More data is being collected on the effect of metabolism of some investigational COVID-19 drugs with a general decrease in metabolism and elimination of these drugs. When studying some drugs used in COVID-19 there were noticeable differences in their plasma concentrations in comparison to healthy individuals. These concentrations were often significantly higher than usual which confirmed the downregulation of CYP enzymes due to infection in COVID-19 patients. These high drug concentrations could prove toxic to the liver and other organs. 

Rutgers University

The liver is one of the major organs targeted by SARS-CoV-2. The S protein of the virus binds to ACE2 receptors to enter host cells in the body. ACE2 is expressed in the liver so the organ is likely affect by both a direct attack from the virus and damage from an overexpression of proinflammatory mediators. To monitor liver health the ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is generally used, both being factors indicative of liver damage when at high levels. This ratio can indicate the liver advancing to cirrhosis or fibrosis.  In studies of COVID-19 patients it was found that levels of markers of liver function were up to five times more than the upper limits of their normal levels and sometimes even higher. In COVID-19 patients that had passed away, about 78% had high levels of markers of abnormal liver function. With the function of the liver in metabolism and protein production, even small changes in the liver that come with the infection may negatively impact the body's response. By altering liver metabolism, there will be consequences seen in the therapeutic and toxic effects of endogenous substances like the medications being taken by COVID-19 patients.

Liver Function Status in COVID-19 Patients

Deb, S., Arrighi, S. Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients. Eur J Drug Metab Pharmacokinet 46, 185–203 (2021). https://doi-org.proxy.libraries.rutgers.edu/10.1007/s13318-020-00668-8

Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients

For the most part, drug metabolism functions to inactivate medications while few drugs are actually activated during the process. CYP enzymes are mainly found in the liver and are responsible for a large amount of drug metabolism. In fact, CYP3A4 is responsible for over 60% of drug metabolism. During viral infection the release of inflammatory proteins and suppress CYP enzymes. Although the effect of SAR-CoV-2 on CYP enzymes has not been fully studied, based on data collected from other viral infections and inflammatory diseases on CYP regulations there is a general downregulation of the enzymes especially with CYP3A4. This is seen with an increase in individual inflammatory markers. The effect of multiple cytokines at once, as seen in a cytokine storm, is unknown but assumed to be additive or synergistic. 

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