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What causes such different reactions to the attack of the SarS-CoV-2 virus? Why do some people get seriously ill and others less? Faced with complex and unstable clinical pictures, is it possible to predict the level of severity of the disease?
A study based on two independent case studies, conducted respectively by an IRCCS Humanitas working group led by prof. Alberto Mantovani which includes researchers and doctors on the front line against Covid 19, and the group of doctors and researchers of the ASST Papa Giovanni XXIII, led by prof. Alessandro Rambaldi, has identified an indicator of the severity of the disease in patients with Covid 19: the PTX3 molecule.
The play “Macrophage Expression and Prognostic Importance of PTX3 Long Pentaxin in COVID-19”, just published in Nature Immunology, involved 96 patients in Humanitas and 54 in Pope John XXIII. In addition, thanks to access to bioinformatic data and analysis supported by Artificial Intelligence, it examined data from patients residing in Israel and the US The researchers investigated the mechanisms of innate immunity in circulating blood and lungs.
“The analysis brought to light the role of a gene discovered by my group years ago, PTX3: a molecule involved in immunity and inflammation – explains prof. Mantovani, Scientific Director of Humanitas and Emeritus Professor of Humanitas University -. In patients with Covid-19, this molecule is present at high levels in circulating blood, lungs, cells of the first line of defense (macrophages) and in cells that line the inner surface of blood vessels (the endothelium vascular). . Important information since patients with Covid-19 have very strong inflammation (macrophage activation syndrome) that leads to thrombosis of the pulmonary microcirculation at the endothelial cell level. Then we verified that PTX3 could be a severity marker, thanks to reagents and a test developed by Humanitas researchers ”.
The two independent case studies, Milan and Bergamo, confirm that the measurement of PTX3 is, to date, the most important prognostic factor associated with the worsening of patients’ conditions. “These data – explains Rambaldi, director of the Hematology Unit and the Oncology and Hematology Department of the Papa Giovanni hospital – confirm the centrality of endothelial damage in the pathogenesis of the most serious manifestations observed in patients with Covid. Circulating levels of PTX3, measured in the blood, will serve to guide the evaluation of the response to treatment in these patients. The validation of the results obtained in two independent cohorts of patients underlines the robustness and reproducibility of this observation and the importance of being able to use properly stored biological material at the time of admission of these patients ”.
The next step will be to transfer the discovery from the research desk to the patient’s bed. “The study, which requires further verification and confirmation, could be an important tool to guide physicians in defining therapies for each patient”, continues prof. Mantovani -. At Humanitas we are putting the test at the service of doctors who work with Covid patients thanks to the collaboration of the Hospital’s Clinical Analysis Laboratory led by the doctor Maria Teresa Sandri. We hope that it will help doctors to quickly assess the severity of the disease and treat the sick even better. ”
Starting from a high-tech approach, the study defines a simple test (a blood test is sufficient to assess the level of PTX3), low-cost and potentially shared with everyone. “The study shows that the advancement of knowledge is made thanks to the collection of biological samples and personal and health data of the population – concludes Rambaldi – essential for an effective investigation on COVID-19, according to internationally consolidated standard operating procedures”.
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