Synergism of CD28 Immune Molecule in Late Immunosuppressive Phase of COVID-19: Effectiveness in Vaccinated Individuals.

CONTEXT: Lymphopenia has been frequently documented and linked to coronavirus disease 2019 (COVID-19) in a severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) attack. A decrease in the T-lymphocyte count has shown promise as a clinical indicator and predictor of COVID-19 severity. OBJECTIVE: The review intended to examine the relationship of COVID-19 infections in individuals to lost expression of CD28 on naive CD4+/CD8+-mediated, vaccine-specific, neutralizing antibody responses. DESIGN: The research team performed a narrative review by searching eight databases: Medline, Elsevier, Cochrane, PubMed, Google Scholar, Mendeley, and Springer Nature. The search used the following key terms: SARS CoV-2, clinical aspects and pathology of SARS CoV-2, involvement of viral spike (S) protein in SARS CoV-2, immunological changes in COVID-19 infection, basic overview of CD28 immuno-molecule ligand, reduction of vaccine therapeutic efficacy in COVID-19 infection, and immunomodulatory response of lost CD28 ligand. SETTING: This study was done in a Maharishi Arvind College of Pharmacy, Jaipur, India. RESULTS: In COVID-19 patients, particularly those with severe disease, had increased levels of IL-2 or IL-2R. Given IL-2's supportive role in the expansion and differentiation of T cells, the authors exhibiting that lymphopenia, particularly in severe COVID-19, could be attributed to nonfunctional and dysfunctional differentiation of CD4+ and CD8+ T cells as a result of low CD28 immuno-molecule expression on naive T cells. CONCLUSIONS: The literature review found that independent, early immunological prognostic markers for a poor prognosis, in addition to higher levels of IL-6, include a substantial proportion of large inflammatory monocytes and a small proportion of chronic CD28+ CD4+T cells. The current findings suggest that a combination of COVID-19 vaccination with SARS CoV-2-reactive naive T cells with the CD28 immune-molecule may be a viable method for establishing T-cell-based, adaptive cellular immunotherapy against COVID-19 infection. Further research is needed, especially larger studies to confirm the current findings, to improve early clinical treatment.

Barriers and facilitators of childhood COVID-19 vaccination among parents: A systematic review.

Background: The acceptance of vaccination against COVID-19 among parents of young children plays a significant role in controlling the current pandemic. A wide range of factors that influence vaccine hesitancy in adults has been reported worldwide, but less attention has been given to COVID-19 vaccination among children. Vaccine hesitancy is considered a major challenge in achieving herd immunity, and it is more challenging among parents as they remain deeply concerned about their child's health. In this context, a systematic review of the current literature is inevitable to assess vaccine hesitancy among parents of young children to ensure a successful ongoing vaccination program. Method: A systematic search of peer-reviewed English literature indexed in Google Scholar, PubMed, Embase, and Web of science was performed using developed keywords between 1 January 2020 and August 2022. This systematic review included only those studies that focused on parental concerns about COVID-19 vaccines in children up to 12 years without a diagnosis of COVID-19. Following PRISMA guidelines, a total of 108 studies were included. The quality appraisal of the study was performed by Newcastle-Ottawa Scale (NOS). Results: The results of 108 studies depict that vaccine hesitancy rates differed globally with a considerably large number of factors associated with it. The highest vaccine hesitancy rates among parents were reported in a study from the USA (86.1%) and two studies from Saudi Arabia (>85%) and Turkey (89.6%). Conversely, the lowest vaccine hesitancy rates ranging from 0.69 and 2% were found in two studies from South Africa and Switzerland, respectively. The largest study (n = 227,740) was conducted in Switzerland while the smallest sample size (n = 12) was represented by a study conducted in the USA. The most commonly reported barriers to childhood vaccination were mothers' lower education level (N = 46/108, 43%), followed by financial instability (N = 19/108, 18%), low confidence in new vaccines (N = 13/108, 12%), and unmonitored social media platforms (N = 5/108, 4.6%). These factors were significantly associated with vaccine refusal among parents. However, the potential facilitators for vaccine uptake among respondents who intended to have their children vaccinated include higher education level (N = 12/108, 11%), followed by information obtained through healthcare professionals (N = 9/108, 8.3%) and strong confidence in preventive measures taken by the government (N = 5/81, 4.6%). Conclusion: This review underscores that parents around the globe are hesitant to vaccinate their kids against COVID-19. The spectrum of factors associated with vaccine hesitancy and uptake varies across the globe. There is a dire need to address vaccine hesitancy concerns regarding the efficacy and safety of approved vaccines. Local context is inevitable to take into account while developing programs to reduce vaccine hesitancy. There is a dire need to devise strategies to address vaccine hesitancy among parents through the identification of attributing factors.

