Factors associated with hospitalizations for Covid-19 in patients with rheumatoid arthritis: data from the Reumacov Brazil registry

Ana Paula Monteiro Gomides Cleandro Pires de Albuquerque Licia Maria Henrique da Mota Guilherme Devidé Laiza Hombre Dias Angela Luzia Branco Pinto Duarte Raquel Altoé Giovelli Thais Evelyn Karnopp Hugo Deleon de Lima Adriana Marinho Marianne Schrader de Oliveira Felipe Omura Aline Ranzolin Gustavo Resende Francinne Machado Ribeiro Sandra Lúcia Euzébio Ribeiro Nathália de Carvalho Sacilotto Wander Gonzaga dos Santos Samuel Katsuyuki Shinjo Samia Araujo de Sousa Studart Flávia Patricia Sena Teixeira Michel Alexandre Yazbek Gilda Aparecida Ferreira Odirlei A. Monticielo Eduardo Paiva Gecilmara Cristina Salviato Pileggi Edgard Torres dos Reis Neto Marcelo de Medeiros Pinheiro Claudia D. L. Marques On behalf of ReumaCoV Brasil RegistryAbout the authors

Abstract

Background:

Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID 19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID 19 hospitalizations in patients with RA.

Methods:

This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID 19 were compared to 220 patients who tested negative for COVID 19 (control group). All patient data were collected from the Research Electronic Data Capture database.

Results:

The participants were predominantly female (90.6%) with a mean age of 53 ±12 years. Of the patients with COVID 19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR =4.61, 95% CI 1.06–20.02. P < 0.001) and current use of glucocorticoids (OR =20.66, 95% CI 3.09–138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR =0.26; 95% CI 0.10–0.67, P < 0.005).

Conclusion:

Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID 19 in patients with RA.

Trial registration: Brazilian Registry of Clinical Trials RBR 33YTQC.

Keywords:
COVID 19; Hospitalization; Immunosuppression; Outcomes; Rheumatoid arthritis

Background

The COVID-19 pandemic has raised additional concerns for rheumatologists, especially related to health care for patients with immune-mediated rheumatic diseases (IMRDs) [11 D’Antiga L. Coronaviruses and immunosuppressed patients: the facts during the third epidemic. Liver Transpl. 2020;26:832-4., 22 Venerito V, Lopalco G, Iannone F. COVID 19, rheumatic diseases and immunosuppressive drugs: an appeal for medication adherence. Rheumatol Int. 2020;40:827-8.]. Notably, immunosuppression resulting from disease or treatment itself is considered a relevant risk factor for higher infection susceptibility and more severe outcomes [33 Falagas ME, Manta KG, Betsi GI, Pappas G. Infection related morbidity and mortality in patients with connective tissue diseases: a systematic review. Clin Rheumatol. 2007;26:663–70.].

Although some evidence on the course of SARS-CoV-2 infections in patients with IMRDs has already been demonstrated, such as a similar COVID-19 prevalence to that of the general population [44 Favalli EG, Ingegnoli F, De Lucia O, Cincinelli G, Cimaz R, Caporali R. COVID 19 infection and rheumatoid arthritis: Faraway, so close! Autoimmun Rev. 2020;19:102523.], there are some knowledge gaps and uncertainties regarding the peculiarities and possible unfavorable outcomes, including hospitalization rate, frequency of admission to intensive care centers and severity [55 D’Silva KM, Serling Boyd N, Wallwork R, Hsu T, Fu X, Gravallese EM, Clinical characteristics and outcomes of patients with coronavirus disease, et al. (COVID 19) and rheumatic disease: a comparative cohort study from a US ‘hot spot.’ Ann Rheum Dis. 2019;79:1156-62.

6 Freites Nuñez DD, Leon L, Mucientes A, Rodriguez Rodriguez L, Font Urgelles J, Madrid García A, et al. Risk factors for hospital admissions related to COVID 19 in patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020;79:1393-9.

