BACKGROUND: Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs. 6 mg dexamethasone intravenously in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) and COVID-19. METHODS: In a multicenter, open-label, randomized trial conducted in nine hospitals in the Czech Republic, we randomized adult patients with ARDS and COVID-19 requiring high-flow oxygen, noninvasive or invasive mechanical ventilation to receive either intravenous high-dose dexamethasone (20 mg/day on days 1-5, 10 mg/day on days 6-10) or standard-dose dexamethasone (6 mg/d, days 1-10). The primary outcome was 28-day ventilator-free days. The five secondary outcomes were 60-day mortality, C-reactive protein dynamics, 14-day WHO (World Health Organization) Clinical Progression Scale score, adverse events and 90-day Barthel index. The long-term outcomes were 180- and 360-day mortality and the Barthel index. The planned sample size was 300, with interim analysis after enrollment of 150 patients. RESULTS: The trial was stopped due to a lack of recruitment, and the follow-up was completed in February 2023. Among 234 randomized patients of 300 planned patients, the primary outcome was available for 224 patients (110 high-dose and 114 standard-dose dexamethasone; median [interquartile range (IQR)] age, 59.0 [48.5-66.0] years; 130 [58.0%] were receiving noninvasive or invasive mechanical ventilation at baseline). The mean number of 28-day ventilator-free days was 8.9 (± 11.5) days for high-dose dexamethasone and 8.0 (± 10.7) days for standard-dose dexamethasone, with an absolute difference of + 0.81 days (95% CI - 2.12-3.73 days). None of the prespecified secondary outcomes, including adverse events, differed between the groups. CONCLUSIONS: Despite not reaching its prespecified enrollment, there was no signal to either benefit or harm high-dose dexamethasone over standard-dose dexamethasone in patients with COVID-19 and moderate-to-severe ARDS. Trial registration Trial registration: ClinicalTrials.gov Identifier: NCT04663555. Registered 10 December 2020, https://clinicaltrials.gov/study/NCT04663555?term=NCT04663555&rank=1 and EudraCT: 2020-005887-70.
- MeSH
- COVID-19 * mortalita komplikace MeSH
- dexamethason * aplikace a dávkování terapeutické užití MeSH
- farmakoterapie COVID-19 * MeSH
- lidé středního věku MeSH
- lidé MeSH
- SARS-CoV-2 MeSH
- senioři MeSH
- syndrom dechové tísně * farmakoterapie mortalita MeSH
- umělé dýchání * MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: To date there remains much ambiguity in the literature regarding the immunological interplay between SARS-CoV-2 and HIV and the true risk posed to coinfected individuals. There has been little conclusive data regarding the use of CD4 cell count and HIV viral load stratification as predictors of COVID-19 severity in this cohort. METHODS: We performed a retrospective, observational cohort study on people living with HIV (PLWH) who contracted COVID-19 in central and eastern Europe. We enrolled 536 patients from 16 countries using an online survey. We evaluated patient demographics, HIV characteristics and COVID-19 presentation and outcomes. Statistical analysis was performed using SPSS 20.1. RESULTS: The majority of the study cohort were male (76.4%) and 152 (28.3%) had a significant medical comorbidity. Median CD4 cell count at COVID-19 diagnosis was 605 cells/μL [interquartile range (IQR) 409-824]. The majority of patients on antiretroviral therapy (ART) were virally suppressed (92%). In univariate analysis, CD4 cell count <350 cells/μL was associated with higher rates of hospitalization (p < 0.0001) and respiratory failure (p < 0.0001). Univariate and multivariate analyses found that an undetectable HIV VL was associated with a lower rate of hospitalization (p < 0.0001), respiratory failure (p < 0.0001), ICU admission or death (p < 0.0001), and with a higher chance of full recovery (p < 0.0001). CONCLUSION: We can conclude that detectable HIV viral load was an independent risk factor for severe COVID-19 illness and can be used as a prognostic indicator in this cohort.
