Whole Genome Profiling of Lung Microbiome in Solid Organ Transplant Recipients Reveals Virus Involved Microecology May Worsen Prognosis

Abstract

Solid organ transplantation (SOT) is the final therapeutic option for recipients with end-stage organ failure, and its long-term success is limited by infections and chronic allograft dysfunction. Viral infection in SOT recipients is considered an important factor affecting prognosis. In this study, we retrospectively analyzed 43 cases of respiratory infections in SOT recipients using metagenomic next-generation sequencing (mNGS) for bronchoalveolar lavage fluid (BALF). At least one virus was detected in 26 (60.5%) recipients, while 17 (39.5%) were virus-negative. Among virus-positive recipients, cytomegalovirus (CMV) was detected in 14 (32.6%), Torque teno virus (TTV) was detected in 9 (20.9%), and other viruses were detected in 6 (14.0%). Prognostic analysis showed that the mortality of the virus-positive group was higher than that of the virus-negative group regardless whether it is the main cause of infection. Analysis of different types of viruses showed that the mortality of the CMV-positive group was significantly higher than that of the CMV-negative group, but no significant difference was observed in other type of virus groups. The diversity analysis of the lung microbiome showed that there was a significant difference between the virus-positive group and the negative group, in particular, the significant differences in microorganisms such as Pneumocystis jirovecii (PJP) and Moraxella osloensiswere detected. Moreover, in the presence of CMV, Pneumocystis jirovecii, Veillonella parvula, and other species showed dramatic changes in the lung of SOT patients, implying that high degree of co-infection between CMV and Pneumocystis jirovecii may occur. Taken together, our study shows that the presence of virus is associated with worse prognosis and dramatically altered lung microbiota in SOT recipients.

Herpesvirus reactivation in respiratory tract is associated with increased mortality of severe pneumonia patients and their respiratory microbiome dysbiosis

“…Unfortunately, no herpesvirus is included as a biomarker ( Zhao et al., 2023 ). Our results align with another study that found an association between herpesvirus reactivation and lung microbiota ( Pan et al., 2022 ). On the other hand, the presence of herpesviruses may alter the respiratory environment, leading to changes in the structure of the microbiome.…”

“…investigated the relationship between viruses and prognosis in lung infections in patients undergoing solid organ transplantation. The results showed that CMV was associated with poor prognosis, while TTV was not ( Pan et al., 2022 ).…”

Pulmonary co-infections by Pneumocystis jirovecii and Herpesviridae: a seven-year retrospective study

“…The diagnosis of pulmonary mixed infections remains challenging but is crucial because clinical manifestations are severe and associate with poor prognosis [ 14 ]. Pulmonary infections associating P. jirovecii and more than one viruses has already been described [ 13 , 19 , 27 , 29 ]. Maartens et al conducted a prospective study including 284 HIV-infected patients with pulmonary symptoms [ 30 ].…”

“…The usefulness of syndromic approach has already been assessed with a multiplex PCR TaqMan ® array card (ThermoFisher) which simultaneously detects 24 viruses (including CMV and HSV 1 + 2), eight bacteria and two fungi (including P. jirovecii ) [ 31 ] and with the “FTD respiratory pathogens 33” kit (Fast-Track Diagnostics, Esch-sur-Alzet, Luxembourg) targeting 33 microorganisms (including P. jirovecii and CMV) [ 30 ]. Recent studies proposed next-generation sequencing methods for a large-scale approach [ 13 , 27 , 29 , 32 ]. These techniques allow thus prompt management of polymicrobial infections frequently associated with a poor prognosis.…”

The clinical significance of in-house metagenomic next-generation sequencing for bronchoalveolar lavage fluid diagnostics in patients with lower respiratory tract infections

“…In many cases, the presence of a DNA virus, such as the Torque teno virus (TTV), is considered to be related to the low immunity of patients (Maggi et al, 2011;Görzer et al, 2014). A previous study showed that solid organ transplant recipients with viral and bacterial co-infections had poor prognoses (Pan et al, 2022). mNGS can also detect viruses that cannot be detected by conventional methods; seven types of respiratory DNA viruses were identified by mNGS, with the most commonly detected virus being the human herpesvirus.…”