Metagenomic Next-Generation Sequencing for Diagnosing Infections in Lung Transplant Recipients: A Retrospective Study

Abstract

Background: Accurate identification of pathogens is essential for the diagnosis and control of infections. We aimed to compare the diagnostic performance of metagenomic next-generation sequencing (mNGS) and conventional detection methods (CDM) in lung transplant recipients (LTRs).Methods: We retrospectively analyzed 107 LTRs with suspected infection of pulmonary, blood, central nervous system or chest wall between March 2018 and November 2020. Bronchoalveolar lavage fluid and other body fluids were subject to pathogen detection by both mNGS and CDM.Results: Of the 163 specimens, 84 (51.5%) tested positive for both mNGS and culture, 19 (11.7%) of which were completely consistent, 44 (27.0%) were partially congruent, and 21 (12.9%) were discordant (kappa = .215; p = .001). Compared with CDM, mNGS detected a higher diversity of pathogens. Moreover, the turn-around time was significantly shorter for mNGS compared with culture (2.7 ± .4 vs. 5.5 ± 1.6 days, p < .001). As an auxiliary method, treatment strategies were adjusted according to mNGS findings in 31 cases (29.0%), including eight patients with non-infectious diseases, who were finally cured.Conclusion: mNGS can identify pathogens with a shorter turn-around time and therefore provide a more accurate and timely diagnostic information to ascertaining pulmonary infections. mNGS might have a role in differentiating infectious from non-infectious lung diseases in LTRs.

Application of plasma donor-derived cell free DNA for lung allograft rejection diagnosis in lung transplant recipients

“…Additionally, DSA should be present for AMR. Pulmonary infection was diagnosed based on our previous studies [27,28]. There were no pathogens in the AR or CLAD groups.…”

Donor-derived infections in solid organ transplant recipients

“…A key issue with respect to diagnosis is the need to develop sensitive and reliable assays [ 50 ]. Of note that nucleic acid tests and metagenomic next-generation sequencing is being explored and has been recently highlighted for fungi diagnosis in the setting of donor-derived transmission of scedosporiosis [ 51 , 52 ].…”

Differentiation between lung allograft rejection and infection using donor-derived cell-free DNA and pathogen detection by metagenomic next-generation sequencing

“…Potential allograft infection was indicated by the detection of pathogens, including bacteria, fungi, and viruses, in BALF detected by mNGS or conventional methodsas described in our previous studies [ 20 , 21 ].…”

“…An adequate volume of plasma (2 mL) was assayed by using a clinical-grade NGS dd-cfDNA system at a certified laboratory (AlloDx Biotech, Co., Ltd). A total of 6200 human single nucleotide polymorphism loci were enriched through liquid hybridization [ 20 ]. Briefly, 8 mL of blood was drawn into a tube for the collection of cfDNA (Streck, Omaha, NE).…”