Atypical clinical features include digestive system symptoms ( Mao et al., 2020), abnormal liver function ( Yadav et al., 2021), dysfunction of smell or taste ( Luers et al., 2020 Liou et al., 2021), insomnia ( Spinato et al., 2020), etc., As the body responds to acute systemic inflammation, pro-inflammatory cytokines can also affect the brain and induce behavioral and physical symptoms, such as fever, nausea, and anorexia ( Dantzer et al., 2008). The main clinical features of COVID-19 include fever, dyspnea, myalgia, dry cough, etc., (Lupia et al., 202 Grasselli et al., 2020 Guan et al., 2020). What’s more, in the autopsy of the patients, the SARS-CoV-2 virus was found in the heart, liver, and other tissue samples ( Varadhana et al., 2020), indicating that many organs were damaged ( Synowiec et al., 2021). T cells, which dominate the adaptive immune cells, differentiate into subsets with different effector cell functions and participate in CS ( Figure 1) ( Kiselevskiy et al., 2020).ĬOVID-19 enters cells through the angiotensin-converting enzyme 2 (ACE2) receptor, and cells that highly express ACE2 become the main targets of COVID-19 invasion ( Zhou et al., 2020). These explosions of cytokines and chemokines then activate cells of the adaptive immune system. After the human body is infected with SARS-CoV-2, innate immune cells such as neutrophils and natural killer (NK) cells ( Hashimoto et al., 2013)are rapidly activated to secrete a variety of cytokines and chemokines, including IL-2, IL-10, TNF-α, IFN-γ, CXCL10, CCL2, CC元, etc., And then activate the inflammatory cytokines storm ( Huang et al., 2020 Wan et al., 2020 Chen et al., 2020). The potential source of CS is the megakaryocyte and some subsets of monocyte indicated by sequencing data of single-cell transcriptome ( Ren et al., 2021). This paper focuses on the mechanism of CS induced by the SARS-CoV-2 virus and its clinical manifestations, and reviews the recently reported immunotherapies for cytokine storm, with the expectation of providing a reference for the treatment of COVID-19. If the immune cascade cannot be properly controlled, the immune response may have adverse effects on the host, and remodeling the balance between inflammation and anti-inflammation may be a more effective method for the treatment of infection ( Puelles et al., 2020). Once the infection develops to the advanced stage, patients often have severe disease symptoms. Of course, this immune response can reduce self-harm to a certain extent ( Cavalli and Dagna et al., 2020). Many acute infections have a strong and potentially destructive effect on the immune response. Virus infection can cause cytokine storm, and then lead to acute respiratory distress syndrome (ARDS), and even multiple organ failure until death ( Zhu et al., 2020). Since the end of 2019, novel coronavirus has been gradually spread worldwide, which not only poses a severe challenge to the global public health system but also brings huge economic losses to the society. We aim to give some conceptual thought to the prevention and immunotherapy of neocoronavirus pneumonia. This article reviews the pathogenesis of neocoronavirus pneumonia and discusses the immunomodulatory therapies currently applied to COVID-19. Immunotherapy through the application of hormones and monoclonal antibodies can alleviate the immune imbalance, but the clinical effectiveness and side effects remain controversial. How to neutralize the cytokine storm and inhibit excessive immune cell activation becomes the key to treating neocoronavirus pneumonia. Antiviral drugs and respiratory support are often used clinically as needed, but are not yet sufficient to alleviate the cytokine storm (CS) and systemic inflammatory response syndrome. Due to the lack of effective treatments, different strategies and treatment methods are still being researched, with the use of vaccines to make the body immune becoming the most effective means of prevention. The pathogenesis caused by the novel coronavirus was found to be a disruption of the pro-inflammatory/anti-inflammatory response. 3Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaĬOVID-19 pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ravaged the world, resulting in an alarming number of infections and deaths, and the number continues to increase.2College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.1Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.Yaqun Li 1,2, Wenjie Zhao 1, Jinhua Liu 1,2, Zichao Chen 1,3*, Qingtao Lv 2* and Zhen Zhang 1*
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