Background/Objectives: This retrospective study analyzed soluble urokinase plasminogen activator receptor (suPAR) plasma levels alongside routine inflammatory markers, including the neutrophil-to-lymphocyte count ratio, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and D-dimers in COVID-19 patients hospitalized during the Omicron wave of the pandemic. Methods: We measured plasma suPAR levels using a suPARnostic® Quick Triage kit. We divided COVID-19 patients into two groups based on the severity of SARS-CoV-2 infection according to the National Institutes of Health (NIH) criteria. The logistic regression analysis tested the predictive value of the biomarkers. Results: We evaluated 160 consecutive COVID-19 patients hospitalized between January and August 2022. The cohort exhibited a high incidence of comorbidities, with an in-hospital mortality rate of 5.6%. Upon admission, the median suPAR plasma levels were not significantly different between patients with mild COVID-19 (n = 110) and those with moderate/severe disease (n = 50), with 7.25 ng/mL and 7.55 ng/mL, respectively. We observed significant differences (p < 0.01) between the groups for CRP and IL-6 levels that were higher in moderate/severe disease than in mild infection. Additionally, suPAR plasma levels were above the normal range (0-2.00 ng/mL) in all patients, with a significant positive correlation identified between suPAR levels and serum IL-6, PCT, and creatinine levels. Conclusions: These findings indicate that COVID-19 during the Omicron wave is strongly associated with elevated suPAR levels; however, these levels do not directly correlate with the severity of SARS-CoV-2 infection.
- Publikační typ
- časopisecké články MeSH
PURPOSE: Convalescent plasma (CP) collected from people who recovered from COVID-19 became a rapidly available treatment modality in numerous countries, including the Czech Republic. The aims of our study were to evaluate the effectiveness and safety of CP in the treatment of COVID-19. METHODS: This retrospective observational study involved six Czech hospitals. This study enrolled patients with and without CP treatment who were hospitalized between April 2020 and April 2021. Propensity score matching and logistic regression analysis were performed to evaluate the influence of CP administration and its timing on the in-hospital survival of COVID-19 patients. RESULTS: A total of 1,498 patients were enrolled in the study; 406 (27%) were administered CP, and 1,092 (73%) were not treated with CP. The propensity score-matched control group consisted of 1,218 subjects. The survival of patients treated with CP was 79%, while that of patients in the matched control group was 62% (P<0.001). Moreover, the chance of survival was significantly greater when CP was administered within three days after the onset of COVID-19 symptoms than when CP was administered after four or more days (87% vs. 76%, P <0.001). In addition, adverse effects related to CP administration were recorded in only 2% of patients and were considered mild in all patients. CONCLUSIONS: Our study demonstrated that the administration of CP was safe and possibly associated with positive effects that were more pronounced if CP was administered within the first three days after the onset of COVID-19 symptoms.
- MeSH
- COVID-19 * terapie mortalita MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- pasivní imunizace * metody MeSH
- protilátky virové krev MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři MeSH
- sérologická léčba covidu-19 * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- infekční nemoci * imunologie MeSH
- lidé MeSH
- zánět * imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- úvodní články MeSH
- úvodníky 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
Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally active receptors to target cells, making them prone to an otherwise unresponsive state. EVs in complex with their agonist, require no further stimulation of the target cells to trigger mobilization of NF-κB. While receptor antagonists were unable to inhibit NF-κB activation, blocking of the fusion between EVs and their target cells with heparin mitigated inflammation in mice challenged with EVs.
- MeSH
- biologický transport MeSH
- extracelulární vezikuly * metabolismus MeSH
- myši MeSH
- NF-kappa B * metabolismus MeSH
- signální transdukce MeSH
- zánět patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The purpose of this study was to identify a panel of biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients. BACKGROUND: Accurate differentiation between trauma-induced sterile inflammation and real infective sepsis poses a complex life-threatening medical challenge because of their common symptoms albeit diverging clinical implications, namely different therapies. The timely and accurate identification of sepsis in trauma patients is therefore vital to ensure prompt and tailored medical interventions (provision of adequate antimicrobial agents and if possible eradication of infective foci) that can ultimately lead to improved therapeutic management and patient outcome. The adequate withholding of antimicrobials in trauma patients without sepsis is also important in aspects of both patient and environmental perspective. METHODS: In this proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and multiplex antibody arrays (MAA) to identify a panel of biomarkers distinguishing actual sepsis from trauma-induced sterile inflammation. RESULTS: By comparing patient groups (controls, infected and non-infected trauma and septic shock patients under mechanical ventilation) at different time points, we uncovered distinct protein patterns associated with early trauma-induced sterile inflammation on the one hand and sepsis on the other hand. SYT13 and IL1F10 emerged as potential early sepsis biomarkers, while reduced levels of A2M were indicative of both trauma-induced inflammation and sepsis conditions. Additionally, higher levels of TREM1 were associated at a later stage in trauma patients. Furthermore, enrichment analyses revealed differences in the inflammatory response between trauma-induced inflammation and sepsis, with proteins related to complement and coagulation cascades being elevated whereas proteins relevant to focal adhesion were diminished in sepsis. CONCLUSIONS: Our findings, therefore, suggest that a combination of biomarkers is needed for the development of novel diagnostic approaches deciphering trauma-induced sterile inflammation from actual infective sepsis.