- MeSH
- COVID-19 * epidemiologie komplikace MeSH
- HIV infekce * komplikace farmakoterapie epidemiologie MeSH
- lidé MeSH
- počet CD4 lymfocytů MeSH
- respirační insuficience * MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- testování na COVID-19 MeSH
- virová nálož MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- východní Evropa 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
BACKGROUND: The dominant feature of COVID-19-associated ARDS is gas exchange impairment. Extravascular lung water index is a surrogate for lung edema and reflects the level of alveolocapillary disruption. The primary aim was the prediction of extravascular lung water index by the alveolar-arterial oxygen difference. The secondary aims were in determining the relationship between the extravascular lung water index and other oxygenation parameters, the [Formula: see text], end-tidal oxygen concentration, pulmonary oxygen gradient ([Formula: see text] minus end-tidal oxygen concentration), and [Formula: see text]. METHODS: This observational prospective single-center study was performed at the Department of Anaesthesiology and Intensive Care, The University Hospital in Ostrava, The Czech Republic, during the COVID-19 pandemic, from March 20, 2020, until May 24, 2021. RESULTS: The relationship between the extravascular lung water index and alveolar-arterial oxygen difference showed only a mild-to-moderate correlation (r = 0.33, P < .001). Other extravascular lung water index correlations were as follows: [Formula: see text] (r = 0.33, P < .001), end-tidal oxygen concentration (r = 0.26, P = .0032), [Formula: see text] minus end-tidal oxygen concentration (r = 0.15, P = .0624), and [Formula: see text] (r = -0.15, P = .01). CONCLUSIONS: The alveolar-arterial oxygen difference does not reliably correlate with the extravascular lung water index and the degree of lung edema in COVID-19-associated ARDS.
- MeSH
- COVID-19 * komplikace patofyziologie MeSH
- dospělí MeSH
- extravaskulární plicní voda * metabolismus MeSH
- kyslík * metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- plicní alveoly * metabolismus patofyziologie MeSH
- plicní edém etiologie patofyziologie MeSH
- prospektivní studie MeSH
- senioři MeSH
- syndrom dechové tísně * patofyziologie etiologie MeSH
- výměna plynů v plicích 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
Cíl: Zaměřili jsme se na stanovení prevalence infekce SARS-CoV-2 se symptomatickým nebo asymptomatickým průběhem a na identifikaci prediktorů symptomatické nebo asymptomatické infekce SARS-CoV-2 u pacientů během sedmi měsíců následujících po transplantaci alogenních hematopoetických kmenových buněk (alo-HSCT) v období cirkulace varianty omikron. Metody: Prevalence proběhlé infekce SARS-CoV-2 byla detekována u pacientů během sedmi měsíců po allo-HSCT v omikronovém období pomocí buněčné a humorální imunitní odpovědi proti nukleoproteinu SARS-CoV-2 (NCP). Výsledky: Pozitivní markery prodělané infekce byly identifikovány u 45,2 % pacientů (n = 42). Infekce byla asymptomatická u 68,4 % pacientů s anti-NCP pozitivitou. Hledání rizikových faktorů pro symptomatickou infekci SARS-CoV-2 u příjemců alo-HSCT odhalilo, že nízká úroveň rekonstituce B buněk byla jediným signifikantně souvisejícím rizikovým faktorem. Závěr: Vysoký podíl příjemců alo-HSCT, kteří byli asymptomaticky infikováni do sedmi měsíců po transplantaci v letech 2022–2023, přestože byli imunokompromitovaní a neočkovaní, ukazuje na oslabení cirkulujícího viru a může signalizovat pro pacienty po transplantaci menší riziko onemocnění SARS-CoV-2 v omikronovém období. Ukázalo se, že očkování těchto pacientů proti SARS- -CoV-2 je spojeno s nízkým, ale významným rizikem exacerbace vyléčené chronické reakce štěpu proti hostiteli (GVHD – Graft Versus Host Disease) a s rizikem de novo GVHD. Nízká úroveň rekonstituce B-buněk byla jediným významným rizikovým faktorem pro symptomatickou infekci SARS-CoV-2 u příjemců alo-HSCT.
