Project description:The coronavirus disease 2019 (COVID-19) is an on-going pandemic caused by the SARS-coronavirus-2 (SARS-CoV-2) which targets the respiratory system of humans. The published data show that children, unlike adults, are less susceptible to contracting the disease. This article aims at understanding why children constitute a minor group among hospitalized COVID-19 patients. Here, we hypothesize that the measles, mumps, and rubella (MMR) vaccine could provide a broad neutralizing antibody against numbers of diseases, including COVID-19. Our hypothesis is based on the 30 amino acid sequence homology between the SARS-CoV-2 Spike (S) glycoprotein (PDB: 6VSB) of both the measles virus fusion (F1) glycoprotein (PDB: 5YXW_B) and the rubella virus envelope (E1) glycoprotein (PDB: 4ADG_A). Computational analysis of the homologous region detected the sequence as antigenic epitopes in both measles and rubella. Therefore, we believe that humoral immunity, created through the MMR vaccination, provides children with advantageous protection against COVID-19 as well, however, an experimental analysis is required.
Project description:COVID-19 pandemic is spreading rapidly worldwide, and drug selection can affect the morbidity and mortality of the disease positively or negatively. Alpha-lipoic acid (ALA) is a potent antioxidant and reduces oxidative stress and inhibits activation of nuclear factor-kappa B (NF-kB). ALA reduces ADAM17 activity and ACE2 upregulation. ALA is known to have antiviral effects against some viruses. ALA may show antiviral effect by reducing NF-kB activation and alleviating redox reactions. ALA increases the intracellular glutathione strengthens the human host defense. ALA activates ATP dependent K+ channels (Na+, K+-ATPase). Increased K+ in the cell raises the intracellular pH. As the intracellular pH increases, the entry of the virus into the cell decreases. ALA can increase human host defense against SARS-CoV-2 by increasing intracellular pH. ALA treatment increases antioxidant levels and reduces oxidative stress. Thus, ALA may strengthen the human host defense against SARS-CoV-2 and can play a vital role in the treatment of patients with critically ill COVID-19. It can prevent cell damage by decreasing lactate production in patients with COVID-19. Using ALA with insulin in patients with diabetes can show a synergistic effect against SARS-CoV-2. We think ALA treatment will be beneficial against COVID-19 in patients with diabetes.
Project description:Cross-protection from previous live attenuated vaccines is proposed to explain the low impact of COVID-19 on children. This study aimed to evaluate the effect of live attenuated MMR vaccines on the risk of being hospitalized for COVID-19 in children. An exposed (MMR vaccine)-non-exposed cohort study was conducted using the nationwide French National Health Data System (SNDS). We included children born between 1 January 2009 and 31 December 2019. Exposure was defined as a claim of at least one dose of MMR vaccine since birth. Hospitalization for COVID-19 was defined using main diagnostic ICD10 codes. Non-conditional logistic regression was used to calculate the adjusted odds ratios (aORs) of the association between MMR exposure and hospitalization for COVID-19, controlling for socio-demographic and socio-economic factors, co-morbidities, and general health. In total, 6,800,542 (median age 6 IQR [3-8] years) children exposed to a MMR vaccine and 384,162 (6 [3-9] years) not exposed were followed up with for 18 months. Among them, 873 exposed to the MMR vaccine and 38 who were not exposed were hospitalized for COVID-19. In a multi-variate analysis, the exposure of children to MMR vaccination was not associated with a decreased risk of COVID-19 hospitalization versus non-exposure (aOR (95%CI) = 1.09 [0.81-1.48]). A stratified analysis by age showed an aOR = 1.03 [0.64-1.66] for children aged 1-4, an aOR = 1.38 [0.82-2.31] for those aged 5-9, and an aOR = 1.11 [0.54-2.29] for those aged 10-12. Our study suggests that the live attenuated MMR vaccine does not protect children against COVID-19 hospitalization.
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.).
Project description:COVID-19 infection caused by the newly discovered coronavirus severe acute respiratory distress syndrome virus-19 (SARS-CoV-2) has become a pandemic issue across the globe. There are currently many investigations taking place to look for specific, safe and potent anti-viral agents. Upon transmission and entry into the human body, SARS-CoV-2 triggers multiple immune players to be involved in the fight against the viral infection. Amongst these immune cells are NK cells that possess robust antiviral activity, and which do not require prior sensitization. However, NK cell count and activity were found to be impaired in COVID-19 patients and hence, could become a potential therapeutic target for COVID-19. Several drugs, including glatiramer acetate (GA), vitamin D3, dimethyl fumarate (DMF), monomethyl fumarate (MMF), natalizumab, ocrelizumab, and IFN-β, among others have been previously described to increase the biological activities of NK cells especially their cytolytic potential as reported by upregulation of CD107a, and the release of perforin and granzymes. In this review, we propose that such drugs could potentially restore NK cell activity allowing individuals to be more protective against COVID-19 infection and its complications.
Project description:Messenger RNA (mRNA) vaccines represent a new class of vaccines that has been shown to be highly effective during the COVID-19 pandemic and that holds great potential for other preventative and therapeutic applications. Understanding the underlying mechanisms of the immune responses induced by this novel vaccine type and their relation to vaccine responses might help to further refine and optimize future vaccine design. In this study, we conducted an in-depth analysis of the blood transcriptome before and 24h after second and third vaccination with licensed mRNA vaccines against COVID-19 in humans, following a prime vaccination with either mRNA or ChAdOx vaccines. Utilizing an unsupervised weighted gene correlation network analysis, we identified distinct gene networks of co-varying genes characterized by either an expressional up- or down-regulation in response to vaccination. Down-regulated networks were associated with cell metabolic processes and regulation of transcription factors, while up-regulated networks were associated with myeloid differentiation, antigen presentation, and antiviral, interferon-driven pathways. Within this interferon-associated network, we identified highly connected hub genes such as STAT2 and RIGI, potentially playing important regulatory roles in the vaccine-induced immune response. The expression profile of this network significantly correlated with S1-specific IgG levels at the follow-up visit in vaccinated individuals. Those findings could be corroborated in an independent cohort of mRNA vaccine recipients. Collectively, insights from this study might contribute to current research endeavors aimed at further enhancing/ or optimizing vaccine-induced immunity.
Project description:Efforts to develop an effective vaccine against the hepatitis C virus (HCV; human hepacivirus) have been stymied by a lack of small animal models. Here, we describe an experimental rat model of chronic HCV-related hepacivirus infection and its response to T cell immunization. Immune-competent rats challenged with a rodent hepacivirus (RHV) develop chronic viremia characterized by expansion of non-functional CD8+ T cells. Single-dose vaccination with a recombinant adenovirus vector expressing hepacivirus non-structural proteins induces effective immunity in majority of rats. Resolution of infection coincides with a vigorous recall of intrahepatic cellular responses. Host selection of viral CD8 escape variants can subvert vaccine-conferred immunity. Transient depletion of CD8+ cells from vaccinated rats prolongs infection, while CD4+ cell depletion results in chronic viremia. These results provide direct evidence that co-operation between CD4+ and CD8+ T cells is important for hepacivirus immunity, and that subversion of responses can be prevented by prophylactic vaccination.