Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52LOF/IκBδGOF). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for NFKB2 variants causing haploinsufficiency of p100 and p52 (hereafter, p52LOF/IκBδLOF) or gain-of-function of p52 (hereafter, p52GOF/IκBδLOF). In contrast to patients with APS-1, patients with disorders of NIK, RELB or NF-κB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-κB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases.

• MeSH
• aktivační mutace MeSH
• autoprotilátky * imunologie   MeSH
• COVID-19 genetika   imunologie   MeSH
• epiteliální buňky štítné žlázy metabolismus   patologie   MeSH
• genetická predispozice k nemoci * MeSH
• heterozygot MeSH
• interferon typ I * antagonisté a inhibitory   imunologie   MeSH
• kinasa indukující NF-kappaB MeSH
• lidé MeSH
• mutace ztráty funkce MeSH
• NF-kappa B - podjednotka p52 nedostatek   genetika   MeSH
• NF-kappa B * nedostatek   genetika   MeSH
• protein AIRE MeSH
• proteiny I-kappa B nedostatek   genetika   MeSH
• thymus abnormality   imunologie   patologie   MeSH
• virová pneumonie genetika   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

COVID-19 is viral respiratory infection with frequently fatal lung complications in the elderly or in people with serious comorbidities. Lung destruction appears to be associated with a cytokine storm related to an increased level of interleukin-6 (IL6). Therapeutic targeting of the interleukin-6 signaling pathway can attenuate such a cytokine storm and can be beneficial for patients with COVID-19 in danger of pulmonary failure. This article demonstrates the importance of IL6 in progression of disease and the possibility of inhibition of IL6 signaling in COVID-19 therapy.

• MeSH
• antiflogistika terapeutické užití   MeSH
• antivirové látky terapeutické užití   MeSH
• cytokinový receptor gp130 antagonisté a inhibitory   fyziologie   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunoterapie MeSH
• indoly terapeutické užití   MeSH
• interleukin-6 antagonisté a inhibitory   fyziologie   MeSH
• klinické zkoušky jako téma MeSH
• koronavirové infekce komplikace   farmakoterapie   imunologie   patofyziologie   MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• pandemie MeSH
• plíce patologie   MeSH
• receptory interleukinu-6 antagonisté a inhibitory   fyziologie   MeSH
• signální transdukce MeSH
• syndrom uvolnění cytokinů farmakoterapie   etiologie   imunologie   patofyziologie   MeSH
• virová pneumonie komplikace   farmakoterapie   imunologie   patofyziologie   MeSH
• virové receptory účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Covid-19 or SARS-CoV-2, a new RNA virus with high infectivity, and seemingly low mutability, which appeared in 2019 in the Wuhan province of China, has created a pandemic with dire consequences. At the end of May 2020, it became the first cause of mortality. As no treatment or vaccine may become available before many months, and because occurrence of similar pandemics is only a matter of time, arguments are presented here for testing the effect of transfer factor (TF), an immunomodulator devoid of toxicity, which has been extensively studied in the past for the treatment and prevention of viral infections.

• MeSH
• adjuvancia imunologická terapeutické užití   MeSH
• Betacoronavirus MeSH
• koronavirové infekce imunologie   terapie   MeSH
• lidé MeSH
• pandemie MeSH
• transfer faktor terapeutické užití   MeSH
• virová pneumonie imunologie   terapie   MeSH
• výzkumný projekt MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

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.

• MeSH
• antigeny CD274 genetika   metabolismus   MeSH
• COVID-19 MeSH
• cytokiny genetika   metabolismus   MeSH
• dendritické buňky imunologie   MeSH
• dospělí MeSH
• imunofenotypizace MeSH
• koronavirové infekce krev   imunologie   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• monocyty imunologie   MeSH
• neutrofily imunologie   MeSH
• pandemie MeSH
• přirozená imunita MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• virová pneumonie krev   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Lidská populace je v současnosti vystavena pandemii nového koronaviru SARS‑CoV‑2. Tento koronavirus s vysokou patogenitou do ní vstoupil na konci roku 2019. Zdrojem jsou velmi pravděpodobně netopýři a k přenosu na člověka došlo zatím neznámým zvířecím vektorem. Virus SARS‑CoV‑2 je vysoce infekční a přenáší se pravděpodobně výlučně respirační cestou. Průběh onemocnění vyvolaného SARS‑CoV‑2 je u většiny lidí mírný, a často dokonce bez klinických příznaků. U malé části infikovaných osob, především u seniorů a pacientů s různými komorbiditami, však infekce probíhá se závažnými klinickými projevy a vede až ke smrti. Tento závažný průběh onemocnění SARS‑CoV‑2 lze vysvětlit nezvládnutou zánětlivou reakcí, která je u disponovaných osob infekcí spuštěna. Infikované epitelové a endotelové buňky jsou ničeny buď cytopatickým efektem viru, nebo obrannou reakcí. To vede k masivnímu uvolnění vzorů vnitřního poškození, jež jsou následně identifikovány buňkami vrozené imunity prostřednictvím PRRs (pattern recognition receptors). Výsledkem je zvýšená tvorba prozánětlivých cytokinů a prozánětlivé formy buněčné smrti, jakými jsou pyroptóza a granulocytární NETóza, jež vedou k respiračnímu selhání.

The human population is now facing the pandemic of a new coronavirus SARS‑CoV‑2. This highly pathogenic coronavirus entered it in late 2019, probably transmitted from bats via still unknown animal vectors. SARS‑CoV‑2 is highly infectious, with a predominant respiratory route of transmission. The course of the disease caused by SARS‑CoV‑2 is largely mild in most people, often even without clinical symptoms. In a small subset of people, predominantly in elderly and patients with comorbidities, the infection has a severe course of action, with severe clinical presentation, and leads to death. This severe course of the disease caused by SARS‑CoV‑2 could be explained by an exaggerated inflammatory response evoked in these predisposed patients. Infected epithelial and endothelial cells are destroyed either by direct cytopathic effects of the virus or by the immune response. Damage‑associated molecular patterns that are released from dying cells are subsequently recognized by innate immunity cells via PRRs (pattern recognition receptors). The result is increased production of proinflammatory cytokines and proinflammatory forms of cell death, such as pyroptosis and granulocytic NETosis. Cytokine production and proinflammatory cell deaths are resulting in severe respiratory distress syndrome.

• Klíčová slova
• Covid 19,
• MeSH
• COVID-19 * etiologie   patofyziologie   přenos   MeSH
• extracelulární pasti MeSH
• lidé MeSH
• neutrofily patologie   MeSH
• SARS-CoV-2 * patogenita   růst a vývoj   MeSH
• virová pneumonie imunologie   patofyziologie   MeSH
• Check Tag
• lidé MeSH

Accumulating evidence suggests that obesity is a major risk factor for the initiation, progression, and outcomes of coronavirus disease 2019 (COVID-19). The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about the concomitant obesity and COVID-19 pandemics and their impact on health and society at large. In this perspective, we will address the inherent immunological perturbations and alterations in the renin-angiotensin-aldosterone system in patients with obesity and COVID-19, and discuss how these impairments may underlie the increased susceptibility and more detrimental outcomes of COVID-19 in people with obesity. Clearly, this has important implications for preventive measures, vaccination, and future therapeutic strategies to combat COVID-19. Furthermore, we will highlight important knowledge gaps and provide suggestions for future research and recommendations for policy actions. Since many new reports on COVID-19 rapidly appear, the present perspective should be seen as a focus for discussion to drive forward further understanding, research initiatives, and clinical management of COVID-19.

• MeSH
• angiotensin konvertující enzym MeSH
• Betacoronavirus imunologie   MeSH
• Coronavirus MeSH
• COVID-19 MeSH
• imunokompetence imunologie   MeSH
• imunologická tolerance imunologie   MeSH
• koronavirové infekce imunologie   terapie   MeSH
• lidé MeSH
• náchylnost k nemoci MeSH
• obezita komplikace   imunologie   MeSH
• pandemie MeSH
• prognóza MeSH
• renin-angiotensin systém fyziologie   MeSH
• rizikové faktory MeSH
• SARS-CoV-2 MeSH
• virová pneumonie imunologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

This paper reviews currently available data on the novel coronavirus and clinical features of COVID-19, followed by a detailed section on possible modifications of immunomodulatory therapy in multiple sclerosis patients with COVID-19, based on what we know so far. There are discussed: (i) The COVID-19 disease (Epidemiological background SARS-CoV-1 coronavirus; Autoimmune response to COVID-19; Asymptomatic course; SARS-CoV-2 test; COVID-19 symptoms), (ii) Treatment of COVID-19 (Experimental plasma treatment; Antiviral therapy; Antimalarial treatment scheme; Biological treatment; Corticosteroid treatment; Symptomatic treatment; Vaccine preparation) and (iii) Multiple sclerosis and SARS-CoV-2 infection (Epidemiological recommendation).

