Effect of biologic therapy on COVID-19 in children suffering from rheumatic diseases

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of the coronavirus disease 19 (COVID-19) pandemic. As of September 30, 2021, over 233 million cases of COVID-19 have been reported, along with over 4.77 million deaths. In Turkey, over 7 million cases of COVID-19 have been reported, along with more than 63,000 cumulative deaths during the same period.

Study: The clinical course of SARS‑CoV‑2 infection among children with rheumatic disease under biologic therapy: a retrospective and multicenter study. Image Credit: MIA Studio / Shutterstock.com

Rheumatic disease, treatments, and COVID-19

The common symptoms of SARS-CoV-2 infection include fever, shortness of breath, cough, myalgia, fatigue, sore throat, and loss of taste or smell. The clinical characteristics of COVID-19 are vast and can range from mild and asymptomatic cases to critical cases that can lead to multi-organ failure and death.

Initially, children were found to develop mild or asymptomatic courses of COVID-19. However, children suffering from rheumatic disease or those receiving immunosuppressant treatments may be more vulnerable to serious SARS-CoV-2 infections.

Previous studies have suggested that patients suffering from rheumatic diseases are at an increased risk of infections due to immune dysfunctions as a result of their disease, as well as the usage of immunomodulatory drugs. Biological disease-modifying anti-rheumatic drugs (bDMARDs) are often used in the treatment of rheumatic diseases. These drugs target the pathway of the immune system through cytokine blockade, thus causing dysregulation of the immune system.

The use of bDMARDs has led to an increased risk of COVID-19 in both children and adults. Therefore, whether these rheumatic diseases or the use of anti-rheumatic drugs affected the course of SARS-CoV-2 infection is of critical importance.

A new study conducted in Turkey aimed to determine the course of SARS-CoV-2 infection in children who were suffering from rheumatic disease and were receiving bDMARD treatment.

About the study

The current retrospective study involved fourteen pediatric rheumatology centers in Turkey. The study included a total of 113 patients who were infected with SARS-CoV-2 and were receiving treatment with bDMARD for their primary rheumatic diseases.

The medical records of patients who were diagnosed with rheumatic disease and treated with bDMARD were reviewed, along with those patients who were diagnosed with COVID-19, which were included in the study. The data was collected between April 2020 and 2021.

The current study also implemented few inclusion and exclusion criteria. The inclusion factors involved case definitions of COVID-19 according to certain criteria.

For example, in asymptomatic patients, the detection of the SARS-CoV-2 ribonucleic acid (RNA) was achieved by reverse-transcriptase polymerase-chain-reaction (RT-PCR) analysis. Comparatively, in symptomatic patients, enzyme-linked immunosorbent assay (ELISA) was performed to determine the presence of immunoglobulin G (IgG) and IgM antibodies. Patients who were infected with SARS-CoV-2 but did not receive bDMARDs were excluded from the study, along with patients who showed symptoms of COVID-19 but refused to undergo RT-PCR testing.

Study findings

The results of the study indicated that out of the 113 selected pediatric patients, 72 were female and 41 were male with a mean age of 12.87±4.69 years. Out of the 113 patients, 35 were diagnosed (30.9%) with systemic autoinflammatory disease (AID), 63 (55.8%) were diagnosed with juvenile idiopathic arthritis (JIA), 10 (8.9%) with vasculitides, and 5 (4.4%) with connective tissue diseases. Nineteen patients were found to have other additional comorbidities.

At the time of diagnosis, 71 of the patients were found to have at least one COVID-19 related symptom, while 42 were asymptomatic. COVID-19 was confirmed in 103 patients through the RT-PCR analysis and in 10 patients through the SARS-CoV-2 antibody test. Among the symptomatic patients, 29 exhibited respiratory symptoms such as dyspnea and cough, while 7 showed abnormal thorax computerized tomography (CT) findings.

A total of 24 patients required hospitalization, out of which 2 were admitted to intensive care and the remaining 89 received ambulatory care. Treatment was required by 35 patients, out of which 21 were hospitalized. Out of the 35 patients, 10 received azithromycin, 22 received favipiravir, seven received oseltamivir, and 10 required steroid treatment.

The results also indicated that 5 patients, of whom 2 were diagnosed with vasculitis, two with JIA, and one with AID, were found to be presented with multisystem inflammatory syndrome in children (MIS-C). Patients with vasculitis were treated with anti-tumor necrosis factor (TNF)-α drugs, whereas those with JIA were treated with anti-interleukin (IL)-1 agents, and the patient with AID was treated with canakinumab.

Two patients, one diagnosed with vasculitis and another JIA, died. No patients reported disease flare or complications post-COVID-19 follow-up.

Comparison of laboratory and clinical findings of the patients who required hospitalization and those who received ambulatory care did not show any difference in the type of rheumatic disease, as well as the biological drug used. Furthermore, it was also found that patients who received hospitalization were younger and exhibited a shorter duration of rheumatic disease. Additionally, the usage of steroids was more common in patients who were hospitalized.

Conclusion

The current study demonstrated that severe COVID-19 was found in patients with underlying comorbidities, irrespective of the use of bDMARDs. Although the study could not show that COVID-19 worsened in patients receiving bDMARDs, it was an important factor in the determination of the clinical characteristics and outcomes of patients infected with SARS-CoV-2.

The two major limitations of the study were the retrospective design and the small number of patients. Further multicenter studies need to be carried out to better understand the risk factors that can result in a severe course of COVID-19 in patients with rheumatic diseases.

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