key: cord-0986573-ev8m7e6m authors: Assar, Shirin; Mohamadzadeh, Dena; Pournazari, Mehran; Soufivand, Parviz title: Frequency, characteristics and outcome of corona virus disease 2019 (COVID-19) infection in Iranian patients with rheumatic diseases date: 2021-12-10 journal: The Egyptian Rheumatologist DOI: 10.1016/j.ejr.2021.12.002 sha: 308d950ca1f688abb25b040efa91992eadf6ba5e doc_id: 986573 cord_uid: ev8m7e6m Aim of the work to investigate the frequency, clinical characteristics and outcome of severe acute respiratory syndromecoronavirus 2(SARS-CoV-2) infection in rheumatic diseases patients. Patients and methods One thousand patients with rheumatic diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (SpA), systemic sclerosis (SSc), Sjögren’s syndrome (SS), Behçets disease (BD), vasculitis, idiopathic inflammatory myositis (IIM), relapsing polychondritis, sarcoidosis and antiphospholipid syndrome (APS) were studied. The following data were collected: age, sex, disease diagnosis, rheumatic disease medication. Rheumatic diseases patients were divided into two groups of infected and non-infected patients with COVID-19 and collected data were compared. Results The 1000 patients mean age was 43.4±13 years and 84.1% were females. The main diagnosis was RA (37.1%), followed by SLE (23.8%), SpA (13.4%), SSc (12.4%), vasculitis, BD and rhupus in 2.4%, 2.3% and 2.2% respectively, SS and SSc in 0.7% each. Most patients were taking glucocorticoids (78.4%). A large majority of patients were taking at least one of the cDMARDs. 16.1% were taking biologic therapy. 221 rheumatic diseases patients with COVID-19 were identified. Of these, 38 patients (17.2%) were hospitalized and 9 patients (4.1%) died. No significant difference was observed for compared variables in patients with and without COVID-19 except for prednisolone >20 mg/d (0.64% vs 2.26%;p=0.048). Conclusion Most rheumatic diseases do not seem to be a risk factor for developing COVID-19 infection and despite immunosuppressive therapies, there is no poorer outcome. Only, patients using prednisolone >20mg/d are at higher risk of developing COVID-19 infection. Intrinsic immunological changes can produce chronic inflammation in multiple organs in autoimmune inflammatory disorders. The disorders themselves, as well as many of their treatments, are related to a higher risk of developing serious infections [1] [2] [3] [4] . There is growing evidence of an association between COVID-19 infection and the development of autoimmune diseases [5] with a remarkable impact on the quality of life of those patients [6] . Whether patients with rheumatic diseases are more vulnerable to corona virus disease 2019 infection is still unknown and the possible susceptibility of rheumatic patients for more severe COVID-19 infection or a poorer outcome has raised serious concerns [7] . Several disease modifying anti-rheumatic drugs (DMARDs) with immune-modulating actions such as hydroxychloroquine and tocilizumab may have a therapeutic or preventative effect on the viral infection or the consequent cytokine storm syndrome seen in COVID-19 [8, 9] .Patients with rheumatoid arthritis (RA) faced remarkable difficulty to obtain their medications during the pandemic with subsequent change in their disease status [10] . During the pandemic, low dose rituximab is an effective treatment option in the treatment of RA [11] . Patients with systemic rheumatic disease and low rate of acceptability to receive the COVID- 19 vaccine, should be encouraged [12] as patient-reported adverse events were typical of those reported in the general population with a relatively low frequency of flare requiring medications [13] . Therefore patients with rheumatic disease represent an interesting study group because, on the one hand, this population is potentially more susceptible to severe COVID-19 infection due to the rheumatic disease and its treatment, on the other hand, many of these patients are receiving immune modulating medications, which have the potential to treat COVID-19 infection and improve prognosis. The aim of this study was to describe the characteristics, clinical manifestations and outcomes of rheumatic patients diagnosed with COVID-19 infection and also to determine the prevalence of COVID-19 infection in the study population and answer to the question whether this specific population have more susceptibility for COVID-19 and poorer outcome. This study was conducted at theoutpatient clinics and inpatient Rheumatology ward of Emam Reza and Golestan Hospitals in Kermanshah, Iran. Between Feb 18 and Aug 22, 2020, data was collected from 1000 patients with rheumatic diseases including systemic lupus erythematosus (SLE) [14] , rheumatoid arthritis (RA) [15] , psoriatic arthritis (PsA) [16] , axial spondyloarthritis (SpA) [17] , systemic sclerosis (SSc) [18] , Sjögren's syndrome [19] ,Behçets disease (BD) [20] , vasculitis, idiopathic inflammatory myositis (IIM) [21] , relapsing infection. Patients were divided into those infected or non-infected during six months of the survey. In cases with COVID-19 the following clinical symptoms were recorded: persistent fever > 37.5°C,myalgia, chills, dyspnea, malaise, non-productive cough, anosmia, ageusia,headache, loss of appetite, sore throat,diarrhoea, abdominal pain, sweating, rhinorrhea,nausea and vomiting, arthritis and arthralgia, deterioration of the rheumatic disease, confusion, hemiplegia, eye redness and skin rash. COVID-19 clinical outcomes were determined by assessing the recovery with and without hospitalization, intensive care admission and death. Variables were reported as frequency, percentage, mean and standard deviation (SD). Mann-Whitney, Chi-square