might result in change in the clinical characteristics of these individuals with COVID-19. Objective : To determine the clinical findings and disease severity of COVID-19 infection in patients with rheumatologic diseases who were on immunosuppressive therapy. Method : We retrospectively investigated 1000 subjects who were more than 18years old with rheumatologic diseases on immunosuppressive therapy in the recent three months. Demographic data, rheumatic disease characteristics, medications, and presence of any co- morbid conditions were documented by detail. Presence of severe COVID-19 infection features were compared between users and non-users of different immunosuppressant agents. Multivariable logistic regression was applied, and adjusted odd ratio (OR) and its 95% CI were estimated. Results : 539 subjects had positive history of COVID-19 (COVID-19+). Pre-exposure to prednisolone was associated with severe disease (OR: 2.52, 95%CI (1.192-4.255)). Pervious use of MTX (OR: 0.348, 95%CI (0.210-0.575)) and biologic drugs (OR: 0.332, 95%CI (0.159-0.694)) had protective effect on the severity of the disease. Other traditional disease modifying anti-rheumatic drugs (DMARD) had no clinical effect on the outcome of COVID-19 infection. Conclusion : In the current study, among rheumatoid patients on immunosuppressants, previous treatment with corticosteroids was associated with increased incidence, poor prognosis, and increased mortality. Pre-exposure to MTX or biologic agents such as anti-TNF and anti-CD20 had protective effect against coronavirus. Further meta-analysis and systematic review in large population is needed to accurately determine the effect and mechanism of these drugs on this new viral illness. COVID-19 immunosuppressants rheumatoid patients Introduction The novel coronavirus, which had initially led to pneumonia of unknown etiology in a series of patients in Hubei province in China,, in December 2019, has now precipitated a global health crisis caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).(1)Old people and those with comorbidities such as diabetes mellitus and cardiovascular disease are at high risk of severe illness.(2) However, the exact mechanisms of this disease and why some people develop a mild form of the disease while others presented a severe disease with fatal outcome are still not well understood. Cytokine storm has been considered as the main pathogenesis in COVID-19 patients with severe disease.(3)Inflammatory cytokines, such as interleukin (IL) 6, IL-1, and tumor necrosis factor alpha (TNF-α) released from the lung epithelium in COVID-19 infection, are very similar to cytokines which release in inflammatory rheumatic diseases. In critically ill patients, especially those who need intensive care unit (ICU) care, serum level of IL-2,6,10 and TNF-α increases significantly. Also, a decrease in the lymphocytes and natural killer cells has been documented in these patients.(4, 5) Many of the anti-inflammatory drugs and immune modulator agents including tocilizumab, a monoclonal antibody against the interleukin-6 receptor, have been used experimentally as the treatment of COVID-19.(6) The use of tocilizumab was associated with better outcome in patients with severe COVID-19 infection in some recent studies.(7) on the other hand, rheumatoid patients with COVID-19 infection who had a history of Anti-CD20 agent ( rituximab) or Janus kinas inhibitors (JAKi: tofacitinib, baricitinib and upadacitinib ) usage, experienced more severe illness and poor outcome in Sparks et al.’s study.(8) Immunosuppressive drugs, based on molecular target therapy, are the cornerstone of treatment in many rheumatologic diseases, and infections are one of the most common causes of morbidity and mortality among these patients. Considering the rising number of affected individuals across the globe, patients with rheumatologic diseases should be considered as high-risk population. Despite the multitude of studies conducted so far to characterize the clinical findings in patients with COVID-19 infection, the full spectrum of the clinical presentations in these patients remain largely unknown.(9, 10) Due to this limitation and since there is no data about this important issue in Iran, we designed this survey to explore the clinical findings and disease severity of COVID-19 among Iranian patients with rheumatic diseases on immunosuppressive agents. Methods Study subjects and setting: We retrospectively investigated 1000 subjects with rheumatologic diseases who are registered in Iran, Shiraz. The information of the patients was collected through the treatment department of Shiraz University of Medical Sciences (SUMS), the hospitalization centers of COVID-19 patients in Shiraz, and the patients referred to rheumatology clinics. The diagnosis of COVID-19 was based on laboratory-confirmed COVID-19 infection using real-time PCR or lung high resolution CT scan (HRCT) compatible with COVID-19 infection. Men and women aged more than 18 years and the rheumatologic patient on immunosuppressive therapy (prednisolone, methotrexate, azathioprine, mycophenolate, cyclosporine, tacrolimus, cyclophosphamide, rituximab and anti-TNFs) in the three months were included in this survey. The aims of the study were explained to the patients or their relatives in full detail and informed consent was obtained from all subjects or their legal guardians. This study was conducted according to the ethical principles and recommendations outlined in the Declaration of Helsinki and approved by the ethics committee of SUMS with contract number of IR.SUMS.MED.REC.99-01-0122393. Exclusion criteria: Unwillingness to take part in the study, pregnant women, history of current active hepatitis, and untreated cancer were the exclusion criteria of this study. Data gathering: Demographic data including age and sex, rheumatic disease characteristics and the duration of disease, medications, and the history of the presence of any co-morbidities including chronic obstructive pulmonary disease, diabetes, high blood pressure, coronary artery disease, cerebrovascular disease, hepatitis, cancer, chronic kidney disease, and thyroid disease were asked and recorded in detail. If any para-clinical studies were performed recently, they were asked to share them with the research team. For patients admitted in hospital, their laboratory findings on admission and during the treatment were evaluated. The oxygen saturation percentage (O2 sat) in the air room, route of oxygen administration (nasal cannula, non-re breather mask, noninvasive and invasive ventilation), and prognosis of the patients were recorded. The percentage of lung involvement in High Resolution Computed Tomography (HRCT) was also reviewed as reported by expert radiologist by using previous studies.(11, 12)Patients were divided into five groups based on the history of using different types of immunosuppressant drugs (prednisolone; methotrexate (MTX); hydroxychloroquine (HCQ); biologic agents including etanercept, infliximab and rituximab; and other traditional disease-modifying anti-rheumatic drugs(DMARDs) including mycopholate mofetil, azathioprine, cyclosporine, cyclophosphamide, leflunomide and tacrolimus).Mean ± standard deviations (SD) of O2sat in the air room, lung parenchymal involvement and the percentage of the presence of dyspnea, hospital admission, noninvasive and invasive ventilation, and mortality rate were compared between the users and non- users of these five immunosuppressant drugs. The presence of two out of the three risk factors: 1) lung involvement ≥ 50% in HRCT(13) , 2) O2saturation≤ 88%(14), and 3) the need for noninvasive or invasive ventilation or death due to COVID-19infection was defined as severe disease. Statistical Analysis We estimated proportions and means±SD to describe the data. 95%confidence interval (CI) of prevalence was estimated. Independent t-test and chi-square test were used. The effect of confounding variables was controlled by using multivariable logistic regression. Two logistic regression models were fitted to assess the correlates of severe COVID-19 categories. The significance level was setat0.05. Stata11.2 software (StataCorp. LP) and SPSS version 21 were used for data analysis. Results Of1000subjects, 981(male =217, female=764) were included in this study. The ratio of people who were infected with COVID-19 (COVID- 19+) to those who were not infected (COVID-19- ) was 1.2/1(539/442). The rate of hospital admission was 48.05% (number (n)=259) and 61 patients died due to severe illness. The underlying rheumatologic diseases in this population were rheumatoid arthritis (RA)(n=403; 41.1%), vasculitis including Wegner, Bechet, giant cell arthritis, Churg Struss, Takayasu arteritis 21.3(n=209),) systematic lupus erythematous 20.9(n=205), seronegative spondyloarthritis4.7(n=46, uveitis 4.5(n=44),) scleroderma3.7(n=36, Sjogren 1.9(n=19), myositis 1.1(n=11), sarcoidosis 0.5(n=5), and undifferentiated connective tissue disease0.3(n=3).Nonspecific symptoms such as fever, fatigue, anorexia, and insomnia were reported by almost 86.46% of COVID-19+ patients. The prevalence of the symptoms of respiratory tract infection and gastrointestinal involvement was 76.8 and 33.58, respectively. Oxygen saturation in the room temperature ranged from 52%to 98% with mean±SD of 88.80±7.65 among COVID-19 +patients. The mean of total lung involvement in HRCT was 29.45±27.36in the affected patients. In the COVID-19+ subjects, presence of HTN (p.value:0.007) and DM(P=0.001) was significantly more than COVID-19- patients. Consumption of prednisolone was statistically more prevalent in COVID+-19 patients (n=403(74.8 %), 95%CI: 71.33-78.67 vs. n=274(62%), 95%CI: 61.95-62.05). (P<0.001) However, MTX usage was lower in COVID-19+ (n=352(65.3%), 95%CI: 60.98-69.02) in contrast to COVID-19- population (n=332(75.1%), 95%CI: 70.96-79.04). (P =0.001) (Table1) Mean±SD of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and lactate dehydrogenase (LDH) were 55.30±34.31, 60.13±30.90 and 703.69±338.42 in COVID-19 patients. Presence of severe COVID-19 infection features was compared between users and non-users of different immunosuppressant agents. (Table 2) Presence of respiratory failure and lung involvement was significantly higher in subjects who used prednisolone. The rate of these complications was significantly lower in MTX and users of biologic agents. According to multivariable analyses, increasing age (OR:1.034,95%CI (1.015-1.053)) and using prednisolone prior to COVID-19infection (OR:2.52,95%CI (1.192-4.255)) were associated with severe disease. Pervious use of MTX (OR: 0.348, 95%CI (0.210-0.575)) and biologic drugs (OR:0.332,95%CI (0.159-0.694)) had protective effect on the severity of the disease. Other traditional DMARDs had no direct effect on the severity of COVID-19 infection. (Table3) Discussion Cytokine storm has been considered as a causative factor in the pathogenesis of COVID-19 infection. Inflammatory cytokines such as IL-6, IL-1, and TNF-α in the infection of COVID-19 are very similar to the cytokines involved in the development of rheumatic diseases.