- Aprotinin: inhibits function of trypsin , kallikrein, and plasmin and inhibits sodium ion transport in endothelial cells
- Hepatocyte growth factor activator inhibitor 
- A1-anti-trypsin inhibits ENaC production, which is elevated when plasmin levels are elevated in pregnant women

Michigan State University

- Elevated plasmin levels are found in COVID-19 patients
- Plasmin allows the SARS-CoV-2 virus to bind with ACE2 receptors by cleaving the S protein on the virus
- Plasmin breaks down fibrin, increasing the levels of D-dimer and decreasing platelet count; this could possibly prevent inflammation in COVID-19 patients, but it could result in hemorrhaging
- Plasminogen is expressed in both endothelial and epithelial cells
- Severe and deceased COVID-19 patients had very low platelet counts
- However, plasmin causes hypertension and dehydration in the lungs due to an increase in sodium ion uptake


Plasmin and COVID-19

Ji, H. L., Zhao, R., Matalon, S., & Matthay, M. A. (2020). Elevated plasmin (ogen) as a common risk factor for COVID-19 susceptibility. Physiological reviews.

ELEVATED PLASMIN(OGEN) AS A COMMON RISK
FACTOR FOR COVID-19 SUSCEPTIBILITY


- D-dimer levels are increased in patients in all the different COVID-19 groups(plasmin is responsible for the amount of D-dimer being produce)
- There is a slight elevation in fibrinogen in deceased COVID-19 patients compared to those who survived
- APPT was less in COVID-19 ICU patients, as thrombosis was occurring at a faster rate

Plasmin associated impacts on COVID-19 Patients

- D-dimer levels are elevated with increased fibrinolysis
- Hyperfibrinolysis was found in 97% of COVID-19 patients in the study; even more hyperfibrinolysis right before death
- More fibrin degradation products 
- Less blood clots formed in COVID-19 patients as a result of reduced platelet counts


Fibrinolysis’ association with COVID-19


Protease Inhibitors

- When the S protein is cleaved, the virus can enter the epithelial tissue of the bronchi of the lungs
- Camostat mesylate (protease inhibitor) inhibits the effect of plasmin
- Plamin can cause hypertension in kidneys by cleaving ENaC (amiloride can reverse the effects)
- High levels of plasmin can cause sepsis
- Diabetics have higher levels of plasminogen; ; high levels of plasmin are also found in cancer patients and in the urine of pregnant women
- The SARS-CoV-2 consists of a furin cleavage site, which is found at the S1/S2 boundary
- RdRp replicates the genetic material of SARS-CoV-2


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