Aim: We aimed to determine the prevalence of SARS-CoV-2 infection, including both symptomatic and asymptomatic courses, and to identify predictors of asymptomatic or symptomatic SARS-CoV-2 infection in patients within seven months after allo-HSCT (allogenic hematopoietic stem cell transplantation) in the Omicron period. Methods: Prevalence of the past SARS-CoV-2 infection was determined in patients within seven months after allo-HSCT in the Omicron period using the cellular and humoral immune response against the SARS-CoV-2 nucleoprotein (NCP). Results: Positive markers of past infection were identified in 45.2% of patients (n = 42). The infection was asymptomatic in 68.4% of anti-NCP positive patients. The search for risk factors for symptomatic SARS-CoV-2 infection in allo-HSCT recipients revealed that a low level of B cell reconstitution was the only significantly associated risk factor. Conclusion: A high proportion of allo-HSCT recipients who were asymptomatically infected within up to seven months after transplantation from 2022 to 2023 despite being immunosuppressed and unvaccinated indicates an attenuation of the circulating virus and may signal less risk for transplanted patients from SARS-CoV-2 infection in the Omicron period. Vaccination of these patients against SARS-CoV-2 was shown to be associated with a low but significant risk of exacerbation of cured chronic GVHD (graft versus host disease) and the risk of de novo GVHD. The low level of B-cell reconstitution was the only significant risk factor for symptomatic SARS-CoV-2 infection in HSCT recipients.
- Klíčová slova
- Omikron,
- MeSH
- asymptomatické infekce * epidemiologie MeSH
- B-lymfocyty imunologie mikrobiologie transplantace MeSH
- COVID-19 * komplikace mikrobiologie MeSH
- homologní transplantace MeSH
- kohortové studie MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli etiologie imunologie MeSH
- rizikové faktory MeSH
- SARS-CoV-2 patogenita MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- vakcíny proti COVID-19 škodlivé účinky MeSH
- Check Tag
- lidé MeSH
Patients undergoing kidney transplant are at risk of severe COVID-19. Our single-center retrospective analysis evaluated the outcomes of kidney transplant outpatients with COVID-19 who were managed with reduced immunosuppression and treatment with molnupiravir. Between January 2022 and May 2023, we included 93 patients (62 men, average age 56 years), serum creatinine 127 (101-153) μmol/L. Molnupiravir was administered, and immunosuppressive therapy was reduced immediately following the confirmation of SARS-CoV-2 infection by PCR, which was 2 (1-3) days after the onset of symptoms. Only three (3.2%) patients required hospitalization, and one patient died. Acute kidney injury was observed in two patients. During the follow-up period of 19 (15-22) months, there was no significant increase in proteinuria, no acute or new chronic graft rejection, and kidney graft function remained stable; serum creatinine was 124 (106-159) μmol/L post-COVID-19 infection and 128 (101-161) μmol/L at the end of the follow-up period. Our results demonstrate that early initiation of molnupiravir treatment combined with a temporary reduction in immunosuppressive therapy results in favorable clinical outcomes in patients with COVID-19, with preservation of good graft function and no episodes of graft rejection.
- MeSH
- antivirové látky terapeutické užití MeSH
- COVID-19 * komplikace MeSH
- dospělí MeSH
- imunosupresiva * terapeutické užití MeSH
- kreatinin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- pacienti ambulantní MeSH
- rejekce štěpu MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- senioři MeSH
- transplantace ledvin * škodlivé účinky 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
BACKGROUND: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF). METHODS: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021. Forced expiratory volume in one second percent predicted (ppFEV1) and body mass index (BMI) twelve months prior to and following a diagnosis of COVID-19 were recorded. Change in mean ppFEV1 and BMI were compared using a t-test. A linear mixed-effects model was used to estimate change over time and to compare the rate of change before and after infection. RESULTS: A total of 6,500 cases of COVID-19 in pwCF from 33 countries were included for analysis. The mean difference in ppFEV1 pre- and post-infection was 1.4 %, (95 % CI 1.1, 1.7). In those not on modulators, the difference in rate of change pre- and post-infection was 1.34 %, (95 % CI -0.88, 3.56) per year (p = 0.24) and -0.74 % (-1.89, 0.41) per year (p = 0.21) for those on elexacaftor/tezacaftor/ivacaftor. No clinically significant change was noted in BMI or BMI percentile before and after COVID-19 infection. CONCLUSIONS: No clinically meaningful impact on lung function and BMI trajectory in the year following infection with COVID-19 was identified. This work highlights the ability of the global CF community to unify and address critical issues facing pwCF.