( 4 , 5 ) Considering the background of abnormal immune response and the use of various immunosuppressants in patients with rheumatic diseases, it is necessary to investigate the characteristics of COVID-19 and its consequences in this population.( 15 ) In the current survey among 981 rheumatic patients in Shiraz, Fars, Iran, 539(54.94%) subjects were infected with COVID-19. Use of prednisolone was associated with higher rates of infection and poor outcome. However, MTX and biologic agents had a lower rate of infection, milder clinical features, and better outcome in our study. In previous studies, the risk of COVID-19 infections was considered high in rheumatic patients due to dysregulation of the immune system and use of immunosuppressant agents which increase the risk of opportunistic infections( 16 ). JAK2 inhibitors, anti-TNF agents and glucocorticoids have been considered as the risk factor for the severity of the disease and ARDS in some studies.( 17 )However, this view has been changed with the identification of the role of cytokines and auto-inflammation in the pathogenesis of COVID-19 in recent studies.( 18 ) Hydroxychloroquine, which was first regarded as one of the useful therapies in COVID-19 patients, had no protective effect in our investigation. In Rentschet al.’s study, among 194637 patients with diagnosis of RA and SLE, no statistically significant difference was detected between prior users and non-users of hydroxychloroquine.( 19 )Post-treatment with hydroxychloroquine had also no significant effect on the rate of hospitalization and better clinical outcome.( 20 ) Corticosteroid is defined as an effective treatment in severe COVID-19 infection ( 21 ).However, the effect of the pervious use of these agents on the severity and outcome of COVID-19 is still not clear. In a cohort study done by Ennio Giulio Favallietal., prior use of corticosteroid even in low dose had a potentially adverse outcome (OR ranging from 1.23 to 3.2).( 22 )These findings were compatible with our study results. Based on COVID-19 Global Rheumatology Alliance (GRA), corticosteroids were associated with unfavorable outcome in rheumatoid patients with COVID-19infection. However, disruption of steroid during acute phase of infection was not recommended in this study.( 23 ) Prior use of biologic DMARDS was accompanied with lower rate of COVID-19 infection and better outcome in our study. TNF is the most pro-inflammatory cytokine- mediating immune factors. Anti-TNF antibody agents may be effective in COVID-19 infection by modulation of the immune system and expression of angiotensin converting enzyme 2 (ACE2) receptor.( 24 )It was shown that the risk of COVID-19 infection in patients with rheumatic disease son biologic DMARDs was the same as the general population and was accompanied with favorable outcomes.( 25 ) Prior use of biologic DMARDs was also not associated with higher rate of COVID-19 infection, hospital admission, and mortality rate.( 26 , 27 ) In our study, pre-exposure to MTX was associated with better outcome, lower mortality rate, and the need for invasive ventilation 0.348, 95%CI (0.210–0.575). In addition to anti-inflammatory effect of MTX, this might be due to the effect of MTX on inhibition of dihydrofolate reductase pathway the efficiency of which on infectious disease had been recently discovered.( 24 ) Further clinical trials are needed to determine the exact effect of MTX on COVID-19 infection. In the current study, other traditional DMARDs including mycophenolate mofetil, azathioprine, cyclosporine, cyclophosphamide, leflunomide, and tacrolimus had no effect on COVID-19infection and its severity. Studies on the effect of prior use of this class of drugs on COVID-19 are limited and have yielded conflicting results.( 28 )Larger sample size might be needed for evaluation of their consequence and their mechanism on COVID-19, which is still unknown.( 29 ) This is the first study in the south of Iran that investigated the clinical characteristics of COVID-19 among patients with different types of rheumatoid diseases who used immunosuppressant agents. One of the most important strengths of the current study was the investigation of the effects of different groups of immunosuppressant drugs with various mechanisms on different aspects of COVID-19 infection. Lack of sufficient laboratory data was an important limitation in our study, and further investigation is recommended to determine the level of inflammatory markers in the presence of immunosuppressant agents. Due to the fact that this was a retrospective study, the dosage and duration of the drugs were not known. The sample size in different drug subgroups was also not enough to compare with other subgroups. Conclusion The characteristics, management, and treatment of COVID-19 infection in patients with auto- immune rheumatoid disease who are on immunosuppressant agents are still challenging. In the current study, previous treatment with corticosteroids was associated with increased incidence, poor prognosis, and mortality. In addition, pre-exposure to MTX or biologic agents such as anti-TNF and anti-CD20 had a protective effect against coronavirus. Further meta-analysis and systematic review in larger population is needed to accurately determine the effect and mechanism of these drugs on this new viral illness. Declarations Funding: The authors received no financial support for the research or publication of this article Consent for publication: Not applicable Competing interests: The authors declare no competing interests. Author Contribution F.S: data gathering, analysis ,drafted the manuscript and revised the manuscript E.A: designing ,data gathering the research and revised the manuscript Acknowledgement The authors would like to thank Shiraz University of Medical Sciences, Shiraz, Iran and also Center for Development of Clinical Research of Namazi Hospital and Dr. Nasrin Shokrpour for editorial assistance. Declarations of Interest: None declared References Habibzadeh P, Stoneman EK. The novel coronavirus: a bird's eye view. The international journal of occupational and environmental medicine. 2020;11(2):65. 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COVID-19 and rheumatic musculoskeletal disease patients: infection rates, attitudes and medication adherence in an Irish population. Rheumatology. 2021;60(2):902-6. Yousaf A, Gayam S, Feldman S, Zinn Z, Kolodney M. Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors or methotrexate: a multicenter research network study. Journal of the American Academy of Dermatology. 2021;84(1):70-5. Pablos JL, Galindo M, Carmona L, Lledó A, Retuerto M, Blanco R, et al. Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study. Annals of the rheumatic diseases. 2020;79(12):1544-9. Mikuls TR, Johnson SR, Fraenkel L, Arasaratnam RJ, Baden LR, Bermas BL, et al. American College of Rheumatology Guidance for the management of rheumatic disease in adult patients during the COVID‐19 Pandemic: version 2. Arthritis & rheumatology. 2020;72(9):e1-e12. Tables Table 1. Demographic and Clinical Characteristics of the Participants Total (n a =981) COVID-19(+hx a ) (n=539) COVID-19(-hx) (n=442) P-value Age(Mean ±SD in years) 49.65±14.43 50.85±14.38 48.11±14.36 0.647 Gender Male 217(22.1) (19.56-24.85) 108(20.0) (16.74-23.67) 109(24.7) (20.71-28.95) 0.049 Female 764(77.9) (75.15-80.44) 431(80) (76.33-83.26) 333(75.3) (71.05-79.29) Medication Prednisolone 677(69) (66.1-71.9) 403(74.8) (71.33-78.67) 274(62.0) (61.95-62.05) <0.001 Methotrexate 684(69.7) (67.12-72.88) 352(65.3) (60.98-69.02) 332(75.1) (70.96-79.04) 0.001 Anti-TNFα a 171(17.4) (14.62-19.38) 97(18.0) (14.75-21.25) 74(16.7) (13.51-20.49) 0.334 Azathioprine 180(18.3) (15.58-20.42) 76(14.1) (11.06-16.94) 104(23.5) (20.41-27.59) <0.001 Mycophenolic acid 82(8.4) (6.26-9.73) 48(8.9) (6.59-11.41) 34(7.7) (5.75-10.25) 0.286 Cyclosporine 66(6.7) (5.43-8.57) 26(4.8) (3.19-6.80) 40(9) (6.58-11.42) 0.006 Hydroxychloroquine 173(17.6) (15.62-20.38) 101 (18.7) (15.70 -22.30) 72(16.3) (12.88-19.22) 0.180 Rituximab 54(5.5) (4.16-7.12) 34(6.3) (3.94-8.05) 20(4.5) (3.24-6.76) 0.140 Leflunomide 65(6.6) (6.19-7.44) 34(6.3) (3.94-8.05) 31(7) (4.84-9.16) 0.376 Tacrolimus 33(3.4) (2.33-4.69) 13(2.4) (1.29-4.09) 20(4.5) (3.24-6.76) 0.050 Sulfasalazine 164(16.7) (14.67-19.33) 84(15.6) (12.94-19.06) 80(18.1) (14.75-21.25) 0.167 Comorbid conditions Ischemic heart disease 56(5.7) (4.55-7.45) 40(7.4) (4.79-9.21) 16(3.6) (2.42-5.58) 0.007 Hypertension 176(17.9) (15.60-20.40) 123(22.8) (19.45-26.55) 53(12) (9.26-14.74) 0.007 Diabetes Mellitus 99(10.1) (8.12-11.88) 70(13) (10.16-15.84) 29(6.6) (4.91-9.09) 0.001 Thyroid disease 89(9.1) (7.20-10.80) 51(9.5) (6.53-11.47) 38(8.6) (6.63-11.37) 0.361 Rheumatologic diseases Rheumatoid arthritis 403(41.1) (37.98-44.23) 252(46.8) (42.48-51.07) 151(34.2) (29.75-38.79) <0.001 Systemic lupus erythematosus 205(20.9) (18.39-7.123.582) 120(22.3) (18.82-26.02) 85(19.2) (15.66-23.22) 0.135 Vasculitis 209(21.3) (18.78-24.00) 72(13.4) (10.60-16.52) 137(31) (26.71-35.54) <0.001 Seronegative spondyloarthropathy 46(4.7) (3.45-6.21) 27(5) (3.33-7.20) 19(4.3) (2.61-6.63) 0.357 Uveitis 44(4.5) (3.28-5.97) 22(4.1) (2.58-6.11) 22(5) (3.15-7.44) 0.301 Systemic sclerosis 36(3.7) (2.58-5.04) 22(4.1) (2.58-6.11) 14(3.2) (1.74-5.26) 0.280 a Abbreviations: hx, history; TNFα, tumor necrosis factor alpha. Table2:Severe COVID-19 Infection Features in The Presence of DifferentImmunosuppressants Other traditional DMARDs * N=181 Biologic agents N=128 HCQ a N=101 MTX a N=352 Predniselone N=403 P a Neg hx a Pos hx a P a Neg hx a Pos hx a P a Neg hx a Pos hx a P a Neg hx a Pos hx a P a Neg hx a Pos hx a 0.084 41.3 (35.89-46.11) 34.8 (28.04-41.96) <0.001 42.8 (38.21-47.79) 27.3 (12.26-27.74) 0.037 37.2 (32.47-41.53) 47.5 (38.21-57.79) <0.001 52.4 (44.82-59.18) 32.1 (27.11-36.89) 0.002 28.7 (21.37 -36.63) 42.7 (38.17- 47.83) Dyspnea prevalence% 0.068 50.6 (45.81-56.19) 43.3 (35.74-50.26) <0.001 54.5 (50.18-59.82) 27.6 (20.22.35.78) 0.196 47.1 (42.32-51.58) 52.5 (42.21-61.79) <0.001 66.8 (60.23-73.77) 38.2 ) 32.91-43.09) <0.001 29.4 (21.32-36.68) 54.5 (49.12- 58.88) Hospital admission prevalence% 0.197 7.5 (5.26-10.73) 4.4 (0.10-7.00) 0.017 7.8 (5.40-10.59) 8.6 (-0.63-4.63) 0.18 7.1 (4.59-9.41) 4 (0.17-7.82) 0.002 11.2 (6.45-15.54) 4 (1.95-6.05) 0.011 2.2 (-0.47-4.47) 7.9 (5.35-10.65) Noninvasive ventilatin prevalence% 0.180 13.7 (10.44-17.56) 10.5 (5.52-14.47) 0.003 14.8 (11.56-18.44) 5.5 (1.05-8.95) 0.522 12.6 (9.89-16.11) 12.9 (6.43-19.57) <0.001 20.3 (14.22-25.78) 8.5 (6.07-11.93) 0.008 6.6 (2.80-11.2) 14.6 (11.54-18.46) Invasive ventilatin prevalence% 0.96 31.06 ± 27.62 26.11 ± 26.63 <0.001 32.08 ± 27.75 19.08 ± 2316 0.041 30.97 ± 27.80 23.95± 