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The continuous increase in the number of systemic lupus erythematosus cases in Brazil in the COVID-19 era

Abstract

This study aims to reevaluate and compare the data from the Brazilian Unified Health System (SUS) on the number of diagnoses of systemic lupus erythematosus (SLE) in the pre-pandemic period with those in the pandemic period, as well as to compare the first year (2020) of the COVID-19 pandemic in Brazil with the last year (2021), to update the data, and to verify whether SLE disease control measures were effective in 2021. There was a consistent and significant increase in the incidence of SLE cases all over Brazil between the first and second pandemic years and between the pre-pandemic triennium and the second pandemic year. Therefore, it is inescapable to have larger clinical studies with different populations to better understand the relationship between these two conditions and find measures to improve the control of this disease.

COVID-19; Lupus Erythematosus, Systemic; Autoimmune Diseases

Introduction

As the Coronavirus 2019 (COVID-19) pandemic goes on around the world, clinical and epidemiological evidence of the incidence and increase in the number of systemic lupus erythematosus (SLE) continues to be discussed, but the real association between SLE and the risk factors associated with worse COVID-19 outcomes in this population are not well established.11. Ugarte-Gil MF, Alarcón GS, Seet A Izadi Z, Sokolova CR, Clarke AE, et al. Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance. Ann Rheum Dis. 2021;80(suppl1). https://doi.org/10.1136/annrheumdis-2021-eular.2984
https://doi.org/10.1136/annrheumdis-2021...
,22. Lee WW, Cheong YK, Teh CL, Wan SA, Chuah SL, Singh BS. Impact of COVID-19 on hospitalization of patients with systemic lupus erythematosus (SLE). Clin Rheumatol. 2021 Nov;40(11):4775-7. https://doi.org/10.1007/s10067-021-05920-3
https://doi.org/10.1007/s10067-021-05920...
Even with the expansion of vaccination in Brazil, with full immunization of 171 million (80.6%) people, COVID-19 variants such as OMICRON have impacted and increased COVID-19 cases. Brazil has experienced approximately 34 million cases of COVID-19 and over 682,358 deaths to date (August 19, 2022) (https://covid.saude.gov.br/).

This scenario still represents a cause for concern about the management of patients with autoimmune diseases, such as SLE. Ugarte-Gil et al.11. Ugarte-Gil MF, Alarcón GS, Seet A Izadi Z, Sokolova CR, Clarke AE, et al. Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance. Ann Rheum Dis. 2021;80(suppl1). https://doi.org/10.1136/annrheumdis-2021-eular.2984
https://doi.org/10.1136/annrheumdis-2021...
demonstrated that more severe COVID-19 outcomes in individuals with SLE are largely driven by factors such as untreated or active SLE. Patients on glucocorticoids also have more severe outcomes. The concern becomes even greater when studies conducted during the pandemic showed a decrease in the hospitalization rate of patients with SLE but an increase in the mortality rate due to the measures implemented to mitigate the pandemic, such as negligence in medical assistance for other diseases.22. Lee WW, Cheong YK, Teh CL, Wan SA, Chuah SL, Singh BS. Impact of COVID-19 on hospitalization of patients with systemic lupus erythematosus (SLE). Clin Rheumatol. 2021 Nov;40(11):4775-7. https://doi.org/10.1007/s10067-021-05920-3
https://doi.org/10.1007/s10067-021-05920...
,33. Ramirez GA, Argolini LM, Bellocchi C, Moroni L, Della-Torre E, Farina N, et al.; SMILE, Milan Lupus Consortium. Impact of the COVID-19 pandemic in patients with systemic lupus erythematosus throughout one year. Clin Immunol. 2021 Oct;231:108845. https://doi.org/10.1016/j.clim.2021.108845
https://doi.org/10.1016/j.clim.2021.1088...

A number of orofacial manifestations have also been reported in patients with SLE, such as nonspecific ulcerations, involvement of salivary glands, and temporomandibular joint disorders.44. Hammoudeh M, Al-Momani A, Sarakbi H, Chandra P, Hammoudeh S. Oral Manifestations of Systemic Lupus Erythematosus Patients in Qatar: A Pilot Study. Int J Rheumatol. 2018 Apr;2018:6052326. https://doi.org/10.1155/2018/6052326
https://doi.org/10.1155/2018/6052326...
A recent study has highlighted the difficulties and damage from the current COVID-19 pandemic to dental services in general and to oral medicine and oral pathology particularly, which makes the possible number of undiagnosed SLE cases even more concerning.55. Marques NP, Silveira DM, Martelli PJ, Martelli DR, Lucena EH, Martelli-Júnior H. Brazilian Oral Medicine and public health system: the enormous impact of the COVID-19 Era. Oral Dis. 2022 Apr;28(Suppl 1 Suppl 1):1001-2. https://doi.org/10.1111/odi.13677
https://doi.org/10.1111/odi.13677...

Methodology

The data on the number of diagnoses of SLE in 2017 – 2019, 2020, and 2021 from five Brazilian regions (north, northeast, southeast, south, and midwest), representing 26 states and the Federal District were extracted from SISAB (Health Information System for Primary Care), a public database maintained by the Brazilian Ministry of Health (https://sisab.saude.gov.br/paginas/acessoRestrito/relatorio/federal/saude/RelSauProduc Re.xhtml).

Statistical analyses were performed using the BioEstat 5.0 statistical software (Biostatistical Institute of Science and Technology). The number of diagnoses of SLE was compared between the pre-pandemic period and the pandemic period. The number of diagnoses of SLE in the first year (2020) of the COVID-19 pandemic in Brazil was compared with the last year (2021). The study also aimed to update the data and verify whether SLE disease control measures were effective in 2021. In addition, binomial regression was used to analyze the longitudinal associations between the impact of the COVID-19 pandemic and the number of diagnoses. Percentage changes were calculated by dividing the change in value by the original value and then multiplying the obtained value by 100. In all analyses, the data were disaggregated by Brazilian regions.

Results

Table 1 presents the previous study by the same research group66. Martelli-Junior H, Marques NP, Marques NCT, Lucena EG, Martelli DRB, Oliveira EA.. Correspondence on ‘Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine’ by Mathian et al; Increase in the number of systemic lupus erythematosus cases in Brazil in the COVID-19 era. Ann Rheum Dis, 2021Apr;annrheumdis-2021-220410. https://doi.org/10.1136/annrheumdis-2021-220410
https://doi.org/10.1136/annrheumdis-2021...
and shows an increase in the number of SLE diagnoses in all Brazilian regions in 2020, compared to the mean number of the pre-pandemic triennium (2017–2019). The increase ranged from +23.4% in the south to +108.9% in northeastern region. The overall Brazilian average increase amounted to 55.9%, corresponding to 13,107 more cases in the first year of the pandemic period.

Table 1
Average number of diagnosed systemic lupus erythematosus cases across Brazilian geographical macroregions in different periods (2017–2019 vs. 2020). Previous study – Martelli-Junior et al., 2021.

Table 2 shows the comparison of the second year of the pandemic period (2021) initially with the first year of the COVID-19 pandemic (2020) and then with the pre-pandemic period. There was a trend towards an increase in the number of SLE cases in the second year of the pandemic throughout Brazil (+ 20.4%), giving special attention to the southern region, the least affected in the first study and now the one with the largest increase (+ 28.1%) during the pandemic. When comparing the subsequent period of the pandemic (2021) with the mean number in the pre-pandemic period (2017–2019), the increase in the number of SLE cases was higher compared to the previous study, showing the northeastern region was the most widely affected (148.4%), in addition to an increase of 20,550 cases throughout Brazil (+ 87.7%).

Table 2
Difference between the number of diagnosed systemic lupus erythematosus cases reported by the Brazilian public health system in all geographical regions in 2020 (previous study) compared to 2021 and comparison of the average number of SLE cases in the pre-pandemic and pandemic periods.

Table 3 shows the comparison of the incidence rate adjusted per million people for the five Brazilian regions and throughout the country. There was a consistent and significant increase in the incidence rate all over Brazil between the first and second pandemic years and between the pre-pandemic triennium and the second pandemic year.

Table 3
Incidence of systemic lupus erythematosus per million people in Brazilian macroregions in 2017–2019 vs. 2021 and 2020 vs. 2021.

Discussion

SLE is clearly an important risk factor for the development of more severe COVID-19.22. Lee WW, Cheong YK, Teh CL, Wan SA, Chuah SL, Singh BS. Impact of COVID-19 on hospitalization of patients with systemic lupus erythematosus (SLE). Clin Rheumatol. 2021 Nov;40(11):4775-7. https://doi.org/10.1007/s10067-021-05920-3
https://doi.org/10.1007/s10067-021-05920...
,77. Sloan M, Gordon C, Harwood R, Lever E, Wincup C, Bosley M, et al. The impact of the COVID-19 pandemic on the medical care and health-care behaviour of patients with lupus and other systemic autoimmune diseases: a mixed methods longitudinal study. Rheumatol Adv Pract. 2020 Dec;5(1):rkaa072. https://doi.org/10.1093/rap/rkaa072
https://doi.org/10.1093/rap/rkaa072...
Patients with SLE develop more severe manifestations of COVID-19, especially when they have other comorbidities and predisposing factors, including smoking, obesity, and chronic use of medications, such as immunosuppressants.22. Lee WW, Cheong YK, Teh CL, Wan SA, Chuah SL, Singh BS. Impact of COVID-19 on hospitalization of patients with systemic lupus erythematosus (SLE). Clin Rheumatol. 2021 Nov;40(11):4775-7. https://doi.org/10.1007/s10067-021-05920-3
https://doi.org/10.1007/s10067-021-05920...
It has been suggested that SARS-CoV-2 could act as a triggering factor for the development of rapid autoimmune and/or autoinflammatory dysregulation due to similar pathogenic mechanisms and clinico-radiological aspects in hyperinflammatory diseases and COVID-19.22. Lee WW, Cheong YK, Teh CL, Wan SA, Chuah SL, Singh BS. Impact of COVID-19 on hospitalization of patients with systemic lupus erythematosus (SLE). Clin Rheumatol. 2021 Nov;40(11):4775-7. https://doi.org/10.1007/s10067-021-05920-3
https://doi.org/10.1007/s10067-021-05920...
,88. Caso F, Costa L, Ruscitti P, Navarini L, Del Puente A, Giacomelli R, et al. Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects? Autoimmun Rev. 2020 May;19(5):102524. https://doi.org/10.1016/j.autrev.2020.102524
https://doi.org/10.1016/j.autrev.2020.10...

At the beginning of the pandemic period, telemedicine came into use because of health service restrictions, having a positive impact for patients who sought rheumatology care.99. Tang W, Inzerillo S, Weiner J, Khalili L, Barasch J, Gartshteyn Y, et al. The Impact of Telemedicine on Rheumatology Care. Front Med (Lausanne). 2022 May;9:876835. https://doi.org/10.3389/fmed.2022.876835
https://doi.org/10.3389/fmed.2022.876835...
Nevertheless, it is still unclear why SLE cases continue to increase during the pandemic even after the adoption of these preventive measures and the decrease in COVID-19 cases.11. Ugarte-Gil MF, Alarcón GS, Seet A Izadi Z, Sokolova CR, Clarke AE, et al. Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance. Ann Rheum Dis. 2021;80(suppl1). https://doi.org/10.1136/annrheumdis-2021-eular.2984
https://doi.org/10.1136/annrheumdis-2021...
,22. Lee WW, Cheong YK, Teh CL, Wan SA, Chuah SL, Singh BS. Impact of COVID-19 on hospitalization of patients with systemic lupus erythematosus (SLE). Clin Rheumatol. 2021 Nov;40(11):4775-7. https://doi.org/10.1007/s10067-021-05920-3
https://doi.org/10.1007/s10067-021-05920...

The fear of patients of seeking medical services during the pandemic, difficulties related to technology and telemedicine, routine care cancellations, difficulties in accessing healthcare, and pandemic-related stress seem to contribute to the physical deterioration of SLE patients and might also have increased the number of patients diagnosed with the disease.1010. Hyrich KL, Machado PM. Rheumatic disease and COVID-19: epidemiology and outcomes. Nat Rev Rheumatol. 2021 Feb;17(2):71-2. https://doi.org/10.1038/s41584-020-00562-2
https://doi.org/10.1038/s41584-020-00562...

Conclusion

Therefore, given the increase of rheumatic diseases, such as SLE,99. Tang W, Inzerillo S, Weiner J, Khalili L, Barasch J, Gartshteyn Y, et al. The Impact of Telemedicine on Rheumatology Care. Front Med (Lausanne). 2022 May;9:876835. https://doi.org/10.3389/fmed.2022.876835
https://doi.org/10.3389/fmed.2022.876835...
described in the literature during the pandemic and demonstrated in this paper, it is inescapable to have larger clinical studies with different populations to better understand the relationship between these two conditions and find measures to improve the control of this disease.

