WASHINGTON: Two recent papers by Brazilian Scientists have improved our scientific understanding of the genetic elements that protect people against SARS-CoV-2 or prevent severe illness. Covid-19. The First, we describe the findings of a study which involved older people who are resilient and more than 90 years old. Second, we examine a case where severe depression is occurring. Covid-19 in identical twins; only one had long-term effects of the disease.
Since 2020: Researchers in many countries, including BrazilThey have been trying to find genes that provide protection against the coronavirus. This could be either to prevent infection or to avoid progression of severe disease.
“If we can really prove that some genes promote resistance to SARS-CoV-2, the same may also be true for other viruses. More research can then be based on these findings to try to understand the mechanisms underlying this resilience and develop medications that enhance protection against viral infections,” Mayana ZatzAuthor of the articles that were published in “Frontiers in” journals, told Agencia FAPESP.
Zatz Is Professor This is Human And Medical Genetics At the University This is Sao Paulo’s Institute This is Biosciences (IB-USP), the heads Human Genome And Stem Cell Research Center (HUG-CELL), One of FAPESP’s Research, Innovation And Dissemination Centers (RIDCs).
In One study was designed to identify genes that confer resistance against SARS-CoV-2. It also examined the mechanisms of two extremes. There were elderly people who were resilient even with co-morbidities, and there was no co-morbidity in younger people who had severe complications. Covid-19 or even death in certain cases
In One study was done by researchers. They analyzed data sets from a group of 87 people. “resilient super-agers” Patients over 90 who have recovered from mild illness Covid-19, or they remained symptomatic after being tested positive for SARS/CoV-2. Their Average age was 94. One The study revealed that the woman was 114 years old at the time and was the oldest person to have been treated with the disease. Brazil.
They The data for these patients were compared to data for 55 patients younger than 60 who had suffered severe injuries or died. Covid-19 and a database that contains whole-genome sequences of elderly residents Sao Paulo city
In They analyzed, in particular, a portion of chromosome 6, known as the major Histocompatibility Complex (MHC), which is a polymorphic DNA segment that contains 130 genes and encodes many of the molecules involved with innate and acquired immune responses. This Analyzing required special equipment and tools.
They We also analysed the exome, which is the sequence of all exons. This reflects the protein-coding portion in the genomes.
Infection SARS-CoV-2 has been confirmed by RTPCR testing of samples from the beginning of 2020 before the onset or mass. Covid-19 vaccination.
They Three very important conclusions were reached, and two of them were possible because of the use of samples taken from a large population with mixed ancestry and ethnicity.
The First, the mild had twice the number of MUC22 variants. Covid-19 group for severe patients; higher for super-agers who are resilient. This The mucin family includes gene that is related to the production mucus. This mucus lubricates and protects your airways. On However, severe lung inflammation is often caused by excessive mucus production. Covid-19.
These Technically, mutations in MUC22 can be called “mutations”. “missense” Variants are DNA changes that cause different amino acids to be encoded in specific positions in the resulting protein. According They may reduce the immune response to SARS-CoV-2, and they play an important role protecting the airways against the disease. One The authors speculate that resilient subjects might have the best control over mucin production.
“It may be the case that the missense variants interfere with not only mucus production but also its composition since amino acids are switched. We need to conduct more studies to understand how they act during infections and in healthy people,” Erick CastelliA researcher at Sao Paulo State University’s Medical School (FM-UNESP). Botucatu Alongside the first author of this article Mateus VidigalHUG-CELL’s postdoctoral fellow is.
The Paper is published in Frontiers In Immunology. The FAPESP via HUGCELL supported the study National Science And Technology Institute On Aging And Genetic Disorders, and four additional projects (19/19998-8; 20/09702-1; 13/17084-2; 17/19223-0).
Another The link between MUC22 variants and an increased expression of the microRNA miR-6891 is something that should be studied. Research This microRNA has been linked to the viral genome through genetic databases. The Researchers speculate that higher levels of miR-689-1p, which is associated with all MUC22 protective variations, may reduce viral reproduction in cells. This could lead to less severe symptoms during SARS/CoV-2 infection.
