Abstract

The activation of the innate immune system during COVID-19 infection, in particular the inflammasome, and the overrepresentation of severe symptoms in patients presenting with overweight and diabetes raises the possibility that excessive inflammasome activation occurs in these patients and that this is the pivotal mechanism that causes the severity of the disease.

The observed effects on fluid homeostasis, respiratory resistance, fibrosis and fibrin deposition in multiple tissues, can be brought together under the umbrella of excessive inflammasome activation in COVID-19 infection.

The proposal is to use specific biochemical measurements or biomarkers in order to

(a) identify patients that have excessive inflammasome activation and cells loaded with pro-cytokines and

(b) follow the disease progression and assessing the effect of experimental treatments using these biomarkers. It is expected that these biomarkers also provide proof of concept for the proposed mechanisms. They may also replace clinical determinants to define the patients at risk more precisely.

In our opinion, the best approach for treatment is to partially inhibit the excessive inflammasome activation and keep the activation intact at a lower level to maintain the antiviral effect.

Specific inhibition of the multiple downstream effects of inflammasome activation, most notably interleukin 1 beta and 6 effects, bradykinin action and coagulation activation, may require treatment with multiple agents to be sufficiently effective.

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