A discovery made entirely in Italy, or more specifically by researchers at the University of Milano-Bicocca, allows us to make significant progress in our understanding of COVID-19. The study was accepted on 26 May by the American Journal of Hematology and is already available on the journal’s website (DOI: https://doi.org/10.1002/ajh.25882).
“We knew that COVID-19 infection leads to a high propensity to develop venous and arterial thrombosis, which may even be fatal, in up to 50% of patients,” comments Prof. Carlo Gambacorti-Passerini, Professor of Haematology and Director of the University Haematology Clinic, located at San Gerardo Hospital in Monza. “However, the cause of this phenomenon was unknown”.
The researchers focused on a marker called sFlt1, produced almost exclusively by endothelial cells, i.e. the cells that cover the internal surface of vessels and are responsible for preventing the onset of coagulation. The sFlt1 values and in particular the ratio between sFlt1 and PlGF (a growth factor for endothelial cells) increase up to 5 times during patient admission.
“This rise takes place at a very early stage, in the days immediately following admission,” adds Andrea Carrer, chief haematologist at San Gerardo.
“This situation does not occur in other pathological conditions. For example, it does not occur in patients suffering from COVID-19-negative pneumonia and its only precedent is a pregnancy condition known as ‘pre-eclampsia’ in which the high sFlt1/PlGF ratio results in thrombosis both in the placenta and in other organs,” adds Valentina Giardini, chief obstetrician at the Fondazione Mamma e Bambino, which is also located at San Gerardo.
However, the most important consequence is that this alteration involves the molecule that the virus uses to enter the cells, known as ACE2. The fact that ACE2 is suppressed after the entry of the virus causes this increase in sFlt1 and therefore suggests that COVID-19 directly infects endothelial cells, at least in patients who develop thrombotic complications.
This fact, together with the early alteration of the sFlt1/PlGF ratio, in addition to clarifying the virus’ mechanism of action, offers a rationale for the early use of anticoagulant drugs (such as heparin), and other drugs such as aspirin or sartans, which can block the increase in sFlt1.
“These results will require confirmation through prospective studies,” concludes Professor Gambacorti-Passerini, “but their rapid dissemination will enable more rational and effective treatment of this new disease.”
The research is funded by AIRC.