“I believe that this program offers a great opportunity for young scientists to test and implement high risk and high reward ideas that would be difficult to fund otherwise.”
What if we could improve treatment for severe cases of COVID-19 to save lives?
FUNDED: JANUARY 2021
FUNDED BY: The generosity of various 2020 SPARK donors.
What was the goal of your SPARK project?
What if it would be possible to change the outcome of severe COVID-19 into a mild-case scenario, or avert long-term damage by changing the levels of certain molecules present in the blood?
The aim of this project was to apply state-of-the-art, high-resolution mass spectrometry to characterize the blood metabolic profile of patients with severe COVID-19, with a focus on vulnerable populations including cancer patients, patients with cardiovascular disease, type II diabetes or obesity, or with different ethnic backgrounds. I was also interested in seeing if there were any male-specific metabolites in the context of severe COVID-19, because men are more vulnerable to severe disease worldwide.
Did you face any challenges?
Yes. My main challenge was organizing the collaborative and analytical work with our off-site collaborator groups during a time when many people were working remotely. Sample preparation and data acquisition were also considerably slower and more time-consuming than I anticipated.
I would like to add that learning to properly pace the work over the past year has taught me a lot about deadlines.
SPARK project results:
My analysis showed that 27,875 metabolites were detectable in most of the samples (~95%), but only one metabolite was significantly associated
with developing severe COVID-19. In contrast, most metabolites were specifically associated with developing mild COVID-19. These results demonstrate that the presence or absence of specific blood-borne metabolites are predictive of mild COVID-19 disease, as opposed to predictive of severe COVID-19 disease. This finding was surprising and different from my original objective of identifying severe COVID-19 metabolites. However, this is also more promising and potentially exciting because mild COVID-19 metabolites can be further developed as biomarkers of mild COVID-19 disease or as immune-stimulatory therapeutic compounds to prevent severe COVID-19 disease.
Regarding sex-specific metabolites, I uncovered metabolites that were specifically associated with the development of either severe or mild disease in males. These results demonstrate that circulating metabolites are a good indicator of sex-specific differences in COVID-19 disease severity, and may be useful in developing sex-specific biomarkers of COVID-19 disease severity or therapies.
What’s next for this project?
Based upon these exciting findings, I would like to validate and extend the initial observations I made during the course of this SPARK project by 1) expanding my metabolite analysis to additional patient cohorts to see if they replicate in other COVID-19 patients; 2) identifying the chemical nature of the mild COVID-19 metabolites and the male-specific COVID-19 metabolites; 3) exploring the use of these metabolites as bio-marker predictors or modulators of COVID-19 disease outcomes. I am applying for R21 or R00/R99 funding from the NIH/NIAID, and coordinating with my PI, Dr. Sonia Sharma, to apply for a collaborative R01 grant from the NIH/NIAID. Additional patient cohorts can be obtained from key collaborations between myself, Dr. Sharma, and Dr. Sujan Shresta at LJI.
What’s next for Artem?
Ultimately, I hope to contribute to the development of new translational approaches in the field of immune-metabolism and immune-therapy. Whether that will be in academia or industry doesn’t matter so much to me as long as I can keep working on developing new metabolite-based treatments for cancer and other immune diseases, including COVID-19. I feel lucky that during my time as a graduate student and as a postdoc there has been a true “renaissance” for understanding how metabolism and metabolites interface with immune diseases.