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.

关节疼痛和骨关节炎可作为感染后的 2019 冠状病毒病 （COVID-19） 后遗症发生。然而，人们对关节软骨的损伤知之甚少。在这里，我们说明了严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 感染的野生型、Delta 和 Omicron 变体在体内感染后的膝关节损伤。在两名 COVID 后骨关节炎患者中观察到骨软骨交界处囊性病变的快速关节损伤，并在金色叙利亚仓鼠模型中进行了概括。SARS-CoV-2 激活的内皮素-1 信号增加血管通透性，并导致病毒刺突蛋白渗漏到软骨下骨。破骨细胞活化、软骨细胞脱落和囊肿形成经组织学证实。美国食品和药物管理局批准的内皮素受体拮抗剂 macitentan 减轻了仓鼠病毒感染急性期的囊性病变并保留了软骨细胞数量。急性感染后延迟 macitentan 治疗减轻了软骨细胞衰老并恢复了软骨下骨质流失。值得注意的是，它还可以减轻病毒刺突引起的关节疼痛。我们的工作表明内皮素受体阻断是 COVID 后关节炎的一种新型治疗策略。