Research Article Pathobiology 2022;89:81–91 Increase in Chondroitin Sulfate and Decline in Arylsulfatase B May Contribute to Pathophysiology of COVID-19 Respiratory Failure Alexandar Tzankov a Sumit Bhattacharyya b, c Kumar Kotlo b, c Joanne K. Tobacman b, c a Pathology, University Hospital Basel, Institute of Medical Genetics and Pathology, University of Basel, Basel, Switzerland; b Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA; c Jesse Brown VA Medical Center, Chicago, IL, USA Received: June 24, 2021 Accepted: September 6, 2021 Published online: November 17, 2021 Correspondence to: Joanne K. Tobacman, jkt @uic.edu © 2021 S. Karger AG, Basel karger@karger.com www.karger.com/pat DOI: 10.1159/000519542 Keywords Chondroitin sulfate · Arylsulfatase B · Sulfotransferase · Angiotensin-converting enzyme 2 · COVID-19 Abstract Introduction: The potential role of accumulation of chon- droitin sulfates (CSs) in the pathobiology of COVID-19 has not been examined. Accumulation may occur by increased synthesis or by decline in activity of the enzyme arylsulfa- tase B (ARSB; N-acetylgalactosamine-4-sulfatase) which re- quires oxygen for activity. Methods: Immunostaining of lung tissue from 28 patients who died due to COVID-19 in- fection was performed for CS, ARSB, and carbohydrate sul- fotransferase (CHST)15. Measurements of mRNA expression of CHST15 and CHST11, sulfotransferase activity, and total sulfated glycosaminoglycans (GAGs) were determined in human vascular smooth muscle cells following angiotensin (Ang) II treatment. Results: CS immunostaining showed in- crease in intensity and distribution, and immunostaining of ARSB was diminished in COVID-19 compared to normal lung tissue. CHST15 immunostaining was prominent in vascular smooth muscle cells associated with diffuse alveolar dam- age due to COVID-19 or other causes. Expression of CHST15 and CHST11 which are required for synthesis of CSE and chondroitin 4-sulfate, total sulfated GAGs, and sulfotrans- ferase activity was significantly increased following AngII exposure in vascular smooth muscle cells. Expression of In- terleukin-6 (IL-6), a mediator of cytokine storm in COVID-19, was inversely associated with ARSB expression. Discussion/ Conclusion: Decline in ARSB and resulting increases in CS may contribute to the pathobiology of COVID-19, as IL-6 does. Increased expression of CHSTs following activation of Ang-converting enzyme 2 may lead to buildup of CSs. © 2021 S. Karger AG, Basel Introduction The COVID-19 pandemic presents unique challenges as the medical and scientific communities develop new therapies, new diagnostic tests, and new insights into the mechanisms by which the SARS-CoV-2 acts [1–3]. In this report, the potential role of chondroitin sulfate (CS) in the pathobiology of COVID-19 is considered. Both in- Alexandar Tzankov, Sumit Bhattacharyya are co-first authors. Downloaded from http://karger.com/pat/article-pdf/89/2/81/3909499/000519542.pdf by guest on 20 October 2023