EMERGING research has linked COVID-19 to joint pain and osteoarthritis, but the precise mechanisms behind this connection and the damage to articular cartilage were previously unclear. A recent study by Man Ting Au et al. at the University of Hong Kong, China, has shed light on how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including the Delta and Omicron variants, can cause knee joint damage.
In two patients with post-COVID osteoarthritis and a hamster model, the virus triggered cystic lesions in the osteochondral junction and chondrocyte loss. SARS-CoV-2 activated endothelin-1 signaling, leading to increased vascular permeability and leakage of viral spike proteins into subchondral bone. This cascade induced osteoclast activation, accelerating joint damage.
The study highlighted the therapeutic potential of macitentan, an FDA-approved endothelin receptor antagonist. Macitentan, when administered early, mitigated joint damage by preserving chondrocyte numbers and reducing lesions. Even in the post-acute phase, delayed treatment reduced chondrocyte senescence and bone loss, offering a promising strategy for clinicians managing post-COVID arthritis.
Given the significant increase in joint pain and osteoarthritis in patients after COVID infection, this research points to a novel therapeutic pathway, positioning endothelin receptor blockers as a key player in future treatments for post-viral arthritis.
Reference: Au MT et al. Blockade of endothelin receptors mitigates SARS-CoV-2-induced osteoarthritis. Nat Microbiol. 2024.
Anaya Malik | AMJ