and Fisher's exact tests were used to compare variables. Odds ratio (OR) with 95% confidence intervals (CI) were determined. Significance was defined at a p<0.05. One thousand rheumatic diseases patients were studied with a mean age of 43.4±13 years and were 841 (84.1%) females. RA was the most common diagnosis (37.1%), followed by SLE A thousand rheumatic diseases patients were investigated and 221 (22.1 %) were diagnosed with COVID-19 infection. Of these, 17.2% were hospitalized, 3.6% were admitted to ICU, and 4.1% died.In line, the frequency of COVID-19 infection was not different from that estimated in the reference general population [22] . However, in this survey, onlysymptomatic rheumatic patients who had at least one positive PCR test for Covid-19, or symptomatic individuals who had close contact with an infected person were considered as COVID-19 infected.Yet, asymptomatic individuals may also be infected and the sensitivity of PCR tests to diagnose the COVID-19 infection is not definitive implying that the presented frequency could be underestimated. The mortality rate was also consistent with the general population [23, 24] . Consistent with the current results, up to now, neither rheumatic diseases nor their treatments were associated with higher infection rates or worsening of COVID-19 outcomes [9, 25] . A previous study from the United States [26] showed higher rates of ICU admission and the need for mechanical ventilation among hospitalized patients suffering from rheumatic disease. The explanation might be the shortage of ICU beds in Iran within the time of the pandemic that led to a low rate of ICU admission. In concordance with Sun et al [24] and D'Silva et al [26] , the most frequently reported symptoms of COVID-19 infection were fever and chills, myalgia, dyspnea, malaise and cough; other symptoms like gastrointestinal symptoms were less common. Type of rheumatic disease, age and sex were similar between rheumatic patients with and without COVID-19 infection. Neither SLE patients nor RA, SpA, PsA, SSc, vasculitis, BD, IIM was more susceptible to COVID-19. While in a large Italian study reported that the prevalence of COVID-19 infection in patients with systemic autoimmune disorders was higher [27] . No association between prior steroids or biologic usage and susceptibility to COVID-19 was detected except for prednisolone dosage> 20 mg/ daily. In contrast, a previous study from Spain reported a greater prevalence of COVID-19 in patients on ts/bDMARDs therapy [28] . It should be noted that, at the time of conducting this work, two drugs: anti interleukin 6 and CTLA4-Ig, were not available for the treatment of rheumatic diseases patients in Iran; therefore therapeutic data resulting fromts/bDMARDs should be interpreted with caution. However, a protective effect of these two therapies against COVID-19 was shown [29, 30] .Analysis from a recent European registry [31] , revealed that rheumatic diseases patients who used glucocorticoids>10 mg/day were at higher risk of COVID-19 related hospitalization. In the present study, a vast majority of patients with COVID-19 were taking glucocorticoids (76.9%) despite that the hospitalization rate (17.2%) was not higher than the general population [32] . It was found that a significantly higher rate of patients using predisolone> 20mg/d, were infected with COVID-19 but not at higher risk of COVID-19 related hospitalization.The preventive or therapeutic effect of hydroxychloroquine (HCQ) in COVID-19 infections was suggested, but still controversial [33] . SLE patients that were under long-term treatment with HCQ and a large survey on rheumatic diseases patients showed that this drug does not have a preventive effect [34, 35] . Inconsistent with these studies, current findings indicate that a similar proportion of patients with and without COVID-19 infection used HCQ.Neither prior NSAIDs use nor DMARDs were associated with susceptibility to COVID-19. Most previous studies showed a similar result [28, 31, 36] . Our findings support the theory that the presence of other risk factors rather than the pre- This study had some limitations. First, we did not have a healthy control group to compare the prevalence and outcome of COVID-19 with the general population of our city. Therefore, the outcome and mortality rate was compared with previous global studies. In addition, due to national PCR test shortage a vast majority of patients were considered as COVID-19 infections just according to clinical symptoms and close contact history with an infected person or chest CT scan findings, and they were not confirmed with PCR testing. Finally, as mentioned above, we did not consider the asymptomatic patients in this survey. In conclusion, there is no significant association between type of rheumatic disease or medications and susceptibility to COVID-19 infection except for prednisolone>20 mg/ daily. The mortality rate in rheumatic patients was similar to the general population. Most rheumatic diseases does not seem to be a risk factor for developing COVID-19 infection, and despite immunosuppressive, and immunomodulatory therapies, there is no poorer outcome in these patients. These findings may be important for managing rheumatologic diseases during COVID-19 pandemic. There are no conflicts of interest stated by the authors. Funding:This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. SA conceived the idea and designed the study. All authors were responsible for data collection. DM was responsible for data analysis. SA and DM draft the article. All the authors read and approved the final manuscript. 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