| 1. |
- Choong, Oi Kuan, 1985, et al.
(författare)
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SARS-CoV-2 replicates and displays oncolytic properties in clear cell and papillary renal cell carcinoma
- 2023
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 virus is currently causing a global pandemic. Infection may result in a systemic disease called COVID-19, affecting primarily the respiratory tract. Often the gastrointestinal tract and kidneys also become involved. Angiotensin converting enzyme 2 (ACE2) serves as the receptor for SARS-CoV-2. The membrane proteins, Transmembrane serine protease 2 (TMPRSS2) and Neuropilin 1 (NRP1) are accessory proteins facilitating the virus entry. In this study we show that the human proximal kidney tubules, express these factors. We hypothesized that cancers derived from proximal tubules as clear cell (CCRCC) and papillary renal cell carcinoma (PRCC), retain the expression of the SARS-CoV-2 entry factors making these cancers susceptible to SARS-CoV-2 infection. We used bioinformatics, western blotting, and assessment of tissue micro arrays (TMA) including 263 cases of CCRCC, 139 cases of PRCC and 18 cases of chromophobe RCC to demonstrate that the majority of CCRCC and PRCC cases retained the RNA and protein expression of the entry factors for SARS-CoV-2. We furthermore show that SARS-CoV-2 virus propagated robustly in primary cultures of CCRCC and PRCC cells with a visible virus cytopathogenic effect correlating with viral RNA expression levels. We also noted that the delta-variant of SARS-CoV-2 causes cancer cells to form syncytia in-vitro. This phenomenon was also identified histologically in CCRCC tissue from a patient that had been hospitalized for COVID-19, twelve months prior to nephrectomy. Our data provide insights into SARS-CoV-2 infectivity in renal cell carcinoma and that the virus causes a distinct cytopathogenic effect.
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| 2. |
- Al-Dury, S., et al.
(författare)
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Catch-up antibody responses and hybrid immunity in mRNA vaccinated patients at risk of severe COVID-19
- 2023
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Ingår i: Infectious Diseases. - 2374-4235. ; 55:10, s. 744-750
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe immunogenicity of repeated vaccination and hybrid immunity in vulnerable patients remains unclear.MethodsWe studied the impact of iterative Covid-19 mRNA vaccination and hybrid immunity on antibody levels in immunosuppressed subjects. Patients with liver cirrhosis (n = 38), survivors of allogeneic haematopoietic stem cell transplantation (allo-HSCT) (n = 36) and patients with autoimmune liver disease (n = 14) along with healthy controls (n = 20) were monitored for SARS-CoV-2-S1 IgG after their 1st-3rd vaccine doses, 31 of whom became infected with the Omicron variant after the 2nd dose. Ten uninfected allo-HSCT recipients received an additional 4th vaccine dose.ResultsUnexpectedly, immunosuppressed patients achieved antibody levels in parity with controls after the 3rd vaccine dose. In all study cohorts, hybrid immunity (effect of vaccination and natural infection) resulted in approximately 10-fold higher antibody levels than vaccine-induced immunity alone.ConclusionsThree doses of the Covid-19 mRNA vaccine entailed high antibody concentrations even in immunocompromised individuals, and hybrid-immunity resulted further augmented levels than vaccination alone.
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| 3. |
- Al-Dury, Samer, et al.
(författare)
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Impaired SARS-CoV-2-specific T-cell reactivity in patients with cirrhosis following mRNA COVID-19 vaccination
- 2022
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Ingår i: JHEP Reports. - : Elsevier BV. - 2589-5559. ; 4:7
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Cirrhosis entails elevated risk of COVID-19-associated mortality. This study determined T cell-mediated and antibody reactivity against the spike 1 (S1) protein of SARS-CoV-2 among 48 patients with cirrhosis and 39 healthy controls after mRNA COVID-19 vaccination. Methods: SARS-CoV-2-specific T-cell reactivity was measured by induced level of T cell-derived interferon-gamma (IFN-gamma) in blood cells stimulated ex vivo with multimeric peptides spanning the N-terminal portion of S1. S1-induced IFN-gamma was quantified before and after the 1st and 2nd vaccination (BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna) alongside serum IgG against the receptor-binding domain (RBD) within S1 (anti-RBD-S1 IgG). Results: T-cell reactivity against S1 was reduced in patients with cirrhosis after the 1st (p < 0.001 vs. controls) and 2nd (p < 0.001) vaccination. Sixty-eight percent of patients lacked detectable S1-specific T-cell reactivity after the 1st vaccination vs. 19% in controls (odds ratio 0.11, 95% CI 0.03-0.48, p = 0.003) and 36% remained devoid of reactivity after the 2nd vaccination vs. 6% in controls (odds ratio 0.12, 95% CI 0.03-0.59, p = 0.009). T-cell reactivity in cirrhosis remained significantly impaired after correction for potential confounders in multivariable analysis. Advanced cirrhosis (Child-Pugh class B) was associated with absent or lower T-cell responses (p < 0.05 vs. Child-Pugh class A). The deficiency of T-cell reactivity was paralleled by lower levels of anti-RBD-S1 IgG after the 1st (p < 0.001 vs. controls) and 2nd (p < 0.05) vaccination. Conclusions: Patients with cirrhosis show deficient T-cell reactivity against SARS-CoV-2 antigens along with diminished levels of anti-RBD-S1 IgG after dual COVID-19 vaccination, highlighting the need for vigilance and additional preventative measures. Clinical trial registration: EudraCT 2021-000349-42 Lay summary: T cells are a pivotal component in the defence against viruses. We show that patients with cirrhosis have impaired SARS-CoV-2-specific T-cell responses and lower antibody levels after mRNA vaccination against COVID-19 compared with healthy controls. Patients with more advanced liver disease exhibited particularly inferior vaccine responses. These results call for additional preventative measures in these patients. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
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| 4. |
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| 5. |
- Busch, K., et al.
(författare)
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Prevalence and comorbidities of chronic hepatitis C: a nationwide population-based register study in Sweden
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:1, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this study was to estimate the prevalence of physician-diagnosed and registered chronic hepatitis C (CHC), and to estimate the reported frequencies of Charlson comorbidities compared with matched comparators from the general population. Materials and methods: Patients were identified according to ICD codes for CHC in the Swedish National Patient Register (1997-2013). Prevalence was estimated according to different patient identification algorithms and for different subgroups. Charlson comorbidities were ascertained from the same register and compared with age/sex/county of residence matched general population comparators. Results: A total of 34,633 individuals with physician-diagnosed CHC were alive in Sweden in 2013 (mean age, 49 years; 64% men), corresponding to a physician-diagnosed prevalence of 0.36%. The prevalence varied by case definition (0.22%-0.36%). The estimate dropped to 0.14% for monitored CHC disease (defined as >= 1 CHC-related visit in 2013). Overall, 41.3% of the CHC patients had >= 1 physician-registered Charlson comorbidity; the most common was liver diseases (22.1%). Compared with matched comparators from the general population (n = 171,338), patients with CHC had more physician-diagnosed and registered diseases such as chronic pulmonary disease (10.2% vs. 4.0%), diabetes (10.6% vs. 5.5%) and liver-related cancer (1.3% vs. 0.2%; all p<.01). No information on behavioural factors, such as smoking, alcohol consumption or on-going illicit drug use, was available. Conclusion: The physician-diagnosed prevalence of CHC was slightly lower than previously reported estimates, and varied by case definition. The additional comorbidities observed in the CHC group should be taken into consideration, as these comorbidities add to the disease burden.
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| 6. |
- Einarsdottir, Sigrun, et al.
(författare)
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Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity.
- 2022
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Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730
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Tidskriftsartikel (refereegranskat)abstract
- Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlapS1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.
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| 8. |
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| 9. |
- Grindebacke, Hanna, 1977, et al.
(författare)
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Dynamic development of homing receptor expression and memory cell differentiation of infant CD4+CD25high regulatory T cells.
- 2009
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 183:7, s. 4360-70
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Tidskriftsartikel (refereegranskat)abstract
- Migration of CD4+CD25+FOXP3+ regulatory T cells (Treg) is important for suppressing immune responses in different tissues. Previous studies show that the majority of Treg at birth express gut homing receptor alpha(4)beta(7) and that only few express CCR4, while the reverse pattern is found in adults. The age at which homing receptor switch occurs in vivo is not known. In this study, we show, in a prospective study of human infants from birth to 3 years of age, that homing receptor switch from alpha(4)beta(7) to CCR4 commences between 1 1/2 and 3 years of age and that Treg at that age also had started their switch to a memory phenotype. The majority of naive Treg express alpha(4)beta(7) in infants but not in adults, while the majority of memory Treg express CCR4 both infants and adults. The homing receptor expression on Treg corresponds to their actual migration properties, because Treg from cord blood migrate foremost toward the gut-associated chemokine CCL25. CD4+FOXP3+ T cell numbers increase rapidly in the circulation during the first days of life indicating conversion to suppressive Treg from CD25(high) Treg precursors. These findings suggest that the gut is the primary site of Treg stimulation to exogenous Ags during the first 18 mo of life and that homing receptor switch toward a more extra-intestinal phenotype occurs thereafter.
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| 10. |
- Karchava, M., et al.
(författare)
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High incidence of the hepatitis C virus recombinant 2k/1b in Georgia: Recommendations for testing and treatment
- 2015
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Ingår i: Hepatology Research. - : Wiley. - 1386-6346. ; 45:13, s. 1292-1298
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The first hepatitis C virus (HCV) recombinant, RF2k/1b, was initially described from Russia and has since then been identified from patients in Ireland, Estonia, Uzbekistan and Cyprus. Many of these patients originated from Georgia; however, there is no information on its prevalence in Georgia or its susceptibility to antiviral treatment. Methods: We retrospectively sequenced the non-structural region 5B (NS5B) of the HCV genome in samples from 72 Georgian patients, 36 of whom had been treated with pegylated interferon and ribavirin. Results: The HCV genotype was determined using the Versant HCV Genotype v2 kit. Based on this typing, 32 patients (44.4%) were infected with genotype 1, 21 (29.1%) genotype 2 and 19 (26.3%) genotype 3. Partial NS5B of these strains was sequenced and analyzed for type, with concordant genotype results for all type 1 and 3 strains. Discrepant results were observed for geno-typed 2 strains, with 16 (76%) having NS5B of subtype 1b. On phylogenetic analysis, 15 NS5B sequences of these strains were found in a clade formed by recombinant RF2k/1b strains. The remaining discordant sequence was found within a clade formed by 1b strains. Conclusion: Our findings show that the RF2k/1b recombinant strain is common among Georgian patients previously assumed to be infected with genotype 2. Because genotyping is mainly performed to decide treatment strategies, there is a need to determine the genotype by analysis of at least two genomic regions in strains from Georgian patients considered infected with genotype 2 based on standard HCV genotyping methods.
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