AI Summary
The article discusses the joint damage and osteoarthritis that can occur as sequelae to COVID-19 infection, particularly focusing on damage to articular cartilage. It highlights rapid joint injury observed in patients and a hamster model infected with SARS-CoV-2 variants, leading to cystic lesions at the osteochondral junction. The study identifies SARS-CoV-2-activated endothelin-1 signaling as a key factor in vascular permeability, viral spike protein leakage, osteoclast activation, chondrocyte dropout, and cyst formation. The FDA-approved endothelin receptor antagonist, macitentan, is shown to mitigate cystic lesions and preserve chondrocytes, potentially offering a novel therapeutic strategy for post-COVID arthritis.
Joint pain and osteoarthritis can occur as coronavirus disease 2019 (COVID-19) sequelae after infection. However, little is known about the damage to articular cartilage. Here we illustrate knee joint damage after wild-type, Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vivo. Rapid joint injury with cystic lesions at the osteochondral junction was observed in two patients with post-COVID osteoarthritis and recapitulated in a golden Syrian hamster model. SARS-CoV-2-activated endothelin-1 signalling increased vascular permeability and caused viral spike proteins leakage into the subchondral bone. Osteoclast activation, chondrocyte dropout and cyst formation were confirmed histologically. The US Food and Drug Administration-approved endothelin receptor antagonist, macitentan, mitigated cystic lesions and preserved chondrocyte number in the acute phase of viral infection in hamsters. Delayed macitentan treatment at post-acute infection phase alleviated chondrocyte senescence and restored subchondral bone loss. It is worth noting that it could also attenuate viral spike-induced joint pain. Our work suggests endothelin receptor blockade as a novel therapeutic strategy for post-COVID arthritis.
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