24.78 <0.001 38.65 ± 28.3 23.49 ± 25.05 0.002 21.98± 24.29 31.67± 27.87 Lung involvement mean±SD,% 0.008 88.14 ± 6.14 90.13 ± 6.14 <0.001 88.06 ± 8.05 91.30 ± 5.45 0.251 88.61± 7.73 89.58 ± 7.33 <0.001 86.68 ± 8.58 90.03 ± 6.78 0.016 90.28 ± 6.78 88.33 ± 7.86 O2 sat a mean±SD,% 0.388 12.3 (8.59-15.41) 9.4 (4.73-13.27) 0.003 13.4 (9.70-16.30) 4.7 (2.37-7.63) 0.521 11.4 (8.02-13.98) 10.9 (4.89-17.10) <0.001 18.7 (13.40-24.60 7.4 (4.26-9.74) 0.012 5.9 (2.03- 9.96) 13.2 (9.70-16.30) Prevalence of death% a Abbreviations: Mtx, methotrexate, HCQ,hydroxychloroquin; poshx: positive history; Neg hx, negative history; P, P-value; o2 sat, oxygen saturation. * other drugs including: cellcept, azathioprine, cyclosporine, cyclophosphamide, leuflonamide and tacrolimus. Table3: Factors Modulating COVID-19 Infection Lower- Upper 95% CI a Adjusted . Odds ratio Crude. Odds ratio P value Coefficient (SE) Coefficient Variables 1.015-1.053 1.034 1.054 <0.001 0.009 0.034 Age 0.493-1.726 0.923 0.752 0.801 0.320 -0.080 Male 1.192-4.255 2.52 2.059 0.012 0.325 0.812 Prednisolon 0.210-0.575 0.348 0.332 <0.001 0.256 -1.056 Methotrexate 0.159-0.694 0.332 0.232 0.003 0.377 -1.103 Biologic drugs 0.248-1.273 0.561 0.426 0.167 0.418 -0.577 Azathioprine 0.322-1.153 0.609 0.714 0.128 0.326 -0.496 Hydroxychloroquin 0.522-2.680 1.183 1.042 0.687 0.417 0.168 Cellcept 0.446-3.575 1.263 1.050 0.660 0.531 0.234 Cyclosporine 0.319-2.080 0.815 0.899 0.668 0.478 -0.205 Leuflonamide 0.057-4.090 0.483 0.285 0.505 1.089 -0.727 Tacrolimus 0.812-2.936 1.544 2.732 0.185 0.328 0.434 Diabetes mellitus 0.932-2.738 1.598 3.218 0.088 0.275 0.469 Hypertention 0.444-2.224 0.994 3.990 0.988 0.411 -0.006 IHD a 0.119-0.887 0.325 0.353 0.028 0.513 -1.125 Thyroid disease a Abbreviations: CI, confidence interval; IHD, ischemic heart disease. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 21 Jun, 2025 Reviews received at journal 13 Jun, 2025 Reviewers agreed at journal 11 Jun, 2025 Reviews received at journal 29 May, 2025 Reviewers agreed at journal 29 May, 2025 Reviewers invited by journal 27 May, 2025 Editor assigned by journal 05 May, 2025 Submission checks completed at journal 05 May, 2025 First submitted to journal 28 Apr, 2025 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-6547229","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":463832228,"identity":"de3e740e-6501-4673-9380-33712661bc1f","order_by":0,"name":"Faezeh Sehatpour","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Faezeh","middleName":"","lastName":"Sehatpour","suffix":""},{"id":463832229,"identity":"f3001403-9023-487d-9646-10f04fee4395","order_by":1,"name":"Elham Aflaki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYDAC5sMNjA0GDHIg9oEHRGlhSwRrMQZrSSBeCwNDYgOIQ5QW/jbGxo8zCmzS54cdfgi0xU5Ot4GAFoljjM2SGwzScjfeTjMAakk2NjtAyJr7jQ2SDwwO526cnQDSciBxGyEt8kBbfj4w+J9uODv9A3FaDI4xtgEddiBBXjqHSFsMgVosZxgkG26Qzik4kGBAhF/kjjEfvtnzx05efnb65g8fKuzkCHsf7kKwSgNilYOAfAMpqkfBKBgFo2BEAQDb1EmXiXlvxgAAAABJRU5ErkJggg==","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Elham","middleName":"","lastName":"Aflaki","suffix":""}],"badges":[],"createdAt":"2025-04-28 11:08:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6547229/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6547229/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83653123,"identity":"807d998a-18f4-4e24-b799-117f4d3d526a","added_by":"auto","created_at":"2025-05-30 07:51:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":791554,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6547229/v1/157681a1-070a-4193-803b-179a19ebbd8a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Investigation of Clinical Characteristics of COVID-19 Infection in Rheumatoid Patients on Immunosuppressive Drugs: A Cross-sectional Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe novel coronavirus, which had initially led to pneumonia of unknown etiology in a series of patients in Hubei province in China,, in December 2019, has now precipitated a global health crisis caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).(1)Old people and those with comorbidities such as diabetes mellitus and cardiovascular disease are at high risk of severe illness.(2) However, the exact mechanisms of this disease and why some people develop a mild form of the disease while others presented a severe disease with fatal outcome are still not well understood. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCytokine storm has been considered as the main pathogenesis in COVID-19 patients with severe disease.(3)Inflammatory cytokines, such as interleukin (IL) 6, IL-1, and tumor necrosis factor alpha (TNF-\u0026alpha;) released from the lung epithelium in COVID-19 infection, are very similar to cytokines which release in inflammatory rheumatic diseases. In critically ill patients, especially those who need intensive care unit (ICU) care, serum level of IL-2,6,10 and TNF-\u0026alpha; increases significantly. Also, a decrease in the lymphocytes and natural killer cells has been documented in these patients.(4, 5)\u003c/p\u003e\n\u003cp\u003eMany of the anti-inflammatory drugs and immune modulator agents including tocilizumab, a monoclonal antibody against the interleukin-6 receptor, have been used experimentally as the treatment of COVID-19.(6) The use of tocilizumab was associated with better outcome in patients with severe COVID-19 infection in some recent studies.(7) on the other hand, rheumatoid patients with COVID-19 infection who had a history of Anti-CD20 agent ( rituximab) or Janus kinas inhibitors (JAKi: tofacitinib, baricitinib and upadacitinib ) usage, experienced more severe illness and poor outcome in Sparks et al.\u0026rsquo;s study.(8)\u003c/p\u003e\n\u003cp\u003eImmunosuppressive drugs, based on molecular target therapy, are the cornerstone of treatment in many rheumatologic diseases, and infections are one of the most common causes of morbidity and mortality among these patients. Considering the rising number of affected individuals across the globe, patients with rheumatologic diseases should be considered as high-risk population. Despite the multitude of studies conducted so far to characterize the clinical findings in patients with COVID-19 infection, the full spectrum of the clinical presentations in these patients remain largely unknown.(9, 10)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Due to this limitation and since there is no data about this important issue in Iran, we designed this survey to explore the clinical findings and disease severity of COVID-19 among Iranian patients with rheumatic diseases on immunosuppressive agents.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003eStudy subjects and setting:\u003c/h2\u003e\n\u003cp\u003eWe retrospectively investigated 1000 subjects with rheumatologic diseases who are registered in Iran, Shiraz. The information of the patients was collected through the treatment department of Shiraz University of Medical Sciences (SUMS), the hospitalization centers of COVID-19 patients in Shiraz, and the patients referred to rheumatology clinics. The diagnosis of COVID-19 was based on laboratory-confirmed COVID-19 infection using real-time PCR or lung high resolution CT scan (HRCT) compatible with COVID-19 infection. Men and women aged more than 18 years and the rheumatologic patient on immunosuppressive therapy (prednisolone, methotrexate, azathioprine, mycophenolate, cyclosporine, tacrolimus, cyclophosphamide, rituximab and anti-TNFs) in the three months were included in this survey. The aims of the study were explained to the patients or their relatives in full detail and informed consent was obtained from all subjects or their legal guardians. This study was conducted according to the ethical principles and recommendations outlined in the Declaration of Helsinki and approved by the ethics committee of SUMS with contract number of IR.SUMS.MED.REC.99-01-0122393.\u003c/p\u003e\n\u003ch2\u003eExclusion criteria:\u003c/h2\u003e\n\u003cp\u003eUnwillingness to take part in the study, pregnant women, history of current active hepatitis, and untreated cancer were the exclusion criteria of this study.\u003c/p\u003e\n\u003ch2\u003eData gathering:\u003c/h2\u003e\n\u003cp\u003e\u0026nbsp;Demographic data including age and sex, rheumatic disease characteristics and the duration of disease, medications, and the history of the presence of any co-morbidities including chronic obstructive pulmonary disease, diabetes, high blood pressure, coronary artery disease, cerebrovascular disease, hepatitis, cancer, chronic kidney disease, and thyroid disease were asked and recorded in detail. If any para-clinical studies were performed recently, they were asked to share them with the research team. For patients admitted in hospital, their laboratory findings on admission and during the treatment were evaluated. The oxygen saturation percentage (O2 sat) in the air room, route of oxygen administration (nasal cannula, non-re breather mask, noninvasive and invasive ventilation), and prognosis of the patients were recorded. The percentage of lung involvement in High Resolution Computed Tomography (HRCT) was also reviewed as reported by expert radiologist by using previous studies.(11, 12)Patients were divided into five groups based on the history of using different types of immunosuppressant drugs (prednisolone; methotrexate (MTX); hydroxychloroquine (HCQ); biologic agents including \u0026nbsp;etanercept, infliximab and rituximab; and other traditional disease-modifying anti-rheumatic drugs(DMARDs) including mycopholate mofetil, azathioprine, cyclosporine, cyclophosphamide, leflunomide and tacrolimus).Mean \u0026plusmn; standard deviations (SD) of O2sat in the air room, \u0026nbsp;lung parenchymal involvement and the percentage \u0026nbsp; of the presence of dyspnea, hospital admission, noninvasive and invasive ventilation, and mortality rate were compared between the users and non- users of these five immunosuppressant drugs.\u003c/p\u003e\n\u003cp\u003eThe presence of two out of the three risk factors: 1) lung involvement \u0026ge; 50% in HRCT(13) , 2) O2saturation\u0026le; 88%(14), \u0026nbsp;and 3) the need for noninvasive or invasive ventilation or death due to COVID-19infection was defined as severe disease.\u003c/p\u003e\n\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n\u003cp\u003eWe estimated proportions and means\u0026plusmn;SD to describe the data. 95%confidence interval (CI) of prevalence was estimated. Independent t-test and chi-square test were used. The effect of confounding variables was controlled by using multivariable logistic regression. Two logistic regression models were fitted to assess the correlates of severe COVID-19 categories. The significance level was setat0.05. Stata11.2 software (StataCorp. LP) and SPSS version 21 were used for data analysis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOf1000subjects, 981(male =217, female=764) were included in this study.