key: cord-264610-kxebc12r authors: Chen, Yu; Dong, Yuanji; Cai, Shaozhe; Ye, Cong; Dong, Lingli title: Clinical characteristics of IgG4-RD patients infected with COVID-19 in Hubei, China date: 2020-05-16 journal: Semin Arthritis Rheum DOI: 10.1016/j.semarthrit.2020.04.015 sha: doc_id: 264610 cord_uid: kxebc12r OBJECTIVE: IgG4-related disease (IgG4-RD) is an immune-mediated multi-organ, chronic and progressive disease. Therefore, we conducted a study to investigate the susceptibility of COVID-19 in IgG4-RD patients in Hubei province, and to characterize the clinical manifestation of COVID-19 in IgG4-RD patients. METHODS: A follow-up system that includes over 200 IgG4-RD patients across the country during the past ten years. A total of ninety-one patients with IgG4-RD who live in Hubei, China were identified and responded to our survey. Medical history, clinical symptoms, laboratory tests, CT imaging, and treatment were obtained through a standardized data collection form, and then independently reviewed by two investigators. RESULTS: 2 of 91 cases were infected with COVID-19. Both of them were classified as moderate type. The symptoms such as fever and cough and radiologic features were similar to other COVID-19 patients. Neither of them episode recurrent of IgG4-RD nor progressed to severe or critical condition of COVID-19 under the condition of continuous oral low-dose of glucocorticoids. Besides, patient 2 took a long time for SARS-CoV-2 nucleic acid to turn negative. CONCLUSION: IgG4-RD patients may belongs to the susceptible population of COVID-19 infection, and thus need more careful personal protection. Early identification and properly treatment are very important to prevent IgG4-RD patients with COVID-19 from progression to severe condition. Coronavirus disease 2019 (COVID- 19) , first recognized in December 2019 [1] , rapidly spread to over 200 countries and territories. The causative agent was soon identified as a new strain of coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on February 11, 2020. According to the early transmission dynamics, the mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with a 95th percentile of the distribution at 12.5 days [2] . Common symptoms are fever, fatigue, myalgia, dry cough, shortness of breath and diarrhea [3] . Laboratory examination usually shows lymphopenia, elevated C-reactive protein and serum ferritin level, prolonged prothrombin time, and elevated lactate dehydrogenase (LDH) [3] . Typical chest computed tomographic (CT) findings include bilateral ground-glass opacity and multifocal patchy consolidation [4] . Advanced age (>60), male sex, and underlying comorbidities (high blood pressure, diabetes, coronary heart disease, etc.) are risk factors for severe disease and death from SARS-Cov-2 infection [5, 6] . IgG4-related disease (IgG4-RD), first identified in 2003, is an immune-mediated multi-organ, chronic and progressive disease characterized by elevated serum IgG4 levels, tumefactive lesions, and characteristic histopathological findings [7] . It occurs most frequently in middle-aged and elderly men. Lesions and persistent inflammation often lead to fibrosis and can cause irreversible damage to surrounding tissues, resulting in IgG4-related autoimmune pancreatitis, sclerosing cholangitis, retroperitoneal fibrosis, kidney disease, and other serious visceral injury and dysfunctions [7, 8] . Glucocorticoids are the first-line agent for all patients with active, untreated IgG4-RD unless contraindications to such treatment are present, and the combination of glucocorticoids and a steroid-sparing immunosuppressive agent is needed for some patients [8] . Rituximab may be considered for failure of conventional therapy, recurrence during steroid reduction, steroid resistance or intolerance, rituximab may be considered [9, 10] . Long-term use of these medications may increase the risk of infection [11] . As one of the major centers of IgG4-RD in China, we have built a follow-up system that includes over 200 IgG4-RD patients across the country during the past ten years. Since IgG4-RD patients may be susceptible to infections due to the immune-related disease itself and the medications they take, we conducted a study to investigate COVID-19 infection rate in Hubei IgG4-RD patients during the recent outbreak in Hubei province, and to characterize the clinical manifestation of COVID-19 in IgG4-RD patients. The study protocol was approved by the institutional review board (IRB) of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. All the IgG4-RD patients were diagnosed according to 2011 comprehensive diagnostic criteria for IgG4-RD [12] and the consensus statement on IgG4-RD pathology [13] or the New Classification Criteria for IgG4-RD released by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) [14] . We excluded patients who were not living in Hubei during the outbreak or lost follow-up from our IgG4-RD follow-up system, and a total of ninety-one patients with IgG4-RD who live in Hubei, China were identified and responded to our survey. Among them, two cases of COVID- 19 Medical history, clinical symptoms, laboratory tests, CT imaging, and treatment were obtained through a standardized data collection form, and then independently reviewed by two investigators. In our follow-up system, all the patients with active IgG4-RD