Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with significant cardiovascular complications, including myocardial infection and pulmonary embolism. This study aims to elucidate the relationship between the presence of SARS-CoV-2 RNA in the myocardium of the left ventricle and the levels of IgG and IgM antibodies against the SARS-CoV-2 virus in deceased COVID-19 patients. We conducted a post-mortem examination on 91 individuals who succumbed to COVID-19-related complications. The presence of SARS-CoV-2 RNA in the myocardium of the left ventricle was analyzed reverse transcription real time PCR (RT-qPCR) (EliGene® COVID19 UKV/SAV RT kit, Elisabeth Pharmacon), and antibody levels in serum were analyzed by serological assays (VIDAS SARS-COV-2 IgM and VIDAS SARS-COV-2 IgG II tests, BioMérieux). Of the heart tissue samples, 44 % tested positive for SARS-CoV-2 RNA. Our findings indicate that any detectable level of IgG antibodies against SARS-CoV-2 reduces the risk of viral penetration into the myocardium by more than fourfold. Specifically, individuals with detectable levels of IgG and IgM antibodies exhibited a significantly reduced presence of SARS-CoV-2 RNA in cardiac tissues (p<0.0001 for IgG and p<0.001 for IgM). Notably, all patients who died from pulmonary embolism had elevated levels of IgG antibodies. The study underscores the protective role of IgG and IgM antibodies in preventing SARS-CoV-2 penetration into cardiac tissues. However, high antibody titers were associated with fatal outcomes such as pulmonary embolism, pointing to the intricate balance of immune response in COVID-19 pathology. Key words SARS-CoV-2, Antibody, IgG, IgM, Cardiac damage, qPCR, Pneumonia, Pulmonary embolism, Heart failure.
- MeSH
- COVID-19 * imunologie virologie MeSH
- dospělí MeSH
- imunoglobulin G * krev MeSH
- imunoglobulin M * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- myokard * imunologie metabolismus MeSH
- protilátky virové * krev MeSH
- RNA virová krev MeSH
- SARS-CoV-2 * imunologie 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
- časopisecké články MeSH
BACKGROUND & AIMS: Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1-6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. METHODS: EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4-6 in the per protocol (PP) population, ii) patients with GT1,2,4-6 in the intention-to-treat (ITT) population, iii) patients with GT1-6 in the PP population, and iv) patients with GT1-6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed. RESULTS: A total of 343 patients were enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1-6 was 99.7% (n/N = 334/335; 95%CI 98.3-99.9) in the PP population and 97.7% (n/N = 335/343; 95% CI 96.1-99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent. CONCLUSIONS: Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1-6 infection and compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03089944. LAY SUMMARY: This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (HCV) in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1-6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV.
- MeSH
- antivirové látky aplikace a dávkování škodlivé účinky MeSH
- benzimidazoly aplikace a dávkování škodlivé účinky MeSH
- chinoxaliny aplikace a dávkování škodlivé účinky MeSH
- chronická hepatitida C krev komplikace farmakoterapie virologie MeSH
- cyklopropany aplikace a dávkování škodlivé účinky MeSH
- fixní kombinace léků MeSH
- genotyp * MeSH
- Hepacivirus enzymologie genetika MeSH
- jaterní cirhóza komplikace farmakoterapie MeSH
- kyseliny aminoisomáselné aplikace a dávkování škodlivé účinky MeSH
- leucin aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrocyklické laktamy aplikace a dávkování škodlivé účinky MeSH
- polymorfismus genetický MeSH
- prolin aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- pyrrolidiny aplikace a dávkování škodlivé účinky MeSH
- RNA virová krev genetika MeSH
- senioři MeSH
- setrvalá virologická odpověď MeSH
- sulfonamidy aplikace a dávkování škodlivé účinky MeSH
- virové nestrukturální proteiny genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
OBJECTIVES: The aim of this study was to detect the seroprevalence of Crimean-Congo haemorrhagic fever virus (CCHFV) in patients with fever of unknown origin (FUO) in endemic (Kyzylorda) and non-endemic (Almaty) oblasts of Kazakhstan. METHODS: Paired serum samples from 802 patients with FUO were collected. Serum samples were investigated by ELISA to detect IgG and IgM antibodies against CCHFV. Sera with suspected acute infection were further investigated by RT-PCR to detect the viral RNA. RESULTS: IgG antibodies were detected in 12.7% of the sera from both oblasts. Acute infection was shown by IgM ELISA in four patients from Kyzylorda, with only one developing severe CCHF. Viral RNA was found by RT-PCR in the other three patients' sera. Phylogenetic analysis of partial L and S segments revealed CCHFV genotype Asia 2 and a possible reassortment between the genotypes Asia 1/Asia 2. Animal husbandry, such as working with cattle and horses, was significantly associated with CCHFV seropositivity. CONCLUSIONS: The antibodies and viral RNA detected in sera indicate that mild or even asymptomatic CCHFV infections are presented in Kazakhstan. This study describes the circulation of CCHFV in the so far non-endemic Almaty oblast for the first time. In conclusion, physicians treating patients with FUO in Kazakhstan should be aware of mild CCHF.