Barriers and facilitators of childhood COVID-19 vaccination among parents: A systematic review

Background The acceptance of vaccination against COVID-19 among parents of young children plays a significant role in controlling the current pandemic. A wide range of factors that influence vaccine hesitancy in adults has been reported worldwide, but less attention has been given to COVID-19 vaccination among children. Vaccine hesitancy is considered a major challenge in achieving herd immunity, and it is more challenging among parents as they remain deeply concerned about their child's health. In this context, a systematic review of the current literature is inevitable to assess vaccine hesitancy among parents of young children to ensure a successful ongoing vaccination program. Method A systematic search of peer-reviewed English literature indexed in Google Scholar, PubMed, Embase, and Web of science was performed using developed keywords between 1 January 2020 and August 2022. This systematic review included only those studies that focused on parental concerns about COVID-19 vaccines in children up to 12 years without a diagnosis of COVID-19. Following PRISMA guidelines, a total of 108 studies were included. The quality appraisal of the study was performed by Newcastle–Ottawa Scale (NOS). Results The results of 108 studies depict that vaccine hesitancy rates differed globally with a considerably large number of factors associated with it. The highest vaccine hesitancy rates among parents were reported in a study from the USA (86.1%) and two studies from Saudi Arabia (>85%) and Turkey (89.6%). Conversely, the lowest vaccine hesitancy rates ranging from 0.69 and 2% were found in two studies from South Africa and Switzerland, respectively. The largest study (n = 227,740) was conducted in Switzerland while the smallest sample size (n = 12) was represented by a study conducted in the USA. The most commonly reported barriers to childhood vaccination were mothers' lower education level (N = 46/108, 43%), followed by financial instability (N = 19/108, 18%), low confidence in new vaccines (N = 13/108, 12%), and unmonitored social media platforms (N = 5/108, 4.6%). These factors were significantly associated with vaccine refusal among parents. However, the potential facilitators for vaccine uptake among respondents who intended to have their children vaccinated include higher education level (N = 12/108, 11%), followed by information obtained through healthcare professionals (N = 9/108, 8.3%) and strong confidence in preventive measures taken by the government (N = 5/81, 4.6%). Conclusion This review underscores that parents around the globe are hesitant to vaccinate their kids against COVID-19. The spectrum of factors associated with vaccine hesitancy and uptake varies across the globe. There is a dire need to address vaccine hesitancy concerns regarding the efficacy and safety of approved vaccines. Local context is inevitable to take into account while developing programs to reduce vaccine hesitancy. There is a dire need to devise strategies to address vaccine hesitancy among parents through the identification of attributing factors.

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases.

The etiology of many neurological diseases affecting the central nervous system (CNS) is unknown and still needs more effective and specific therapeutic approaches. Gene therapy has a promising future in treating neurodegenerative disorders by correcting the genetic defects or by therapeutic protein delivery and is now an attraction for neurologists to treat brain disorders, like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, spinocerebellar ataxia, epilepsy, Huntington's disease, stroke, and spinal cord injury. Gene therapy allows the transgene induction, with a unique expression in cells' substrate. This article mainly focuses on the delivering modes of genetic materials in the CNS, which includes viral and non-viral vectors and their application in gene therapy. Despite the many clinical trials conducted so far, data have shown disappointing outcomes. The efforts done to improve outcomes, efficacy, and safety in the identification of targets in various neurological disorders are also discussed here. Adapting gene therapy as a new therapeutic approach for treating neurological disorders seems to be promising, with early detection and delivery of therapy before the neuron is lost, helping a lot the development of new therapeutic options to translate to the clinic.

Gut Microbiota Disruption in COVID-19 or Post-COVID Illness Association with severity biomarkers: A Possible Role of Pre / Pro-biotics in manipulating microflora.

