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Source: Medical News - Genes - COVID-19 Severity  Sep 03, 2022  9 months ago
BREAKING! German Study Discovers Eight Human Proteins And Genes That Determine COVID-19 Outcomes With The ELF5 Gene Being Most Important
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BREAKING! German Study Discovers Eight Human Proteins And Genes That Determine COVID-19 Outcomes With The ELF5 Gene Being Most Important
Source: Medical News - Genes - COVID-19 Severity  Sep 03, 2022  9 months ago
A new study led by researchers from Berlin Institute of Health (BIH) at Charité-Universitäts-medizin-Germany has found that eight human proteins and genes paly a very critical role in the determination of COVID-19 outcomes in individuals with the ELF5 gene being the most important.

The other proteins and genes include OAS1, HSP40, RAB2A, NUDT5, CSF3, SFTPD and ABO.
The study was also supported by scientist from Max Planck Institute for Evolutionary Anthropology-Germany, University of Cambridge-UK and McGill University-Canada.
With almost 33 months into the COVID-19 pandemic and despite an array of research, host genetic factors that predispose to a poorer prognosis of COVID-19 infection remain poorly understood.
The study team prioritized eight robust or suggestive but unreported candidate protein mediators of COVID-19 outcomes by integrating results from the COVID-19 Host Genetics Initiative with population-based plasma proteomics using statistical colocalization.
Interestingly, the transcription factor ELF5 (ELF5) gene showed robust and directionally consistent associations across different outcome definitions, including a >4-fold higher risk (odds ratio: 4.88; 95%-CI: 2.47–9.63; p-value < 5.0 × 10−6) for severe COVID-19 per 1 s.d. higher genetically predicted plasma ELF5.
The study team utilized single-cell RNA sequencing and immunohistochemistry to derive these results.
The study findings showed that ELF5 is specifically expressed in epithelial cells of the respiratory system, such as secretory and alveolar type 2 cells.
Importantly, these cells are also likely targets of SARS-CoV-2 by colocalization with key host factors, including ACE2 and TMPRSS2.
The study findings concluded that ELF5 as a risk gene for severe COVID-19, supporting a role of epithelial cells of the respiratory system in the adverse host response to SARS-CoV-2. The other 7 proteins and genes also played a important role in COVID-19 outcomes.
The study findings were published in the peer reviewed journal: Nature Communications.
With the various ongoing COVID-19 surges due to various emerging SARS-CoV-2 variants, many individuals are getting infected with the novel coronavirus but fortunately many are either asymptomatic or only experience mild symptoms initially during infection. (Kindly note that post-infections or continued viral persistence and also Long COVID are another issue!)
However, for some individuals, the COVID-19 disease takes a much more severe course and to date, the current understanding of the underlying reasons is still insufficient.
Physicians and scientists around the world have been confused as to why some individuals become severely ill when infected with SARS-CoV-2, while others experience only mild symptoms.
For a long time, it was already suspected that the human genome may hold a key to why COVID-19 is more serious for some individuals than others.
The study team identified pro teins and genes that in addition to known risk factors such as age and sex predisposed individuals to experience a more serious infection.
The study’s lead author, Dr Maik Pietzner, a Professor at the  Department of Computational Medicine, Berlin Institute of Health (BIH) at Charité -Universitäts-medizin and also a visiting  and also a visiting Professor at the MRC Epidemiology Unit, University of Cambridge-UK told Thailand Medical News,  “It has been observed relatively early on that susceptibility to infection depends on a person’s blood group, for example, which is inherited. Hence it was clear that the course of the disease is at least in part determined by genetics.”
He further explained, “Medical researchers at the Berlin Institute of Health BIH were given access to genetic data that researchers had collected from COVID-19 patients worldwide, which also included disease severity. At the time, there were some 17 genomic regions observed to be associated with a higher risk of severe COVID-19 but the causal genes and underlying mechanism remained unknown for many.”
Corresponding author Dr Claudia Langenberg, Head of the Computational Medicine Group, explains at BIH continued with the explanation, “Previously, the Computational Medicine Group at BIH had developed a ‘proteogenomic’ approach to link protein-encoding regions of DNA to diseases via the protein product. In this new study, our study team applied this method to COVID-19 and came across eight particularly interesting proteins. One of these included a protein responsible for an individual’s blood group.”
She continued, “Our study team was aware that this gene was associated with the risk of infection, so it was like a proof of concept. The protein ELF5, meanwhile, seemed like it could be much more relevant. Our study data found that COVID-19 patients carrying a variant in the gene that encodes ELF5 were more much more likely to be hospitalized and ventilated, in some cases even died hence our study team decided to take a closer look.”
The study team turned to their colleagues from the Intelligent Imaging Group at the Center for Digital Health, Berlin Institute of Health (BIH) led by Dr Christian Conrad, due to their expertise in single-cell analyses.
Dr Lorenz Chua, a doctoral student in the group was immediately enthusiastic to figure out which cells displayed a particular abundance of the ELF5 protein.
Dr Chua said, “Our study team found that ELF5 is present in all surface cells of the skin and mucous membranes, but is produced in particularly large quantities in the lungs. Since this is where the virus causes most of its damage, this seemed very plausible.”
However, Dr Conrad puts a damper on any hopes that the researchers may have identified a new target molecule for drug development.
He explained, “ELF5 is what is known as a transcription factor, and controls how frequently or infrequently other genes are switched on and off throughout the body.”
He continued, “Unfortunately, it is difficult to imagine interfering with this protein in any way, as that would undoubtedly cause many undesirable side effects.”
However, among the eight identified human proteins and genes, the study team discovered another intriguing candidate: the protein G-CSF or CSF3, which acts as a growth factor for blood cells.
The study team discovered that COVID-19 patients who make genetically more G-CSF had a milder disease course.
Interestingly, synthetic G-CSF has long been available as a drug, therefore it is possible for it to be used as a treatment for COVID-19.
It should be noted that the translation of such genetic discoveries into clinical application is not an easy or quick process.
The study and findings were only possible through the support of many scientists and clinicians of the BIH and Charité, and open access results from studies around the world.
Such a study highlights how open science and an international team effort can step by step uncover how the smallest changes in our genetic make-up alter the course of a disease, COVID-19 in this case.
Dr Pietzner concluded, “We started with global data from 100,000 participants and ended up looking at single molecules in individual cells. We believe that collaborations that allow us to rapidly move from the bigger picture and studying large populations to in-depth molecular follow-up can help to better understand the clinical consequences of this virus and teach us important lessons for future pandemics.”
Thailand Medical News would like to add that variety of naturally derived phytochemicals are able to upregulate or even repair damaged genes and even cause mutated genes to self-repair via epigenetic changes. For example, in the case of downregulated or damaged or mutated OAS1 gene causing COVID-19 severity, a phytochemical extracted from blueberries was able to upregulate and also repair damaged or mutated OAS1 gene. Thailand Medical News has been exploring and studying the usage of various phytochemicals to not also deal with the genetic issues that influence COVID-19 outcomes but also phytochemicals that act as antiviral targeting the MPro proteins to prevent replication and inhibit the virus, phytochemicals  that prevent the various COVID-19 induced inflammatory pathways, phytochemicals that repair the various damaged cellular pathways, tissues and organs. We will be published numerous articles and also supporting studies on all these in our soon to be launched premium section.
For the latest COVID-19 Research, keep on logging to Thailand Medical News.
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