- MeSH
- COVID-19 * patofyziologie komplikace epidemiologie MeSH
- cystická fibróza * patofyziologie komplikace MeSH
- dospělí MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- nutriční stav * MeSH
- respirační funkční testy metody MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- usilovný výdechový objem MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Koronavirus typu 2, jako původce těžkého akutního respiračního syndromu (SARS-CoV-2) zapříčinil celosvětovou pandemii onemocnění COVID-19, která vypukla již koncem roku 2019. Virus postihuje různé orgány, vč. nervového systému. Tato studie zkoumá neurologické komplikace u dětí s COVID-19 nebo multisystem inflammatory syndrome in children (MIS-C) v Jihomoravském kraji (ČR), kde vysoká četnost infekce COVID-19 u dětí (35 790/100 000) umožňuje komplexní analýzu. Metodika: Data Fakultní nemocnice Brno (březen 2020 až únor 2022) byla analyzována pro dvě skupiny hospitalizovaných dětí s diagnózou COVID-19 nebo MIS-C: jednu s neurologickými komplikacemi a druhou bez neurologických komplikací. Analýza zahrnovala demografické údaje, důvod přijetí, tíži infekce a její vývoj, objektivní neurologický nález, detaily hospitalizace, přítomnost MIS-C a specifikaci terapeutických postupů. K posouzení jednotlivých faktorů ovlivňujících výskyt neurologických komplikací v rámci těchto skupin byly použity metody deskriptivní statistiky a statistické testy. Výsledky: Ze 420 hospitalizovaných dětí s COVID-19 nebo MIS-C mělo 26 (6,2 %) neurologické komplikace. Dřívější neurologický deficit zvyšoval pravděpodobnost horšího výsledného stavu (p = 0,0224). Mezi skupinami se objevily významné rozdíly v délce hospitalizace (p = 0,0012), závažnosti průběhu infekce (p = 0,0052) a výsledném stavu (p < 0,0001). Závěr: Pro lepší pochopení průběhu onemocnění a minimalizaci komplikací po infekci je zásadní průběžné sledování a další výzkum neurologických projevů u dětí s COVID-19 nebo MIS-C.
Introduction: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused the enduring global COVID-19 pandemic, which has already begun in late 2019. The virus affects various organs, including the nervous system. This study investigates neurological complications in children with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) in the South Moravia region (Czech republic), where a high COVID-19 rate among children (35.790/100.000) allows for a comprehensive analysis. Methods: Data from the University Hospital Brno (from March 2020 to February 2022) were analyzed to study two groups of hospitalized children diagnosed with COVID-19 or MIS-C: one experiencing neurological complications, and the other without neurological symptoms. The analysis included demographics, admission reasons, infection severity and progression, objective neurological findings, hospitalization details, MIS-C presence and therapies used. Descriptive statistics and statistical testing were employed to assess how individual factors influenced neurological complication rates within these groups. Results: Among 420 hospitalized children with COVID-19 or MIS-C, 26 (6.2%) had neurological complications. Preexisting neurological deficits increased the likelihood of worse outcomes (P = 0.0224). Significant differences in hospitalization length (P = 0.0012), infection severity (P = 0.0052), and outcome (P < 0.0001) occurred between groups. Conclusion: Continuous monitoring and further research on neurological complications in children with COVID-19 or MIS-C are crucial for better understanding of the course of the disease and minimize complications after infection.
- MeSH
- COVID-19 * mortalita komplikace MeSH
- dexamethason * terapeutické užití MeSH
- dospělí MeSH
- farmakoterapie COVID-19 * MeSH
- hematologické nádory * mortalita farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- registrace * MeSH
- SARS-CoV-2 * izolace a purifikace 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
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90 days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.
- MeSH
- časové faktory MeSH
- COVID-19 * komplikace mortalita epidemiologie terapie MeSH
- hodnocení rizik MeSH
- krvácení * mortalita epidemiologie etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- recidiva MeSH
- registrace * MeSH
- rizikové faktory MeSH
- SARS-CoV-2 MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vakcíny proti COVID-19 MeSH
- žilní tromboembolie * epidemiologie etiologie mortalita MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