7 Cheng C, Li C, Zhao T, Yue J, Yang F, Yan Y, Liu X. COVID 19 with rheumatic diseases: a report of 5 cases. Clin Rheumatol. 2020;39:2025-9.

8 Zhong J, Shen G, Yang H, Huang A, Chen X, Dong L, et al. COVID 19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study. Lancet Rheumatol. 2020;2:e557-64.

9 Michelena X, Borrell H, López Corbeto M, López Lasanta M, Moreno E, Pascual Pastor M, et al. Incidence of COVID 19 in a cohort of adult and paediatric patients with rheumatic diseases treated with targeted biologic and synthetic disease modifying anti rheumatic drugs. Semin Arthritis Rheum. 2020;50:564-70.

10 Murray K, Quinn S, Turk M, O’Rourke A, Molloy E, O’Neill L, et al. COVID 19 and rheumatic musculoskeletal disease patients: infection rates, attitudes and medication adherence in an Irish population. Rheumatology (Oxford). 2021;60:902-6.
-1111 Ye C, Cai S, Shen G, Guan H, Zhou L, Hu Y, et al. Clinical features of rheumatic patients infected with COVID 19 in Wuhan. China Ann Rheum Dis. 2020;79:1007-13.]. In addition, immunosuppressive treatments for underlying diseases, glucocorticoids, and cyclophosphamide may contribute to unfavorable outcomes [1212 Marques CDL, Kakehasi AM, Pinheiro MM, Mota LMH, Albuquerque CP, Silva CR, et al. High levels of immunosuppression are related to unfavourable outcomes in hospitalised patients with rheumatic diseases and COVID 19: first results of ReumaCoV Brasil registry. RMD Open. 2021;7:e001461., 1313 Gianfrancesco 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. Ann Rheum Dis. 2020;79:859-66.]. On the other hand, a hypothesis has been presented that some immunomodulatory drugs, such as conventional or biological disease-modifying anti-rheumatic drugs (DMARDs), can help to mitigate the inflammation and cytokine storm induced by SARS-CoV-2 [1414 Nuño L, Novella Navarro M, Bonilla G, Franco Gómez K, Aguado P, Peiteado D, et al. Clinical course, severity and mortality in a cohort of patients with COVID 19 with rheumatic diseases. Ann Rheum Dis. 2020;79:1659-61., 1515 Haberman RH, Castillo R, Chen A, Yan D, Ramirez D, Sekar V, et al. COVID19 in patients with inflammatory arthritis: a prospective study on the effects of comorbidities and disease modifying antirheumatic drugs on clinical outcomes. Arthritis Rheumatol. 2020;72:1981-9.].

Considering the rheumatoid arthritis (RA) treatment scenario, which includes disease activity, low-dose prednisone, methotrexate, TNF blockers, IL-6 antagonists, JAK inhibitors, and anti-CD20 therapy, as a prototype for these findings, this study had the main aim of evaluating the risk factors associated with COVID-19 hospitalizations in patients with RA.

Methods

This was a cross-sectional analysis performed only in patients with RA who were enrolled in the ReumaCoV-Brazil Registry, a multicenter, prospective cohort study, used to evaluate and monitor patients with IMRDs during the COVID-19 pandemic. The complete methodology and initial data were published previously [1212 Marques CDL, Kakehasi AM, Pinheiro MM, Mota LMH, Albuquerque CP, Silva CR, et al. High levels of immunosuppression are related to unfavourable outcomes in hospitalised patients with rheumatic diseases and COVID 19: first results of ReumaCoV Brasil registry. RMD Open. 2021;7:e001461., 1616 Marques C, Kakehasi AM, Gomides APM, Paiva EDS, Dos Reis Neto ET, Pileggi GCS, et al. A Brazilian cohort of patients with immuno mediated chronic inflammatory diseases infected by SARS CoV 2 (ReumaCoV Brasil Registry): protocol for a prospective. Observational Study. JMIR Res Protoc. 2020;9:e24357.]. Eligible patients were selected through a convenience sample after the researchers contacted patients with RA and COVID-19 via telephone calls and noted similar patients in outpatient care or hospitals. They then compared the patients with RA who had COVID-19 with patients with RA who did not have COVID-19.

The following inclusion criteria were considered: (a) an age older than 18 years; (b) a diagnosis of COVID19, according to the Ministry of Health; and (c) a previous diagnosis of RA, according to the American College of Rheumatology or the European League against Rheumatism criteria. The exclusion criteria were patients with HIV or other immunodeficiency diseases, previous organ or bone marrow transplants, neoplasms in the last five years, current chemotherapy treatment and diseases of the thymus.

The Research Electronic Data Capture (REDCap) (https://www.project-redcap.org/) electronic database was used to collect and record the patients’ sociodemographic aspects and information on RA (time of disease, disease activity, laboratory data, use of DMARDs and other concomitant medications, comorbidities and details about the COVID-19 infection (clinical manifestations, treatment and outcomes)). Information was obtained by telephone or a face-to-face consultation, according to the local recommendations due to the pandemic, and through medical records in the event of hospitalization.

Statistical analysis

Initially, the data were analyzed descriptively. For categorical variables, absolute and relative frequencies were presented, and for numerical variables, summary measures (mean, median, minimum, maximum and standard deviation) were presented. For associations among categorical variables, the chi-square test was used, or Fisher’s exact test was used when cells had expected values of less than five counts. In cases of discrepancies, the standardized adjusted residue was used to identify local differences–cells with absolute values above 1.96 indicated significant deviations from expected values assignable only to random variations.

The comparisons of the means between two groups and more than two groups were performed using Student’s t-test for independent samples and analysis of variance (ANOVA), respectively. Normality in data distribution was verified by the Kolmogorov–Smirnov test. In the event of assumption violations to Student’s t-test and ANOVA, the Mann–Whitney and Kruskal–Wallis nonparametric tests were used, respectively. Once the Kruskal–Wallis test was significant, the location of paired differences was determined by Dunn Bonferroni tests, maintaining an overall significance level of 5%.

To assess the simultaneous effects of the demographic and clinical characteristics (e.g., predictor variables) on hospitalizations (e.g., dependent variable), univariate and multivariate logistic regressions were adjusted. For the initial multivariate models, predictor variables whose associations with the dependent variable were significant at 10% in the univariate logistic regression were selected. Then, a backward procedure was conducted by excluding the variables one by one in order of significance that were not found to be more significant at 5% in the multivariate regression than those in the final model. The final model fit was then evaluated by a Hosmer and Lemeshow test. Due to the large number of predictor variables and the small number of events, the variables whose associations with the dependent variable were significant amounted to 10% in the univariate logistic regression. Then, the variables that were not significant to 5% were excluded one by one in order of significance (backward method). In addition, the adjustment adequacy of the final model was evaluated by the Hosmer and Lemeshow test.

For all statistical tests, a significance level of 5% was used. Statistical analyses were performed using SPSS 20.0 statistical software.

This study was approved by the Brazilian Committee of Ethics in Human Research on April 5, 2020, (CAAE 30,186,820.2.1001.8807) and registered on the Brazil-ian Registry of Clinical Trials (RBR-33YTQC) on June 1, 2020. All patients signed informed consent forms, and the results of the study are presented in an aggregated form, guaranteeing confidentiality and ensuring that there are no risks to patients’ well-being and care.

Results

From May 24, 2020, to January 31, 2021, 489 patients with RA were included: 269 tested positive for COVID-19, and 220 tested negative for COVID-19 (control group). There was a female predominance (n =442; 90.6%) with a mean age of 53 ±12 years. Considering only the patients with COVID-19, 54 (20.1%) patients required hospitalization.

Comparing hospitalized patients with COVID-19 with outpatients, patients with COVID-19 were older, and had one, two or more comorbidities present. Diabetes mellitus and hypertension were significantly more prevalent in those who required hospital care (Table 1). In addition, patients with shortness of breath, cough and vomiting were significantly more likely to be hospitalized. On the other hand, patients with anosmia and dysgeusia had a lower hospitalization rate (Table 2).

Table 1
General characteristics and comorbidities of patients with rheumatoid arthritis and COVID-19
Table 2
Symptoms related to COVID-19 in patients with rheumatoid arthritis

Considering specific findings related to RA, including autoantibody status and cumulative damage (erosions), extra-articular manifestations, withdrawal therapy, and the current use of azathioprine and corticosteroids were associated with hospitalization. On the other hand, patients on TNF inhibitors had a significantly lower frequency of hospitalization (Tables 3 and 4).

Table 3
Characteristics of rheumatoid arthritis in the studied population
Table 4
Disease-modifying antirheumatic or immunossupressive drugs used by patients with rheumatoid arthritis at the time of the study

After multiple adjustments, the final regression model showed that the risk factors significantly associated with hospitalization were shortness of breath (OR 6.12; 95% CI 2.34–16.06, P< 0.001), vomiting (OR 4.06; 95% CI 1.4–11.79, P< 0.01), heart disease (OR 4.61; 95% CI 1.06–20.02, P< 0.001), and the current use of glucocorticoids (OR 20.66; 95% CI 3.09– 138, P< 0.002). Moreover, anosmia was associated with a lower chance of hospitalization (OR 0.26; 95% CI 0.10–0.67, P< 0.005) (Table 5). The results of the univariate logistic regression model are presented in the Additional file 1.

Table 5
Multivariate logistic regression models for the outcome variable hospitalization in patients with rheumatoid arthritis and covid-19”

Discussion

Our data demonstrated that approximately 20% ofpatients with RA required hospitalization because ofCOVID-19, a rate lower than that in another large registry study (38%) [1313 Gianfrancesco 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. Ann Rheum Dis. 2020;79:859-66.] but similar to the second analysis from the same database (21%) [1717 Klopfenstein T, Kadiane Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, et al. Features of anosmia in COVID 19. Med Mal Infect. 2020;50:436-9.]. The findings suggest that other details beyond disease alone could beinvolved, including genetic background and epidemiological differences (e.g., spreading time or viral community transmission) among the countries.

The main advantage of our study was the inclusionof a large sample of patients with RA. In addition, alldata were preparametrized, prestandardized and captured by a trained rheumatologist and with laboratory test confirmation for those who tested positive forCOVID-19.

Considering the traditional risk factors related to COVID-19 severity, our results did not find a significant association with age after multiple adjustments for cofounders, which is contrary to other studies from the general population and IMRD cohorts [1313 Gianfrancesco 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. Ann Rheum Dis. 2020;79:859-66., 1818 Ilardi A, Politi C, Ciarambino T. COVID 19: could sex and age be a risk factor? Minerva Med. 2020. https://doi.org/10.23736/S0026-4806.20.06705-1.
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However, heart disease, as a comorbidity, was significantly associated with hospitalization, which is in accordance with the current literature [2222 Ahmed S, Gasparyan AY, Zimba O. Comorbidities in rheumatic diseases need special consideration during the COVID 19 pandemic. Rheumatol Int. 2021;41:243-56.

23 Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID 19 in the New York City Area. JAMA. 2020;323:2052-9.

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].

These results suggest that the comorbidity burden seems to be similar to several reports from the general population, regardless of underlying rheumatic disease [1313 Gianfrancesco 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. Ann Rheum Dis. 2020;79:859-66., 3131 Cancarevic I, Malik BH. SARS CoV 2 (COVID 19) Infection in hypertensive patients and in patients with cardiac disease. Cureus. 2020;12:e8557.

