Manuela Callari
Some people get severely sick with COVID-19. Others don’t even notice they’ve caught the infection.
The phenomenon intrigued scientists, who began to probe the human genome in search of clues that could help them understand why some people quickly succumb to the coronavirus and others are unaffected by it.
Over the past months, several studies have shown that some genes are potentially involved in the congenital resistance some people have towards COVID-19.
In a review paper published today in Nature Immunology, a team of human genetic experts, in collaboration with the COVID Human Genetic Effort, proposed several potential sites in the genome that could control resistance to COVID-19.
For example, the authors wrote that evidence suggested that people with O type blood groups may be slightly more resistant than people with other blood types.
In vitro studies have identified candidate genes that might be involved in how SARS-CoV2 enters human cells and triggers the infection.
SARS-CoV-2 penetrates human cells by binding the ACE2 receptor, which sits in the cell’s membrane. Scientists have discovered that a rare variant located close to ACE2 confers protection against COVID-19. The hypothesis is that the variant decreases ACE2 expression.
In other in vitro studies, scientists found that some human ACE2 polymorphisms (a gene is polymorphic if more than one allele occupies that gene’s locus) bind the SARS-CoV-2 spike protein with different affinities.
Historically, therapeutics for infectious diseases have focused primarily on the pathogen rather than the host. The most common idea has been to prevent the disease by vaccinating against the pathogen or stop the infection by interfering with the pathogen using drugs.
Understanding the role of genetic variants in infection outcomes could help prevent or treat infectious diseases by restoring deficient immunity.
“These variants are of particular interest for two reasons,” the authors wrote. “First, they can provide a deep understanding of the essential biological pathways involved in infection with SARS-CoV-2. Second, they will allow for the development of innovative therapeutic interventions to prevent or treat SARS-CoV-2 infection in others.”
The proof of principle for this second reason has been provided by CCR5 – a genetic mutation occurring in roughly one per cent of the population, which prevents HIV from binding to the surface of white blood cells. After discovering CCR5, scientists developed an anti-retroviral drug called maraviroc, which mimics the effect of the mutation.
“No specific drug effective against COVID-19 has been discovered since the start of the pandemic,” the authors wrote. “Lessons learned [from genetics] could potentially guide us toward such specific treatments for COVID-19.”