Longitudinal immune and inflammatory responses in the respiratory mucosa and blood of patients after hospitalisation with COVID-19.

新冠肺炎是由严重急性呼吸综合征冠状病毒2型引起的疾病。它于2020年3月11日被世界卫生组织宣布为全球大流行。仅在英国，到目前为止已有超过10万人死亡，许多幸存下来的人可能会遭受令人虚弱的长期影响，称为长期COVID。由于采取了包括封锁在内的控制病毒传播的措施，新冠肺炎也对全球经济和社会产生了毁灭性的影响。一个仍未得到回答的关键问题是，感染后是否会形成持久的免疫力，以及这种免疫力是如何发生的。了解这一点对于预测大流行的未来进程和开发有效的疫苗至关重要。人类免疫系统有许多可能的方法来预防SARS-CoV-2的再次感染。大多数研究都集中在血液中循环的免疫细胞和抗体上。然而，通过只检查血液，我们无法检测到可能保护身体其他部位免受病毒感染的免疫反应。特别是，人们对发生在呼吸道内的免疫反应知之甚少，呼吸道是鼻子、嘴巴和肺部之间的连接通道。这是病毒能够首先感染人类细胞的地方，也是感染一旦确定后炎症的主要部位。因此，呼吸道可能是预防再次感染的关键。鼻衬很容易接触到，并提供呼吸道免疫反应的代表。我们知道，对于其他呼吸道病毒，血液中的抗体不一定能提供免疫力，而呼吸道中有抗体可能更重要。事实上，我们之前已经证明，对其他呼吸道感染的易感性可以受到鼻腔内抗体或细胞活动的影响，而不是血液。因此，如果我们要真正了解人体如何对病毒产生保护性免疫，以及这种免疫力持续多长时间，检查血液和鼻腔对新冠肺炎的免疫反应是至关重要的。在我们对新冠肺炎的理解中，第二个同样至关重要的差距是，为什么一些患者在住院后会出现持续的新冠肺炎症状。为了开发有效的治疗方法，我们必须对此进行研究。我们现在了解到，严重新冠肺炎的发生是由于我们的免疫系统对病毒的反应引发了炎症。然而，我们还不知道这种炎症在康复过程中是如何变化的。尽管从最初的感染中恢复过来，但长期COVID的症状可能是持续的炎症所致。这项研究旨在了解新冠肺炎的免疫力是否与呼吸道中的持久抗体和免疫细胞反应有关。它还旨在了解长期COVID是否与感染后体内的持续性炎症有关。这是第一项也是最大规模的纵向研究，在一年的时间里检查呼吸道对新冠肺炎的免疫反应。这项研究将加深我们对新冠肺炎免疫力如何形成的理解，从而对遏制疫情的发展至关重要。

COVID-19 is a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It was declared a global pandemic by the World Health Organization on 11th March 2020. In the UK alone there have been over 100,000 deaths to date and many of those who survive may suffer debilitating long lasting effects, termed Long COVID. COVID-19 has also had a devastating impact on economies and societies worldwide due to measures taken to control the spread of the virus, including lockdowns. A key question which remains unanswered is whether long lasting immunity can develop following infection and how this occurs. Understanding this is critical to predicting the future course of the pandemic and to develop effective vaccines. There are many possible ways in which the human immune system can protect against reinfection with SARS-CoV-2. Most studies have focused on immune cells and antibodies which circulate in the blood. However, by examining the blood only, we are unable to detect immune responses which may protect against the virus in other areas of the body. In particular, very little is understood about immune responses which occur within the airways - the connecting passages between the nose, mouth and lungs. This is where the virus is able to first infect human cells and is also the main site of inflammation once infection is established. The airways are therefore likely to be key to protecting against re-infection.The lining of the nose is easily accessible and provides a representation of the immune response in the airways. We know that for other respiratory viruses, antibodies in the blood do not necessarily provide immunity and having antibodies in the airways may be more important. In fact, we have previously shown that susceptibility to other respiratory infections can be influenced by antibody or cell activity within the nose rather than the blood. Therefore, it is vital that we examine immune responses to COVID-19 in both the blood and nasal passages if we are to truly understand how the body creates protective immunity against the virus and how long it lasts. A second, yet equally crucial gap in our understanding of COVID-19 is why some patients suffer from persistent symptoms of COVID-19 after hospitalization. It is essential that we investigate this in order to develop effective treatments. We now understand that severe COVID-19 occurs due to inflammation triggered by our immune system's response to the virus. However, we do not yet understand how this inflammation changes during recovery. It is possible that symptoms of Long COVID may be explained by ongoing inflammation, despite recovery from the initial infection. This study aims to understand whether immunity to COVID-19 is associated with long lasting antibody and immune cell responses in the airways. It also aims to understand if Long COVID is associated with persistent inflammation in the body after infection. This is the first and largest study to longitudinally examine immune responses to COVID-19 in the airways over the course of a year. This study will develop our understanding of how immunity to COVID-19 develops and thus be critical in curbing the progression of the pandemic.