COVID-19 Pandemic from Pediatric Rheumatologists Perspective

At least part of the world has finally emerged from the pandemic, and this extraordinary and challenging period has provided us with valuable information. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 from coronoviridae family, emerged in December 2019 in China as a fatal epidemic and rapidly spread throughout the planet.^1,2 The World Health Organization (WHO) declared COVID-19 a global pandemic on March 11th, 2020. Healthcare community, with all its departments, adapted very quickly to this new international health crisis.³ Rapidly, case reports and case series emerged from across the world.

Although coronaviruses often cause mild respiratory infections, they previously threatened humanity in 2002 with the severe acute respiratory syndrome (SARS-CoV-2) and in 2012 with the Middle East respiratory syndrome (MERS), as well. Most patients affected by COVID-19 experience only a mild cold, but it may also cause severe clinical manifestations with high mortality and morbidity, such as acute respiratory distress syndrome (ARDS) and cytokine storm. Since the true number of the whole infected people is not known, the estimated mortality rate associated with COVID-19 ranges between 1% and 4%.^4,5 Individuals with immunodeficiencies and underlying chronic medical conditions like diabetes or heart disease, and the elderly (> 60 years) constitute the main risk group for the mortality.⁶

In the beginning of the pandemic, it was thought that children were affected rarely and if affected have only mild symptoms. In May 2020, Riphagen et al. have reported from England, hyperinflammatory shock in eight children with similar features to atypical Kawasaki disease and Kawasaki disease shock syndrome that manifested late in the course of SARS-CoV-2 infection.⁷ With the awareness of this mysterious post-COVID hyper-inflammatory syndrome, now known as multisystem inflammatory syndrome in children (MIS-C), increasing number of pediatric cases were reported from the entire world. All reported children had a similar temporal association with COVID-19 and manifested with persistent fever, and various symptoms of organ involvement such as cardiovascular and gastrointestinal systems. A striking feature of MIS-C is that it shares many similarities with some diseases well known to pediatric rheumatologists, such as Kawasaki disease, Kawasaki shock syndrome, and macrophage activation syndrome. Thus, unexpectedly, pediatric rheumatologists have played a key role in the recognition and management of those patients. Beside the experience from similar diseases, with the help of published and shared data with as much speed as possible, American Rheumatology Academy (ACR) developed a clinical guidance for pediatric patients with MIS-C associated with SARS-CoV-2 on July 23, 2020.⁸ The latest ACR guidance continued to be updated as our understanding of the diagnosis and management of MIS-C improved.

Patients with MIS-C are managed by a multidisciplinary team including pediatric rheumatologists, cardiologists, infectious disease specialists, and pediatric intensive care specialists. Treatment modalities for this life-threatening condition have been effectively developed through communication globally among multidisciplinary specialists at pediatric centers. Therapies have included intravenous immune globulin, glucocorticoids, and cytokine targeted biological agents. However, there is no evidence-based data, since we lack randomized controlled studies.

It was not known whether patients with rheumatic diseases on immunosuppressant drugs would be at higher risk for COVID-19. This was a challenging issue as discontinuing the immunosuppressant drugs could lead to disease flares. As rheumatologists, we learned one more time from our experiences.⁹ Current data suggest that rheumatic diseases are associated with a small additional risk of SARS-CoV-2 infection.¹⁰ However, in the presence of comorbidities, high disease activity, and treatment with glucocorticoids or rituximab, the risk increases for patients having COVID-19 of poor outcomes.¹⁰ According to ACR guidelines for the Management of Pediatric Rheumatic Disease during the COVID- 19 pandemic, for children with rheumatic disease who experience symptomatic COVID-19, immunosuppressants should be temporarily delayed and steroids should be continued using the lowest effective dose possible to control underlying disease.¹¹ However, the treatment should be discussed on a case-by-case basis.

The development of effective vaccines against SARS-CoV-2, which threats all humanity, has once again demonstrated the utility of science. Vaccination against SARS-CoV-2 significantly reduces the risk of poor outcomes in the general population. Although the SARS-CoV-2 vaccine causes additional concerns for rheumatic disease flares, patients with rheumatic disease are strongly recommended to receive SARS-CoV-2 vaccination.¹² Nevertheless, safety and immunogenicity data regarding anti-SARS-CoV-2 vaccines among adolescents with rheumatic diseases are lacking and pediatric rheumatologists only have data from adult studies.

While we move past the 2-year of the pandemic, our increasing knowledge of the interaction between COVID-19 and autoimmunity renewed insights into pathogenesis and therapeutic targets. Since rheumatologists have a strong background in dealing with the uncontrolled response of the immune system, their involvement in the multidisciplinary team to diagnose and treat those patients, has undoubtedly contributed to the prognosis of these patients.