Coronavirus disease (COVID-19), a coronavirus-induced illness attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, is thought to have first emerged on November 17, 2019. According to World Health Organization (WHO). COVID-19 has been linked to 379,223,560 documented occurrences and 5,693,245 fatalities globally as of 1st Feb 2022. Influenza A virus that has also been discovered diarrhea and gastrointestinal discomfort was found in the infected person, highlighting the need of monitoring them for gastro intestinal tract (GIT) symptoms regardless of whether the sickness is respiration related. The majority of the microbiome in the intestines is Firmicutes and Bacteroidetes, while Bacteroidetes, Proteobacteria, and Firmicutes are found in the lungs. Although most people overcome SARS-CoV-2 infections, many people continue to have symptoms months after the original sickness, called Long-COVID or Post COVID. The term "post-COVID-19 symptoms" refers to those that occur with or after COVID-19 and last for more than 12 weeks (long-COVID-19). The possible understanding of biological components such as inflammatory, immunological, metabolic activity biomarkers in peripheral blood is needed to evaluate the study. Therefore, this article aims to review the informative data that supports the idea underlying the disruption mechanisms of the microbiome of the gastrointestinal tract in the acute COVID-19 or post-COVID-mediated elevation of severity biomarkers.

Nuclear factor-kappa B and its role in inflammatory lung disease.

Nuclear factor-kappa B, involved in inflammation, host immune response, cell adhesion, growth signals, cell proliferation, cell differentiation, and apoptosis defense, is a dimeric transcription factor. Inflammation is a key component of many common respiratory disorders, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and acute respiratory distress syndrome. Many basic transcription factors are found in NF-κB signaling, which is a member of the Rel protein family. Five members of this family c-REL, NF-κB2 (p100/p52), RelA (p65), NF-κB1 (p105/p50), RelB, and RelA (p65) produce 5 transcriptionally active molecules. Proinflammatory cytokines, T lymphocyte, and B lymphocyte cell mitogens, lipopolysaccharides, bacteria, viral proteins, viruses, double-stranded RNA, oxidative stress, physical exertion, various chemotherapeutics are the stimulus responsible for NF-κB activation. NF-κB act as a principal component for several common respiratory illnesses, such as asthma, lung cancer, pulmonary fibrosis, COPD as well as infectious diseases like pneumonia, tuberculosis, COVID-19. Inflammatory lung disease, especially COVID-19, can make NF-κB a key target for drug production.

Calcium sensing receptor hyperactivation through viral envelop protein E of SARS CoV2: A novel target for cardio-renal damage in COVID-19 infection.

Over the recent decades, a number of new pathogens have emerged within specific and diverse populations across the globe, namely, the Nipah virus, the Ebola virus, the Zika virus, and coronaviruses (CoVs) to name a few. Recently, a new form of coronavirus was identified in the city of Wuhan, China. Interestingly, the genomic architecture of the virus did not match with any of the existing genomic sequencing data of previously sequenced CoVs. This had led scientists to confirm the emergence of a new CoV strain. Originally, named as 2019-nCoV, the strain is now called as SARS-CoV-2. High serum levels of proinflammatory mediators, namely, interleukin-12 (IL-12), IL-1ß, IL-6, interferon-gamma (IFNγ), chemoattractant protein-1, and IFN-inducible protein, have been repeatedly observed in subjects who were infected with this virus. In addition, the virus demonstrated strong coagulation activation properties, leading to further the understanding on the SARS-CoV2. To our understanding, these findings are unique to the published literature. Numerous studies have reported anomalies, namely, decline in the number of lymphocytes, platelets and albumins; and a rise in neutrophil count, aspartate transaminase, alanine aminotransaminase, lactate dehydrogenase, troponins, creatinine, complete bilirubin, D-dimers, and procalcitonin. Supplementation of calcium during the SARS CoV-2 associated hyperactive stage of calcium-sensing receptors (CaSR) may be harmful to the cardio-renal system. Thus, pharmacological inhibition of CaSR may prevent the increase in the levels of intracellular calcium, oxidative, inflammatory stress, and cardio-renal cellular apoptosis induced by high cytokines level in COVID-19 infection.