COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host–pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.

Despite the progress in the understanding how COVID-19 infection may impact immunocompromised patients, the data on inborn errors of immunity (IEI) remain limited and ambiguous. Therefore, we examined the risk of severe infection course and hospital admission in a large cohort of patients with IEI. In this multicenter nationwide retrospective survey-based trial, the demographic, clinical, and laboratory data were collected by investigating physicians from 8 national referral centers for the diagnosis and treatment of IEI using a COVID-19-IEI clinical questionnaire. In total, 81 patients with IEI (including 16 with hereditary angioedema, HAE) and confirmed SARS-CoV-2 infection were enrolled, and were found to have a 2.3-times increased (95%CI: 1.44–3.53) risk ratio for hospital admission and a higher mortality ratio (2.4% vs. 1.7% in the general population). COVID-19 severity was associated with the presence of clinically relevant comorbidities, lymphopenia, and hypogammaglobulinemia, but not with age or BMI. No individuals with HAE developed severe disease, despite a hypothesized increased risk due to perturbed bradykinin metabolism. We also demonstrated a high seroconversion rate in antibody-deficient patients and the safety of anti-spike SARS CoV-2 monoclonal antibodies and convalescent plasma. Thus, IEI except for HAE, represent significant risk factors for a severe COVID-19. Therefore, apart from general risk factors, immune system dysregulation may also be involved in the poor outcomes of COVID-19. Despite the study limitations, our results support the findings from previously published trials.

The number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients keeps rising in most of the European countries despite the pandemic precaution measures. The current antiviral and anti-inflammatory therapeutic approaches are only supportive, have limited efficacy, and the prevention in reducing the transmission of SARS-CoV-2 virus is the best hope for public health. It is presumed that an effective vaccination against SARS-CoV-2 infection could mobilize the innate and adaptive immune responses and provide a protection against severe forms of coronavirus disease 2019 (COVID-19) disease. As the race for the effective and safe vaccine has begun, different strategies were introduced. To date, viral vector-based vaccines, genetic vaccines, attenuated vaccines, and protein-based vaccines are the major vaccine types tested in the clinical trials. Over 80 clinical trials have been initiated; however, only 18 vaccines have reached the clinical phase II/III or III, and 4 vaccine candidates are under consideration or have been approved for the use so far. In addition, the protective effect of the off-target vaccines, such as <i>Bacillus</i> Calmette-Guérin and measles vaccine, is being explored in randomized prospective clinical trials with SARS-CoV-2-infected patients. In this review, we discuss the most promising anti-COVID-19 vaccine clinical trials and different vaccination strategies in order to provide more clarity into the ongoing clinical trials.

There is a growing demand for efficient medical therapies without undesired side effects that limit their application. Targeted therapies such as deliveries of pharmacologically active compounds to a specific site of action in the human body are still a big challenge. Encapsulation is an effective tool for targeted deliveries of drugs and sensitive compounds. It has been exploited as a technique that can manage the required distribution, action and metabolism of encapsulated agents. Food supplements or functional foods containing encapsulated probiotics, vitamins, minerals or extracts are often part of therapies and currently also a consumption trend. For effective encapsulation, optimal manufacturing has to be ensured. Thus, there is a trend to develop new (or modify existing) encapsulation methods. The most-used encapsulation approaches are based on barriers made from (bio)polymers, liposomes, multiple emulsions, etc. In this paper, recent advances in the use of encapsulation in the fields of medicine, food supplements and functional foods are highlighted, with emphasis on its benefits within targeted and supportive treatments. We have focused on a comprehensive overview of encapsulation options in the field of medicine and functional preparations that complement them with their positive effects on human health.

X-linked inhibitor of apoptosis (XIAP) is the most potent human inhibitor of apoptosis, and is also involved in NOD2dependent NFκB and MAPK signalling cascade activation. The absence or defective function of XIAP leads to the development of a rare and severe primary immunodeficiency known as X-linked lymphoproliferative syndrome type 2 (XLP-2), which is characterized by a triad of clinical manifestations, including a high incidence of haemophagocytic lymphohistiocytosis (HLH), lymphoproliferation and inflammatory bowel disease (IBD), usually with very early onset. Here, we present a novel XIAP mutation identified in a patient with atypical adult-onset IBD complicated by relapsing HLH, splenomegaly and sarcoid-like disease. The c.266delA mutation in the XIAP gene creates a premature stop codon, and causes a severe reduction in XIAP protein expression. The mutation is also associated with impaired spontaneous and staurosporine-and PMA-induced apoptosis accompanied by significantly increased expression of pro-apoptotic genes. We also confirmed the negative impact of this particular XIAP mutation on NOD2-dependent NFκB and MAPK activation, while NOD2-independent activation was found to be unaffected. Moreover, we assume that the mutation has an impact on the overproduction of IL-12 and IFNγ, the shift towards the Th1 immune response and increased numbers of central memory and effector memory CD4+ and CD8+ T cells. All these changes contribute to immune dysregulation and the clinical manifestation of XLP-2.

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Purpose of reviewAntisevere acute respiratory syndrome-corona virus 2 (SARS-CoV-2) vaccines may provide prompt, effective, and safe solution for the COVID-19 pandemic. Several vaccine candidates have been evaluated in randomized clinical trials (RCTs). Furthermore, data from observational studies mimicking real-life practice and studies on specific groups, such as pregnant women or immunocompromised patients who were excluded from RCTs, are currently available. The main aim of the review is to summarize and provide an immunologist's view on mechanism of action, efficacy and safety, and future challenges in vaccination against SARS-CoV-2.Recent findings mRNA and recombinant viral vector-based vaccines have been approved for conditional use in Europe and the USA. They show robust humoral and cellular responses, high with efficacy in prevention of COVID-19 infection (66.9 95%) and favorable safety profile in RCTs. High efficacy of 80-92% was observed in reallife practice. A pilot study also confirmed good safety profile of the mRNA vaccines in pregnant women. Unlike in those with secondary immunodeficiencies where postvaccination responses did not occur, encouraging results were obtained in patients with inborn errors of immunity. SummaryAlthough both RCTs and observational studies suggest good efficacy and safety profiles of the vaccines, their long-term efficacy and safety are still being discussed. Despite the promising results, clinical evidence for specific groups such as children, pregnant and breastfeeding women, and immunocompromised patients, and for novel virus variants are lacking.