Pain Mechanisms in long-Covid

新冠肺炎大流行影响了数以亿计的人，虽然许多人完全康复，但约十分之一的人患有被称为慢性冠状病毒病的长期症状。我们已经知道，一些患者在一年多后仍然会出现症状。肌肉和关节疼痛和疲劳是长期冠状病毒感染以及呼吸问题和嗅觉丧失的常见症状。一些患者还会有异常感觉(针刺痛和灼热感)，这可能是由于某些感觉神经受损所致。Long-COVID患者疼痛和异常感觉的潜在机制尚不清楚，也没有有效的治疗方法。此外，目前还没有实验室方法来诊断长冠状病毒病。我们的研究结合了患者和基于实验室的研究，以了解长期冠状病毒感染患者遭受疼痛的原因。为此，我们将描述长期冠状病毒感染患者的疼痛性质、强度和位置，测试疼痛感知神经是否受到损害，并测量疼痛和疲劳对日常生活的影响。Long-CoVID患者的疼痛和疲劳类似于纤维肌痛患者的症状，我们最近表明，身体的正常防御机制--免疫系统--是导致纤维肌痛患者疼痛的原因。免疫细胞产生抗体，通常帮助我们对抗感染。我们的结果表明，纤维肌痛患者会产生抗体来攻击自己的身体，并刺激痛觉神经。因此，我们将进行测试，以确定抗体是否也是长期冠状病毒感染患者疼痛和疲劳的原因。为此，我们将从长期感染COVID的人身上提纯抗体，将它们注射到小鼠体内，并测量小鼠是否出现疼痛和疲劳的症状。我们还将检查从感觉神经受损的人那里获得的长冠状病毒抗体是否针对小鼠中类似的感觉神经。我们将在分子水平上找出神经的哪一部分是目标，并开始了解抗体是如何发挥作用的。我们的工作将改善对长期冠状病毒感染的管理，并有可能为诊断这种情况提供一种实验室方法。

The COVID-19 pandemic has affected hundreds of millions of people and while many individuals recover fully about 1 in 10 suffer from long term symptoms known as long-COVID. We know already that some patients still experience symptoms after more than one year. Muscle and joint pain and fatigue are common symptoms of long-COVID along with breathing problems and loss of smell. Some patients also suffer from abnormal sensations (pins and needles and burning pain) which could be due to damage to some sensory nerves. The mechanisms underlying pain and abnormal sensations in long-COVID are unknown and there are no effective therapies. Also there is currently no laboratory method to diagnose long-COVID. Our research combines patient and lab-based studies to understand why long-COVID patients suffer from pain To do this, we will characterise the qualities, intensities and location of pain in long-COVID patients, test whether there is damage to pain-sensing nerves, and measure the impact of pain and fatigue on daily life. The pain and fatigue seen in long-COVID resembles the symptoms found in patients with fibromyalgia, and we have very recently shown that the body's normal defence mechanism, the immune system, is responsible for pain in fibromyalgia patients. Immune cells produce antibodies which normally help us to fight infections. Our results showed that fibromyalgia patients produce antibodies that attack their own bodies and stimulate pain sensing nerves. We will therefore test to see whether antibodies are also responsible for pain and fatigue in long-COVID. To do this we will purify antibodies from people with long-COVID, inject them into mice and measure if the mice develop symptoms of pain and fatigue. We will also examine if long-COVID antibodies obtained from people who have sensory nerve damage, targets the similar sensory nerves in the mice. We will find out at a molecular level what part of the nerves are being targeted and begin to understand how the antibodies have their effects. Our work will improve management of long-COVID and potentially provide a laboratory method for diagnosing this condition.