The incredible speed with which scientists developed vaccines against COVID-19 – from uncovering the viral sequence of SARS-CoV-2 in January 2020 to getting shots in the arms of frontline workers in December – has been a widely celebrated breakthrough with global impact.
More locally – and more quietly – researchers with Milwaukee-based Versiti Inc. have worked at a similarly expedited pace, redirecting their attention from other blood-related projects to advancing discoveries related to COVID and vaccine complications throughout the pandemic.
“Normally, we think of research as taking years to go from point A to point B,” said Dr. Roy Silverstein, senior investigator and interim director of the Blood Research Institute at Versiti BloodCenter of Wisconsin. “With some of these (COVID-related) discoveries, we were able to go from A to B to C in months – in some cases even weeks – rather than years. That’s really a testament to the quality of the science here in Milwaukee and innovative spirit of the investigators at Versiti who were able to take the knowledge they had gained from years of research and immediately apply that to the world of COVID.”
At the pandemic’s onset, Versiti initiated a convalescent plasma program for what at the time was an investigational therapy to treat patients severely affected by the virus. The plasma treatment, which involves transferring the antibodies from recovered patients to critically ill patients, had previously been used to treat Spanish flu and Ebola virus patients, but its effectiveness for treating COVID-19 was unknown at the time.
Versiti – which includes the BloodCenter of Wisconsin in Milwaukee and blood centers in Illinois, Indiana, Michigan and Ohio – was among the first in the country to begin receiving plasma donations and led a large clinical trial with Froedtert & the Medical College of Wisconsin to determine its effectiveness.[gallery size="full" ids="527937,527938,527936"]
That program received a visibility boost when a Children’s Wisconsin pediatric surgeon, who tested positive in mid-March 2020 for COVID, donated his blood to Versiti for treatment. Silverstein attributed Versiti’s existing partnerships with Froedtert & MCW and Children’s with that program being able to take shape so quickly.
“It actually happens all the time in Milwaukee – the partnership between the research community and the clinical community, they’re led through the Medical College, and it’s really what drives our innovation,” said Silverstein, who is also the Linda and John Mellowes Professor and Chair of the Department of Medicine at MCW.
In the end, the plasma treatment showed some benefit to select patients, but the benefits weren’t as widespread as hoped for.
However, the effort provided lots of blood and DNA samples for Versiti to continue researching the body’s immune response to COVID, Silverstein said.
As the virus continued to spread, hospitals globally observed a trend of increased blood clotting among hospitalized COVID patients. But it was unclear whether increased doses of blood thinners would be safe and effective for patients.
Versiti was granted three multi-center research contracts from the National Institutes of Health totaling $5 million to coordinate nationwide clinical trials aimed at determining the best treatment plans for preventing blood clots in COVID patients. The studies included hospitalized COVID patients, those in outpatient settings and those who have been discharged.
Results from the trials showed that full-dose blood thinner treatments for hospitalized patients outside of the ICU reduced how many people required vital organ support.
“In less than a year, the entire protocols have been written, funded, studies completed and manuscripts completed,” said Dr. Lisa Baumann Kreuziger, medical director of hematology for Versiti and the research director for the project.
The findings from the studies could be applied to future infectious diseases with similar patterns, as well as other, more common health conditions, Baumann Kreuziger said.
“The focus is on COVID-19 for now because it’s the most pressing public health issue that we have,” she said. “But 600,000 to 900,000 Americans every year get blood clots, and that’s outside the pandemic, so we are trying to figure out how to care for all of those patients better.”
Meanwhile, Versiti researchers were alerted in March by colleagues in Europe, where the AstraZeneca COVID-19 vaccine was widely distributed, that a small number of patients were presenting with blood clotting and low platelet counts after receiving the vaccine. Later, blood clots were also discovered among a very small number of patients who received the Johnson & Johnson vaccine in the U.S.
Versiti researchers found that the condition – called vaccine-induced immune thrombotic-thrombocytopenia (VITT) – was similar to another familiar disease, called Heparin Induced Thrombocytopenia.
“We know how to treat (HIT), we know there is a special class of blood thinners, called direct acting anticoagulants, so we immediately were able to educate physicians around the world that when you see a patient with the syndrome that you should not treat them with heparin. Instead, you should be treating them with these newer classes of blood thinners,” Silverstein said. “And that was really a dramatic discovery.”
Versiti quickly developed a diagnostic testing menu for those suspected to have VITT that determines the presence of platelet-activating antibodies in patients’ blood, with the goal of helping clinicians accurately diagnose patients and provide them the correct therapies.
“We all know that vaccination is the key to controlling this pandemic but the goal is still to increase awareness and educate our clinicians so we can aid in prompt and accurate diagnosis and treatment of this very rare side effect – but a serious side effect – that we’re seeing,” said Dr. Ruchika Sharma, assistant investigator with the Versiti Blood Research Institute and associate medical director of the Platelet and Neutrophil Immunology/Hemostasis Reference Laboratories at the BloodCenter of Wisconsin.
Versiti researchers say the past 15 months underscore the importance of continually funding research – the basic science that underpins discoveries in times of crisis – before the crisis presents itself.
“It really speaks to the need to fund infrastructure prior to understanding it’s going to be required,” Baumann Kreuziger said.
“No one expected there to be a pandemic in 2020, but because we had decades of investment to all of these (research) infrastructures, we were ready to move quickly,” Silverstein said.
He said each of the recent discoveries makes clinicians more effective at responding to the ongoing COVID crisis and vaccine rollout, while also preparing the medical community for the next wave of the pandemic – or a new virus altogether.
“With what we’ve learned from this one, we’ll be much more prepared to deal with the next one,” Silverstein said.