The role of adipocytes and adipocyte‐like cells in the severity of COVID‐19 infections

Kruglikov, Ilja L.; Scherer, Philipp E.

Coronavirus disease‐2019 (COVID‐19), caused by the highly pathogenic virus SARS‐CoV‐2, demonstrates high morbidity and mortality caused by development of a severe acute respiratory syndrome connected with extensive pulmonary fibrosis (PF). In this Perspective, we argue that adipocytes and adipocyte‐like cells, such as pulmonary lipofibroblasts, may play an important role in the pathogenic response to COVID‐19. Expression of angiotensin‐converting enzyme 2 (ACE2 ‐ the functional receptor for SARS‐CoV) ‐ is upregulated in adipocytes of obese and diabetic patients, which turns adipose tissue into a potential target and viral reservoir. This may explain why obesity and diabetes are potential comorbidities for COVID‐19 infections. Similar to the recently established adipocyte‐myofibroblast transition (AMT), pulmonary lipofibroblasts located in the alveolar interstitium and closely related to classical adipocytes, demonstrate the ability to transdifferentiate into myofibroblasts that play an integral part of PF. This may significantly increase the severity of the local response to COVID‐19 in the lung. To reduce the severity and mortality with COVID‐19, we propose to probe for the clinical response to thiazolidinediones (TZDs), PPARγ agonists, that are the well‐known anti‐diabetic drugs. TZDs are able to stabilize lipofibroblasts in their “inactive” state, preventing the transition to myofibroblasts and thereby reducing the development of pulmonary fibrosis and stimulating its resolution.