Liver Injury as a Surrogate for Inflammation and Predictor of Outcomes in COVID-19.

Respiratory failure is the most common cause of death in patients with corona virus disease 2019 (COVID-19). There have been many investigations to determine predictors of bad outcomes in patients with this illness. Liver enzyme elevation has been described in hospitalized patients with severe COVID-19; however, little is known about the significance of liver injury regarding outcomes. We conducted a retrospective chart review of 348 patients admitted with COVID-19 in our quaternary care center. Liver injury on admission was defined based on the laboratory cutoff of aspartate aminotransferase >35 IU/L and/or alanine aminotransferase >52 IU/L. Patients were divided into two cohorts based on the presence or absence of liver injury. These cohorts were compared to assess differences in presentation, complications, and outcomes. The primary outcome was respiratory failure requiring intubation, and the secondary outcome was in-hospital mortality. The presence of new onset liver enzyme elevation on presentation was associated with increased severity of illness, need for mechanical ventilation, and mortality. Presence of liver injury increased the chance of acute hypoxic respiratory failure requiring mechanical ventilation by 1.79 times. The degree and timeline of liver enzyme elevation during hospitalization corresponded with elevations of other inflammatory markers. Conclusion: Liver injury appears to correlate with the inflammatory syndrome caused by COVID-19, with the degree of liver injury corresponding with severity of inflammation. We suggest early and continued monitoring of liver enzymes as they can be useful to identify patients who may need early escalation of care.

Structural, catalytic and stabilizing consequences of aromatic cluster variants in human carbonic anhydrase II.

The presence of aromatic clusters has been found to be an integral feature of many proteins isolated from thermophilic microorganisms. Residues found in aromatic cluster interact via π-π or C-H⋯π bonds between the phenyl rings, which are among the weakest interactions involved in protein stability. The lone aromatic cluster in human carbonic anhydrase II (HCA II) is centered on F226 with the surrounding aromatics F66, F95 and W97 located 12 Å posterior the active site; a location which could facilitate proper protein folding and active site construction. The role of F226 in the structure, catalytic activity and thermostability of HCA II was investigated via site-directed mutagenesis of three variants (F226I/L/W) into this position. The measured catalytic rates of the F226 variants via (18)O-mass spectrometry were identical to the native enzyme, but differential scanning calorimetry studies revealed a 3-4 K decrease in their denaturing temperature. X-ray crystallographic analysis suggests that the structural basis of this destabilization is via disruption and/or removal of weak C-H⋯π interactions between F226 to F66, F95 and W97. This study emphasizes the importance of the delicate arrangement of these weak interactions among aromatic clusters in overall protein stability.

Carbonic anhydrases and their biotechnological applications.

The carbonic anhydrases (CAs) are mostly zinc-containing metalloenzymes which catalyze the reversible hydration/dehydration of carbon dioxide/bicarbonate. The CAs have been extensively studied because of their broad physiological importance in all kingdoms of life and clinical relevance as drug targets. In particular, human CA isoform II (HCA II) has a catalytic efficiency of 108 M-1 s-1, approaching the diffusion limit. The high catalytic rate, relatively simple procedure of expression and purification, relative stability and extensive biophysical studies of HCA II has made it an exciting candidate to be incorporated into various biomedical applications such as artificial lungs, biosensors and CO2 sequestration systems, among others. This review highlights the current state of these applications, lists their advantages and limitations, and discusses their future development.