Immune damage mechanisms of COVID-19 and novel strategies in prevention and control of epidemic

Abstract

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) has diverse clinical manifestations, which is the main feature of the disease, and the fundamental reason is the different immune responses in different bodies among the population. The damage mechanisms of critical illness by SARS-CoV-2 and its variants, such as hyperinflammatory response, a double-edged function of type I interferon, and hyperactivation of the complement system, are the same as other critical illnesses. Targeting specific immune damage mechanisms of COVID-19, we scored the first to put forward that the responses of T cells induced by acute virus infection result in "acute T-cell exhaustion" in elderly patients, which is not only the peripheral exhaustion with quantity reduction and dysfunction of T cells but also the central exhaustion that central immune organs lost immune homeostasis over peripheral immune organs, whereas the increased thymic output could alleviate the severity and reduce the mortality of the disease with the help of medication. We discovered that immune responses raised by SARS-CoV-2 could also attack secondary lymphoid organs, such as the spleen, lymphoid nodes, and kidneys, in addition to the lung, which we generally recognize. Integrated with the knowledge of mechanisms of immune protection, we developed a coronavirus antigen diagnostic kit and therapeutic monoclonal antibody. In the future, we will further investigate the mechanisms of immune damage and protection raised by coronavirus infection to provide more scientific strategies for developing new vaccines and immunotherapies.

Keywords: COVID-19; SARS-CoV-2; immune damage; inflammation; kidney; lymph organs; t cell exhaustion.

Figure 1

SARS-CoV-2 damage mechanisms on the innate immune system (A) and adaptive immune system (B). SARS-CoV-2 could infect not only human type I alveolar cells but also the innate immune cells and tubular epithelial cells (TECs). SARS-CoV-2 infection could give rise to the accumulation of cytokine storms and hyperactivation of inflammasome. Apart from lymphopenia, the critical factor for poor prognosis in patients with severe COVID-19. Part of the acquired immune system damage, patients with severe COVID-19 are also accompanied by acute function exhaustion of T cells.

Figure 2

SARS-CoV-2 directly infects the human kidney and the second lymphoid tissues, including lymph nodes and spleens, by thus deteriorating tissue damage. SARS-CoV-2 could directly infect secondary lymphoid organs in severe or dead patients leading to the secretion of inflammatory factors such as IL-6 and TNF-α in infected cells, which causes necrosis and apoptosis of immune cells and further the quantity reduction of lymphocytes. Pathological examination of kidney tissue from patients with COVID-19 and autopsy revealed that SARS-CoV-2 directly invade human kidney through ACE2 receptor and mediate acute kidney injury and severe tubular injury.