Extensive diversity of unusual microorganisms associated with severe pneumonia in kidney transplant recipients

Although pneumonia is a common lung disease with a high morbidity and mortality, aside from well-known pathogens little is known about why, which and how many microorganisms are associated with the disease, particularly in immunocompromised individuals. We enrolled 32 kidney transplant cases with severe pneumonia admitted to Shanghai Zhongshan Hospital between 2019 and 2025, and performed both metagenomic and metatranscriptomic sequencing on the bronchoalveolar lavage fluid (BALF) and blood samples from each case. Comprehensive analyses of immune cells and cytokines, as well as BALF and blood metatranscriptomes, revealed that both adaptive and innate immunity inside and outside of their lungs were severely suppressed. Notably, a high diversity of unusual microorganisms were present in BALF samples, including bacteria and DNA viruses that are rare or absent in healthy individuals, as well as RNA viruses and fungi. Of these, 17 bacteria, 46 DNA viruses, eight RNA viruses and two fungi, which were at high abundance, were considered to be responsible for the lung infections. Remarkably, the majority of these patients experienced co-infections of multiple bacteria, DNA and RNA viruses and fungi, reaching 32 virus species in one individual. In sum, these data indicate that the prosperity or overgrowth of accidental, opportunistic and rare microorganisms within the lungs of these kidney transplant patients substantially altered their lung microbiota, with multiple co-infections further exacerbating the severity of pneumonia.