• MeSH
• asymptomatické nemoci epidemiologie   MeSH
• autoimunita MeSH
• Betacoronavirus fyziologie   MeSH
• COVID-19 MeSH
• imunologické faktory farmakologie   MeSH
• imunomodulace imunologie   MeSH
• koronavirové infekce * epidemiologie   imunologie   terapie   virologie   MeSH
• lidé MeSH
• pandemie * MeSH
• roztroušená skleróza * epidemiologie   imunologie   terapie   MeSH
• SARS-CoV-2 MeSH
• virová pneumonie * epidemiologie   imunologie   terapie   virologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

We report a case of an 8-year-old girl who underwent a SARS-CoV-2 infection manifesting with atypical symptoms spearheaded by abdominal discomfort and systemic inflammation and partially mimicking hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS), which however did not fulfill the HLH/MAS diagnostic criteria. In this case of what has since been described as Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-COV-2 (PIMS-TS) we documented excellent clinical response to immunosuppression with systemic corticosteroids and intravenous immunoglobulins. We show a detailed longitudinal development of neutrophil immunophenotype which suggests activation and engagement of neutrophils during PIMS-TS with compensatory contraction of the response and contra-regulation of neutrophil phenotype during recovery.

• MeSH
• Betacoronavirus * imunologie   metabolismus   MeSH
• dítě MeSH
• hormony kůry nadledvin aplikace a dávkování   MeSH
• imunosupresivní léčba * MeSH
• intravenózní imunoglobuliny aplikace a dávkování   MeSH
• koronavirové infekce * krev   diagnóza   farmakoterapie   imunologie   MeSH
• lidé MeSH
• lymfohistiocytóza hemofagocytární * diagnóza   farmakoterapie   imunologie   MeSH
• neutrofily MeSH
• pandemie * MeSH
• syndrom aktivovaných makrofágů * diagnóza   farmakoterapie   imunologie   MeSH
• virová pneumonie * krev   diagnóza   farmakoterapie   imunologie   MeSH
• zánět diagnóza   farmakoterapie   imunologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association-European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.

• MeSH
• antivirové látky MeSH
• Betacoronavirus MeSH
• dialýza ledvin MeSH
• hodnocení rizik MeSH
• imunosupresiva terapeutické užití   MeSH
• koronavirové infekce komplikace   imunologie   terapie   MeSH
• lidé MeSH
• nefrologie normy   MeSH
• nemoci ledvin komplikace   imunologie   terapie   MeSH
• pandemie MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• společnosti lékařské MeSH
• virová pneumonie komplikace   imunologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Evropa MeSH

A close interaction between the virus SARS-CoV-2 and the immune system of an individual results in a diverse clinical manifestation of the COVID-19 disease. While adaptive immune responses are essential for SARS-CoV-2 virus clearance, the innate immune cells, such as macrophages, may contribute, in some cases, to the disease progression. Macrophages have shown a significant production of IL-6, suggesting they may contribute to the excessive inflammation in COVID-19 disease. Macrophage Activation Syndrome may further explain the high serum levels of CRP, which are normally lacking in viral infections. In adaptive immune responses, it has been revealed that cytotoxic CD8+ T cells exhibit functional exhaustion patterns, such as the expression of NKG2A, PD-1, and TIM-3. Since SARS-CoV-2 restrains antigen presentation by downregulating MHC class I and II molecules and, therefore, inhibits the T cell-mediated immune responses, humoral immune responses also play a substantial role. Specific IgA response appears to be stronger and more persistent than the IgM response. Moreover, IgM and IgG antibodies show similar dynamics in COVID-19 disease.

• MeSH
• adaptivní imunita MeSH
• Betacoronavirus imunologie   MeSH
• COVID-19 MeSH
• interakce hostitele a patogenu imunologie   MeSH
• koronavirové infekce imunologie   prevence a kontrola   MeSH
• lidé MeSH
• pandemie MeSH
• přirozená imunita MeSH
• SARS-CoV-2 MeSH
• vakcíny proti COVID-19 MeSH
• virová pneumonie imunologie   MeSH
• virové vakcíny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH