Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.
- MeSH
- COVID-19 * imunologie prevence a kontrola MeSH
- dospělí MeSH
- glykoprotein S, koronavirus imunologie MeSH
- humorální imunita MeSH
- lidé středního věku MeSH
- lidé MeSH
- neutralizující protilátky * krev imunologie MeSH
- příjemce transplantátu * MeSH
- protilátky virové * krev imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- sekundární imunizace MeSH
- senioři MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vakcína BNT162 imunologie aplikace a dávkování MeSH
- vakcíny proti COVID-19 imunologie aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.
- MeSH
- butyrofiliny * genetika metabolismus MeSH
- COVID-19 * genetika komplikace imunologie virologie MeSH
- dítě MeSH
- genetická predispozice k nemoci MeSH
- heterozygot MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- SARS-CoV-2 * MeSH
- syndrom systémové zánětlivé reakce * genetika MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Extensive research has been conducted on the SARS-CoV-2 virus in association with various infectious diseases to understand the pathophysiology of the infection and potential co-infections. In tropical countries, exposure to local viruses may alter the course of SARS-CoV-2 infection and coinfection. Notably, only a portion of the antibodies produced against SARS-CoV-2 proteins demonstrate neutralizing properties, and the immune response following natural infection tends to be temporary. In contrast, long-lasting IgG antibodies are common after dengue virus infections. In cases where preexisting antibodies from an initial dengue virus infection bind to a different dengue serotype during a subsequent infection, there is a potential for antibody-dependent enhancement (ADE) and the formation of immune complexes associated with disease severity. Both SARS-CoV-2 and dengue infections can result in immunodeficiency. Viral proteins of both viruses interfere with the host's IFN-I signaling. Additionally, a cytokine storm can occur after viral infection, impairing a proper response, and autoantibodies against a wide array of proteins can appear during convalescence. Most of the reported autoantibodies are typically short-lived. Vaccines against both viruses alter the immune response, affecting the course of viral infection and enhancing clearance. A comprehensive analysis of both viral infections and pathogenicity is revisited to prevent infection, severity, and mortality.
- MeSH
- COVID-19 * imunologie virologie MeSH
- dengue * imunologie virologie MeSH
- koinfekce imunologie virologie MeSH
- lidé MeSH
- protilátky virové * imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- virus dengue * imunologie MeSH
- zvýšená infektivita v přítomnosti protilátek imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
As of the 7th of July 2024, 775,754,322 confirmed cases of COVID-19, including 7,053,902 deaths worldwide, had been reported to the WHO (World Health Organization). Nevertheless, untill the 15th of July 2024, a total of 13,578,710,228 vaccine doses had been administered, with almost no country spared from COVID-19 attacks. The pathophysiology of this virus is complicated, and several symptoms require a deep understanding of the actual mechanisms. It is unclear why some patients develop severe symptoms while others do not, although literature suggests a role for vitamin D. Vitamin D plays a crucial role in the infection or in ameliorating the severity of symptoms. The mechanism of action of vitamin D and vitamin D deficiency (VDD) is well understood. VDD is associated with increased hospitalization of severely ill patients and increased levels of COVID-19-caused mortality. Recent studies suggest that vitamin D levels and genetic variations in the vitamin D receptor (VDR) gene significantly impact the severity and outcomes of COVID-19, especially in the infections caused by Delta and Omicron variants. Furthermore, VDD causes immune system dysregulation upon infection with SARS-CoV-2, indicating that vitamin D sufficiency is crucial in fighting against COVID-19 infection. The therapeutic effect of vitamin D raises interest in its potential role as a prophylactic and treatment adjunct. We evaluate the immunomodulatory effects of vitamin D and its ability to enhance the efficacy of new antiviral drugs like molnupiravir and paxlovid against SARS-CoV-2. This review discusses the role of vitamin D sufficiency and VDD in COVID-19 initiation and progression, emphasizing the molecular mechanisms by which vitamin D exerts its actions as a proactive step for the next pandemic. However, there is still no clear evidence of vitamin D's impact on prevention and treatment, leading to contradictory findings. Therefore, large-scale randomized trials are required to reach a definitive conclusion. A bibliometric analysis of publications related to vitamin D, immunity, and COVID-19 revealed a significant increase in research activity in this area, particularly in 2020-2024, underscoring the growing recognition of vitamin D's potential role in the context of the pandemic.
