A blood enzyme might be the link between Covid-19 severity and comorbidities

• Increased levels of plasmin might be making the coronavirus more infectious and deadly
• This enzyme is responsible for getting rid of blood clots and leads to hyperfibrinolysis
• By targeting it directly, doctors might be able to reduce the severity of Covid-19

Scientists might have found a new link between chronic disease and Covid-19 that could explain why patients with comorbidities are so susceptible to the virus.

They think the answer may lie with plasmin, a type of enzyme in the blood that degrades plasma proteins. Its levels are normally elevated in those with underlying medical conditions like hypertension, diabetes, cardiovascular disease, cerebrovascular disease, and kidney disease.

One of these plasma proteins is fibrin, which appears when the blood is clotting and impedes the flow of blood. When the fibrin is broken down through fibrinolysis, protein fragments remain behind called D-dimer.

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Making virus more deadly

According to the study published in Physiological Reviews, the plasmin makes the virus more deadly and infectious by cleaving the spike proteins it uses to invade cells through the ACE2 receptors.

"Extracellular cleavage of virus envelope fusion glycoproteins by host cellular proteases is a prerequisite for the infectivity of respiratory viruses. The presence of a polybasic cleavage site that can be cleaved by furin-like proteases is a signature of several highly pathogenic avian influenza viruses."

D-dimer levels

Covid-19 patients show high levels of D-dimer, indicating higher levels of plasmin, which is an independent risk factor of disease severity and death alongside age and comorbidities. 

"The existence of significantly increased fibrin degradation products and reduced platelets in severe Covid-19 patients is consistent with the presence of hyperfibrinolysis."

This condition was found in 97% of Covid-19 patients upon admission and increased in all patients up until death. In those who recovered from the disease, D-dimer levels were very low.

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Death rate

High-risk factors for death from Covid-19 include developing acute respiratory distress syndrome and admittance to ICU, while the leading causes of death from the disease include multi-organ failure, haemorrhage/coagulopathy, acute heart/liver/kidney injury, and secondary bacterial infections.

About 71% of non-survivors met the criteria for disseminated intravascular coagulation, a condition where blood clots start forming throughout the body. 

Targeted treatment

So how do we combat the situation? If doctors can prescribe medication to target hyperfibrinolysis in Covid-19 patients, it may help reduce the severity of the virus in patients with comorbidities. Anti-protease agents could also reduce the levels of plasmin – which is currently being trialled in China.

"The administration of anti-proteases to suppress plasmin activity in the respiratory system may prevent, or at least decrease, SARS-CoV-2 entry into respiratory cells and improve the clinical outcome of patients with Covid-19."

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