Immune dysregulation in hospitalized COVID-19 patients is associated with worse clinical outcome

Background: COVID-19 is a viral disease affecting mostly respiratory system with variable severity of the clinical course. Several clinical and laboratory parameters are associated with poor outcome. Progression of the clinical stage is associated with the exaggerated immune response and the cytokine storm. Method(s): We focused on the search of potential prognostic markers of fatal outcome among immune parameters. To this end, we examined the immune profile in 823 COVID-19 patients hospitalized in University Teaching Hospital in Martin (Slovakia) on admission and its changes over time during the first week of hospitalization. The examined immune profile consisted of the differential blood cell counts, serum concentration of immunoglobulins and basic complement compounds C4 and C3, flow cytometric lymphocyte subsets phenotyping and the measurement of selected activation and inhibition markers. Result(s): Although none of examined parameters alone had sufficient AUC value to be considered as a marker of (un)favourable outcome, we found several significant differences among different severity groups of patients, as well as between survivors and non-survivors. Severity of COVID-19 correlated with the severity of neutrophilia, thrombocytopenia, depletion of leukocyte (except for neutrophils) and lymphocyte subsets. In comparison to the fatal outcome, survival was associated with higher concentration of C3 and IgM, lower proportion of CD8+CD38+ cells, higher proportion of CD8+NKG2A+ and NK NKG2A+ cells on admission and with the significant increase in the expression on HLA-DR on both CD3+ and CD8+ cells over the first week. Conclusion(s): Our results point out to the dysregulated functional status of depleted CD8+ cells with their over-activation and possibly insufficient compensatory inhibition in COVID-19 non-survivors. Based on our results, the increase in HLA-DR expression on CD3+ and CD8+ cells is necessary for recovery.

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.

Inhibitory immune checkpoint molecules and exhaustion of T cells in COVID-19

COVID-19 (Coronavirus Disease) is an infectious disease caused by the coronavirus SARS-CoV-2 (Severe acute respiratory syndrome Coronavirus 2), which belongs to the genus Betacoronavirus. It was first identified in patients with severe respiratory disease in December 2019 in Wuhan, China. It mainly affects the respiratory system, and in severe cases causes serious lung infection or pneumonia, which can lead to the death of the patient. Clinical studies show that SARS-CoV-2 infection in critical cases causes acute tissue damage due to a pathological immune response. The immune response to a new coronavirus is complex and involves many processes of specific and non-specific immunity. Analysis of available studies has shown various changes, especially in the area of specific cellular immunity, including lymphopenia, decreased T cells (CD3+, CD4+ and CD8+), changes in the T cell compartment associated with symptom progression, deterioration of the condition and development of lung damage. We provide a detailed review of the analyses of immune checkpoint molecules PD-1, TIM-3, LAG-3 CTLA-4, TIGIT, BTLA, CD223, IDO-1 and VISTA on exhausted T cells in patients with asymptomatic to symptomatic stages of COVID-19 infection. Furthermore, this review may help to better understand the pathological T cell immune response and improve the design of therapeutic strategies for patients with SARS-CoV-2 infection.

Vaccination against COVID-19 from the point of view of an allergist

Vaccination against COVID-19 is currently one of the most important topics for discussion. Due to published information about severe allergic reactions after vaccination with mRNA vaccines abroad, specialists in the field of clinical immunology and allergology are frequently asked to assess the risk of vaccination. At the same time, clinical immunologist and allergist has a key role in the differential diagnosis and subsequent management of post-vaccination reactions. In the following article, we present current knowledge about vaccination against COVID-19 from the perspective of a clinical immunologist and allergist with reference to standard vaccination recommendations and guidelines of medical societies.

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.