- MeSH
- COVID-19 * imunologie MeSH
- farmakoterapie COVID-19 MeSH
- lidé MeSH
- nedostatek vitaminu D * farmakoterapie imunologie MeSH
- pandemie MeSH
- receptory kalcitriolu metabolismus MeSH
- SARS-CoV-2 imunologie MeSH
- vitamin D * terapeutické užití aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
V souboru očkovaných a neočkovaných jedinců, kteří prodělali nebo neprodělali onemocnění Covid-19, jsme sledovali vztah mezi anti-SARS-CoV-2 IgG a některými parametry, které mají dle literatury význam při rozvoji a průběhu onemocnění Covid-19. Šlo o celkové IgG, podtřídy IgG1-4, složky komplementu C3c, C4 a cirkulující imunokomplexy (CIK). Zjistili jsme, že neočkovaní, očkovaní vakcínou Pfizer/BioNTech a Moderna a rovněž prodělavší a neprodělavší onemocnění Covid-19 se významně liší v hladině antiSARS-CoV-2 IgG. Očkování mělo na výši hladiny protilátek větší vliv než prodělání onemocnění. IgG4 se zvýšilo u očkovaných po vakcíně Pfizer/BioNTech. Ostatní podtřídy IgG, celkové IgG, CIK a složky komplementu se mezi skupinami statisticky významně nelišily.
In a group of vaccinated and unvaccinated individuals who did or did not experience Covid-19 disease, we monitored the relationship between anti-SARS-CoV-2 IgG and some parameters that, according to the literature, are important in the development and course of illness of Covid-19. These were total IgG, IgG1-4 subclasses, complement components C3c, C4 and circulating immune complexes (CIC). We found that unvaccinated, vaccinated with Pfizer/BioNTech and Moderna vaccine, as well as advanced and non-advanced Covid-19 patients differed significantly in the level of anti-SARS-CoV-2 IgG. Vaccination had a greater effect on the level of antibodies than experiencing the disease. IgG4 increased in vaccinees after the Pfizer/BioNTech vaccine. Other IgG subclasses, total IgG, CIC and complement components were not statistically significantly different between groups.
- MeSH
- COVID-19 * imunologie prevence a kontrola MeSH
- dospělí MeSH
- ELISA přístrojové vybavení MeSH
- imunoglobulin G analýza imunologie účinky léků MeSH
- imunokomplex MeSH
- indikátory a reagencie klasifikace MeSH
- komplement MeSH
- lidé středního věku MeSH
- lidé MeSH
- nefelometrie a turbidimetrie přístrojové vybavení MeSH
- vakcinace * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
BackgroundCOVID-19 remains a major infectious disease with substantial implications for individual and public health including the risk of a post-infection syndrome, long COVID. The continuous changes in dominant variants of SARS-CoV-2 necessitate a careful study of the effect of preventative strategies.AimWe aimed to estimate the effectiveness of post-vaccination, post-infection and hybrid immunity against severe cases requiring oxygen support caused by infections with SARS-CoV-2 variants BA1/2 and BA4/5+, and against long COVID in the infected population and their changes over time.MethodsWe used a Cox regression analysis with time-varying covariates and calendar time and logistic regression applied to national-level data from Czechia from December 2021 until August 2023.ResultsRecently boosted vaccination, post-infection and hybrid immunity provide significant protection against a severe course of COVID-19, while unboosted vaccination more than 10 months ago has a negligible protective effect. The post-vaccination immunity against the BA1/2 or BA4/5+ variants, especially based on the original vaccine types, appears to wane rapidly compared with post-infection and hybrid immunity. Once infected, however, previous immunity plays only a small protective role against long COVID.ConclusionVaccination remains an effective preventative measure against a severe course of COVID-19 but its effectiveness wanes over time thus highlighting the importance of booster doses. Once infected, vaccines may have a small protective effect against the development of long COVID.
- MeSH
- COVID-19 * imunologie prevence a kontrola epidemiologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- postakutní syndrom COVID-19 MeSH
- SARS-CoV-2 * imunologie MeSH
- sekundární imunizace MeSH
- senioři MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 * imunologie aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
SARS-CoV-2 je virus, který infikuje respirační trakt a může způsobit závažné, někdy až život ohrožující onemocnění COVID-19. U více než 5 % symptomatických pacientů je infekce spojena s výskytem postakutních následků. První kontakt viru s imunitním systémem nazofaryngu a orofaryngu vyvolává slizniční imunitní odpověď spojenou s lokální produkcí sekrečních protilátek třídy imunoglobulinů A (sIgA), což může přispět k lokalizaci viru na horní cesty dýchací a asymptomatické či pouze klinicky mírné infekci. Během pandemie rychle vyvinuté systémově působící vakcíny úspěšně chrání před závažnou formou onemocnění a jeho postakutními následky, nicméně neindukují protilátky ve slizničních sekretech u dosud SARS-CoV-2-naivních jedinců. U těch, kteří již infekci prodělali, mohou přesto systémové vakcíny posílit tvorbu protilátek sIgA. Je třeba zdůraznit, že klinická prospěšnost systémové imunizace vakcínami proti COVID-19 přesvědčivě dokumentovaná u desítek milionů jedinců zastiňuje vzácné, mnohdy sporně dokumentované komplikace očkování. Neschopnost současných vakcín navodit slizniční imunitní odpověď a zabránit šíření viru sekrety infikovaných jedinců poukazuje na vzájemnou nezávislost slizniční a systémové imunity. To podtrhuje potřebu vývoje vakcín, které vyvolají patřičné odpovědi v obou kompartmentech imunitního systému.
SARS-CoV-2 is a virus which infects the respiratory tract and may cause severe, occasionally life-threatening disease COVID-19. In more than 5% of symptomatic patients the infection is associated with post-acute symptoms. The initial contact of the virus with the immune system of the nasopharynx and oropharynx induces a mucosal immune response manifested by the production of secretory IgA (sIgA) antibodies which may contribute to the restriction of the infection to the upper respiratory tract and an asymptomatic or clinically mild disease. The current systemically administered vaccines protected against the severe COVID-19 infection and its post-acute sequelae. However, they do not induce antibodies in mucosal secretions in SARS-CoV-2-naive individuals. In contrast, in those who previously experienced mucosal infection, systemically administered vaccines may stimulate sIgA production. The clinical benefit of systemic vaccination convincingly documented in tens of millions of individuals overshadows the rare, sometimes controversial reports of complications encountered after vaccination. The inability of current SARS-CoV-2 vaccines to induce mucosal immune responses and to prevent the spreading of the virus by external secretions demonstrates the mutual independence of mucosal and systemic compartments of the immune system, and thus emphasizes need for the development of vaccines inducing protective immune responses in both compartments.
- MeSH
- COVID-19 imunologie prevence a kontrola MeSH
- lidé MeSH
- slizniční imunita imunologie účinky léků MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Secretory (S) IgA antibodies against severe acute respiratory syndrome (SARS)-CoV-2 are induced in saliva and upper respiratory tract (URT) secretions by natural infection and may be critical in determining the outcome of initial infection. Secretory IgA1 (SIgA1) is the predominant isotype of antibodies in these secretions. Neutralization of SARS-CoV-2 is most effectively accomplished by polymeric antibodies such as SIgA. We hypothesize that cleavage of SIgA1 antibodies against SARS-CoV-2 by unique bacterial IgA1 proteases to univalent Fabα antibody fragments with diminished virus neutralizing activity would facilitate the descent of the virus into the lungs to cause serious disease and also enhance its airborne transmission to others. Recent studies of the nasopharyngeal microbiota of patients with SARS-CoV-2 infection have revealed significant increases in the proportions of IgA1 protease-producing bacteria in comparison with healthy subjects. Similar considerations might apply also to other respiratory viral infections including influenza, possibly explaining the original attribution of influenza to Haemophilus influenzae, which produces IgA1 protease.