\u003c/p\u003e\n\u003cp\u003eThe ratio of people who were infected with COVID-19 (COVID- 19+) to those who were not infected (COVID-19- ) was 1.2/1(539/442). The rate of hospital admission was 48.05% (number (n)=259) and 61 patients died due to severe illness.\u003c/p\u003e\n\u003cp\u003eThe underlying rheumatologic diseases in this population were rheumatoid arthritis (RA)(n=403; 41.1%), vasculitis including Wegner, Bechet, giant cell arthritis, Churg Struss, Takayasu arteritis 21.3(n=209),) systematic lupus erythematous 20.9(n=205), seronegative spondyloarthritis4.7(n=46, uveitis 4.5(n=44),) scleroderma3.7(n=36, Sjogren 1.9(n=19), myositis 1.1(n=11), sarcoidosis 0.5(n=5), and undifferentiated connective tissue disease0.3(n=3).Nonspecific symptoms such as fever, fatigue, anorexia, and insomnia were reported by almost 86.46% of COVID-19+ patients. \u0026nbsp;The prevalence of the symptoms of respiratory tract infection and gastrointestinal involvement was 76.8 and 33.58, respectively.\u003c/p\u003e\n\u003cp\u003eOxygen saturation in the room temperature ranged from 52%to 98% with mean\u0026plusmn;SD of 88.80\u0026plusmn;7.65 among COVID-19 +patients. The mean of total lung involvement in HRCT was 29.45\u0026plusmn;27.36in the affected patients.\u003c/p\u003e\n\u003cp\u003eIn the COVID-19+ subjects, presence of HTN (p.value:0.007) and DM(P=0.001) was significantly more than COVID-19- patients. Consumption of prednisolone was statistically more prevalent in COVID+-19 patients (n=403(74.8 %), 95%CI: 71.33-78.67 vs. n=274(62%), 95%CI: 61.95-62.05). (P\u0026lt;0.001) However, MTX usage was lower in COVID-19+ (n=352(65.3%), 95%CI: 60.98-69.02) in contrast to COVID-19- population (n=332(75.1%), 95%CI: 70.96-79.04). (P =0.001) (Table1)\u003c/p\u003e\n\u003cp\u003eMean\u0026plusmn;SD of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and lactate dehydrogenase (LDH) were 55.30\u0026plusmn;34.31, 60.13\u0026plusmn;30.90 and 703.69\u0026plusmn;338.42 in COVID-19 patients. Presence of severe COVID-19 infection features was compared between users and non-users of different immunosuppressant agents. (Table 2) Presence of respiratory failure and lung involvement was significantly higher in subjects who used prednisolone. The rate of these complications was significantly lower in MTX and users of biologic agents.\u003c/p\u003e\n\u003cp\u003eAccording to multivariable analyses, increasing age (OR:1.034,95%CI (1.015-1.053)) and using prednisolone prior to COVID-19infection (OR:2.52,95%CI (1.192-4.255)) were associated with severe disease. Pervious use of MTX (OR: 0.348, 95%CI (0.210-0.575)) and biologic drugs (OR:0.332,95%CI (0.159-0.694)) had protective effect on the severity of the disease. Other traditional DMARDs had no direct effect on the severity of COVID-19 infection. (Table3)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCytokine storm has been considered as a causative factor in the pathogenesis of COVID-19 infection. Inflammatory cytokines such as IL-6, IL-1, and TNF-α in the infection of COVID-19 are very similar to the cytokines involved in the development of rheumatic diseases.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Considering the background of abnormal immune response and the use of various immunosuppressants in patients with rheumatic diseases, it is necessary to investigate the characteristics of COVID-19 and its consequences in this population.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) In the current survey among 981 rheumatic patients in Shiraz, Fars, Iran, 539(54.94%) subjects were infected with COVID-19. Use of prednisolone was associated with higher rates of infection and poor outcome. However, MTX and biologic agents had a lower rate of infection, milder clinical features, and better outcome in our study.\u003c/p\u003e \u003cp\u003eIn previous studies, the risk of COVID-19 infections was considered high in rheumatic patients due to dysregulation of the immune system and use of immunosuppressant agents which increase the risk of opportunistic infections(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). JAK2 inhibitors, anti-TNF agents and glucocorticoids have been considered as the risk factor for the severity of the disease and ARDS in some studies.(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)However, this view has been changed with the identification of the role of cytokines and auto-inflammation in the pathogenesis of COVID-19 in recent studies.(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eHydroxychloroquine, which was first regarded as one of the useful therapies in COVID-19 patients, had no protective effect in our investigation. In Rentschet al.\u0026rsquo;s study, among 194637 patients with diagnosis of RA and SLE, no statistically significant difference was detected between prior users and non-users of hydroxychloroquine.(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)Post-treatment with hydroxychloroquine had also no significant effect on the rate of hospitalization and better clinical outcome.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCorticosteroid is defined as an effective treatment in severe COVID-19 infection (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).However, the effect of the pervious use of these agents on the severity and outcome of COVID-19 is still not clear. In a cohort study done by Ennio Giulio Favallietal., prior use of corticosteroid even in low dose had a potentially adverse outcome (OR ranging from 1.23 to 3.2).(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)These findings were compatible with our study results. Based on COVID-19 Global Rheumatology Alliance (GRA), corticosteroids were associated with unfavorable outcome in rheumatoid patients with COVID-19infection. However, disruption of steroid during acute phase of infection was not recommended in this study.(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003cp\u003ePrior use of biologic DMARDS was accompanied with lower rate of COVID-19 infection and better outcome in our study. TNF is the most pro-inflammatory cytokine- mediating immune factors. Anti-TNF antibody agents may be effective in COVID-19 infection by modulation of the immune system and expression of angiotensin converting enzyme 2 (ACE2) receptor.(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)It was shown that the risk of COVID-19 infection in patients with rheumatic disease son biologic DMARDs was the same as the general population and was accompanied with favorable outcomes.(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) Prior use of biologic DMARDs was also not associated with higher rate of COVID-19 infection, hospital admission, and mortality rate.(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn our study, pre-exposure to MTX was associated with better outcome, lower mortality rate, and the need for invasive ventilation 0.348, 95%CI (0.210\u0026ndash;0.575). In addition to anti-inflammatory effect of MTX, this might be due to the effect of MTX on inhibition of dihydrofolate reductase pathway the efficiency of which on infectious disease had been recently discovered.(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) Further clinical trials are needed to determine the exact effect of MTX on COVID-19 infection.\u003c/p\u003e \u003cp\u003eIn the current study, other traditional DMARDs including mycophenolate mofetil, azathioprine, cyclosporine, cyclophosphamide, leflunomide, and tacrolimus had no effect on COVID-19infection and its severity. Studies on the effect of prior use of this class of drugs on COVID-19 are limited and have yielded conflicting results.(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)Larger sample size might be needed for evaluation of their consequence and their mechanism on COVID-19, which is still unknown.(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThis is the first study in the south of Iran that investigated the clinical characteristics of COVID-19 among patients with different types of rheumatoid diseases who used immunosuppressant agents. One of the most important strengths of the current study was the investigation of the effects of different groups of immunosuppressant drugs with various mechanisms on different aspects of COVID-19 infection.\u003c/p\u003e \u003cp\u003eLack of sufficient laboratory data was an important limitation in our study, and further investigation is recommended to determine the level of inflammatory markers in the presence of immunosuppressant agents. Due to the fact that this was a retrospective study, the dosage and duration of the drugs were not known. The sample size in different drug subgroups was also not enough to compare with other subgroups.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe characteristics, management, and treatment of COVID-19 infection in patients with auto- immune rheumatoid disease who are on immunosuppressant agents are still challenging. In the current study, previous treatment with corticosteroids was associated with increased incidence, poor prognosis, and mortality. In addition, pre-exposure to MTX or biologic agents such as anti-TNF and anti-CD20 had a protective effect against coronavirus. Further meta-analysis and systematic review in larger population is needed to accurately determine the effect and mechanism of these drugs on this new viral illness.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eThe authors received no financial support for the research or publication of this article\u003c/p\u003e\n\u003ch2\u003eConsent for publication:\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch2\u003eCompeting interests:\u003c/h2\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eF.S: data gathering, analysis ,drafted the manuscript and revised the manuscript E.A: designing ,data gathering the research and revised the manuscript\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors would like to thank Shiraz University of Medical Sciences, Shiraz, Iran and also Center for Development of Clinical Research of Namazi Hospital and Dr. Nasrin Shokrpour for editorial assistance.\u003c/p\u003e\u003ch2\u003eDeclarations of Interest:\u003c/h2\u003e\n\u003cp\u003eNone declared\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHabibzadeh P, Stoneman EK. The novel coronavirus: a bird\u0026apos;s eye view. The international journal of occupational and environmental medicine. 2020;11(2):65.\u003c/li\u003e\n\u003cli\u003eGe E, Li Y, Wu S, Candido E, Wei X. Association of pre-existing comorbidities with mortality and disease severity among 167,500 individuals with COVID-19 in Canada: A population-based cohort study. PLoS One. 2021;16(10):e0258154.\u003c/li\u003e\n\u003cli\u003eOsuchowski MF, Winkler MS, Skirecki T, Cajander S, Shankar-Hari M, Lachmann G, et al. The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. The Lancet Respiratory Medicine. 2021;9(6):622-42.