Uncovering aspects of the pathogenicity of a novel virus

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When the coronavirus pandemic emerged in Wuhan, LMU medical student Alexander Leunig happened to be in Singapore. “We talked a lot about what was happening in China, and we were pretty sure that the pathogen would at some point reach the city and spread further afield. But at that time, no one knew anything about the virus,” he recalls.

In January 2020, Leunig returned to Munich to continue his doctoral research on platelets in the spleen in cardiologist Professor Steffen Massberg’s laboratory at the LMU Medical Center. In the months that followed, as the numbers of coronavirus cases rose, and many patients who required intensive care were being treated at the Center, Leunig and his colleagues in Massberg’s team were among the first clinical researchers in Germany who were in a position to study the effects of the novel pathogen.

Leunig soon became interested in the role of immune cells in cases of aberrant blood clotting in patients infected with COVID-19. “Establishing completely new methodologies in medical research is a difficult and time-consuming task,” he explains. “So we decided to adapt methods that my supervisor had developed for the study of platelets and thrombosis in the context of heart attacks and strokes for use in the investigation of COVID-associated cases of thrombosis.”

Reconfiguring methodologies for the study of a new pathogen

The initial phase of the project posed many challenges, and was indeed exhausting at times. “No one knew at that point how virulent the pathogen would prove to be,” Leunig points out. “We were among the first in the LMU Medical Center to undertake basic research using clinical samples obtained from COVID patients. But all those involved were highly motivated and cooperative – writing grant applications, for instance. – And quite suddenly, things began to happen very fast.” Leunig and his collaborators analyzed blood samples from patients who were being treated in Grosshadern. “We noticed that severely ill COVID patients in Munich often developed intravascular blood clots, and we learned of similar observations in Italy. Since that was what we were interested in, we began to analyze changes in the cellular composition of the blood, and in the coagulation system.”

The fact that infections with the novel coronavirus could result in severe pneumonia was recognized very early on. But the mechanisms that subsequently led to respiratory failure, and complications owing to damage to the kidneys and the heart muscle, were unknown in the initial stage of the pandemic. The results obtained by Leunig and his colleagues were first published in the journal Circulation in 2020. In collaboration with his co-authors, he was able to demonstrate that severely ill COVID-19 patients were prone to develop characteristic intravascular clots in various organ systems – lungs, heart and kidneys – and that clot formation was triggered by activated cells of the innate immune system. “With these findings, Leunig was able to make a significant contribution to our understanding of this novel respiratory syndrome at a very early stage in the developing COVID-19 pandemic,” says Dean of Studies Martin Fischer. In a subsequent paper, Leunig and co-authors went on to show that this form of immunothrombosis in the lung is specific to SARS-CoV-2 infection – and does not occur in severe cases of influenza, for example.

International resonance

Both publications aroused a great deal of interest internationally. Among others, the New England Journal of Medicine’s Journal Watch drew attention to them, and the first paper – on which Leunig and his supervisor Dr. Leo Nicolai were listed as joint first authors – was chosen as Paper of the Month by the German Center for Cardiovascular Research. Leunig‘s colleagues and mentors also strongly supported the nomination of his work for one of the annual prizes for excellent research performed by LMU students.

Alexander Leunig, who had already obtained a Bachelor degree in Physics and Mathematics from Columbia University in New York before taking up his medical studies in Munich, is now in his last year of medical training, and intends to pursue his research career. “Research fascinates me,” he says, and further publications on immunothrombosis are now in preparation. On completion of his medical studies, as well as caring for patients, he hopes to continue his research at the LMU Medical Center. He would like to learn more about how COVID infections can be effectively treated. “This is something we still know very little about,” he says. He also intends to study sporadic cases of thrombosis in patients vaccinated with DNA-based vector vaccines, such as that produced by Astra-Zeneca. – So when he qualifies as a physician, he has lots of work ahead of him.