Paper of the Month

August 2020

Immunothrombotic Dysregulation in COVID-19 Pneumonia is Associated with Respiratory Failure and Coagulopathy. CIRCULATION 28 Jul 2020, DZHK authors: Leo Nicolai, Alexander Leunig, Rainer Kaiser, Tobias Weinberger, Clemens Scherer, Stefan Kääb, Steffen Massberg. Kami Pekayvaz, Konstantin Stark

Infection with SARS-CoV2 leads to respiratory disease, which in severe cases, can be associated with respiratory failure and the need for invasive ventilation. These patients also often have thrombotic complications such as pulmonary embolism or venous thrombosis. Whether respiratory failure and a systemic prothrombotic phenotype in COVID-19 are related was not known until now.

In a paper recently published in the journal Circulation, DZHK scientists from the Medical Clinic I of the Ludwig-Maximilians University of Munich were able to uncover a pathophysiological interface between changes in the pulmonary vessels and thrombotic complications: The pulmonary vessels of seriously ill COVID-19 patients showed multiple thromboses in the microcirculation. The researchers also found thrombotic vessel occlusions in the heart and kidneys. The thrombi consisted mainly of platelets and activated inflammatory cells (neutrophilic granulocytes). The immunothrombotic occlusions detected here arise because inflammatory processes trigger the activation of blood coagulation and platelets, which aims to prevent the spread of viruses and bacteria in the body. However, such vascular occlusions also impair the blood supply to the tissue – which contributes to lung failure – and a systemic tendency to thrombosis develops.

The current work shows through multidimensional FACS analyses that strongly activated neutrophil granulocytes and blood platelets are found in the blood of COVID-19 patients with respiratory failure who require ventilation. The interaction of these two cell types is characterised by mutual activation, which ultimately leads to vascular occlusion in the lung. An essential component of this occlusion formation are neutrophil extracellular traps (NETs), consisting of DNA and granule proteins of the neutrophil granulocytes, which stabilise the blood clots. In the blood, this initially local process is reflected in the lungs by marked activation of blood clotting, which manifests in an increased systemic tendency to thrombosis.

This work contributes to a better understanding of the pathophysiological mechanisms involved in COVID-19 and shows immunothrombosis as a promising starting point in the prevention and therapy of respiratory failure and other thrombotic complications in this new disease.