Unlocking the Secrets of COVID-19 In Our Cells
COVID-19 has infected millions worldwide and claimed hundreds of thousands of lives since becoming a pandemic in early 2020. Social distancing and the proliferation of face masks has helped to “flatten the curve” considerably, but there are still many questions to answer before we can safely reopen society. Among the most pressing is understanding the factors that influence morbidity and mortality. Why do some people experience few or even no symptoms whatsoever, while others rapidly decline on ventilators?
Much of the answer lies in understanding what’s happening in our bodies at a cellular level. What we can discover in our DNA could be instrumental to solving the mysteries that remain and informing the path forward for individuals and society.
Rethinking Risk Factors
From an outside perspective, it’s easy to assume COVID-19 attacks indiscriminately. The virus can present to some like an aggressive flu while others are left fighting for their lives. In many cases, these are people like actor Nick Cordero, a healthy 41-year-old with no pre-existing conditions. Cordero faced insurmountable odds, including two strokes and the amputation of his leg, in his fight to survive. Although the Tony-nominated actor recently woke from a coma and showed promise for recovery, he succumbed to complications caused by the virus on July 5. Why his condition became so severe remains a mystery.
We do know that these critical cases are predominantly connected to an aberrant immune response known as a cytokine storm. Those cell-signaling proteins cause the body to overproduce immune cells and these cells migrate to the lungs, resulting in damage to key lung tissue. This leads to acute respiratory distress syndrome that can force people onto ventilators. The resulting inflammation can also lead to cardiovascular complications, such as acute cardiac injury and chronic cardiac damage resulting in cardiomyopathy. What remains to be seen is why some people have this reaction while others don’t. Can we better define who most needs to be shielded from infection and importantly, how doctors can begin to predict and preempt the worst clinical outcomes?
Cases like Cordero’s illustrate why we need to rethink predisposition to disease to answer these questions. The known risk factors we’ve come to associate with traditional sickness – age, weight, environmental exposure, chronic conditions – only scratch the surface of what could influence a COVID-19 patient’s experience. They certainly couldn’t have predicted Cordero’s. Increasingly, we’re seeing these criteria fail to serve as the only trusted guide for anticipating an individual’s susceptibility to this virus. Truly turning the tide will require us to look deeper, and research shows that a comprehensive analysis of the associated cellular biology – including assessment of genetic risk (inherited and accumulated) and biomarkers – could hold the answers we seek.
Understanding immune response is critical to identifying individuals at high risk of severe morbidity and mortality. Emerging research suggests that certain biomarkers could be early indicators of a potential excessive inflammatory response and that this information, paired with genetic analysis, including both inherited genetic predispositions and genetic damage accumulated as we age, could provide researchers and doctors with a better means for stratifying those at the greatest risk for the most adverse outcomes.
GoodCell, which aims to set a new standard for self-care through comprehensive blood and genetic testing combined with cell storage for potential analysis and use in cell therapies, is uniquely positioned to fuel this research. We safely and securely isolate and preserve three key components from blood – DNA, plasma and nucleated blood cells. Through this biobanking and analysis, GoodCell provides members with a detailed view of their current health and future risks, helping them make more informed decisions about their health. When viewed in combination, these data streams could prove critical to establishing a more robust picture of disease predisposition that will be essential for identifying individuals at the greatest risk of COVID-19 complications.
Notably, GoodCell is uniquely able to measure and monitor both inherited genetic variants and acquired cellular mutations in blood over time. Research suggests this accumulated change/damage has been linked to higher risk of certain diseases, including predisposition to certain cancers, heart disease and a dysfunctional response to inflammation and infection. In the case of COVID-19, it is believed that certain genetic variations are at the root of the deadly cytokine storm, reinforcing the value of testing for these changes as a means to identify at-risk individuals. As evidence of this, research shows that genetic variations accumulated over time in genes such as TET2 and DNMT3A are associated with a dysfunctional response to inflammation and infection. Additionally, elevated levels of serum IL-6 and IL-8, two biomarkers closely associated with inflammation and the cytokine storm, have been shown to be elevated in people with variations in these same genes. Moreover, DNA damage to the JAK2 gene has been found in a higher-than-expected proportion of cancer-free patients with venous thrombosis, which is a known complication in COVID-19. These findings, while preliminary, demonstrate intriguing correlations between accumulated genetic change/damage in blood cells and the life-threatening inflammatory response to COVID-19 that should be explored further.
GoodCell is the only company that can report accumulated genetic change/damage in combination with storing the potentially therapeutic cells contained within blood. This enables us to establish baseline levels and to also retest patients over time. The ability to detect and monitor these accumulated (somatic) changes over time could be the key to identifying those at increased risk for adverse clinical outcomes associated with COVID-19 infection. Pairing this with GoodCell’s proven ability to screen for inherited genetic variants associated with cardiovascular disease, cancer and inflammation provides a compelling opportunity to play a central role in unraveling the complexities between all of these factors, and to draw important – and actionable – conclusions to improve COVID-19 outcomes.
Informing the Next Best Action for Society
As the essential starting material for the treatments of tomorrow, our cells are critical information sources to better monitor and track health risk. We need these insights more than ever as we seek to reopen our economies safely and bolster our biological defenses against potential resurgences or future outbreaks. Imagine the information that millions of stored cell samples could unlock in the face of a pandemic? This information could be the only way to identify commonalities among various demographic groups that could help understand virus predisposition and penetration across cities, states and nations at the most baseline level.
With research mounting around accumulation of genetic damage in our blood cells over time and its potential as a disease modifier, the need for biobanking has never been more acute. Understanding how the genes in our blood change over time – from cells stored pre-COVID, to those post or cells stored today, to several months post-recovery – could be the missing piece to identifying patients most likely to experience rapid decline due to virus exposure. Moreover, it could help discern which treatments to administer and aid in developing new, more targeted drug therapies. Identifying highly susceptible individuals through blood testing could also have applications months from now as vaccines come to market, giving business and government sectors insight into true risk factors that can inform inoculation strategies to the most vulnerable in society, and perhaps inform decisions around who should and should not be on the front lines.
The field of cell biobanking offers a window into the potential to correlate gene mutations with immuno-response for the betterment of society, providing a more robust and accurate set of risk factors upon which we can base therapeutic response, vaccine development and critical reopening decisions.
GoodCell is currently in discussions with multiple partners around ways to apply its genetic data and stored cellular materials to quantify risk associated with COVID 19 and other diseases. To learn more, please contact us.
(updated July 7, 2020)