Can Tofacitinib Offer Protection against COVID-19 Infection?
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ABSTRACT:
SUBMITTER: Goldberger T
PROVIDER: S-EPMC8089460 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen vaccines and treatments. We show that African green monkeys (AGMs) support robust SARS-CoV-2 replication and develop pronounced respiratory disease, which may more accurately reflect human COVID-19 cases than other nonhuman primate species. SARS-CoV-2 was detected in mucosal samples, including rectal swabs, as late as 15 days after exposure. Marked inflammation and coagulopathy in blood and tissues were prominent features. Transcriptome analysis demonstrated stimulation of interferon and interleukin-6 pathways in bronchoalveolar lavage samples and repression of natural killer cell- and T cell-associated transcripts in peripheral blood. Despite a slight waning in antibody titers after primary challenge, enhanced antibody and cellular responses contributed to rapid clearance after re-challenge with an identical strain. These data support the utility of AGM for studying COVID-19 pathogenesis and testing medical countermeasures.
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Project description:The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a useful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vaccine response has been observed in liver transplant recipients, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data comparing the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavirus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospective studies are required to investigate the duration of immunity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.
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Project description:Background and aimCytokine release syndrome is a dangerous complication of the coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy and safety of tofacitinib in the management of this complication.MethodsThe retrospective study included COVID-19 patients with C-reactive protein (CRP) levels of 60-150 mg/L.ResultsThirty-two patients who received tofacitinib (TOF group) and 30 patients who did not receive any anti-cytokine drugs (control [CON] group) were enrolled. Mortality and the incidence of admission to the intensive care unit were lower in the TOF group than in the CON group (16.6% vs. 40.0%, p = 0.009; and 15.6% vs. 50.0%, p = 0.004). There was a significant decrease in the volume of the affected part of the lungs (p = 0.022) and a significant increase in oxygen saturation (p = 0.012) in the TOF group than in the CON group 7-10 days after the beginning tofacitinib administration. CRP level was lower in the TOF group than in the CON group (7 [3-22] vs. 20 [5-52] mg/L; p = 0.048) 7-10 days after the start of the administration of tofacitinib. During this period, the number of patients requiring mechanical ventilation or those in the prone position increased in the CON group compared to those in the TOF group (26.7% vs. 0.0%, p = 0.002; 33.3% vs. 6.7%, p = 0.020). There was no significant difference in the development of secondary infections, liver or kidney injury, and cytopenia between the two groups.ConclusionTofacitinib was effective and safe for managing the cytokine release syndrome in COVID-19. Randomized controlled double-blind trials with tofacitinib with and without the simultaneous use of glucocorticoids are required to confirm our findings.
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| S-SCDT-EMM-2021-15227 | biostudies-other
Project description:Down syndrome (DS) is the most common genetic cause of learning difficulties and intellectual disabilities. DS patients often present with several congenital defects and chronic diseases, including immunity disorders. Elevated levels of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) have been seen, which appear to vary with age. At birth, patients present with combined immunodeficiency, with frequent infections that decrease with age. Furthermore, high levels of IL-4 and IL-10 with anti-inflammatory properties and low levels of IL-6 and TNF-α are described in children. The immune system is believed to play an essential role in SARS-CoV-2 pathogenesis, and it has been associated with elevated levels of pro-inflammatory cytokines and an exaggerated cytokine release syndrome (CRS) that may eventually trigger a severe situation called cytokine storm. On the other hand, genetic features seem to be involved in the predisposition to illness and its severity. Overexpression of DSCR1 and ZAKI-4 inhibits the translocation of activated T lymphocyte nuclear factor (NF-AT) to the nucleus, a main step in the inflammatory responsiveness. We discuss here the possible role of immunology and genetic features of DS in the infection and prognosis in COVID-19.
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Project description:Whole transcriptome Differential Gene Expression (DGE) analysis was carried out on four biological replicates of both Mw (0.1 ml Mw administrated intradermally in each arm) and Control group at 6 months following exposure to Mycobacterium-w. Sequencing was done through Direct cDNA Sequencing (oxford nanopore technologies, Oxford, UK) using RNA isolated from Peripheral blood mononuclear cells (PBMC) by Trizol method. Native barcoding and adaptor ligation was done according to the manufacturer’s instructions. Ligated cDNA was loaded on the flow cell (R9.4.1) in MinION and were sequenced specifying 72 hours protocol. MinKNOW (v21.06.10, Microsoft Windows OS based) was used to generate FAST5 files. FAST5 files were base-called with CPU based Guppy basecaller (v.5.0.11) (ONT) to generate FASTQ files. DGE analysis was done using “pipeline-transcriptome-de” (https://github.com/nanoporetech/pipeline-transcriptome-de) pipeline. DGE analysis confirmed that upregulation of ANK pathway was evident at 6 months in the Mw group. Apart from upregulation of KLRC2 and B3GAT1 and downregulation of KLRC1, the key transcription factor in the ANK pathway, BCL11b, was persistently upregulated. Downregulation of EAT-2 and PLZF further corroborated the classic gene expression signature of ANK cells. Moreover, increased expression of AT-rich interaction domain 5B (ARID5B), as demonstrated in the Mw group plays an important role in enhanced metabolism in ANK cells as well as increased IFN-γ release and survival. DGE analysis also revealed an enhancement of ANK mediated ADCC pathway, with significant upregulation of CD247 along with downregulation of FCER1G, which is a typical signature of ANK-ADCC. Both CD247 and FCER1G are adapter molecules for FCGRIIIA (CD16) with CD247 possessing 3 ITAMs against one ITAM of FCER1G, increasing the ADCC several folds. It is possible that Mw induced augmentation of NK-ADCC might potentiate the efficacy of SARS-CoV2 vaccines as well.
2022-04-25 | GSE197976 | GEO
Project description:Studies demonstrating the waning of post-vaccination and post-infection immunity against covid-19 generally analyzed a limited range of vaccines or subsets of populations. Using Czech national health data from the beginning of the covid-19 pandemic till November 20, 2021 we estimated the risks of reinfection, breakthrough infection, hospitalization and death by a Cox regression adjusted for sex, age, vaccine type and vaccination status. Vaccine effectiveness against infection declined from 87% at 0-2 months after the second dose to 53% at 7-8 months for BNT162b2 vaccine, from 90% at 0-2 months to 65% at 7-8 months for mRNA-1273, and from 83% at 0-2 months to 55% at 5-6 months for the ChAdOx1-S. Effectiveness against hospitalization and deaths declined by about 15% and 10%, respectively, during the first 6-8 months. Boosters (third dose) returned the protection to the levels observed shortly after dose 2. In unvaccinated, previously infected individuals the protection against infection declined from 97% after 2 months to 72% at 18 months. Our results confirm the waning of vaccination-induced immunity against infection and a smaller decline in the protection against hospitalization and death. Boosting restores the original vaccine effectiveness. Post-infection immunity also decreases over time.
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