Plasma Levels of Glycohydrolase Activities in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Patients Open Access

To the Editor.—Glycohydrolases are distributed everywhere, especially in lysosomes, but also in plasma membranes, in cytosol and plasma. Over the years, plasma glycohydrolases have become increasingly important as potential serologic markers in several diseases¹  characterized by lysosomal apparatus deregulation and altered plasmatic glycohydrolase levels.

It is known that during the inflammatory process, an activation of lysosomal apparatus occurs, with consequent alterations in the plasma levels of several glycohydrolases, including β-d-glucuronidase (GCR).² 

In early 2020, a new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), appeared in Wuhan, China, and rapidly spread worldwide. The hallmark of COVID-19 is tissue damage resulting from overproduction of reactive oxygen species due to the hyperinflammatory process known as cytokine storm. In recent years, a new method for the evaluation of total plasma antioxidant defenses, known as lag time,³  has proved to be a valid marker of oxidative stress (OS) in different diseases.⁴ 

In this study we collected plasma samples from 13 COVID-19 patients and 52 non–COVID-19 patients presenting with COVID-19–like symptoms at the emergency room of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, San Donato Milanese, Milano, Italy. All patients were admitted to the intensive care units of the hospital. Thirty age-matched volunteers were used as the control group. The study was approved by the local ethics committee (75/INT/2020).

C-reactive protein (CRP) was measured by a Cobas 600 analyzer (Roche Diagnostic, Milan, Italy). The plasma activities of hexosaminidase, GCR, and α-d-glucosidase, as well as kinetics of plasma oxidation, were fluorometrically determined^1,3  by Victor³  (PerkinElmer).

Enzymatic activities and lag-time values showed no significant difference from normal distribution, and the means were compared by Student t test. C-reactive protein showed a nonnormal distribution, and the means were compared by Mann-Whitney U test. The Pearson correlation coefficient (r²) was calculated to determine the correlations between values measured by different assays. Statistical analyses were performed by SPSS STATISTIC 26 package (SPSS Inc, Chicago, Illinois).

In all patients, CRP was significantly altered compared with the reference clinical ranges, and in COVID-19 patients it was significantly higher than in non–COVID-19 patients (Table). All glycohydrolase activities were significantly increased in all patients with respect to the controls and were significantly higher in COVID-19 patients than in non–COVID-19 patients (Table). Lag-time values were significantly lower in all patients compared with controls (Table). In the COVID-19–positive group, lag-time values showed a significant negative linear correlation with GCR level, suggesting that this parameter could be a good indicator of OS in COVID-19 patients (Figure).

Until now there has been little information on the involvement of plasma glycohydrolases in infectious diseases, such as HIV infection.⁵  In this regard, to our knowledge, our data highlight for the first time an activation of the lysosomal apparatus in SARS-CoV-2 infection. In particular, our results indicate a negative correlation between total plasma antioxidant defenses and GCR, suggesting a link between OS and lysosomal apparatus activation. Therefore, because of the clinical relevance of OS in COVID-19, the evaluation of both glycohydrolase levels and plasmatic antioxidant defenses could be suggested as a new possible tool for future studies characterizing the role of OS in COVID-19 infection.

We acknowledge Camilla Mocchi, BSci, for her precious help in the enzymatic assay realization and Judy Baggott, PhD, for English editing.