32 Pinheiro MM, Pileggi GS, Kakehasi AM, Reis APMG, Reis Neto ET, Abreu MM, et al. Incidence and risk factors for moderate/severe COVID 19 in rheumatic diseases patients on hydroxychloroquine: a 24 week prospective cohort. Clin Exp Rheumatol. 2021. https://doi.org/10.55563/cline-xprheumatol/67oyux.
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33 Cacciapaglia F, Manfredi A, Erre G, Piga M, Sakellariou G, Viapiana O, et al. Correspondence on “Characteristics associated with hospitalisation for COVID 19 in people with rheumatic disease: data from the COVID 19 global rheumatology alliance physician reported registry” by Gianfrancesco M et al. The impact of cardiovascular comorbidity on COVID 19 infection in a large cohort of rheumatoid arthritis patients. Ann Rheum Dis. 2020. https://doi.org/10.1136/annrheumdis-2020-218813.
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34 Fredi M, Cavazzana I, Moschetti L, Andreoli L, Franceschini F. COVID 19 in patients with rheumatic diseases in northern Italy: a single centre observational and case control study. Lancet Rheumatol. 2020;2:e549-56.

35 Montero F, Martínez Barrio J, Serrano Benavente B, González T, Rivera J, Molina Collada J, et al. Coronavirus disease 2019 (COVID 19) in autoimmune and inflammatory conditions: clinical characteristics of poor outcomes. Rheumatol Int. 2020;40:1593-8.

36 Pistone A, Tant L, Soyfoo MS. Clinical course of COVID 19 infection in inflammatory rheumatological patients: a monocentric Belgian experience. Rheumatol Adv Pract. 2020;4:55.

37 Santos CS, Morales CM, Álvarez ED, Castro CÁ, Robles AL, Sandoval TP. Determinants of COVID 19 disease severity in patients with underlying rheumatic disease. Clin Rheumatol. 2020;39:2789-96.

38 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. Ann Rheum Dis. 2020;79:1544-9.

39 Characteristics associated with Covid 19 in patients with Rheumatic Disease in Latin America: data from the Covid 19 Global Rheumatology Alliance physician reported registry. Available at https://www.globalrheumpanlar.org/node/254. Accessed on 12/03/20222
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40 Gimeno Miguel A, Bliek Bueno K, Poblador Plou B, Carmona Pírez J, Poncel Falcó A, González Rubio F, et al. Chronic diseases associated with increased likelihood of hospitalization and mortality in 68, 913 COVID 19 confirmed cases in Spain: a population based cohort study. PLoS ONE. 2021;16(11):e0259822.
-4141 Korakas E, Ikonomidis I, Kousathana F, Balampanis K, Kountouri A, Raptis A, et al. Obesity and COVID 19: immune and metabolic derangement as a possible link to adverse clinical outcomes. Am J Physiol Endocrinol Metab. 2020;319(1):E105-9.].

Although some clinical findings were associated with hospitalization in our cohort, such as shortness of breath and vomiting, these findings may be redundant because they are considered red flags or parameters for hospitalization [3737 Santos CS, Morales CM, Álvarez ED, Castro CÁ, Robles AL, Sandoval TP. Determinants of COVID 19 disease severity in patients with underlying rheumatic disease. Clin Rheumatol. 2020;39:2789-96.

38 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. Ann Rheum Dis. 2020;79:1544-9.

39 Characteristics associated with Covid 19 in patients with Rheumatic Disease in Latin America: data from the Covid 19 Global Rheumatology Alliance physician reported registry. Available at https://www.globalrheumpanlar.org/node/254. Accessed on 12/03/20222
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40 Gimeno Miguel A, Bliek Bueno K, Poblador Plou B, Carmona Pírez J, Poncel Falcó A, González Rubio F, et al. Chronic diseases associated with increased likelihood of hospitalization and mortality in 68, 913 COVID 19 confirmed cases in Spain: a population based cohort study. PLoS ONE. 2021;16(11):e0259822.

