Metabolism Of Influenza Virus Infection,co-infection Mechanism Of Influenza Virus/SARS-CoV-2 And Clinical Immunology Study Of SARS-CoV-2

In the past five years,the world has been faced with the dual threat of seasonal influenza virus epidemics and outbreaks of coronavirus,which have caused serious health impacts to human society.Viruses are intracellular parasitic self-replicators that need to hijack and exploit the metabolic pathways of the host cell to complete a cycle of infection.For a long time,the study of viruses utilizing host metabolism and pathogenesis has been split between two orientations,and there is a lack of investigation of immune changes due to metabolic hijacking of viruses.Understanding the host metabolic pathways affected by influenza virus replication would broaden the range of existing antiviral targets and facilitate the development of new therapeutic approaches based on targeted inhibition of specific metabolic changes.To this end,we used mass spectrometry(MS)to identify changes in host metabolites induced by influenza A virus(IAV)infected during the first cycle in A549 cells in order to mimic the metabolic process of the infection of IAV in vivo,and found that IAV utilizes and interferes with host cell metabolic pathways during the first cycle of infection to provide the energy and metabolites required to complete its replication cycle.The tricarboxylic acid cycle(TCA)provided key intermediate metabolites and connected with other metabolic pathways such as purines,lipids and glutathione.Further analysis suggests that post-infection host secretion and release of a variety of physiologically active metabolites is involved in the development of antiviral immunity.Here we map and construct a complex link between cellular metabolism,immunity and infection.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)caused an pandemic that broke out in late 2019,posing a major threat to public health institutions due to its spread rapidly.In our clinical studies,we found that secondary viral infections or mixed infections are one of the main causes of death in severe SARS-CoV-2 patients in clinic.Synergistic facilitation of IAV and SARS-CoV-2 co-infection has been well established in animal models,but whether there is a facilitative relationship between influenza B virus(IBV)and SARS-CoV-2 is not yet known,so we constructed an IBV/SARS-CoV-2 co-infection model in our study and found that the infected mice showed massive immune cell infiltration,inflammatory cytokines increased in the lungs.Most of the mice died due to co-infection.These findings confirm for the first time the possibility of co-infection between IBV and SARS-CoV-2,and that it prompts a loss of host immunity system control,causing more severe lung damage in mice,highlighting the significant public health risk of IBV and SARS-CoV-2 co-infection.At the same time,the specific antibodies for SARS-CoV-2 were detected in patients approximately two weeks after the onset of symptoms,but the duration of antibody persistence is unclear.In this study,the self-built ELISA platform and the pseudovirus neutralization system expressing Spike protein were used to evaluate the antibody response and neutralization titer level of serum samples from adult convalescent patients.Our experiments show that after approximately six months of recovery,92%recovered patients still had positive anti Spike protein IgG(anti-S IgG).In addition,62%patients also observed moderate or greater neutralizing activity,which correlated significantly with the anti-S IgG response;in addition,we performed long-term antibody testing in some of the recovered patients:the antibody response declined but was still present,with anti-S IgG being the most stable.The neutralization levels continued to decline 6 months after infection,with only 23%of patients still showing potent neutralizing activity at 12 months of recovery.These studies strongly support the hypothesis that antibodies to SARS-CoV-2 are chronically present in naturally infected individuals.A more in-depth immunological memory study was conducted in recovered COVID-19 children aged between 0 and 14 years in another major newly infected group.The study is carried out by regular follow-up of recovered children,detection of antibody levels and neutralizing titers in children,and detection of the presence of immune memory cells in children’s peripheral blood mononuclear cells(PBMC).However,the lung lesions persisted for a longer time(about 6-8 months)and the specific IgG secretion response was weak in some children.In contrast,IgG-specific antibody responses were strongest in the adolescent group.In addition,we found a memory B/T cell response in children of all ages.Our study highlights that specific antibody responses and cellular immune responses are detectable in most children despite pulmonary lesions that may persist for 6-8 months.In conclusion,by investigating the mechanisms of infection and immunological characteristics of influenza viruses and novel coronaviruses,we not only found that there is a complex metabolic regulation of the host in IAV,but also conducted an in-depth investigation for co-infection of SARS-CoV-2 with IBV,confirming that co-infection of IBV with SARS-CoV-2 will cause severe damage to the immune system.Finally,we confirmed that the antibody exists for up to 1 year after infection in adult recovered patients.The existence of adaptive immune memory in recovered COVID-19 children.