Solving COVID-19 mysteries today

Decoding the immune system’s response to COVID-19

As soon as the virus enters the body, immune cells see SARS-CoV2 as foreign and begin to mount a response. In most COVID-19 cases, patients produce antibodies that take care of the virus and get rid of it. But when there is a large inoculation of the active virus, it may overwhelm the immune system. These patients are the ones who are most often moved into the intensive care unit or are put on ventilators. One of the biggest mysteries that today’s COVID investigators are working to solve is what factors cause a mild reaction in some patients but prove fatal for others.

The perfect storm

In some cases, the immune system is hyper-activated and powerful molecules called cytokines are deployed by the immune cells with the goal of killing the virus. In some of the most severe COVID cases, too many of these cytokines are released, causing a “cytokine storm” within the patient. In these rare instances, this overreaction within the immune system can kill the patient all under the guise of trying to fight the virus. An expert in immunobiology, Senior Investigator Subramaniam Malarkannan, PhD, is studying this phenomenon and seeking to understand how to prevent it while preserving the ability of the lymphocytes to do their job and kill the virus.

Future protection from the virus

The immune response to SARS-CoV2 starts with the activation of T-type immune cells. You may have read about Versiti’s ongoing research around T cells, especially in our efforts to combat blood disorders like leukemia and advance lifesaving cellular therapies. Versiti BRI Investigator Weiguo Cui, MD, PhD, has plans to examine the changes that occur in these T cells using an incredibly powerful approach called single-cell genomics. He will examine how T cell responses change over time in individuals actively infected with COVID-19. His goal is to better understand how cell memory to SARS-CoV2 develops and provides future protection from the virus.

Understanding the protein responsible for COVID-19

In the case of SARS-CoV2, a protein on the outer surface of cells called the S protein (or spike protein) attaches to a protein on cells in the human respiratory tract called ACE2. This attachment occurs through very specific parts of both the S protein and ACE2. These parts of the S protein are the target for vaccines and understanding the molecular architecture of their attachments will enable the design of better vaccines. Versiti BRI Investigator Jieqing Zhu, PhD, is using highly sophisticated X-ray crystallography to identify the specific part of the S protein involved in binding to ACE2 to aid in COVID-19 vaccine development. This work will be critical to ensuring the solutions created will have long-term impact for tackling this virus.

The impact of COVID-19 on blood clots

A recent but potentially devastating complication in COVID-19 is the development of blood clots. These may take the form of strokes in children, purple toes due to small vessel inflammation, or more common clots such as venous thromboembolism or even heart attacks. Versiti’s Shawn Jobe, MD, PhD, Renren Wen, PhD, and Lisa Baumann Kreuziger, MD, MS, are working to understand these clots and why they occur. Through the Venous thromboEmbolism Network U.S. (VENUS) that she co-founded, Dr. Baumann Kreuziger is working with other institutions across the country to characterize the clinical syndrome of clots and assess treatments. Additionally, Dr. Jobe and Dr. Wen are researching the interface between immunology and coagulation to understand its mechanism. They believe that the immune response to SARS-CoV2 initiates an inflammatory process that damages the cells lining the blood vessels and causes clotting.

Developing groundbreaking vaccines to fight COVID-19

The patients who survive COVID-19 develop antibodies to the virus. These antibodies are highly specific and thought to protect against reinfection with the virus. Traditional vaccines like the polio vaccine or mumps use live attenuated or dead virus to stimulate the formation of these antibodies. Senior Investigator Demin Wang, PhD, is attempting to bypass traditional vaccine development by cloning the antibodies to COVID-19 from individuals who have recovered from the virus. Those antibodies could be used to help treat people with active COVID-19 infection or to protect frontline workers. While the cloned antibodies would last only a month or two, compared to a vaccine, which would last many years, the antibodies would constitute an important frontline treatment alone or in combination with anti-viral drugs.

Investing in the future: Versiti and Medical College of Wisconsin awarded $400,000 to study convalescent plasma

Versiti Blood Research Institute takes pride in the collaborative environment among our own research team and the partnerships we have cultivated across the country and around the world. Executive Vice President for Research Gilbert C. White, II, MD, and a team at Versiti are working with Mary Beth Graham and her team in the Department of Medicine and Division of Infectious Diseases at the Medical College of Wisconsin to perform a clinical trial of recovered or convalescent plasma in the treatment of active COVID-19. Plasma obtained from Versiti donors who have recovered from the coronavirus is given to individuals who are actively infected to determine the plasma’s effect on the course of the disease.

Together, Versiti Blood Research Institute investigators are responding to the COVID-19 outbreak with both cutting-edge laboratory research and important clinical trials that will contribute to knowledge about how to treat and prevent this virus.