| Severe community-acquired pneumonia(SCAP)is a common infectious disease in clinic.The mortality rate is as high as 30%-50%,which brings the serious burden of disease.The pathogenic mechanism of SCAP is complex.The type and composition of pathogens infected by patients may be closely related to the occurrence and development of the disease.However,the traditional pathogen diagnosis method has a high success rate only for the infection of extracellular pathogens such as Streptococcus pneumonia and Haemophilus influenzae,but it faces great challenges for the diagnosis of atypical pathogens and respiratory viruses;Although nucleic acid detection technology(NAATs)makes the diagnosis of influenza and other viruses possible,it can not cover a variety of important pathogens outside the scope of application of the kit,resulting in an insufficient understanding of the pathogen spectrum composition related to the clinical prognosis of SCAP,difficult to verify the appropriate empirical antibiotic scheme,and lack of guidance on the research and development direction of specific antiviral drugs.Therefore,it is of great significance for the optimization of antibiotic treatment and the development of new therapies to establish an accurate diagnosis method of infectious pathogens in SCAP patients and understand the composition of infectious disease spectrum in SCAP patients.Firstly,the pathogen spectrum of 367 patients with SCAP in Xiamen was mapped by metagenomic next-generation sequencing(mNGS),supplemented by NAATs and bacterial culture.It was found that virus infection accounted for 27.8%,of which influenza virus was the main pathogen,accounting for 25%;Bacterial infection accounted for 29.7%,followed by Klebsiella pneumonia and Acinetobacter,accounting for 15.5%and 12%respectively.Herpes simplex virus(HSV)and Chlamydia psittaci were not rare,accounting for 2.5%and 2.2%respectively;At the same time,influenza co-infection accounted for 44%,and the risk of death increased by 2.72 times compared with the non co-infection group.The lung lesions were more diffuse,the proportion of mechanical ventilation(MV),and the incidence of cardiovascular events were higher,suggesting that influenza co-infection is a high-risk factor for the poor prognosis of SCAP.In terms of improving the clinical treatment scheme of SCAP,we should pay attention to the rationality of the antibiotic combination scheme,and it is necessary to explore specific antiviral drugs for the high incidence of severe influenza pneumonia.Secondly,to achieve more efficient treatment of bacterial pathogen infection in SCAP patients,this paper analyzes and compares the empirical antibiotic treatment schemes of SCAP,uses propensity score matching and multifactor Cox risk regression model β Amide like(β Group)β Amides combined with intravenous macrocyclic lipids(β+Group A)or fluoroquinolones(β+Group Q)the efficacy of antibiotics was evaluated and found β+The risk of death in group A was significantly lower than that in the other two groups,and the length of stay in ICU was significantly shorter β+The proportion of MV,multiple organ dysfunction,shock and ARDS in group A also decreased significantly,which provides useful scientific guidance for the optimization of antibiotic use in the clinical treatment of SCAP.Finally,the above pathogen spectrum analysis shows that the incidence rate of severe influenza pneumonia caused by influenza virus infection is high,and there is no specific and effective drugs in clinical treatment.This article further explores the broad spectrum therapeutic antibody targeting influenza virus.By collecting respiratory tract samples of influenza patients for influenza virus isolation,gene sequencing comparison,and hemagglutination inhibition assay analysis of influenza vaccine serum,it is found that the hemagglutinin(HA)gene of multiple H3N2 influenza viruses isolated from influenza positive patients has obvious antigenicity drift,which may lead to the lack of immunity of pre-existing influenza antibodies in patients to the influenza variant strains infected by patients,Then it developed into severe influenza pneumonia.In order to cope with the variation of H3N2 influenza virus,this study developed a broad-spectrum therapeutic antibody targeting H3N2 through the optimization of immune strategy and successfully obtained a broad-spectrum antibody 9A2 targeting H3N2.Animal protection experiments showed that 9A2 could protect mice from lethal infection by three representative H3N2 influenza viruses isolated from 1968 to 2017 and two representative H7N9 avian influenza viruses.The further research on the treatment mechanism found that 9A2 mainly recognized the highly conserved HA2 region of HA and could act through antibody-dependent cellular cytotoxicity(ADCC)to mediate a broad-spectrum anti-influenza function:The acquisition of the antibody provides new candidate molecules for the development of clinical therapeutic drugs for severe influenza pneumonia,and the research on its therapeutic mechanism also brings enlightenment to the development of new therapeutic antibodies.In conclusion,this paper used mNGS combined with NAATs technology to map the pathogen spectrum of 367 patients with SCAP in Xiamen from 2016 to 2020.It was found that influenza virus infection is an important cause of SCAP,and the co-infection of influenza virus and Other pathogens can cause higher mortality;Further exploration of antibiotic treatment schemes and discovery β Amides combined with intravenous macrocyclic lipid antibiotics can effectively reduce the risk of death in patients with SCAP;A broad-spectrum monoclonal antibody 9A2 with therapeutic potential against H3N2 and H7N9 influenza viruses was successfully obtained,which provides a new candidate for exploring the development of therapeutic drugs for influenza SCAP patients.In conclusion,this study provides a scientific reference for the accurate diagnosis and treatment of SCAP and is expected to provide directional guidance for the optimization of the clinical treatment strategy of SCAP. |
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