The Value Of Metagenomic Next-generation Sequencing In The Diagnosis Of Classical Fever Of Unknown Origin

Objective: Fever of unknown origin(FUO)has a variety of clinical manifestations and a complex etiology.metagenomic next?generation sequencing(mNGS)technology is a new diagnostic tool that can assist clinicians in the etiological diagnosis of FUO.This study focuses on the value of mNGS in the diagnosis of classical FUO.Methods: Sixty-two cases of classic FUO hospitalized in the infection department of the First Hospital of China Medical University from December 2018 to July 2022 were collected,and their clinical data and laboratory findings and mNGS results were retrospectively analyzed.A chi-square test was applied to compare the sensitivity and negative predictive value of traditional culture methods and mNGS assays to assess the diagnostic value of mNGS in FUO cases.Results: Of the 62 patients with classic FUO,bacterial infections accounted for 62.90%(39/62),fungal infections 6.45%(4/62),viruses infections 6.45%(4/62),rickettsial infections 3.23%(2/62),non-infectious inflammatory diseases 8.07%(5/62),tumors4.84%(3/62),and other diseases 8.07%(5/62).49 had a final diagnosis of infectious disease and 13 had a diagnosis of non-infectious disease.These included 14 cases of pathogens that were difficult to detect by conventional culture(3 Mycobacterium tuberculosis,3 Mycobacterium non-tuberculosis,4 viruses,2 rickettsiae,and 2pneumocystis).In infectious diseases(excluding pathogens difficult to culture by conventional methods),the sensitivity of mNGS was 48.57%(17/35)and the sensitivity of conventional culture was 14.29%(5/35).The negative predictive value for conventional culture was 33.33%(13/39)and 46.67%(7/15)for mNGS,which were not statistically different(P=0.363).mNGS had a time from sending to reporting of 1-3 days.Conventional culture time from sending to result return was 1-7 days.48 patients had febrile syndrome,34 patients had fever with respiratory syndrome,28 patients were finally diagnosed with infectious disease,17 of them sent the corresponding specimens for respiratory syndrome for mNGS with a sensitivity of 52.94%(9/17),7 patients sent peripheral blood with a sensitivity of 28.57%(2/7)for mNGS,and 4 patients sent other specimens.Fifteen patients had focal infections and most of their specimens were localized,with a sensitivity of 60%(9/15).34 patients had non-focal infections and most of their specimens were sent for peripheral blood,with a sensitivity of 47.06%(16/34).Conclusion: 1.In cases with a final diagnosis of infectious disease,mNGS is a more sensitive test compared to conventional culture methods,facilitating the identification of the etiology in patients with classical FUO;no significant difference was found between mNGS and conventional culture for excluding infection in this study.2.mNGS is of value in the diagnosis of infections with pathogens that are difficult to culture conventionally(e.g.,Mycobacterium,Rickettsia,Pneumocystis,etc.).3.mNGS is useful in the diagnosis of sepsis,infective endocarditis with negative conventional culture.