41 Korakas E, Ikonomidis I, Kousathana F, Balampanis K, Kountouri A, Raptis A, et al. Obesity and COVID 19: immune and metabolic derangement as a possible link to adverse clinical outcomes. Am J Physiol Endocrinol Metab. 2020;319(1):E105-9.

42 Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China Lancet. 2020;395:497-506.

43 Johnson KD, Harris C, Cain JK, Hummer C, Goyal H, Perisetti A. Pulmonary and extra pulmonary clinical manifestations of COVID 19. Front Med (Lausanne). 2020;7:526.

44 Du RH, Liu LM, Yin W, Wang W, Guan LL, Yuan ML, et al. Hospitalization and critical care of 109 decedents with COVID 19 pneumonia in Wuhan. China Ann Am Thorac Soc. 2020;17:839-46.

45 Zhang T, Liu D, Tian D, Xia L. The roles of nausea and vomiting in COVID 19: did we miss something? J Microbiol Immunol Infect. 2020. https://doi.org/10.1016/j.jmii.2020.10.005.
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46 Zhong P, Xu J, Yang D, Shen Y, Wang L, Feng Y, et al. COVID 19 associated gastrointestinal and liver injury: clinical features and potential mechanisms. Signal Transduct Target Ther. 2020;5:256.

47 Mao R, Qiu Y, He JS, Tan JY, Li XH, Liang J, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID 19: a systematic review and meta analysis. Lancet Gastroenterol Hepatol. 2020;5:667-78.
-4848 Symptoms of Coronavirus, US Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/sympt-oms.html. Acessed 20 May 2021.
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]. Therefore, this particular result should be interpreted with caution, especially in a cross-sectional analysis.

Interestingly, anosmia, an important specific clinical marker for COVID-19 [4848 Symptoms of Coronavirus, US Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/sympt-oms.html. Acessed 20 May 2021.
https://www.cdc.gov/coronavirus/2019-nco...
], had a protective behavior against hospitalization, as previously reported by other authors [4444 Du RH, Liu LM, Yin W, Wang W, Guan LL, Yuan ML, et al. Hospitalization and critical care of 109 decedents with COVID 19 pneumonia in Wuhan. China Ann Am Thorac Soc. 2020;17:839-46.

45 Zhang T, Liu D, Tian D, Xia L. The roles of nausea and vomiting in COVID 19: did we miss something? J Microbiol Immunol Infect. 2020. https://doi.org/10.1016/j.jmii.2020.10.005.
https://doi.org/10.1016/j.jmii.2020.10.0...

46 Zhong P, Xu J, Yang D, Shen Y, Wang L, Feng Y, et al. COVID 19 associated gastrointestinal and liver injury: clinical features and potential mechanisms. Signal Transduct Target Ther. 2020;5:256.

47 Mao R, Qiu Y, He JS, Tan JY, Li XH, Liang J, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID 19: a systematic review and meta analysis. Lancet Gastroenterol Hepatol. 2020;5:667-78.

48 Symptoms of Coronavirus, US Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/sympt-oms.html. Acessed 20 May 2021.
https://www.cdc.gov/coronavirus/2019-nco...

49 Yan CH, Faraji F, Prajapati DP, Ostrander BT, De Conde AS. Self reported olfactory loss associates with outpatient clinical course in COVID 19. Int Forum Allergy Rhinol. 2020;10:821-31.
-5050 Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, et al. Self reported olfactory and taste disorders in patients with severe acute respiratory coronavirus 2 infection: a cross sectional study. Clin Infect Dis. 2020;28(71):889-90.]. Thus, our data suggest that anosmia could be seen as a potential clinical marker of mild COVID-19 severity in patients with RA.

It is worth emphasizing that the clinical and laboratory characteristics of RA and DMARDs (e.g., conventional, biological and targeted synthetic medications) were not associated with hospitalization in the final analysis, except for the current use of glucocorticoids (dosage equal to or greater than 10 mg/day). This is a recurrent finding among the studies [1212 Marques CDL, Kakehasi AM, Pinheiro MM, Mota LMH, Albuquerque CP, Silva CR, et al. High levels of immunosuppression are related to unfavourable outcomes in hospitalised patients with rheumatic diseases and COVID 19: first results of ReumaCoV Brasil registry. RMD Open. 2021;7:e001461., 1313 Gianfrancesco 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. Ann Rheum Dis. 2020;79:859-66.].