or other special situation such as infection were followed up at an one month interval. Patients who were at stable remission condition were followed up every three months. Data were analyzed using IBM SPSS, version 21 (SPSS Inc, Chicago, IL) and GraphPad Prism version 7.00 (GraphPad Software, La Jolla). All statistical data were expressed as mean ±SEM. A total of 91 patients(mean age 56±1.321 years; 73.63% male) diagnosed with IgG4-RD in Hubei province were enrolled in the study(Suppl The clinical manifestations of the primary disease and disease condition on the last on-site visit of the two IgG4-RD patients infected with COVID-19 were as follows: concentration, and the ratio of IgG4/IgG decreased dramatically, especially after the third visit (Figure 1 ). Both patients have been taking 5mg prednisone daily for more than 6 months before the infection of COVID-19 ( Table 1) . To the best of our knowledge, our study is the first to report the susceptibility of COVID-19 in IgG4-RD patients, although a newly initial data from the COVID-19 Global Rheumatology Alliance provider registries analyzed 110 individuals with rheumatic disease who have been diagnosed with COVID-19 showed that patients with rheumatoid arthritis(RA), psoriatic arthritis(PsA) and systemic lupus erythematosus(SLE) were the main infected population, while 17 of 110 cases were listed as having other rheumatic disease [15] . We followed up 91 IgG4-RD patients in Hubei province, the epicenter of COVID-19 outbreak in China, and found two case of IgG4-RD patients had infected with COVID-19. Consistent with the reports, most of IgG4-RD patients were middle-aged to elderly men [7, 16] . In addition, the majority of the patients in our study had at least one chronic medical condition, such as hypertension and diabetes. The available data at present suggested that advanced age, male sex and chronic comorbidities are risk factors of mortality in patients with SARS-Cov-2 infection [17] [18] [19] . Therefore, theoretically IgG4-RD patients have a high risk of progressing to severe/critical COVID-19 once infected and thus need to be identified and properly treated as early as possible. Our study is also the first to describe the clinical characteristics of COVID-19 in The use of glucocorticoids remains controversial in patients infected with COVID-19. There are many studies supporting the use of corticosteroids in patients with coronavirus infection [3, 20, 21] . However, high-dose corticosteroids may be associated with increased risks of secondary infections, long-term complications, and prolonged virus shedding in COVID-19 patients [22] . In fact, it has been reported that the duration of viral RNA clearance as detected in oropharyngeal swabs and fecal samples was longer in glucocorticoid treatment group than that in non-glucocorticoid treatment group [23] . In our study, patient 2 took a long time for SARS-Cov-2 nucleic acid to turn negative, which may implicated that the viral load in such patients may need to be monitored for a longer time after discharge. Besides, the clearance of viral RNA in patients' stools may take a longer time compared to that in oropharyngeal swabs [23] , it is better to test the viral RNA in stools or in combination with oropharyngeal swabs. In summary, we describe the infection status and clinical characteristics of COVID-19 among IgG4-RD patients under the pandemic situation in this study. IgG4-RD patients may belong to the susceptible population of COVID-19 infection, and thus need more careful personal protection. Early identification and properly treatment are very important to prevent IgG4-RD patients with COVID-19 from progression to severe condition. As COVID-19 has become a global health threat, our study could help rheumatologists to better manage IgG4-RD under the pandemic situation. None. This work was supported by grants from the National Natural Science Foundation of China (no. 81771754 and no. 81901651) and the Tongji Hospital Clinical Research Flagship Program (no. 2019CR206). The authors have declared no conflicts of interest. A Novel Coronavirus from Patients with Pneumonia in China Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia Clinical features of patients infected with 2019 novel coronavirus in CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV) Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study IgG4-related disease International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease Rituximab for IgG4-related disease: a prospective, open-label trial Therapeutic Mechanisms of Glucocorticoids Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD) Consensus statement on the pathology of IgG4-related disease American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries Sex disparities in clinical characteristics and prognosis of immunoglobulin G4-related disease: a prospective study of 403 patients Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan: A Retrospective Observational Study COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease COVID-19: immunopathology and its implications for therapy Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Treatment of severe acute respiratory syndrome with glucosteroids: the Guangzhou experience On the use of corticosteroids for 2019-nCoV pneumonia Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients