The Lung Tissue Microbiota Feature of Fatal COVID-19

Background: Coronavirus disease 2019 (COVID-19) has become a public health emergency of international concern. About 5·0% of infected patients had severe lung injury or developed multiorgan dysfunction. Secondary infection and sepsis were common complications in critically ill patients, but the underlying pathogen was not clear. We used culture-independent methods to explore the microbiota characteristic of lung tissue from 20 deceased patients infected with COVID-19. Methods: Lung specimens were obtained by minimally invasive autopsy (MIA) from 20 deceased patients with COVID-19. The demographic data, clinical information, laboratory values, comorbidities, and treatments were all collected. The samples underwent pathological evaluation and were analyzed by sequencing the 16S rRNA gene hypervariable region 3-4 (V3-4) and internal transcribed spacer (ITS) DNA regions using barcoded primers for microbial community varieties.Findings: The mean age of the 20 subjects was 67·35 (SD 12·86) year-old. Among them 14 (70%) were men, and 15 (75%) had a comorbidity and the median duration from presentation to death was 33·5 (IQR 27·75–38·25) days. Sepsis was developed in 18 (90%) of 20 patients. The main morphological finding was diffuse alveolar damage (DAD). In 8 of 20 cases, bacteria or fungi were present under the microscope. Using culture-independent techniques, we found that the predominate taxon of the bacterial was Acinetobacter spp.. Meanwhile, gut-specific bacteria (Enterobacteriaceae spp.) were detected commonly in the lung tissues. The fungal population was typically dominated by Cutaneotrichosporon (Cryptococcus) and Issatchenkia at genus level. Furthermore, most fatal COVID-19 patients have a both bacterial and fungal co-infections in lung tissues.Interpretation: Our findings highlight that fatal COVID-19 is associated with complex mixed infections in lung tissue. It is important to serially monitor the microbiota in the lower respiratory tract and peripheral blood, so as to provide the accurate etiological evidence for timely personalized treatment.Funding Statement: The Key Special Project of Ministry of Science and Technology, China (No.2020YFC 0845700); the National Natural Science Foundation of China (No. 81773022); the Fundamental Research Funds for the Central Universities (No. 2020 kfyXG YJ101). Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The study was approved by health commission of Hubei province and the ethics committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (protocol code:2020-0043-1).