- MeSH
- dospělí MeSH
- ELISA MeSH
- hemoragická horečka krymská komplikace epidemiologie MeSH
- horečka neznámého původu etiologie MeSH
- koně MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- protilátky virové krev MeSH
- RNA virová krev MeSH
- séroepidemiologické studie MeSH
- skot MeSH
- virus krymsko-konžské hemoragické horečky genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- skot MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Kazachstán MeSH
In tick-borne encephalitis (TBE) endemic areas, consumption of unpasteurized milk or milk products from grazing domestic ruminants (goats, cattle, and sheep) represents a risk of TBE virus (TBEV) infection for humans. In addition to vaccination of humans, human alimentary TBEV infections can be avoided by pasteurizing milk or by vaccination of the ruminants. However, there is presently no TBEV vaccine for veterinary use. Here, we developed a new veterinary TBE vaccine candidate based on cell culture-derived, purified, and formaldehyde-inactivated TBEV (strain Hypr). The safety and immunogenicity of the vaccine was evaluated in mice and sheep and was well-tolerated while eliciting the production of high levels of virus-neutralizing antibodies. Vaccination provided full protection against lethal TBE in mice, prevented development of viremia in sheep and presence of TBEV in milk of lactating ewes. This vaccine is a good candidate for immunization of ruminants to prevent alimentary milk-borne TBEV infections in humans.
- MeSH
- buněčné kultury MeSH
- formaldehyd farmakologie MeSH
- imunogenicita vakcíny MeSH
- inaktivované vakcíny aplikace a dávkování imunologie MeSH
- klíšťová encefalitida prevence a kontrola veterinární MeSH
- laktace MeSH
- mléko virologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- neutralizující protilátky krev imunologie MeSH
- ovce MeSH
- polymerázová řetězová reakce MeSH
- protilátky virové krev imunologie MeSH
- RNA virová analýza krev MeSH
- virové vakcíny aplikace a dávkování imunologie MeSH
- viry klíšťové encefalitidy MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- DNA virů krev MeSH
- Hepacivirus genetika MeSH
- RNA virová krev MeSH
- testování odbornosti laboratoří MeSH
- virus hepatitidy B genetika MeSH
- Publikační typ
- tabulky MeSH
OBJECTIVES: The number of HIV-infected individuals from developed countries travelling to tropical and subtropical areas has increased as a result of the clinical and survival benefits of combination antiretroviral therapy. The aim of our study was to describe the traveler population in the SHCS and to determine the frequency of viral rebound in virologically suppressed individuals after a travel episode to the tropics compared to non-travelers. METHODS: Swiss HIV Cohort Study participants with at least one follow-up visit between 1 January 1989 and 28 February 2015 were eligible for inclusion in the study. The primary outcome was the occurrence of viral rebound (viral load > 200 HIV-1 RNA copies/mL) after a travel episode compared with a nontravel episode in previously suppressed individuals (≤ 200 copies/mL). All virologically suppressed patients contributed multiple travel or nontravel episodes to the analysis. Logistic regression was performed including factors associated with viral rebound. RESULTS: We included 16 635 patients in the study, of whom 6084 (36.5%) had ever travelled to the tropics. Travel frequency increased over time, with travellers showing better HIV parameters than nontravellers [less advanced Centers for Disease Control and Prevention (CDC) stage and higher CD4 count nadir]. Viral rebound was seen in 477 (3.9%) of 12 265 travel episodes and in 5121 (4.5%) of 114 884 nontravel episodes [unadjusted odds ratio (OR) 0.87; 95% confidence interval (CI) 0.78-0.97]. Among these 477 post-travel viral rebounds, 115 had a resistance test performed and 51 (44%) of these showed new resistance mutations. Compared with European and North American patients, the odds for viral rebound were significantly lower in Southeast Asian (OR 0.67; 95% CI 0.51-0.88) and higher in sub-Saharan African (SSA) patients (OR 1.41; 95% CI 1.22-1.62). Travel further increased the odds of viral rebound in SSA patients (OR 2.00; 95% CI 1.53-2.61). CONCLUSIONS: Region of origin is the main risk factor for viral rebound rather than travel per se. Pre-travel adherence counselling should focus on patients of SSA origin.
