The Omicron variant was first detected in October 2021, which evolved from the original SARS‐CoV‐2 strain and was found to possess many mutations. Immune evasion was one of the notable consequences of these mutations. Despite Omicron exhibiting increased transmissibility, the rates of hospitalizations and deaths among patients infected with this variant were substantially lower when compared to other strains. However, concluding that the Omicron variant is less severe than other variants of SARS‐CoV‐2 requires consideration of multiple factors, including the vaccination status of infected patients as well as any previous infections with other variants. This review compiled data about any reported indicators of severity in Omicron‐infected patients, including studies comparing Omicron with other variants while adjusting for confounders. A comprehensive search was conducted using different databases to target any studies about Omicron. In total, 62 studies met our inclusion criteria and were included in this study. Many studies reported a significantly reduced risk of hospitalization, ICU admission, need for oxygenation/ventilation, and death in Omicron‐infected patients compared to patients infected with other variants, such as Delta. Some studies, however, reported comparable severity in Omicron infected patients as to other variants emphasizing a substantial risk for severe illness. Furthermore, the COVID‐19 vaccines were less effective against Omicron relative to previous lineages, except after receiving the booster dose. One study recommended vaccination during pregnancy, which may help prevent future cases of severe SARS‐CoV‐2 pneumonia in neonates and young infants due to the transfer of humoral response from the mother.
29 December 2021 in Journal of Cellular and Molecular Medicine
Since COVID‐19 took a strong hold around the globe causing considerable morbidity and mortality, a lot of effort was dedicated to manufacturing effective vaccines against SARS‐CoV‐2. Many questions have since been raised surrounding the safety of the vaccines, and a lot of media attention to certain side effects. This caused a state of vaccine hesitancy that may prove problematic in the global effort to control the virus. This review was undertaken with the aim of putting together all the reported cardiovascular and haematological events post COVID‐19 vaccination in published literature and to suggest possible mechanisms to explain these rare phenomena.
Myeloid cells, including antigen-presenting cells (APCs) and myeloid-derived suppressor cells (MDSCs) play opposing roles to orchestrate innate and adaptive immune responses during physiological and pathological conditions. We investigated the role of DNA methylation in regulating the transcription of inhibitory/suppressive molecules in myeloid suppressive cells (identified as CD33+HLA-DR–) in comparison to APCs. We selected a number of immune checkpoints (ICs), IC ligands, and immunosuppressive molecules that have been implicated in MDSC function, including PD-L1, TIM-3, VISTA, galectin-9, TGF-β, ARG1 and MMP9. We examined their mRNA expression levels, and investigated whether DNA methylation regulates their transcription in sorted myeloid cell subpopulations. We found that mRNA levels of PD-L1, TIM-3, TGF-β, ARG1 and MMP9 in CD33+HLA-DR– cells were higher than APCs. However, VISTA and galectin-9 mRNA levels were relatively similar in both myeloid subpopulations. CpG islands in the promoter regions of TGF-β1, TIM-3 and ARG1 were highly unmethylated in CD33+HLA-DR–cells, compared with APCs, suggesting that DNA methylation is one of the key mechanisms, which regulate their expression. However, we did not find differences in the methylation status of PD-L1 and MMP9 between CD33+HLA-DR– and APCs, suggesting that their transcription could be regulated via other genetic and epigenetic mechanisms. The promoter methylation status of VISTA was relatively similar in both myeloid subpopulations. This study provides novel insights into the epigenetic mechanisms, which control the expression of inhibitory/suppressive molecules in circulating CD33+HLA-DR– cells in a steady-state condition, possibly to maintain immune tolerance and haemostasis.
Immune checkpoint inhibitors (ICIs) are yet to have a major advantage over conventional therapies, as only a fraction of patients benefit from the currently approved ICIs and their response rates remain low. We investigated the effects of different ICIs—anti-programmed cell death protein 1 (PD-1), anti-programmed death ligand-1 (PD-L1), and anti-T cell immunoglobulin and mucin-domain containing-3 (TIM-3)—on human primary breast cancer explant cultures using RNA-Seq. Transcriptomic data revealed that PD-1, PD-L1, and TIM-3 blockade follow unique mechanisms by upregulating or downregulating distinct pathways, but they collectively enhance immune responses and suppress cancer-related pathways to exert anti-tumorigenic effects. We also found that these ICIs upregulated the expression of other IC genes, suggesting that blocking one IC can upregulate alternative ICs, potentially giving rise to compensatory mechanisms by which tumor cells evade anti-tumor immunity. Overall, the transcriptomic data revealed some unique mechanisms of the action of monoclonal antibodies (mAbs) targeting PD-1, PD-L1, and TIM-3 in human breast cancer explants. However, further investigations and functional studies are warranted to validate these findings.
Background: There has been a growing global interest in the role of gut microbiota in the pathogenesis of diseases and the potentials of targeting the microbiome in clinical interventions. Very few clinical studies in Qatar focused on gut microbiome. This study aimed to assess the awareness of healthcare professionals, scientists, and the general public on the role of gut microbiota in health and diseases and, more specifically, in disorders of the gut–brain axis such as neurodevelopmental disorders (NDDs) or gastrointestinal (GI) disorders. It also aimed to evaluate the readiness of the population to engage in clinical trials involving dietary interventions or fecal transplants. Methods: A total of 156 participants were recruited to answer questionnaires—from healthcare professionals and scientists (HSs; n = 44) and the general public (n = 112). Participants from the general public self-reported their diagnosis of NDDs—autism or attention deficit hyperactivity disorder (n = 36)—or GI diseases or disorders (n = 18) or as having none of them (n = 58). Two questionnaires for HSs and for the general public were distributed, and basic descriptive and statistical analyses were conducted using the Fisher's exact test. Results: Among the participating HSs, 95% admitted that they had minimum to no knowledge on the role of gut microbes in health and diseases, and only 15.9% felt that their peers were knowledgeable about it. Nevertheless, 97.7% of HSs thought that gut microbiota should be considered when devising treatment plans as 79.1% believed that gut dysbiosis is involved in the pathogenesis of diseases. For the general public, 54% stated that they have read about studies on the potential benefits of microbes in the prevention, treatment, and management of diseases, with a higher proportion of them belonging to the GI group ( p = 0.0523). The GI group was also more aware of the existence of the use of fecal transplants for treating their condition (p = 0.01935). Awareness was also reflected in participants’ attempts to engage in dietary changes, as 40% tried a dietary intervention, which has noticeably changed their or their child's symptoms. This study reported a highly significant association between being exposed to multiple antibiotic courses before three years of age and being part of the NDD group (p = 0.0003). Public readiness to engage in interventions that target the gut microbiome, such as intensive dietary interventions or even fecal transplants, was perceived by HSs to be lower than what was stated by the public, with 87.96% of public being ready to engage in intensive dietary interventions and 66.98% in fecal transplants. Conclusion: The study revealed that the role of gut microbes in health and diseases, and especially through the gut–brain axis, is still unclear in both the scientific community and general public. While acknowledging the importance of gut microbes, the lack of information regarding the link between lifestyle and gut microbes is considered to hold the public in the precontemplation/contemplation stages of the transtheoretical model of behavioral change. An interdisciplinary approach to new knowledge produced by microbiome studies is needed to run awareness campaigns and continue professional development activities on the benefits of lifestyle-based modulation of gut microbiome, thus engaging the general public in lifestyle changes and facilitating clinical research in human microbiome investigations in Qatar.
16 June 2020 in Biochemistry and Molecular Biology Education