Tocilizumab for Severe COVID-19 Infection and Multisystem Inflammatory Syndrome in Adults and Children

Abstract

Coronavirus disease 2019 (COVID-19) rapidly emerged as a global pandemic, placing imminent stress and burden on healthcare resources and workers worldwide. Many patients who present with a severe COVID-19 infection are at high risk of developing severe acute respiratory distress syndrome (ARDS), leading to a vast number of patients requiring mechanical ventilation and a high mortality rate. Similar to Middle East respiratory syndrome, COVID-19 demonstrates an initial viral replication phase that manifests as a variety of symptoms typically flu-like in nature, followed by a profound inflammatory response leading to rapid production of cytokines and uncontrolled inflammation. There have also been many cases of COVID-19 in pediatric patients presenting with elevated inflammatory markers and multisystem involvement labeled as a multisystem inflammatory syndrome (MIS-C) by the world health organization (WHO). The recent treatment of systemic inflammatory response to COVID-19 targets the secondary phase involving cytokine release syndrome. The detrimental effects of IL-6 can be profound and elevated levels are associated with a higher mortality rate and mechanical ventilation. Tocilizumab is an IL-6 inhibitor most widely investigated to target cytokine storm syndrome. Since June 2021, the FDA enacted an emergency use authorization for tocilizumab in the treatment of COVID-19. Several clinical trials have investigated tocilizumab combined with corticosteroids for treating severe ARDS associated with COVID-19. An increasing amount of evidence suggests that targeting the cytokine storm syndrome related to COVID-19 can lead to improved outcomes, especially in those patients requiring mechanical ventilation and with a critical illness. Additional studies are warranted to further look at the positive effects of tocilizumab in the COVID-19 population while additionally defining possible adverse effects.

Vitamin D Supplementation in Neonatal and Infant MIS-C Following COVID-19 Infection

“…Moreover, the common gastrointestinal involvement observed in MIS-C is less frequent in Kawasaki disease-affected children [11,13,[24][25][26]29,33,34,40]. Furthermore, it is noteworthy that MIS-C results from an abnormal immune response to acute SARS-CoV-2, supporting the current view of its post-infectious nature [13,16,24,34,41,42]. Even if the MIS-C pathogenic mechanism is still unknown, it is strongly supposed to be an autoimmune vasculitis, in which higher anti-SARS-CoV-2 IgG antibodies are associated with a cytokine storm characterized by increased levels of pro-inflammatory cytokines (i.e., TNFα, IL1β, IL6, IL8, IL18) and with increased coronary disease biomarkers, thus resulting in diffuse endothelial damage through immune complexes and complement pathways' activation.…”

“…To date, there is mounting evidence that a small minority of children infected with SARS-CoV-2 later develop MIS-C, especially in those regions where the COVID-19 burden was higher [16,19,21,22]. According to the CDC diagnostic criteria, MIS-C patients are younger than 21 years, present with fever and laboratory evidence of multisystem involvement (two or more domains involved), and need hospitalization in the absence of an alternative diagnosis.…”

“…Due to the observed similarities with KD, especially for what concerns cardiac dysfunction, therapeutic approaches are usually extrapolated from such condition, with intravenous immunoglobulin (IVIG) infusion as first-line therapy, usually in association with steroids and anticoagulants (in those cases where these drugs are clinically contraindicated). In those clinical presentations refractory to first-line therapies, anti-cytokine approaches (i.e., IL1 blockade (with anakinra or cankinumab) and/or IL6r blockade (with tocilizumab)) have proven to be useful [16,21,[24][25][26]30,32,34,40,44,46].…”

“…Furthermore, as highlighted by a recent review, the SARS-CoV-2-specific antibody response differs between the two age groups, with children showing the highest levels of anti-COVID-19 IgG and neutralizing antibody titers compared to adults, an immunological signature accounting for the observed reduced viral load and faster virus clearance in this population, further supporting the assumption of a quicker and more effective humoral response in children rather than in adults. Last but not least, it has been observed that in pediatric patients, their immune response to acute SARS-CoV-2 infection is characterized by lower amounts of proinflammatory cytokines, as the involved mechanism is more skewed toward a Th2-mediated response [7,8,13,[15][16][17].…”

Clinical Features of COVID-19 in Pediatric Rheumatic Diseases: 2020–2022 Survey of the Pediatric Rheumatology Association of Japan

“…Our results suggest that, with regard to glucocorticoids, it was common for Japanese pediatricians/physicians to continue at the same (or higher) dose when treating COVID-19 cases ( Table 3 ). On the other hand, the biologic tocilizumab is not only used for PRD treatment but also for COVID-19 treatment [ 33 ]. It was recently suggested that the Janus kinase (JAK) inhibitor baricitinib may be effective for COVID-19 treatment [ 34 ].…”