Can Tofacitinib Offer Protection against COVID-19 Infection?
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ABSTRACT:
SUBMITTER: Goldberger T
PROVIDER: S-EPMC8089460 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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Can Tofacitinib Offer Protection against COVID-19 Infection?
Goldberger Tal T Zlotogorski Abraham A
Skin appendage disorders 20210323
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Project description:BackgroundThe duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters.MethodsWe investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2.ResultsOf 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 95% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer-BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously.ConclusionsTwo doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050.).
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Project description:Cancer patients often face severe organ toxicity caused by chemotherapy. Among these, chemotherapy-induced hepatotoxicity and cardiotoxicity are the main causes of death of cancer patients. Chemotherapy-induced cardiotoxicity even creates a new discipline termed "cardio-oncology". Therefore, relieving toxicities induced by chemotherapy has become a key issue for improving the survival and quality of life in cancer patients. In this work, mesenchymal stem cell exosomes with the "G-C" abundant tetrahedral DNA nanostructure (TDN) are modified to form a decoy exosome (Exo-TDN). Exo-TDN reduces DOX-induced hepatotoxicity as the "G-C" base pairs scavenge DOX. Furthermore, Exo-TDN with cardiomyopathic peptide (Exo-TDN-PCM) is engineered for specific targeting to cardiomyocytes. Injection of Exo-TDN-PCM significantly reduces DOX-induced cardiotoxicity. Interestingly, Exo-TDN-PCM can also promote macrophage polarization into the M2 type for tissue repair. In addition, those decoy exosomes do not affect the anticancer effects of DOX. This decoy exosome strategy serves as a promising therapy to reduce chemo-induced toxicity.
| S-EPMC9661835 | biostudies-literature
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.
| S-EPMC10037513 | biostudies-literature
Project description:The real-world vaccine protection rates (VPRs) against the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection are critical in formulating future vaccination strategies against the virus. Based on a varying coefficient stochastic epidemic model, we obtain 7 countries' real-world VPRs using daily epidemiological and vaccination data, and find that the VPRs improved with more vaccine doses. The average VPR of the full vaccination was 82% (SE: 4%) and 61% (SE: 3%) in the pre-Delta and Delta-dominated periods, respectively. The Omicron variant reduced the average VPR of the full vaccination to 39% (SE: 2%). However, the booster dose restored the VPR to 63% (SE: 1%) which was significantly above the 50% threshold in the Omicron-dominated period. Scenario analyses show that the existing vaccination strategies have significantly delayed and reduced the timing and the magnitude of the infection peaks, respectively, and doubling the existing booster coverage would lead to 29% fewer confirmed cases and 17% fewer deaths in the 7 countries compared to the outcomes at the existing booster taking rates. These call for higher full vaccine and booster coverage for all countries.
| S-EPMC10202182 | biostudies-literature
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.
| S-EPMC7790436 | biostudies-literature
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| S-EPMC7280470 | biostudies-literature
Project description:Films of poly(carboxybetaine methacrylate), poly(CBMA), grafted onto microetched gold slides are effective in preventing nonspecific adhesion of cells of different types. The degree of adhesion resistance is comparable to that achieved with the self-assembled monolayers, SAMs, of oligo(ethylene glycol) alkanethiolates. In sharp contrast to the SAMs, however, substrates protected with poly(CBMA) can be stored in dry state without losing their protective properties for periods up to 2 weeks.
| S-EPMC3597224 | biostudies-literature
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.
| S-EPMC8137353 | biostudies-literature
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.
| S-EPMC7683327 | biostudies-literature