Kostní dysplazie jsou širokou, heterogenní skupinou chorob. Thanatoforická dysplazie patří mezi nejčastější letální kostní dysplazie. Základem diagnostiky je kvalitní ultrazvukové vyšetření ve II. trimestru a nejnovější metody genetického testování vč. vyšetření klinického exomu. Znalost správné diagnózy je klíčová pro budoucnost plodu i páru.
Bone dysplasias are a broad, heterogeneous group of diseases. Thanatophoric dysplasia is a rare bone dysplasia, but it is the most common lethal skeletal dysplasias. The major role in diagnostics plays a high-quality ultrasound examination in the 2nd trimester and the latest methods of genetic testing, including clinical exome testing. Knowing the correct diagnosis is crucial for the future of the fetus and the couple.
- MeSH
- dospělí MeSH
- indukovaný potrat MeSH
- lidé MeSH
- nemoci plodu diagnostické zobrazování genetika patologie MeSH
- progrese nemoci MeSH
- sekvenování exomu * MeSH
- těhotenství MeSH
- thanatoforní dysplazie * diagnostické zobrazování genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Although vaccines against COVID-19 are effective tools in preventing severe disease, recent studies have shown enhanced protection after vaccine boosters. The aim of our study was to examine the dynamics and duration of both humoral and cellular immune responses following a three-dose regimen of the BNT162b2 mRNA vaccine. In a longitudinal prospective study we enrolled 86 adults who received the BNT162b2 vaccine, 35 unvaccinated individuals with a history of mild COVID-19 and a control group of 30 healthy SARS-CoV-2 seronegative persons. We assessed the SARS-CoV-2-specific T cell responses and IgG production up to 12 months post the third BNT162b2 dose in 24 subjects. The vaccinated group had significantly higher IgG antibody levels after two doses compared to the convalescent group (p<0.001). After the third dose, IgG levels surged beyond those detected after the second dose (p<0.001). Notably, these elevated IgG levels were maintained 12 months post the third dose. After two doses, specific T cell responses were detected in 87.5% of the vaccinated group. Additionally, there was a significant decrease before the third dose. However, post the third dose, specific T cell responses surged and remained stable up to the 12-month period. Our findings indicate that the BNT162b2 vaccine induces potent and enduring humoral and cellular responses, which are notably enhanced by the third dose and remain persistant without a significant decline a year after the booster. Further research is essential to understand the potential need for subsequent boosters.
