A lesson from an old friend: high molecular weight kininogen (HMWK)
impact in COVID-19.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a newly
identified coronavirus which has spread from China to the rest of the
world causing the pandemic coronavirus disease 19 (COVID-19). It has
fatality rate that floats from 5 to 15% and the symtoms are fever,
cough, myalgia and/or fatigue up to dyspnea, responsible for
hospitalization and in most of the cases of artificial oxygenation. In
the attempt to understand how the virus spreads and how to
pharmacologically abolish it, it was highlighted that SARS-CoV2 infects
human cells by means of angiotensin converting enzyme 2 (ACE2),
transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin-like
protease (3CLpro), also known as Mpro. Once bound to its receptor ACE2,
the other two proteases, in concert with the receptor-mediated
signaling, allow virus replication and spread throughout the body. Our
attention has been focused on the role of ACE2 in that its blockade by
the virus increases Bradykinin and its metabolites, well known to
facilitate inflammation in the lung (responsible for cough and fever),
facilitate both the coagulation and complement system, three mechanisms
that are typical of angioedema, cardiovascular dysfunction and sepsis,
pathologies which symptoms occur in COVID-19 patients. Thus, we propose
to pharmacologically block the kallicrein-kinin system upstream
bradykinin and the ensuing inflammation, coagulation and complement
activation by means of lanadelumab, which is a clinically approved drug
for hereditary angioedema.