Severity of the Omicron SARS-CoV-2 variant compared with the previous lineages: A systematic review.

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.

Effectiveness of the pre-Omicron COVID-19 vaccines against Omicron in reducing infection, hospitalization, severity, and mortality compared to Delta and other variants: A systematic review.

Despite widespread mass rollout programs, the rapid spread of the SARS-CoV-2 Omicron variant called into question the effectiveness of the existing vaccines against infection, hospitalization, severity, and mortality compared to previous variants. This systematic review summarizes and compares the effectiveness of the COVID-19 vaccines, with respect to the above outcomes in adults, children, and adolescents. A comprehensive literature search was undertaken on several databases. Only 51 studies met our inclusion criteria, revealing that the protection from primary vaccination against Omicron infection is inferior to protection against Delta and Alpha infections and wanes faster over time. However, mRNA vaccine boosters were reported to reestablish effectiveness, although to a lower extent against Omicron. Nonetheless, primary vaccination was shown to preserve strong protection against Omicron-associated hospitalization, severity, and death, even months after last dose. However, boosters provide more robust and longer-lasting protection against hospitalizations due to Omicron as compared to only primary series.

Cardiovascular and haematological events post COVID-19 vaccination: A systematic review.

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.

Attitudes and Intentions toward COVID-19 Vaccination among Health Professions Students and Faculty in Qatar.

A population's desire to take the COVID-19 vaccine is an important predictor of a country's future pandemic management. This cross-sectional study examines the impact of psychological and sociodemographic factors on attitudes toward and intentions to take the COVID-19 vaccine among students and faculty at four colleges of health professions and sciences at Qatar University. The data were collected through an online survey using Google Forms. The survey was distributed through various online platforms. Data analysis was conducted using Stata 16. Of the 364 participants, 9.89% expressed a high mistrust of vaccine safety, and 21.7% were uncertain about their levels of trust; 28% expressed strong worries about unforeseen side effects, whereas 54.95% expressed moderate worries. Furthermore, 7.69% expressed strong concerns and 39.84% showed moderate concerns about commercial profiteering. Approximately 13% of the participants expressed a strong preference towards natural immunity, whilst 45.33% appeared to believe that natural immunity might be better than a vaccine. Importantly, 68.13% of the participants intended to receive the COVID-19 vaccine once it became available, compared to 17.03% who were uncertain and 14.83% who were unwilling to be vaccinated. Our findings differ from the data on vaccine hesitancy among the general population of Qatar. We argue that this gap is due to scientific knowledge and domain of education. Furthermore, although knowledge and awareness may affect vaccine attitudes, mental health and sociodemographic factors play a role in shaping attitudes towards vaccines.

Fecal microbiota transplants: A review of emerging clinical data on applications, efficacy, and risks (2015-2020).

As the importance of the gut microbiota in health and disease is a subject of growing interest, fecal microbiota transplantation (FMT) was suggested as an attractive therapeutic strategy to restore homeostasis of the gut microbiota, thereby treating diseases that were associated with alteration of the gut microbiota. FMT involves the administration of fresh, frozen, or dried fecal microorganisms from the gut of a healthy donor into the intestinal tract of a patient. This rediscovery of the potential benefits of an ancient practice was accompanied by a rapid progression of our understanding of the roles and mechanisms of gut microbes in the pathogenesis of disease. With a growing number of diseases being associated with dysbiosis or the alteration of gut microbiota, FMT was suggested as an attractive therapeutic strategy to "reset the gut" and initiate clinical resolutions or remissions. The number of FMT clinical trials is increasing worldwide, but no trials are registered in the Gulf region; this suggested the need for raising awareness of the latest studies on FMT. This review presented the emergent preclinical and clinical data to give an overview of the potential clinical applications, the benefits, and inconveniences that were worth considering for eventual future testing of fecal transplants in Qatar and the Middle East. This study highlighted the diversity of methods tested and commented on the variables that can affect the assessment of the effectiveness of FMT in specific diseases. The risks associated with FMT and the threat of antimicrobial resistance for this therapeutic approach were reviewed. From gastrointestinal diseases to neurodevelopmental disorders, understanding the roles of the gut microbiota in health and disease should be at the heart of developing novel, standardized, yet personalized, methods for this ancient therapeutic approach.

A Comparative Pilot Study of Bacterial and Fungal Dysbiosis in Neurodevelopmental Disorders and Gastrointestinal Disorders: Commonalities, Specificities and Correlations with Lifestyle.