\u003c/li\u003e\n\u003cli\u003eMehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The lancet. 2020;395(10229):1033-4.\u003c/li\u003e\n\u003cli\u003eLiu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? Journal of autoimmunity. 2020;111:102452.\u003c/li\u003e\n\u003cli\u003eLuo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID‐19: a single center experience. Journal of medical virology. 2020;92(7):814-8.\u003c/li\u003e\n\u003cli\u003eGuaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R. Tocilizumab in patients with severe COVID-19: a retrospective cohort study, Lancet Rheumatology, Published Online June 24, 2020. 2020.\u003c/li\u003e\n\u003cli\u003eSparks JA, Wallace ZS, Seet AM, Gianfrancesco MA, Izadi Z, Hyrich KL, et al. Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry. Annals of the rheumatic diseases. 2021;80(9):1137-46.\u003c/li\u003e\n\u003cli\u003eFavalli EG, Ingegnoli F, De Lucia O, Cincinelli G, Cimaz R, Caporali R. COVID-19 infection and rheumatoid arthritis: Faraway, so close! Autoimmunity reviews. 2020;19(5):102523.\u003c/li\u003e\n\u003cli\u003eMonti S, Balduzzi S, Delvino P, Bellis E, Quadrelli VS, Montecucco C. Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies. Annals of the rheumatic diseases. 2020;79(5):667-8.\u003c/li\u003e\n\u003cli\u003eParry AH, Wani AH, Shah NN, Yaseen M, Jehangir M. Chest CT features of coronavirus disease-19 (COVID-19) pneumonia: which findings on initial CT can predict an adverse short-term outcome? BJR| Open. 2020;2:20200016.\u003c/li\u003e\n\u003cli\u003eSun D, Li X, Guo D, Wu L, Chen T, Fang Z, et al. CT quantitative analysis and its relationship with clinical features for assessing the severity of patients with COVID-19. Korean journal of radiology. 2020;21(7):859.\u003c/li\u003e\n\u003cli\u003eRuch Y, Kaeuffer C, Ohana M, Labani A, Fabacher T, Bilbault P, et al. CT lung lesions as predictors of early death or ICU admission in COVID-19 patients. Clinical Microbiology and Infection. 2020;26(10):1417. e5-. e8.\u003c/li\u003e\n\u003cli\u003ePetrilli C, Jones S. yang J, rajagopalan H, o\u0026rsquo;Donnel l, Chernyak y, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New york City: prospective cohort study. BMJ. 2020.\u003c/li\u003e\n\u003cli\u003eGianfrancesco MA, Hyrich KL, Gossec L, Strangfeld A, Carmona L, Mateus EF, et al. Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries. The Lancet Rheumatology. 2020;2(5):e250-e3.\u003c/li\u003e\n\u003cli\u003eChoudhary S, Sharma K, Silakari O. The interplay between inflammatory pathways and COVID-19: A critical review on pathogenesis and therapeutic options. Microbial pathogenesis. 2021;150:104673.\u003c/li\u003e\n\u003cli\u003eKilian A, Chock YP, Huang IJ, Graef ER, Upton LA, Khilnani A, et al., editors. Acute respiratory viral adverse events during use of antirheumatic disease therapies: a scoping review. Seminars in arthritis and rheumatism; 2020: Elsevier.\u003c/li\u003e\n\u003cli\u003eSantos CS, F\u0026eacute;rnandez XC, Morales CM, \u0026Aacute;lvarez ED, Castro C\u0026Aacute;, Robles AL, et al. Biological agents for rheumatic diseases in the outbreak of COVID-19: friend or foe? RMD open. 2021;7(1):e001439.\u003c/li\u003e\n\u003cli\u003eRentsch CT, DeVito NJ, MacKenna B, Morton CE, Bhaskaran K, Brown JP, et al. Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform. The Lancet Rheumatology. 2021;3(1):e19-e27.\u003c/li\u003e\n\u003cli\u003eSelf WH, Semler MW, Leither LM, Casey JD, Angus DC, Brower RG, et al. Effect of hydroxychloroquine on clinical status at 14 days in hospitalized patients with COVID-19: a randomized clinical trial. Jama. 2020;324(21):2165-76.\u003c/li\u003e\n\u003cli\u003eVan Paassen J, Vos JS, Hoekstra EM, Neumann KM, Boot PC, Arbous SM. Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. Critical Care. 2020;24:1-22.\u003c/li\u003e\n\u003cli\u003eFavalli EG, Bugatti S, Klersy C, Biggioggero M, Rossi S, De Lucia O, et al. Impact of corticosteroids and immunosuppressive therapies on symptomatic SARS-CoV-2 infection in a large cohort of patients with chronic inflammatory arthritis. Arthritis research \u0026amp; therapy. 2020;22:1-12.\u003c/li\u003e\n\u003cli\u003eGianfrancesco M, Hyrich KL, Al-Adely S, Carmona L, Danila MI, Gossec L, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Annals of the rheumatic diseases. 2020;79(7):859-66.\u003c/li\u003e\n\u003cli\u003ePerricone C, Triggianese P, Bartoloni E, Cafaro G, Bonifacio AF, Bursi R, et al. The anti-viral facet of anti-rheumatic drugs: lessons from COVID-19. Journal of Autoimmunity. 2020;111:102468.\u003c/li\u003e\n\u003cli\u003eQuartuccio L, Valent F, Pasut E, Tascini C, De Vita S. Prevalence of COVID-19 among patients with chronic inflammatory rheumatic diseases treated with biologic agents or small molecules: a population-based study in the first two months of COVID-19 outbreak in Italy. Joint bone spine. 2020;87(5):439-43.\u003c/li\u003e\n\u003cli\u003eMurray K, Quinn S, Turk M, O\u0026rsquo;Rourke A, Molloy E, O\u0026rsquo;Neill L, et al. COVID-19 and rheumatic musculoskeletal disease patients: infection rates, attitudes and medication adherence in an Irish population. Rheumatology. 2021;60(2):902-6.\u003c/li\u003e\n\u003cli\u003eYousaf A, Gayam S, Feldman S, Zinn Z, Kolodney M. Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors or methotrexate: a multicenter research network study. Journal of the American Academy of Dermatology. 2021;84(1):70-5.\u003c/li\u003e\n\u003cli\u003ePablos JL, Galindo M, Carmona L, Lled\u0026oacute; A, Retuerto M, Blanco R, et al. Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study. Annals of the rheumatic diseases. 2020;79(12):1544-9.\u003c/li\u003e\n\u003cli\u003eMikuls TR, Johnson SR, Fraenkel L, Arasaratnam RJ, Baden LR, Bermas BL, et al. 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Arthritis \u0026amp; rheumatology. 2020;72(9):e1-e12.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cem\u003eTable 1.\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;Demographic and Clinical Characteristics of the Participants\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\" dir=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"721\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003eTotal\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(n\u003csup\u003ea\u003c/sup\u003e=981)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003eCOVID-19(+hx\u003csup\u003ea\u003c/sup\u003e)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(n=539)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003eCOVID-19(-hx) (n=442)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eAge(Mean \u0026plusmn;SD in years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e49.65\u0026plusmn;14.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e50.85\u0026plusmn;14.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e48.11\u0026plusmn;14.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.647\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp dir=\"LTR\"\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp dir=\"LTR\"\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e217(22.1)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(19.56-24.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e108(20.0)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(16.74-23.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e109(24.7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(20.71-28.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.049\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp dir=\"LTR\"\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e764(77.9)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(75.15-80.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e431(80)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(76.33-83.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e333(75.3)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(71.05-79.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eMedication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 487px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003ePrednisolone\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e677(69)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(66.1-71.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e403(74.8)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(71.33-78.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e274(62.0)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(61.95-62.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eMethotrexate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e684(69.7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(67.12-72.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;352(65.3)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(60.98-69.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e332(75.1)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(70.96-79.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eAnti-TNF\u0026alpha;\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e171(17.4)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(14.62-19.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e97(18.0)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(14.75-21.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e74(16.7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(13.51-20.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.334\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eAzathioprine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e180(18.3)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(15.58-20.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e76(14.1)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(11.06-16.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e104(23.5)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(20.41-27.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eMycophenolic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e82(8.4)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(6.26-9.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e48(8.9)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(6.59-11.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e34(7.7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(5.75-10.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.286\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eCyclosporine\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e66(6.7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(5.43-8.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e26(4.8)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(3.19-6.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e40(9)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(6.58-11.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eHydroxychloroquine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e173(17.6)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(15.62-20.