COVID-19 and the differences in physiological background between children and adults and their clinical consequences

The SARS-CoV-2 pandemic has indeed been one of the most significant problems facing the world in the last decade. It has affected (directly or indirectly) the entire population and all age groups. Children have accounted for 1.7 % to 2 % of the diagnosed cases of COVID-19. COVID-19 in children is usually associated with a mild course of the disease and a better survival rate than in adults. In this review, we investigate the different mechanisms which underlie this observation. Generally, we can say that the innate immune response of children is strong because they have a trained immunity, allowing the early control of infection at the site of entry. Suppressed adaptive immunity and a dysfunctional innate immune response is seen in adult patients with severe infections but not in children. This may relate to immunosenescence in the elderly. Another proposed factor is the different receptors for SARS-CoV-2 and their differences in expression between these age groups. In infants and toddlers, effective immune response to viral particles can be modulated by the pre-existing non-specific effect of live attenuated vaccines on innate immunity and vitamin D prophylaxis. However, all the proposed mechanisms require verification in larger cohorts of patients. Our knowledge about SARS-CoV-2 is still developing.

Immune paralysis in paediatric patients with multisystem inflammatory syndrome associated with COVID-19

Background: Paediatric SARS-CoV-2 infection is usually mild and often asymptomatic. Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 is a complication that occurs 4 to 6 weeks after primary infection. Typical symptoms are high fever, organ dysfunction and strongly elevated markers of inflammation. The immunopathology includes T-lymphocyte paralysis that is characterised by severely reduced circulating T-cells that have dysregulated activation and differentiation mechanisms, mainly CD4+ T-lymphocytes. Immune paralysis is defined as increased expression of PD-1 and TIM-3. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. Method: We present 3 paediatric patients (2 males, 1 female) with MIS-C aged 11 to 13 years admitted to paediatric intensive care unit in our University teaching hospital in Martin. Immunological parameters were measured after the admission to the hospital and continuously evaluated during the treatment. Results: In all patients we detected in immunological profile significant signs of immune paralysis of T-lymphocytes, both CD4+ and CD8+ T-lymphocytes. One patient had increased expression of PD-1 and TIM-3, other two patients had increased expression of PD-1. In two patients we detected depletion of NK cells. All patients had lymphopenia (moderate to severe) and highly elevated inflammatory markers (CRP, IL-6, ferritin) and procoagulant factors (fibrinogen, D-dimers). They were treated according to the protocol with combined immunomodulatory and anti-inflammatory therapies (intravenous immunoglobulins, corticosteroids, one patient with anakinra) with positive effect on immune profile and also on clinical condition. Conclusion: Children with MIS-C show various immunological abnormalities including T-cell reduction and cytokine release syndrome, which can be fatal. It is poorly understood how T-cell dysregulation can contribute to the pathogenesis, but hyperactivation of CD4+ T-lymphocytes and immune paralysis that promote further viral infection can drive pulmonary damage, cardiorenal syndrome and organ failure. Understanding of the immunopathology in MIS-C can help in development of better immune intervention therapies to prevent serious long-term effect of COVID-19 infection also in paediatric patients.

Allergic diseases in the era of covid-19 pandemic

Allergic diseases affect one third of general population and usually require regular application of anti-allergic treatment of allergen immuno-therapy. Allergic people and patients with chronic allergic respiratory diseases, based on the published studies and case report series, do not yield an increased risk for obtaining COVID-19 compared to the general population. Anti-allergic medicaments /with the exception of systemic corticosteroids) do not represent a risk in relation with COVID-19 and its complicated course. Patients should continue in their chronic anti-allergic treatment (including biologicals, immunosuppressants, and corticosteroids) without the withdrawal or tapering the dose. Patients should continue also in the applied allergen immunotherapy. In case of acquiring COVID-19, it is necessary to contact the caring specialists with the highly-individualized re-assessment of the therapeutic strategy. The aim is to maintain the achieved control over allergic disease.