This study describes the presentation and outcomes of a cohort of pediatric patients with rheumatic diseases and laboratory-confirmed COVID-19. Overall, approximately 20% of our patients required hospitalization and 7.5% required ICU care. Although these rates are slightly higher than those reported in the general pediatric population, our study had a limited sample size relying mostly on voluntary reporting, and laboratory confirmation was required.(10, 11) As such, some milder cases may have gone unreported, and untested and/or asymptomatic cases were likely excluded. Additionally, severe COVID-19 has been linked to older pediatric age and African American race which were overrepresented in the hospitalized group.(2, 12) Cardiovascular disease has been identified as a risk factor for hospitalization in adults;(5) similarly, it was found more frequently in the hospitalized group in our cohort, potentially having influenced these patients’ outcomes, even if the confidence interval for this association was wide.(5) Reassuringly, none of our patients required mechanical ventilation and there were no fatalities, supporting previous reports that patients with rheumatic diseases and COVID-19 overall recover well.(6–9)
Symptoms of acute COVID-19 were similar to those described in the general pediatric population.(2, 10, 11) Symptom reporting in the hospitalized group may have been less subject to recall bias. Notably, while respiratory and gastrointestinal symptoms are typically attributable to acute infection, fever and myalgias are also features of rheumatic disease flares. Fever, myalgias, and dyspnea predominated in hospitalized patients; furthermore, patients with active rheumatic disease were more likely to be in the hospitalized group, although the strength of this association was weak. These observations suggests that the interplay between rheumatic disease activity and flare, and severe COVID-19 may influence the need for admission, as proposed by Ye et al.(6)
Interestingly, while all JDM patients were managed in the ambulatory setting, SLE diagnosis was associated with hospitalization, raising the possibility of disease type playing a role in the outcomes as well. Indeed, the pattern of immune activation in patients with severe COVID-19 has been recently described, and is reported to bear many similarities to active SLE.(13) Moreover, therapy and presence of comorbidities vary by disease, offering another possible explanation for this observation.
Echoing the findings of Gianfrancesco et al., medium/high-dose corticosteroid use was associated with increased odds of hospitalization.(5) Similar associations were observed for mycophenolate and severe immunosuppression; the latter may have been driven by the effect of medium/high-dose steroid use or reflect the underlying disease and its severity. Patients receiving rituximab therapy were also more likely to be in the hospitalized group, although the confidence interval for this association was substantially wide. While mycophenolate use has not been reported to increase the hospitalization risk in adults, rituximab use was found to be associated with higher rates of hospitalization and death from COVID-19 in a small cohort of adult patients with rheumatic diseases.(14) Larger, multicenter studies are still in need to further investigate and confirm these findings.
Our results align with the reported inverse association of TNFi and hospitalization in adults with rheumatic diseases,(5) as none of our TNFi recipients were hospitalized. Similar observations were noted for IVIG and IV pulse CS users, a previously unreported trend. Despite these findings not reaching statistical significance, they merit further exploration. Therapy with other DMARDs or NSAIDs did not influence hospitalization status, comparable to adults.(5, 15)
Importantly, management of immunomodulators did not significantly differ between groups. Withholding immunosuppression in patients with rheumatic diseases and symptomatic COVID-19 has been reinforced by the American College of Rheumatology (ACR).(16) Each case should be assessed individually, as both COVID-19 and rheumatic disease exacerbations entail risks for hospitalization, especially considering that disease flare usually warrants an increase in immunosuppression.
Our study's major strength is that, to our knowledge, this is the largest case series describing laboratory-confirmed COVID-19 in pediatric patients with rheumatic diseases. Limitations include its retrospective nature, and the method of patient selection which precludes us from calculating incidence and obtaining generalizable conclusions regarding severity compared to children without rheumatic diseases. The relatively small sample size precluded us from testing for collinearity between variables and performing multivariable analyses. Despite these limitations, we were able to achieve our aim of conveying the outcomes of COVID-19 in a cohort of pediatric rheumatic disease patients, setting precedent for larger studies needed to confirm the potential associations described in this manuscript. Multicenter studies would be useful to more comprehensively define the spectrum of COVID-19 and its natural history in children with rheumatic diseases.