Most people who are infected by COVID-19 develop mild symptoms or none at all. In severe cases, however, the virus triggers an uncontrolled immune reaction that damages vital organs and can lead to death. In recent research, Prof. Ido Amit and his group in the Weizmann Institute of Science, together with researchers in China and France, determined what differentiates COVID-19 progression in seriously ill patients from that in those who are only mildly affected.
Their discoveries, published in Cell may pave the way for methods of early diagnosis that could predict which patients should receive preemptive treatment, and could point to ways of improving the design of anti-viral drugs.
Prof. Amit, of the Department of Immunology, studies the genomic code that controls how cells of the immune system differentiate into specific subtypes, as well as how these various cell populations respond to invading pathogens. This complex dynamic is central to understanding COVID-19, as current research indicates that many coronavirus fatalities result from the over-activation of the patient’s immune system. This phenomenon, called a “cytokine storm,” could ultimately provide clues as to how to prevent the virus’s deadly effects.
To determine what happens in seriously ill coronavirus patients, Prof. Amit used the technology for single-cell RNA analysis that had been developed in his lab. He and his team tuned their system to scan for viral RNA—the genetic information inserted into a host cell during the process of infection. This tool enables precise, global mapping of the genes and communication pathways activated in infected cells – both viral and host. This data could be tracked over time as the virus and host cell interacted, and overall cellular activity could be compared as it played out in tissue samples from severely- and lightly-affected individuals.
The scientists discovered that the COVID-19 infection causes macrophages—cells that normally assist in ridding the lungs of unwanted viruses and microbes—to be replaced by cells that rather than helping, tend to exacerbate the illness. They also discovered that in seriously ill patients, another type of immune cell — the T-cells — are neutralized, so that other viruses, already present in the body, are able to inflict damage.
This study, in addition to these findings, demonstrates that the methodology developed in Prof Amit’s lab could be broadly applied to dissect the mechanisms of viral infection, which, in the clinical setting could lead to both improved testing and more effective personalized treatments.