Coronavirus: Study finds why some people are more prone to long COVID

Understanding the SARs-CoV-2 virus and its implications has remained a task for many scientists and medical professionals. With different variants emerging time and again, the vaccine-makers have also faced quite many challenges. But currently, one of the top most concerns of health experts and common people remains to be long COVID, a condition that occurs in people who have a history of coronavirus infection and are still battling the lingering effects of the same.

Irrespective of whether one experiences severe or mild symptoms, long COVID or post COVID-19 conditions can affect anyone. There's no telling who might be more susceptible to it. However, research has listed down certain risk factors and also claimed that genes have a role to play in it.

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As is known, long COVID is a condition that can last weeks and months after recovery. From fatigue, cough, muscle pain to loss of sense of smell and taste, there are several long haule symptoms.

While the condition is most prevalent in people who develop moderate to severe COVID-19 infection, studies suggest those who have mild symptoms or people who did not have COVID-19 symptoms immediately after contracting SARS-CoV-2 can also develop long COVID

So far, scientists have not reached a definite conclusion as to who is more prone to long COVID, but one study published in the Cell Press journal found that four factors could increase a person's risk of long COVID. These include:

- A higher viral load

- Present of certain autoantibodies that mistakenly attack the body’s own tissues

- Reactivation of the Epstein-Barr virus (EBV)

- Type 2 diabetes

But that's not all! A very recent study, conducted in the US, claimed that our genes may also have a lot to do with who develops long COVID. Let us find out more.

In a major breakthrough study, which is one of the first studies to link COVID-associated genes to specific biological functions, a team of researchers from the University of Sheffield and Stanford University in the US found that there are specific genetic indicators in people who experience long COVID.

The study published in the journal Cell Systems, used machine learning and detected more than 1,000 genes linked to the development of severe COVID-19 cases that required intense medical intervention or were fatal.

"During the research we discovered the genetic architecture underlying coronavirus infection, and found that these 1,000 genes account for three quarters of the genetic drivers for severe COVID-19. This is significant in understanding why some people have had more severe symptoms of Covid-19 than others," says Doctor Johnathan Cooper-Knock, NIHR Clinical Lecturer in the Department of Neuroscience at the University of Sheffield and co-author of the study.

The study authors used many large data sets to decode the genetics behind severe COVID infections.

According to the first data set that contained genetic information from healthy human lung tissue, there were gene expression in 19 different types of lung cells, including epithelial cells that line the respiratory tract and are the first wall of defense against infection.

Researchers looked into other data from the COVID-19 Host Genetics Initiative that helped identify genetic clues in the data - DNA mutations, called single nucleotide polymorphisms. This according to the scientists could indicate if someone is at a greater risk of severe COVID.

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They continued tracking the mutations and concluded that the variations i.e. mutations that continued to appear or were absent in those who had severe infections, might be behind the infection's severity.

However, the genetic mutations could be difficult to interpret on their own, which is why the researchers chose to overlap them onto the cell-specific genomes. This helped the researchers to pinpoint which genes were dysfunctional and within which cell types.

The researchers, with the help of their machine learning tool, determined that severe COVID-19 is largely associated with a weakened response from two well-known immune cells - natural killer (NK) cells and T cells.

"NK cells, which humans are born with and are the body's first line of defence against infection, are known for their ability to destroy viruses and cancer cells. NK cells also help produce a range of immune system proteins called cytokines. One cytokine, interferon gamma, is a key activator of immune cells. Acting in concert with interferon gamma, NK cells mount an immediate and coordinated defence against viral infections," says Doctor Cooper-Knock.

"NK cells are like the generals directing the war. They mobilize other immune cells, telling them where to go and what to do. We found that in people with severe coronavirus infection, critical genes in NK cells are expressed less, so there's a less robust immune response. The cell isn't doing what it's supposed to do," he adds.

The senior author of the study Professor Michael P Snyder from the University of Stanford notes a similarity between COVID-19 risk genes and harmful variants of the BRCA genes, which are used to predispose some people to breast and ovarian cancers.

Professor Snyder said, "Our findings lay the foundation for a genetic test that can predict who is born with an increased risk for severe COVID-19.

"Imagine there are 1,000 changes in DNA linked to severe COVID-19. If you have 585 of these changes, that might make you pretty susceptible, and you'd want to take all the necessary precautions," he adds.