- MeSH
- COVID-19 * prevence a kontrola MeSH
- dospělí MeSH
- imunita MeSH
- imunoglobulin G MeSH
- lidé MeSH
- messenger RNA MeSH
- prospektivní studie MeSH
- SARS-CoV-2 MeSH
- vakcína BNT162 MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Úvod: Výroba a použití rekonvalescentní plazmy (RP) získané od osob, které prodělaly onemocnění COVID-19, se v době pandemie SARS-CoV-2 stala rychle dostupnou léčebnou metodou v řadě zemí, vč. České republiky. V období od dubna 2020 do dubna 2021 bylo v ČR vyrobeno celkem 19 079 transfuzních jednotek (T.U.) RP, z toho 14 197 T.U. bylo vydáno pro cca 7 100 pacientů v 61 nemocnicích. Z celkového počtu 131 000 hospitalizovaných pacientů s COVID-19 za dané období byla RP podána 5,4 % pacientům. Pro zhodnocení účinnosti a bezpečnosti léčby RP onemocnění COVID-19 byla provedena retrospektivní multicentrická studie RESCOVID-19. Materiál a metodika: Primárním cílem studie, do které se zapojilo 6 nemocnic, bylo zhodnocení klinické účinnosti RP v léčbě COVID-19 oproti shodné standardní terapii bez podání RP. Sekundárním cílem bylo zhodnocení vlivu výše hladiny anti-SARS-CoV-2 protilátek (VNP) v RP na přežití a rychlost zotavení. Dále byl zjištěn výskyt a závažnost nežádoucích reakcí spojených s podáním RP. Výsledky: Do studie bylo zařazeno celkem 1 506 pacientů, z toho 414 (27,3 %) léčených RP a 1 092 (72,7 %) bez této léčby (kontrolní skupina). Výsledky modelu logistické regrese ukázaly odhad střední hodnoty pravděpodobnosti přežití 91,8 % u pacientů skupiny s RP podanou do 3 dnů od počátku příznaků (n = 100), což je podobné jako u kontrolní skupiny s pravděpodobností přežití 91,7 %. Nejhorší výsledky pak byly zjištěny u skupiny pacientů s podanou RP po 3. dnu (n = 313), kdy přežití bylo pouze 82,3 %. Nicméně pacienti s RP aplikovanou do 3. dne se zotavili významně dříve oproti kontrolám i nemocným s RP podanou po 3. dnu. Ve studii nebyl prokázán vliv obsahu anti-SARS-CoV-2 protilátek v RP na přežití (78% přežití při VNP ≤ 320, 78% přežití u VNP ≥ 320). Nežádoucí účinky související s podáním RP byly zaznamenány u 2,17 % pacientů; ve všech případech klinicky málo závažné. Závěr: Výsledky studie prokázaly, že podání RP nemělo příznivý vliv na přežití COVID-19, ale pokud byla podána do 3 dnů od počátku příznaků infekce SARS-CoV-2, alespoň vedla k časnějšímu zotavení. Koncentrace anti-SARS-CoV-2 protilátek v RP neměla vliv na přežití ani na rychlost zotavení z COVID-19.
Introduction: The production and use of convalescent plasma (CP) collected from persons after COVID-19 disease became a rapidly available treatment modality in a number of countries, including the Czech Republic, during the SARS-CoV-2 pandemic. Between April 2020 and April 2021, a total of 19,079 CP units were produced in the Czech Republic, of which 14,197 units were dispensed to approximately 7,100 patients in 61 hospitals. Of the total number of 131,000 hospitalized patients with COVID-19 during the given period, CP was administered to 5.4%. The retrospective multicentre RESCOVID-19 study was conducted to evaluate the eff ectiveness and safety of CP treatment of COVID-19 disease. Material and methods: The primary objective of the study, which involved 6 hospitals, was to evaluate the clinical eff ectiveness of CP in the treatment of COVID-19 compared to standard therapy without the administration of CP. The secondary objective was to evaluate the impact of the level of anti-SARS-CoV-2 antibodies in CP on survival and speed of recovery. The incidence and severity of adverse reactions associated with the administration of CP were also determined. Results: A total of 1,506 patients were enrolled in the study, of which 414 (27.3%) were treated with CP and 1092 (72.7%) were without this treatment (control group). The results of the logistic regression model showed a mean survival probability estimate of 91.8% for patients in the CP group administered within 3 days of symptom onset (N = 100), which is similar to the control group with a survival probability of 91.7%. The worst results were found in the group of patients with CP administered after the 3rd day (N = 313) where survival was only 82.3%. However, patients with CP transfused by the 3rd day recovered signifi cantly earlier compared to controls and patients with CP transfused after the 3rd day. The study did not demonstrate an eff ect of the amount of anti-SARS-CoV-2 antibodies in the CP on survival (78% survival with VNP ≤ 320, 78% survival with VNP ≥ 320). Adverse eff ects related to CP administration were recorded in 2.17% of patients; clinically mild in all cases. Conclusion: The results of the study showed that early application of CP accelerated recovery but had no eff ect on COVID-19 survival. The anti-SARS-CoV-2 antibody concentration in CP had no eff ect on survival and speed of recovery.
- Klíčová slova
- rekonvalescentní plazma, studie RESCOVID-19,
- MeSH
- analýza přežití MeSH
- COVID-19 * krev terapie MeSH
- dospělí MeSH
- komorbidita MeSH
- krevní plazma * MeSH
- lidé středního věku MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- protilátky virové analýza krev MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH