Fatty Acid Metabolism Is Related To Disease Severity After H7N9 Infection

Objective: Human infection with influenza A virus(H7N9)may bring about lung injury and cause serious consequences such as multiple organ failure,which is closely related to high mortality.However,the metabolic basis for this systemic change awaits further study.We detected the changes of serum metabolomics in patients with H7N9 avian influenza virus infection by clinical investigation and serum metabolomics analysis,and preliminarily explored which metabolic pathways and metabolites changed after H7N9 infection,and its impact on the prognosis of patients.Methods: The clinical data of four cases of H7N9 avian influenza virus infection confirmed by CDC during the experimental observation period were collected,and the main medical records of the control group(including healthy control group and disease control group)with similar general clinical and basic conditions were collected in standard form.The clinical manifestations,Steroids use and high level of H7N9 patients were analyzed and summarized.Differences in life support,prognosis and so on.In addition,fasting serum samples were collected for metabolomic analysis to clarify the difference between the changes of metabolites in serum of patients after H7N9 infection and that of normal serum.Results:(1)Laboratory confirmed H7N9 avian influenza virus infection were elderly patients,with a history of poultry contact and basic medical history,all had symptoms of high fever,cough,dyspnea and other symptoms,and symptoms of septic shock and acute respiratory distress appeared in the late course.Severe patients also developed acute renal failure and secondary infections.All patients received antiviral therapy,steroids,mechanical ventilation and other support treatment.After that,the mild patients tended to improve,and severe patients deteriorate.Extracorporeal membrane oxygenation therapy and continuous renal replacement therapy were used.(2)Ultra-high performance liquid chromatography mass spectrometry(UPLC-MS)was used to determine the difference between healthy control group and severe pneumonia group.Ten potential serum metabolites,such as Palmitic acid,erucic acid,phytal,palmitic amide,have been identified to be associated with H7N9 virus infection.The level of serum palmitic acid in convalescent period may reflect the decrease of virus.The significant decrease of serum erucic acid and phytal levels after H7N9 infection was negatively correlated with the rapid replication of H7N9 virus.Conclusions:(1)H7N9 avian influenza virus is predisposed to middle-aged and elderly people with low immunity,more basic diseases and long-term medication.Its source of transmission is infected birds,and its transmission route is air droplets.Therefore,supervision and prevention of the live poultry market should be strengthened,and the influenza vaccine for birds should be developed.The early stage of H7N9 avian influenza virus infection can be characterized by influenza-like symptoms.Acute exacerbation can quickly progress to severe pneumonia,and emerge acute respiratory distress symptoms(ARDS),shock,respiratory failure and other critical conditions.Early antiviral therapy,symptomatic support therapy,timely initiation of advanced respiratory support when vital signs are unstable,including oxygen therapy,mechanical ventilation,extracorporeal membrane oxygenation therapy(ECMO)and continuous renal replacement therapy(CRRT),play a significant role in improving the general condition and prognosis of patients.(2)After the infection of H7N9 virus,serum metabolomics analysis after infection confirmed that 10 metabolites were associated with H7N9 virus infection.The serum abundance of palmitic acid,erucic acid and phytal was negatively correlated with disease severity.These metabolites belong to fatty acid metabolism.This indicates that fatty acid metabolism is closely related to influenza virus infection.In addition to angiotensin II,hypercytokineemia,serum albumin levels and other factors,the serum abundance of palmitic acid,erucic acid and phytal can also provide some guidance for the severity and prognosis of H7N9 avian influenza virus infection.In brief,this study provides preliminary data indicating that H7N9 infection leads to changes in fatty acid metabolism.Potential serum metabolites identified here,such as palmitic acid,erucic acid and phytal,may be instructive in future rating of prognosis of H7N9 infected patients,and may also carve out train of thought for the manufacture of new antiviral target drugs in the future.