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e101 (18.7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(15.70 -22.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e72(16.3)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(12.88-19.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.180\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eRituximab\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e54(5.5)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(4.16-7.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e34(6.3)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(3.94-8.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e20(4.5)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(3.24-6.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.140\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eLeflunomide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e65(6.6)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(6.19-7.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e34(6.3)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(3.94-8.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e31(7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(4.84-9.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.376\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eTacrolimus\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e33(3.4)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(2.33-4.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e13(2.4)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(1.29-4.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e20(4.5)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(3.24-6.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eSulfasalazine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e164(16.7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(14.67-19.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e84(15.6)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(12.94-19.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e80(18.1)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(14.75-21.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.167\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eComorbid conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 487px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eIschemic heart disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e56(5.7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(4.55-7.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e40(7.4)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(4.79-9.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e16(3.6)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(2.42-5.58)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;176(17.9)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(15.60-20.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e123(22.8)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(19.45-26.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e53(12)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(9.26-14.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eDiabetes Mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e99(10.1)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(8.12-11.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e70(13)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(10.16-15.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e29(6.6)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(4.91-9.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eThyroid disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e89(9.1)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(7.20-10.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e51(9.5)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(6.53-11.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e38(8.6)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(6.63-11.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eRheumatologic diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 487px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eRheumatoid arthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e403(41.1)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(37.98-44.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e252(46.8)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(42.48-51.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e151(34.2)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(29.75-38.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eSystemic lupus erythematosus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e205(20.9)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(18.39-7.123.582)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e120(22.3)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(18.82-26.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e85(19.2)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(15.66-23.22)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.135\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eVasculitis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e209(21.3)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(18.78-24.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e72(13.4)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(10.60-16.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e137(31)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(26.71-35.54)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eSeronegative spondyloarthropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e46(4.7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(3.45-6.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e27(5)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(3.33-7.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e19(4.3)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(2.61-6.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eUveitis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e44(4.5)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(3.28-5.97)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e22(4.1)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(2.58-6.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e22(5)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(3.15-7.44)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.301\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 234px;\"\u003e\n \u003cp dir=\"LTR\"\u003eSystemic sclerosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp dir=\"LTR\"\u003e36(3.7)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(2.58-5.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp dir=\"LTR\"\u003e22(4.1)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(2.58-6.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp dir=\"LTR\"\u003e14(3.2)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(1.74-5.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.280\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 dir=\"LTR\"\u003e\u003csup\u003ea\u003c/sup\u003eAbbreviations: hx, history; TNF\u0026alpha;, tumor necrosis factor \u0026nbsp;alpha.\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cem\u003eTable2:Severe COVID-19 Infection Features in The Presence of DifferentImmunosuppressants\u003c/em\u003e\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"\" dir=\"\"\u003e\n \u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"784\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp dir=\"LTR\"\u003eOther traditional DMARDs\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eN=181\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp; \u0026nbsp;Biologic agents\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eN=128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003eHCQ\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eN=101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp dir=\"LTR\"\u003eMTX\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eN=352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp dir=\"LTR\"\u003ePredniselone\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eN=403\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003eP\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003eNeg\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ehx\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003ePos\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ehx\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003eP\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003eNeg\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ehx\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp dir=\"LTR\"\u003ePos\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ehx\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp dir=\"LTR\"\u003eP\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003eNeg\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ehx\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003ePos\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ehx\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003eP\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003eNeg\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ehx\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003ePos\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ehx\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003eP\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003eNeg\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ehx\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003ePos\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003ehx\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e0.084\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e41.3\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(35.89-46.11)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e34.8\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(28.04-41.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e42.8\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(38.21-47.79)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e27.3\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(12.26-27.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp dir=\"RTL\"\u003e0.037\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e37.2\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(32.47-41.53)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e47.5\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(38.21-57.79)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e52.4\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(44.82-59.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e32.1\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(27.11-36.