- MeSH
- adherence k farmakoterapii psychologie MeSH
- cestování * MeSH
- dospělí MeSH
- etnicita * MeSH
- HIV infekce farmakoterapie virologie MeSH
- HIV-1 izolace a purifikace MeSH
- kohortové studie MeSH
- lidé MeSH
- prospektivní studie MeSH
- RNA virová krev MeSH
- virová nálož * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Švýcarsko MeSH
OBJECTIVE: To investigate if plasma HIV-1 tropism testing could identify subjects at higher risk for clinical progression and death in routine clinical management. DESIGN: Nested case-control study within the EuroSIDA cohort. METHODS: Cases were subjects with AIDS or who died from any cause, with a plasma sample with HIV-1 RNA >1000 copies/mL available for tropism testing 3 to 12 months prior to the event. At least 1 control matched for age, HIV-1 RNA and HCV status at the time of sampling were selected per each case. Conditional logistic regression was used to investigate exposures associated with clinical progression to AIDS or death. A linear mixed model with random intercept was used to compare CD4+T-cell slopes by HIV tropism over the 12 months following the date of sampling. RESULTS: The study included 266 subjects, 100 cases and 166 controls; one quarter had X4 HIV; 26% were ART-naïve. Baseline factors independently associated with clinical progression or death were female gender (OR = 2.13 vs. male, 95CI = 1.04, 4.36), p = 0.038), CD4+T-cell count (OR = 0.90 (95CI = 0.80, 1.00) per 100 cells/mm3 higher, p = 0.058), being on ART (OR = 2.72 vs. being off-ART (95CI = 1.15, 6.41), p = 0.022) and calendar year of sample [OR = 0.84 (95CI = 0.77, 0.91) per more recent year, p<0.001). Baseline tropism was not associated with the risk of clinical progression or death. CD4+T-cell slopes did not differ within or between tropism groups. CONCLUSIONS: The predictive role of plasma tropism determined using 454 sequencing in the context of people receiving cART with detectable VL is not helpful to identify subjects at higher risk for clinical progression to AIDS or death.
- MeSH
- AIDS krev genetika mortalita virologie MeSH
- CD4-pozitivní T-lymfocyty virologie MeSH
- dospělí MeSH
- HIV-1 genetika patogenita MeSH
- látky proti HIV terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- počet CD4 lymfocytů MeSH
- progrese nemoci MeSH
- RNA virová krev MeSH
- tropismus virů genetika MeSH
- virová nálož genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- directly acting antiviral (DAA), přímo působící virostatika (DAA), ledipasvir, dasabuvir, ombitasvir, daclatasvir, pegylovaný interferon,
- MeSH
- anilidy aplikace a dávkování MeSH
- antivirové látky * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- benzimidazoly aplikace a dávkování MeSH
- chronická hepatitida C * diagnóza farmakoterapie komplikace MeSH
- dlouhodobá péče MeSH
- fixní kombinace léků MeSH
- fluoreny aplikace a dávkování MeSH
- genotyp MeSH
- heterocyklické sloučeniny tricyklické aplikace a dávkování MeSH
- imidazoly aplikace a dávkování MeSH
- interferon alfa aplikace a dávkování MeSH
- jaterní cirhóza diagnóza farmakoterapie komplikace MeSH
- karbamáty aplikace a dávkování MeSH
- klinické laboratorní techniky MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- management nemoci * MeSH
- monitorování léčiv MeSH
- polyethylenglykoly aplikace a dávkování MeSH
- ribavirin aplikace a dávkování MeSH
- ritonavir aplikace a dávkování MeSH
- RNA virová krev MeSH
- simeprevir MeSH
- sofosbuvir MeSH
- stupeň závažnosti nemoci MeSH
- sulfonamidy aplikace a dávkování MeSH
- uracil analogy a deriváty aplikace a dávkování MeSH
- uridinmonofosfát analogy a deriváty aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
x
x
- Klíčová slova
- studie START, plazmatická virémie,
- MeSH
- adherence k farmakoterapii MeSH
- antiretrovirové látky * farmakologie terapeutické užití MeSH
- CD4-pozitivní T-lymfocyty MeSH
- fixní kombinace léků MeSH
- HIV infekce * farmakoterapie virologie MeSH
- HIV séropozitivita farmakoterapie MeSH
- HIV-integrasa farmakologie terapeutické užití MeSH
- HIV genetika účinky léků MeSH
- inhibitory HIV fúze farmakologie terapeutické užití MeSH
- inhibitory HIV-integrasy farmakologie terapeutické užití MeSH
- inhibitory HIV-proteasy farmakologie terapeutické užití MeSH
- inhibitory reverzní transkriptasy farmakologie terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- látky proti HIV farmakologie terapeutické užití MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- počet CD4 lymfocytů MeSH
- randomizované kontrolované studie jako téma MeSH
- RNA virová krev MeSH
- viremie MeSH
- virová nálož MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
x
x
- Klíčová slova
- ledipasvir, studie ION-1, studie ION-2, studie ION-3,
- MeSH
- antivirové látky aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- benzimidazoly farmakologie škodlivé účinky terapeutické užití MeSH
- chronická hepatitida C * farmakoterapie virologie MeSH
- fixní kombinace léků * MeSH
- fluoreny farmakologie škodlivé účinky terapeutické užití MeSH
- Hepacivirus genetika MeSH
- klinické zkoušky, fáze III jako téma MeSH
- lidé MeSH
- RNA virová krev MeSH
- sofosbuvir * farmakologie škodlivé účinky terapeutické užití MeSH
- virová léková rezistence MeSH
- virová nálož MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH