key: cord-030594-xhp8kin0
authors: nan
title: Dear the Editor,
date: 2020-08-19
journal: J Infect
DOI: 10.1016/j.jinf.2020.08.021
sha: 
doc_id: 30594
cord_uid: xhp8kin0

nan

Kunutsor SK et al. have written to this journal regarding elevated admission levels of markers of liver injury (alanine aminotransferase and aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase and total bilirubin) may be associated with progression to severe disease or death in COVID-19. [1] On the other hand, serum cholinesterase plays an important role in the inflammatory response and may be associated with prognosis in sepsis. [2] [3] [4] We focused on the similarities between severe COVID-19 pneumonia and sepsis.

We examined associations between cholinesterase levels on admission and the severity, and mortality of patients with COVID-19 pneumonia, as well as the interaction between cholinesterase and the previously reported factors of severity and mortality. We included patients who had tested positive for severe acute respiratory syndrome coronavirus 2 from February to May 2020 at Yokohama City University Hospital and Yokohama City University Medical Center. Ultimately, 26 patients were included in the study. Outcomes were aggravation of symptoms and in-hospital death.

The clinical characteristics of the patients grouped by severity are shown in Table 1 .

There was no significant difference in patient characteristics between the groups.

Supplementary Materials 1 shows the time course of cholinesterase and other factors in critically ill patients with good outcome and death. In critically ill patients with favorable outcome, cholinesterase, lymphocytes, albumin, and PaO 2 /FiO 2 ratio decreased but C-reactive protein increased toward the peak of inflammation. Later, C-reactive protein decreased with improvement in inflammation, but there was a tendency for cholinesterase, lymphocytes, albumin, and PaO 2 /FiO 2 ratio to increase. In contrast, in the severely ill patient who died, C-reactive protein poorly decreased, and cholinesterase, lymphocytes, albumin, and PaO 2 /FiO 2 ratio were not elevated. Our results demonstrate that the potential of cholinesterase levels and their interactions were significantly associated with severity and mortality in COVID-19 pneumonia patients.

Cholinesterase is an enzyme produced in the liver that hydrolyzes cholinesters, and measured as a liver function test. Cholinesterase levels are high in patients with nephrotic syndrome, diabetes, hyperthyroidism, fatty liver, dyslipidemia, and obesity and low in patients with liver cirrhosis, hepatitis, malignant tumor, malnutrition, sepsis, and organophosphate poisoning. [5] Although the mechanism underlying cholinesterase reduction in sepsis has not yet been determined, it is thought to be affected by acute-phase infections and inflammatory processes. [6] It has been hypothesized that cholinesterase synthesis decreases owing to hepatic dysfunction with disease progression, capillary permeability enhancement, dilution with fluid challenges, cholinesterase catabolism enhancement, and cholinesterase inhibition by inflammatory mediators (cytokines). [7] Levels of "positive" acute-phase proteins such as C-reactive protein, amyloid A, and ferritin generally increase in patients with inflammatory diseases. In contrast, levels of "negative" acute-phase proteins such as albumin, prealbumin, and transferrin decrease in response to inflammation and increase during the recovery period. [2, 8] Cholinesterase and lymphocytes behave similar to the "negative" acute-phase proteins in response to inflammation. [9, 10] Even in patients with COVID-19 pneumonia, amyloid A, which is classified as a "positive" acute-phase protein; albumin, which is classified as a "negative" acute-phase protein; and lymphocytes showing similar reactions as those of "negative" acute-phase proteins against inflammation have been suggested to be related to severity. [4] Our study suggests that cholinesterase, which responds similar to the "negative" acute-phase proteins in response to inflammation, is reduced even in the acute phase of severe COVID-19 pneumonia. Following the changes in cholinesterase over time, we found that it decreased with deterioration of the condition and increased with improvement.

Cholinesterase level on admission is suggested to be an independent predictor of severity and mortality for COVID-19 pneumonia. Cholinesterase levels on admission were significantly lower in the severe group than in the mild-to-moderate group, and they were also significantly lower in the death group than in the survival group. Cholinesterase was comparable to other markers, such as C-reactive protein, PaO 2 /FiO 2 ratio, albumin, ・Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 

Markers of liver injury and clinical outcomes in COVID-19 patients: A systematic review and meta-analysis

Butyrylcholinesterase as a prognostic marker: a review of the literature

A sustained reduction in serum cholinesterase enzyme activity predicts patient outcome following sepsis

Value of serum cholinesterase in the prognosis of septic shock

Serum cholinesterase is an excellent biomarker of cirrhosis

Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation

Value of serum cholinesterase activity in the diagnosis of septic shock due to bacterial infections

Advances in understanding and assessing malnutrition

Protein-energy malnutrition: its effects on 4 metabolic parameters

Plasma esterases and inflammation in ageing and frailty

Median laboratory values (IQR) ChE (U/L)

*The mild-to-moderate group was defined based on the need for oxygen inhalation or no oxygen inhalation

The severe group was defined as having a respiratory condition requiring ventilator management (PaO2/FiO2 ratio <200 mmHg to respiratory rate >30 /min)