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e28.7\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(21.37 -36.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e42.7\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(38.17-\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e47.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp dir=\"LTR\"\u003eDyspnea prevalence%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e0.068\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e50.6\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(45.81-56.19)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e43.3\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(35.74-50.26)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e54.5\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(50.18-59.82)\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp dir=\"RTL\"\u003e27.6\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(20.22.35.78)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e47.1\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(42.32-51.58)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e52.5\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(42.21-61.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e66.8\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(60.23-73.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e38.2\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e)\u003c/span\u003e32.91-43.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e29.4\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(21.32-36.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e54.5\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(49.12-\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e58.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp dir=\"LTR\"\u003eHospital admission prevalence%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e7.5\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(5.26-10.73)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e4.4\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(0.10-7.00)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e7.8\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(5.40-10.59)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp dir=\"RTL\"\u003e8.6\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(-0.63-4.63)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e7.1\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(4.59-9.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e4\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(0.17-7.82)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e11.2\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(6.45-15.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e4\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(1.95-6.05)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e2.2\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(-0.47-4.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e7.9\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(5.35-10.65)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp dir=\"LTR\"\u003eNoninvasive ventilatin prevalence%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e0.180\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e13.7\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(10.44-17.56)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e10.5\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(5.52-14.47)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e14.8\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(11.56-18.44)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp dir=\"RTL\"\u003e5.5\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(1.05-8.95)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.522\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e12.6\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(9.89-16.11)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e12.9\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(6.43-19.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e20.3\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(14.22-25.78)\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e8.5\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(6.07-11.93)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e6.6\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(2.80-11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e14.6\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(11.54-18.46)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eInvasive ventilatin prevalence%\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e0.96\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e31.06\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e27.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e26.11\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e26.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e32.08\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e27.75\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp dir=\"LTR\"\u003e19.08\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026plusmn;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e2316\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp dir=\"RTL\"\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e30.97\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e27.80\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e23.95\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e24.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e38.65\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026plusmn;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e28.3\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e23.49\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e25.05\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e21.98\u0026plusmn;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e24.29\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e31.67\u0026plusmn;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e27.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp dir=\"LTR\"\u003eLung involvement mean\u0026plusmn;SD,%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e0.008\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e88.14\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e6.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e90.13\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e6.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e88.06\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e8.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp dir=\"RTL\"\u003e91.30\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e5.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.251\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e88.61\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e7.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e89.58\u003c/span\u003e\u0026plusmn;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e7.33\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e86.68\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e8.58\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e90.03\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026plusmn;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e6.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e90.28\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026plusmn;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e6.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e88.33\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026plusmn;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e7.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp dir=\"LTR\"\u003eO2 sat\u003csup\u003ea\u003c/sup\u003emean\u0026plusmn;SD,%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e0.388\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e12.3\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(8.59-15.41)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e9.4\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(4.73-13.27)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e13.4\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(9.70-16.30)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp dir=\"RTL\"\u003e4.7\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(2.37-7.63)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp dir=\"RTL\"\u003e0.521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e11.4\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(8.02-13.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e10.9\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(4.89-17.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e18.7\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(13.40-24.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e7.4\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(4.26-9.74)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"RTL\"\u003e5.9\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e(2.03-\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e9.96)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp dir=\"LTR\"\u003e13.2\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(9.70-16.30)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp dir=\"LTR\"\u003ePrevalence of \u0026nbsp;death%\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 dir=\"LTR\"\u003e\u003csup\u003ea\u003c/sup\u003eAbbreviations: Mtx, methotrexate, HCQ,hydroxychloroquin; poshx: positive history; Neg hx, negative history; P, P-value; o2 sat, oxygen saturation.\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u003csup\u003e*\u003c/sup\u003eother drugs including: \u0026nbsp;cellcept, azathioprine, cyclosporine, cyclophosphamide, leuflonamide and tacrolimus.\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cem\u003eTable3:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eFactors Modulating COVID-19 Infection\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\" dir=\"\"\u003e\n \u003ctable dir=\"\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"662\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003eLower- Upper 95% CI\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"LTR\"\u003eAdjusted .\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eOdds ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eCrude.