One of the enduring mysteries of COVID-19 is how the virus affects different people in different ways. Some become seriously ill or develop long COVID, while others test positive for the virus and remain asymptomatic.
That raises the question: What’s different about the people themselves? The answer may hold the key to a future in which infectious disease prevention and treatments not only focus on the microbe, but on the unique attributes of the host.
“The belief and the hope of our field is that understanding of the human genetic and biological determinants of severe infectious diseases may pave the way for new preventive and therapeutic approaches,” said Dr. Jean-Laurent Casanova, co-leader of the COVID Human Genetic Effort, an international consortium of researchers and scientists from dozens of countries. Over the course of four years, the program has sequenced the genomes of roughly 25,000 people from around the world to tease out the genetic components of severe COVID infection.
“The aim is to crack the different enigmas,” Casanova said, referring to mysteries such as COVID pneumonia, multisystem inflammatory syndrome in children, neurocognitive effects and pathogen resistance.
Research has already begun to “crack” some of these enigmas. For instance, Casanova and his team found that hospitalized COVID patients with neutralizing type-I interferon autoantibodies were more likely to be admitted to the ICU and cleared the virus more slowly than patients without those autoantibodies.
Understanding the genetic components of infectious disease may also help pharma and biotech companies develop preventive tools and treatments.
“This may become reality in the not-too-distant future,” Casanova said. “I think we're … possibly at the beginning of a new era when we're going to consider not only the infectious agent in terms of preventive and therapeutic measures.”
A shifting biotech focus in infectious disease
The Brooklyn biotech company Mirimus, for instance, is developing a test to screen for the autoantibodies that can contribute to severe COVID infection, potentially helping those at risk take needed precautions, and better monitor and treat the infection if they get sick.
“That is a sign that at least some companies are understanding what's going on,” Casanova said.
And with the first CRISPR approval last month, it’s not far-fetched to imagine that scientists might eventually develop a way to genetically intervene.
"The belief and the hope of our field is that understanding of the human genetic and biological determinants of severe infectious diseases may pave the way for new preventive and therapeutic approaches."
Dr. Jean-Laurent Casanova
Co-leader, COVID Human Genetic Effort
Efforts to fight pathogens, whether through prevention or treatment, have been historically spotty. Some viruses respond well to vaccines while others don’t respond at all, and antibiotic-resistant infections are common. The infectious disease market is growing, but only a handful of companies dominate the field.
Casanova and his colleagues hope that infectious disease prevention and treatments will someday include solutions that “boost the host,” as well as fight the pathogen.
“What people in my field think, or hope, or dream of is … the understanding of the root cause of infectious diseases, the host component of infectious disease, the reason that makes one in 100 or 1,000 people infected by any given microbe end up in the ICU when all others are completely fine,” he said.