Patients with RA on TNF inhibitors had a lower rate of hospitalizations in the initial analysis but this finding was not confirmed after multivariate analysis which is contrary to own findings when considering the entire sampling of patients with IMRDs [1212 Marques CDL, Kakehasi AM, Pinheiro MM, Mota LMH, Albuquerque CP, Silva CR, et al. High levels of immunosuppression are related to unfavourable outcomes in hospitalised patients with rheumatic diseases and COVID 19: first results of ReumaCoV Brasil registry. RMD Open. 2021;7:e001461.] and the Global Alliance Rheumatology (GRA) database [1313 Gianfrancesco 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. Ann Rheum Dis. 2020;79:859-66., 5151 Sparks JA, Wallace ZS, Seet AM, Gianfrancesco MA, Izadi Z, Hyrich KL, et al. COVID 19 global rheumatology. Alliance 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. Ann Rheum Dis. 2021;80:1137-46.] andanother study published in the literature [5252 Izadi Z, Brenner EJ, Mahil SK, Dand N, Yiu ZZN, Yates M, et al. Association between tumor necrosis factor inhibitors and the risk of hospitalization or death among patients with immune mediated inflammatory disease and COVID 19. JAMA Netw Open. 2021;4(10):e2129639.].

In addition, the second analysis of the GRA database that involved 2869 patients with RA found that rituximab (OR =4.15; 95% CI 3.16–5.44) and JAK inhibitors (OR =2.06; 95% CI 1.60–2.65) were significantly associated with COVID-19 severity [1717 Klopfenstein T, Kadiane Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, et al. Features of anosmia in COVID 19. Med Mal Infect. 2020;50:436-9.]. Our data did not confirm the last reports.

Our study has some limitations, such as the convenience sample and small number of patients, cross-sectional analysis of an ongoing prospectivecohort, the low number of rituximab users and specific DMARD targets and the lack of information ondisease activity. On the other hand, our study includeda national sample with a more homogeneous rate ofcommunity viral transmission, social distancing measures and immunization.

Conclusions

Our data showed traditional risk factors, including heart disease as a comorbidity, and the current use of glucocorticoids are more involved with hospitalizations for COVID-19 in patients with RA than the underlying IMRDs alone.

  • Funding
    This work has been funded by the Research Funding of the Brazilian Society of Rheumatology and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico –MCTIC/CNPq/FNDCT/MS/SCTIE/Decit N° 07/2020).
  • Availability of data and materials
    The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
  • Declarations
    Ethics approval and consent to participate
    This study was approved by the Brazilian Committee of Ethics in Human Research on April 5, 2020, (CAAE 30186820.2.1001.8807) and registered on the Brazilian Registry of Clinical Trials (RBR 33YTQC) on June 1, 2020. All patients signed informed consent forms.
  • Consent for publication
    Not applicable.
  • Publisher’s Note
    Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abbreviations

  • RA:  Rheumatoid arthritis
  • IMRDS:  Immune mediated rheumatic diseases
  • DMARDS:  Disease modifying anti rheumatic drugs.

Acknowledgements

The authors thank to the Brazilian Society of Rheumatology for technical support and rapid nationwide mobilization and to all collaborators on behalf of the ReumaCoV Brasil registry.

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Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s42358-022-00244-5.

Additional file 1

Results of univariate logistic regression models - hospitalization in patients with rheumatoid arthritis.

Publication Dates

  • Publication in this collection
    16 May 2022
  • Date of issue
    2022

History

  • Received
    01 Nov 2021
  • Accepted
    10 Apr 2022
  • Published
    03 May 2022
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