The Covid-19 Inflammatory Storm

One of the main features of COVID-19 disease is the dramatically high proportion of patients who need intensive care to survive. In these cases, physicians and nurses face a very insidious pathology, which cannot be described in terms of a classic interstitial pneumonia: it is an inflammatory storm, primarily affecting the internal walls of blood vessels in the lungs and sometimes causing blood clots, and then moving towards other vital organs, such as the brain and the kidney.

The San Raffaele team – led by Professor Alberto Zangrillo, Director of the General and Cardiothoracic Anaesthesia and Intensive Care Units, Professor Giovanni Landoni, Director of the Anaesthesia and Intensive Care Research Centre, and Professor Fabio Ciceri, deputy scientific director for Clinical Research of IRCCS Ospedale San Raffaele – has defined this inflammatory syndrome as "MicroClots". The observations have been published recently in the Journal of Critical Care and Resuscitation.


Definition of MicroClots

"We are not dealing with classic pneumonia, but with a complex and different disease, much more systemic. In fact, the name 'MicroClots' stands for Microvascular Covid-19 lung vessels obstructive thrombo-inflammatory syndrome: a sort of progressive endothelial syndrome starting in the lungs" explains Zangrillo.

The new coronavirus enters the alveoli inside the lungs. Here, over several days, it affects the endothelium (the inner wall of blood vessels) and triggers thrombotic manifestations in a significant percentage of cases. This means that clots form inside the vessels and obstruct normal blood flow.

The thrombotic inflammatory syndrome sometimes evolves and, from the lungs, starts to affect also the micro vascular system of the brain and other vital organs, leading to multiple failure and in some cases death. "It's a very peculiar syndrome, we've never seen anything similar," remarked Professor Landoni.


Different stages of Covid-19

Thanks to the definition of the MicroClots syndrome, it is now possible to describe different stages of Covid-19 disease. Understanding the sequence of events will help to explain the peculiarities observed in patients and to act in the most effective way possible.

“For the patients with a slight fever, cough or cold, we need targeted antivirals – explains Fabio Ciceri. “Then, when the patients start to get worse and need intensive care, we should move to anti-inflammatory drugs, because the inflammation phase is already underway. Many of these drugs are already intensively studied in clinical trials”.

"Finally, there are patients that – for genetic predisposition, underlying diseases or just bad luck – evolves into MicroClots: the obstructive thrombo-inflammatory syndrome. This phase should be prevent or treated with anticoagulants or antiplatelet drugs. Which option is more suitable has yet to be defined," says Landoni.


Future developments

The hypothesis of alveolar damage, followed by an inflammatory reaction and a micro vascular pulmonary thrombosis, is a new promising attempt to understand a very complex and still mysterious lung disease.

"We have seen more than 800 severe pneumonia and more than 110 patients needed intensive care. This new theoretical framework has emerged thanks to the contribution of cardiologists, heart surgeons, vascular surgeons, hematologists, internists and radiologists, but we know there is still a lot of research that needs to be done and I’m sure it will provides new insights and solutions to fight this disease" Landoni concludes.