Accumulated Knowledge
The Other important results from the study relate to gene variants which are most often found in Africans And South Americans. One is the allele *01:02 of the gene HLA-DOB. Computational HLA-DOB was found to influence cellular trafficking and localization of the protein. This could lead to insufficient antigen presentation, which is the process by macrophages and other cell types to capture the antigen. It allows cytotoxic cells to recognize it and trigger a response against a foreign body. The Researchers found that protein movement could be altered from the inside to the outside of cells, thereby causing the infection to worsen. The The frequency of this gene was three-fold higher in severe cases than it was in milder cases. Covid-19.
“This is the second time this HLA-DOB variant has been detected in our research. We found it in our study of married couples, where it was associated with COVID-19 cases as compared with non-infected subjects,” Castelli said. “This time we found it in severe cases. We were able to locate it only because of the admixed composition of our samples, with African and South American ancestral components. Most research in this field is done in Europe, and they’re unlikely to find it there.”
Castelli He was referring to a 2021 study by a group which included him. Zatz And VidigalThis was the beginning of understanding why certain people are more resilient to infection by SARS/CoV-2 than others. The Researchers analyzed the genetic material of 86 married couples, which was a term that means only one person (the husband or wife) was infected even though both were exposed to this virus.
The The results showed that certain genetic variants more often found in resilient subjects were associated more efficiently with activation cells known as natural killers (NKs). When NKs are correctly activated, they are able To recognize and destroy infected cells, preventing the disease from developing in the organism (read more at: agencia.FAPESP.br/35839).
According to VidigalThe cohort is important because of the significant role played by, who was instrumental in sample collection. “We analyzed the extremes, both in terms of cases – mild, severe and fatal – and age, focusing on super-agers. We continue to follow these patients and we’re developing new projects with centenarians,” He stated.
The The third and most important result was HLA-A. This gene is responsible for the creation of a. “window” to identify which proteins are in the cells. In severe cases, a variant of this gene was twice as common. Covid-19 patients.
Post-Covid
In In the second study, scientists analysed a case involving monozygotic (identical), twins who were 32 years of age and presented severe health problems simultaneously. Covid-19. They They were admitted to the hospital and provided oxygen support despite their good health. CoincidentallyThey were both admitted to intensive care immediately and then intubated the next day. HoweverOne of the brothers stayed a week longer in hospital, and this twin was able to live long. CovidEven seven months after the infection, you may still experience fatigue and other symptoms.
After Researchers analyzed the twins’ immune cell profiles and responses to the virus. Also sequencing their exomes led them to conclude that the differences in their clinical progressions reinforced both the role and importance of genetics in the development and course of the disease.
In A study article published in Frontiers In MedicineThe brothers’ clinical development was different, despite having the same genetic mutations which could have been associated with an increased chance of developing severe illnesses. Covid-19, and that post-Covid A syndrome was seen in one of them. This indicated that there was a correlation between hospital stay, long-term disability and long-term hospital stay.Covid symptoms.
“Cases involving seven pairs of adult identical twins who died from the disease only days apart had already been reported in Brazil, drawing attention to the genetic component of the disease. When we heard about these twin brothers who had severe Covid-19 at the same time and only discovered the fact in the hospital, we wanted to investigate. The fact that they were infected simultaneously and developed the severe form of the disease reinforced the genetic factor hypothesis,” VidigalAuthor of the article. This FAPESP supported study as well.
The Modified systemic parameters in relation to post-operative conditionsCovid Iron (a protein made by the liver that is involved in iron metabolism) was one of the causes of fatigue. The other was creatine-kinase, which can be found in the brain, heart and skeletal muscles.
“In studies like these, teamwork is extremely important, as they involve genomics, immunology and clinical assessment, among other disciplines,” Zatz said. “When you want to answer complex questions, you must know how to design the experiment and identify the patients who can best help you find answers, and that’s not easy.”
The The difficulty of life is too great to be overcome October An international team of researchers published In Nature A call for genetically resistant people to SARS-CoV-2