- MeSH
- Bacteria enzymologie MeSH
- COVID-19 * přenos imunologie virologie mikrobiologie MeSH
- Haemophilus influenzae enzymologie imunologie MeSH
- imunoglobulin A sekreční * metabolismus MeSH
- imunoglobulin A imunologie MeSH
- lidé MeSH
- nazofarynx mikrobiologie virologie MeSH
- neutralizující protilátky imunologie MeSH
- protilátky virové imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- serinové endopeptidasy metabolismus imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
COVID-19 has been associated with high mortality in patients treated with Chimeric Antigen Receptor (CAR) T-cell therapy for hematologic malignancies. Here, we investigated whether the outcome has improved over time with the primary objective of assessing COVID-19-attributable mortality in the Omicron period of 2022 compared to previous years. Data for this multicenter study were collected using the MED-A and COVID-19 report forms developed by the EBMT. One-hundred-eighty patients were included in the analysis, 39 diagnosed in 2020, 35 in 2021 and 106 in 2022. The median age was 58.9 years (min-max: 5.2-78.4). There was a successive decrease in COVID-19-related mortality over time (2020: 43.6%, 2021: 22.9%, 2022: 7.5%) and in multivariate analysis year of infection was the strongest predictor of survival (p = 0.0001). Comparing 2022 with 2020-2021, significantly fewer patients had lower respiratory symptoms (21.7% vs 37.8%, p = 0.01), needed oxygen support (25.5% vs 43.2%, p = 0.01), or were admitted to ICU (5.7% vs 33.8%, p = 0.0001). Although COVID-19-related mortality has decreased over time, CAR T-cell recipients remain at higher risk for complications than the general population. Consequently, vigilant monitoring for COVID-19 in patients undergoing B-cell-targeting CAR T-cell treatment is continuously recommended ensuring optimal prevention of infection and advanced state-of-the art treatment when needed.
- MeSH
- chimerické antigenní receptory imunologie MeSH
- COVID-19 * terapie imunologie mortalita MeSH
- dítě MeSH
- dospělí MeSH
- hematologické nádory * terapie mortalita imunologie MeSH
- imunoterapie adoptivní * metody škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- předškolní dítě MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: SARS-CoV-2, which causes COVID-19, has killed more than 7 million people worldwide. Understanding the development of postinfectious and postvaccination immune responses is necessary for effective treatment and the introduction of appropriate antipandemic measures. OBJECTIVES: We analysed humoral and cell-mediated anti-SARS-CoV-2 immune responses to spike (S), nucleocapsid (N), membrane (M), and open reading frame (O) proteins in individuals collected up to 1.5 years after COVID-19 onset and evaluated immune memory. METHODS: Peripheral blood mononuclear cells and serum were collected from patients after COVID-19. Sampling was performed in two rounds: 3-6 months after infection and after another year. Most of the patients were vaccinated between samplings. SARS-CoV-2-seronegative donors served as controls. ELISpot assays were used to detect SARS-CoV-2-specific T and B cells using peptide pools (S, NMO) or recombinant proteins (rS, rN), respectively. A CEF peptide pool consisting of selected viral epitopes was applied to assess the antiviral T-cell response. SARS-CoV-2-specific antibodies were detected via ELISA and a surrogate virus neutralisation assay. RESULTS: We confirmed that SARS-CoV-2 infection induces the establishment of long-term memory IgG+ B cells and memory T cells. We also found that vaccination enhanced the levels of anti-S memory B and T cells. Multivariate comparison also revealed the benefit of repeated vaccination. Interestingly, the T-cell response to CEF was lower in patients than in controls. CONCLUSION: This study supports the importance of repeated vaccination for enhancing immunity and suggests a possible long-term perturbation of the overall antiviral immune response caused by SARS-CoV-2 infection.
- MeSH
- B-lymfocyty imunologie MeSH
- buněčná imunita imunologie MeSH
- COVID-19 * imunologie MeSH
- dospělí MeSH
- ELISPOT MeSH
- glykoprotein S, koronavirus imunologie MeSH
- humorální imunita MeSH
- imunologická paměť MeSH
- leukocyty mononukleární imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- protilátky virové * krev imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři MeSH
- T-lymfocyty imunologie MeSH
- vakcíny proti COVID-19 imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH