Children With RMDs Not at High Risk for Severe COVID-19

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The vast majority of children and young people with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 are not hospitalized, according to the most significant global investigation of short-term COVID-19 outcomes in this patient group to date.

In the study, only 1 in 15 (7%) children and young people (younger than 19 years) with RMDs and COVID-19 were hospitalized, and even then, they experienced only mild symptoms; 4 of 5 of those hospitalized did not require supplemental oxygen or ventilatory support.

The study also found that those with severe systemic RMDs and obesity were more likely to be hospitalized than children with juvenile idiopathic arthritis (JIA).

Treatment with biologics, such as tumor necrosis factor inhibitors, did not appear to be associated with more severe COVID-19; however, the study found that children and young people with obesity (body mass index [BMI] ≥30) were more likely to be hospitalized, although only 6% of patients in this study had a BMI in this category. Three patients died — two from areas of lower resources who were diagnosed with systemic lupus erythematosus (SLE) at approximately the same time they were diagnosed with COVID-19, and one with a preexisting autoinflammatory syndrome who was being treated with low-dose glucocorticoids and methotrexate.

Dr Kimme Hyrich

Published in the March issue of Annals of Rheumatic Diseases, the study was led by Kimme L. Hyrich, MD, PhD, and Lianne Kearsley-Fleet, PhD, both from the University of Manchester, United Kingdom. Hyrich is also a consultant rheumatologist at Manchester University Hospitals NHS Foundation Trust, United Kingdom.

In an interview with Medscape Medical News, Hyrich explained that overall, these data are reassuring and show that the majority of children and young people with RMDs are not at high risk of severe COVID-19.

"Many parents and families with children who have RMDs have lived with great fear over the pandemic about whether or not their children are at an increased risk of severe COVID-19," said Hyrich. "Many are immunosuppressed or take other immunomodulatory medications. This has also had a great impact on schooling and children's well-being."

In the study, children with SLE, mixed-connective tissue disease, or vasculitis were more likely to have severe COVID-19. "[This] is not surprising given the typically greater systemic involvement and need for more aggressive immunosuppressive therapy than the majority of individuals with JIA," write the researchers.

Hyrich added, "There may be times when children are on particularly high doses of immunosuppression or their disease is particularly active, when they may need more protection, and rheumatology teams can advise parents and young people about this."

Studies such as those by Zimmerman and colleagues and Viner and colleagues have found that generally, children with no underlying disease are less susceptible to symptomatic COVID-19 and that reports of death are rare. Findings show that the younger the child, the less likely they will be symptomatic.

Adult data suggest a higher risk of COVID-related death among patients with arthritis, lupus, or psoriasis. A recent systematic review of the literature suggested that increased risk of COVID-related death only applies to subgroups of people with RMDs.

However, whether children and young people with RMDs are likely to have more severe COVID-19 and whether there is additional risk attributable to either their underlying disease or its therapy remain unknown. The goal of the study by Hyrich and colleagues was to address these questions.

The global analysis aimed to describe characteristics of those children and young people (younger than 19 years) with preexisting RMDs who also had COVID-19; to describe outcomes following COVID-19; and to identify characteristics associated with more severe COVID-19 outcomes.

Data were drawn from the European Alliance of Associations for Rheumatology (EULAR) COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database.

Demographic information included primary RMD diagnosis; RMD disease activity (remission, low, moderate, high, or unknown); RMD treatments, including glucocorticoid use and which disease-modifying antirheumatic drug (DMARD) the patient was taking at the time of COVID-19; and comorbidities (none, ocular inflammation, interstitial lung disease, asthma, diabetes, obesity, hypertension, cerebrovascular accident, renal disease, inflammatory bowel disease, and heart disease).

With respect to COVID-19, information collected included diagnosis date, whether the case was presumptive or confirmed, clinical symptoms, hospitalization and/or death due to COVID-19, and whether the patient stopped receiving rheumatic therapies.

Rheumatology diagnoses were categorized into four groups: JIA; SLE, mixed-connective tissue disease (MCTD), vasculitis, or other RMD; autoinflammatory syndromes; and "other," including chronic recurrent multifocal osteomyelitis, sarcoidosis, or ocular inflammation.

Of the 607 children and young people with reported SARS-CoV-2 infection from 25 different countries (464 from the EULAR COVID-19 Registry), 499 (82%) cases were PCR-confirmed, and 399 (66%) patients were female (median age, 14 years). Most (62%) had JIA: 37%, polyarticular JIA; 30%, oligoarticular JIA; 12%, enthesitis-related JIA; 9%, systemic JIA; 4%, psoriatic JIA; and 9%, JIA of unknown subcategory. Furthermore, 13% of patients had autoinflammatory syndromes, 8% with SLE or MCTD, 3% with vasculitis, and 2% with inflammatory myopathy.

No associations were seen between DMARD treatment (conventional-synthetic, biologic/targeted-synthetic, or combination therapy), compared with no DMARD treatment, glucocorticoid use, and hospitalization.

Owing to substantial differences in reporting of race and ethnicity between data sources, the researchers were unable to analyze whether Black, Asian, and minority ethnic groups with pediatric RMDs are at higher risk of COVID-19-related death compared with those of White ethnicity, as has been reported for the general population.

The study also did not account for variants of SARS-CoV-2 other than to note that data were collected prior to the spread of the Omicron variant. Also, the registries did not capture vaccination status (though very few children had received vaccines at the time of data collection) or information on long COVID or multisystem inflammatory syndrome in children.

Hyrich and Kearsley-Fleet have disclosed no relevant financial relationships. Other authors' disclosures can be found in the original article.

Ann Rheum Dis. Published online March 25, 2022. Full text

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