Acknowledgements

The authors would like to thank the State Research Foundation (Fapemig), Minas Gerais, Brazil, the National Council for Scientific and Technological Development (CNPq), Brazil, and the Coordination for the Improvement of Higher Education Personnel (Capes), Brazil.

References

  • 1
    Ugarte-Gil MF, Alarcón GS, Seet A Izadi Z, Sokolova CR, Clarke AE, et al. Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance. Ann Rheum Dis. 2021;80(suppl1). https://doi.org/10.1136/annrheumdis-2021-eular.2984
    » https://doi.org/10.1136/annrheumdis-2021-eular.2984
  • 2
    Lee WW, Cheong YK, Teh CL, Wan SA, Chuah SL, Singh BS. Impact of COVID-19 on hospitalization of patients with systemic lupus erythematosus (SLE). Clin Rheumatol. 2021 Nov;40(11):4775-7. https://doi.org/10.1007/s10067-021-05920-3
    » https://doi.org/10.1007/s10067-021-05920-3
  • 3
    Ramirez GA, Argolini LM, Bellocchi C, Moroni L, Della-Torre E, Farina N, et al.; SMILE, Milan Lupus Consortium. Impact of the COVID-19 pandemic in patients with systemic lupus erythematosus throughout one year. Clin Immunol. 2021 Oct;231:108845. https://doi.org/10.1016/j.clim.2021.108845
    » https://doi.org/10.1016/j.clim.2021.108845
  • 4
    Hammoudeh M, Al-Momani A, Sarakbi H, Chandra P, Hammoudeh S. Oral Manifestations of Systemic Lupus Erythematosus Patients in Qatar: A Pilot Study. Int J Rheumatol. 2018 Apr;2018:6052326. https://doi.org/10.1155/2018/6052326
    » https://doi.org/10.1155/2018/6052326
  • 5
    Marques NP, Silveira DM, Martelli PJ, Martelli DR, Lucena EH, Martelli-Júnior H. Brazilian Oral Medicine and public health system: the enormous impact of the COVID-19 Era. Oral Dis. 2022 Apr;28(Suppl 1 Suppl 1):1001-2. https://doi.org/10.1111/odi.13677
    » https://doi.org/10.1111/odi.13677
  • 6
    Martelli-Junior H, Marques NP, Marques NCT, Lucena EG, Martelli DRB, Oliveira EA.. Correspondence on ‘Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine’ by Mathian et al; Increase in the number of systemic lupus erythematosus cases in Brazil in the COVID-19 era. Ann Rheum Dis, 2021Apr;annrheumdis-2021-220410. https://doi.org/10.1136/annrheumdis-2021-220410
    » https://doi.org/10.1136/annrheumdis-2021-220410
  • 7
    Sloan M, Gordon C, Harwood R, Lever E, Wincup C, Bosley M, et al. The impact of the COVID-19 pandemic on the medical care and health-care behaviour of patients with lupus and other systemic autoimmune diseases: a mixed methods longitudinal study. Rheumatol Adv Pract. 2020 Dec;5(1):rkaa072. https://doi.org/10.1093/rap/rkaa072
    » https://doi.org/10.1093/rap/rkaa072
  • 8
    Caso F, Costa L, Ruscitti P, Navarini L, Del Puente A, Giacomelli R, et al. Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects? Autoimmun Rev. 2020 May;19(5):102524. https://doi.org/10.1016/j.autrev.2020.102524
    » https://doi.org/10.1016/j.autrev.2020.102524
  • 9
    Tang W, Inzerillo S, Weiner J, Khalili L, Barasch J, Gartshteyn Y, et al. The Impact of Telemedicine on Rheumatology Care. Front Med (Lausanne). 2022 May;9:876835. https://doi.org/10.3389/fmed.2022.876835
    » https://doi.org/10.3389/fmed.2022.876835
  • 10
    Hyrich KL, Machado PM. Rheumatic disease and COVID-19: epidemiology and outcomes. Nat Rev Rheumatol. 2021 Feb;17(2):71-2. https://doi.org/10.1038/s41584-020-00562-2
    » https://doi.org/10.1038/s41584-020-00562-2

Publication Dates

  • Publication in this collection
    19 June 2023
  • Date of issue
    2023

History

  • Received
    1 July 2022
  • Accepted
    6 Feb 2023
  • Reviewed
    2 Mar 2023
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