\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eOdds ratio\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"LTR\"\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp dir=\"LTR\"\u003eCoefficient (SE)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp dir=\"LTR\"\u003eCoefficient\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"LTR\"\u003eVariables\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.015-1.053\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.034\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.054\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eAge\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.493-1.726\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.923\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.752\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.801\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.320\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e-0.080\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eMale\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.192-4.255\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e2.52\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e2.059\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.012\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e0.325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.812\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003ePrednisolon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.210-0.575\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.348\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.332\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.256\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e-1.056\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eMethotrexate\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.159-0.694\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.332\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.232\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.003\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.377\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e-1.103\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eBiologic drugs\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.248-1.273\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.561\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.426\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.167\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.418\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e-0.577\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"LTR\"\u003eAzathioprine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.322-1.153\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.609\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.714\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.128\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.326\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e-0.496\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eHydroxychloroquin\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.522-2.680\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.183\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.042\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.687\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.417\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.168\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eCellcept\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.446-3.575\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.263\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.050\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.660\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.531\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.234\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eCyclosporine\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.319-2.080\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.815\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.899\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.668\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.478\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e-0.205\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eLeuflonamide\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.057-4.090\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.483\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.285\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.505\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.089\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e-0.727\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eTacrolimus\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.812-2.936\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.544\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e2.732\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.185\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.328\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.434\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eDiabetes mellitus\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.932-2.738\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e1.598\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e3.218\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.088\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.275\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.469\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eHypertention\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.444-2.224\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.994\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e3.990\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.988\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.411\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e-0.006\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eIHD\u003csup\u003ea\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.119-0.887\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.325\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.353\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp dir=\"RTL\"\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.513\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e-1.125\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eThyroid disease\u0026nbsp;\u003c/span\u003e\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 dir=\"LTR\"\u003e\u003csup\u003ea\u003c/sup\u003eAbbreviations: CI, confidence interval; IHD, ischemic heart disease.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-internal-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Internal Medicine](https://ejim.springeropen.com/)","snPcode":"43162","submissionUrl":"https://submission.springernature.com/new-submission/43162/3","title":"The Egyptian Journal of Internal Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, immunosuppressants, rheumatoid patients","lastPublishedDoi":"10.21203/rs.3.rs-6547229/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6547229/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackgrounds\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eCytokine storm has been considered as the main pathogenesis in COVID-19 patients with severe disease. Inflammatory cytokines, such as interleukin-6(IL-6), IL-1, and tumor necrosis factor alpha (TNF-α) released from the lung epithelium in COVID-19 infection are very similar to cytokines which are released in inflammatory rheumatic diseases. Immunosuppressive drugs are the cornerstone of treatment in many rheumatologic diseases. Prolonged use of these agents might result in change in the clinical characteristics of these individuals with COVID-19.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eTo determine the clinical findings and disease severity of COVID-19 infection in patients with rheumatologic diseases who were on immunosuppressive therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eWe retrospectively investigated 1000 subjects who were more than 18years old with rheumatologic diseases on immunosuppressive therapy in the recent three months. Demographic data, rheumatic disease characteristics, medications, and presence of any co- morbid conditions were documented by detail. Presence of severe COVID-19 infection features were compared between users and non-users of different immunosuppressant agents. Multivariable logistic regression was applied, and adjusted odd ratio (OR) and its 95% CI were estimated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003e539 subjects had positive history of COVID-19 (COVID-19+). Pre-exposure to prednisolone was associated with severe disease (OR: 2.52, 95%CI (1.192-4.255)). Pervious use of MTX (OR: 0.348, 95%CI (0.210-0.575)) and biologic drugs (OR: 0.332, 95%CI (0.159-0.694)) had protective effect on the severity of the disease. Other traditional disease modifying anti-rheumatic drugs (DMARD) had no clinical effect on the outcome of COVID-19 infection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eIn the current study, among rheumatoid patients on immunosuppressants, previous treatment with corticosteroids was associated with increased incidence, poor prognosis, and increased mortality. Pre-exposure to MTX or biologic agents such as anti-TNF and anti-CD20 had protective effect against coronavirus. Further meta-analysis and systematic review in large population is needed to accurately determine the effect and mechanism of these drugs on this new viral illness.\u003c/p\u003e","manuscriptTitle":"Investigation of Clinical Characteristics of COVID-19 Infection in Rheumatoid Patients on Immunosuppressive Drugs: A Cross-sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-30 07:43:39","doi":"10.21203/rs.3.rs-6547229/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-21T16:49:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-13T05:31:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97336604209224824939411419211264500706","date":"2025-06-11T04:20:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-29T20:54:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"336274696786060616336878152998630472189","date":"2025-05-29T20:29:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-27T23:43:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-05T19:03:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-05T16:30:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Egyptian Journal of Internal Medicine","date":"2025-04-28T11:01:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-internal-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Internal Medicine](https://ejim.springeropen.com/)","snPcode":"43162","submissionUrl":"https://submission.springernature.com/new-submission/43162/3","title":"The Egyptian Journal of Internal Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e61dc4d3-f075-4c7a-9cb0-121149f8d593","owner":[],"postedDate":"May 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-08-21T05:53:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-30 07:43:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6547229","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6547229","identity":"rs-6547229","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}