The Potential Risk of Reduced Serum Cholinesterase Activity in COVID-19 Patients Suffering From Cytokine Storm

TL;DR

This study explores how reduced serum cholinesterase activity in severe COVID-19 patients with cytokine storms could help assess risk and how the chemical dichlorvos affects this enzyme.

Contribution

The study identifies reduced serum cholinesterase activity as a potential risk marker in cytokine storm patients and evaluates its susceptibility to dichlorvos inhibition.

Findings

Female COVID-19 patients with cytokine storm had significantly lower serum cholinesterase activity compared to non-cytokine storm patients.

Dichlorvos at 0.25 μM and 0.5 μM significantly inhibited serum cholinesterase activity in all groups, with the cytokine storm group being the least affected.

Cytokine storm patients showed reduced susceptibility to cholinesterase inhibition, with altered inhibition kinetics including shorter half-life and total inhibition time.

Abstract

Background and objective

Several blood biochemical parameters are used to biomonitor coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Reduced serum cholinesterase (ChE) has been suggested to be a predictive indicator of the severity and outcome of COVID-19 infection. This study aimed to examine serum ChE activity in hospitalized and terminally ill COVID-19 patients with cytokine storm and evaluate the enzyme for the in vitro ChE-inhibitory activity of the organophosphate dichlorvos.

Methods

We determined the serum ChE activity, electrometrically, among hospitalized COVID-19-cytokine storm patients and their non-cytokine storm counterparts. Aliquots of serum samples from healthy volunteers, COVID-19-cytokine storm patients, and non-cytokine storm COVID-19 patients were pooled separately. They were incubated in vitro for 10 minutes with dichlorvos at 0.25 or 0.5 μM. Serum samples from the three groups were subjected to ChE inhibition temporally (5-60 minutes) by 0.25 μM dichlorvos to evaluate the kinetics of enzyme inhibition using steady-state kinetics.

Results

Of the 165 hospitalized patients with COVID-19, 33 (20%) suffered from the cytokine storm. Serum ChE activity of female COVID-19 patients with cytokine storm was significantly lower than that of the non-cytokine storm counterparts. Risk analysis of reduced serum ChE activity (≥20%) among the 33 COVID-19 patients with cytokine storm compared to 111 non-cytokine storm COVID-19 patients revealed that the former were significantly at risk of reduced enzyme activity. In vitro, dichlorvos at 0.25 μM and 0.5 μM significantly inhibited serum ChE activity in all the groups. The COVID-19-cytokine storm group was the least affected. Dichlorvos at 0.25 μM progressively (5-60 minutes) inhibited serum ChE activity. The inhibition kinetic parameters in COVID-19-cytokine storm patients showed a decrease in the half-life of inhibition (14.54%), inhibition rate (51.46%), and total inhibition time (14.55%).

Conclusions

Reduced serum ChE in COVID-19 patients with cytokine storm could be adopted as a potential additional laboratory examination tool for bedside risk assessment. The in vitro inhibition profile of serum ChE activity by dichlorvos in COVID-19-cytokine storm patients suggests reduced susceptibility of the enzyme to inhibition. The response of COVID-19 patients to ChE-inhibiting medications should be cautiously evaluated with prior in vitro tests.