Gastrointestinal disorders (GIDs) are a common comorbidity in patients with neurodevelopmental disorders (NDDs), while anxiety-like behaviors are common among patients with gastrointestinal diseases. It is still unclear as to which microbes differentiate these two groups. This pilot study aims at proposing an answer by exploring both the bacteriome and the mycobiome in a cohort of 55 volunteers with NDD, GID or controls, while accounting for additional variables that are not commonly included such as probiotic intake and diet. Recruited participants answered a questionnaire and provided a stool sample using the Fisherbrand collection kit. Bacterial and fungal DNA was extracted using the Qiagen Stool minikit. Sequencing (16sRNA and ITS) and phylogenetic analyses were performed using the PE300 Illumina Miseq v3 sequencing. Statistical analysis was performed using the R package. Results showed a significant decrease in bacterial alpha diversity in both NDD and GID, but an increased fungal alpha diversity in NDD. Data pointed at a significant bacterial dysbiosis between the three groups, but the mycobiome dysbiosis is more pronounced in NDD than in GID. Fungi seem to be more affected by probiotics, diet and antibiotic exposure and are proposed to be the main key player in differentiation between NDD and GID dybiosis.

The Interplay Between the Immune System, the Renin-Angiotensin-Aldosterone System (RAAS), and RAAS Inhibitors May Modulate the Outcome of COVID-19: A Systematic Review.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), numerous research has been undertaken to delineate the various effects of the virus which manifests in many ways all over the body. The association between the SARS-CoV-2 invasion mechanism and the renin-angiotensin-aldosterone system (RAAS) receptors, created many debates about the possible consequences of using RAAS-modulating drugs including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) during the pandemic. Many clinical studies were conducted to assess the outcomes of coronavirus disease 2019 (COVID-19) in patients who use ACEi/ARBs following the arguments claiming to discontinue these drugs as a precautionary measure. Although several studies mainly analyzed the outcomes of the disease, this review aimed to compare specific blood markers in both groups of COVID-19 patients to gain better insight into the interaction of ACEi/ARBs with different body functions during the infection. Several databases were searched using a combination of keywords followed by screening and data extraction. Only 28 studies met our inclusion criteria, the majority of which showed no significant difference between the inflammation markers of COVID-19 patients who used or did not use ACEi/ARBs. Interestingly, 6 studies reported lower inflammatory markers in COVID-19 patients who used ACEi/ARBs, and 6 studies reported better outcomes among the same group. We therefore concluded that the use of ACEi/ARBs may not lead to worse prognosis of COVID-19 and may even play a protective role against the hyperinflammatory response associated with COVID-19.

Blockade of PD-1, PD-L1, and TIM-3 Altered Distinct Immune- and Cancer-Related Signaling Pathways in the Transcriptome of Human Breast Cancer Explants.

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.

Biochemistry course-based undergraduate research experience: Purification, characterization, and identification of an unknown lactate dehydrogenase isoenzyme.

Enzyme purification, characterization, and identification are some of the best ways to introduce undergraduate students to many aspects of biochemistry, particularly as part of project-based learning (PBL). These kinds of multi-step laboratory experiments not only help students to better understand basic biochemistry concepts but also serve to introduce them to the scaffolded nature of the research environment. A 13-week enzyme-based laboratory project was designed as one of three components associated with the course titled Capstone Laboratory, which is delivered to second-year undergraduate students at Weill Cornell Medicine in Qatar (WCM-Q). The project incorporated several fundamental biochemical laboratory techniques, such as chromatography, centrifugation, spectrophotometry, electrophoresis, and kinetic assays, as well as enzyme inhibition and bioinformatic exercises. The aims of the project were to first purify, then to quantify, and finally to study a particular lactate dehydrogenase (LDH) isoenzyme extracted from different chicken organs. LDH was selected for investigation because its inhibition has potential as a therapeutic strategy for cancer treatment. Students enrolled in the Capstone Laboratory course were divided into three groups. Each group conducted experiments associated with one of the project's three aims over consecutive 3-week periods. Relevant data and materials were passed from one group to the next, with individual students writing reports describing the results from their respective collection of experiments. Students in the third and final group gave presentations summarizing the results of the overall project. In the associated bioinformatic exercises, students assessed the similarities and differences between chicken-sourced and human-sourced LDH as well as the interaction between the LDH enzyme and the inhibitors. This PBL in biochemistry is a successful addition to the WCM-Q premedical curriculum because (a) it affords the second-year premedical students opportunities to improve and develop content knowledge and technical and communication skills, and also (b) it provides an opportunity to engage many of the undergraduate students in research.

DNA methylation in the promoters of PD-L1, MMP9, ARG1, galectin-9, TIM-3, VISTA and TGF-ß genes in HLA-DR- myeloid cells, compared with HLA-DR+ antigen-presenting cells.

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-ß, 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-ß, 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-ß1, 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.

Targeting the gut microbiome: A brief report on the awareness, practice, and readiness to engage in clinical interventions in Qatar.

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.