Alterations of Oropharyngeal Microbiome Reflected Disease Severity and Long-Term Dysbiosis in Patients With COVID-19

Abstract Background: Recent evidences have shown that gut microbiome of patients with COVID-19 significantly changes and can reflect the severity of the disease. And gut microbiota richness was not restored to normal levels after 6-month recovery. However, SARS-CoV-2 primarily infects the respiratory tract, few studies investigate whether the alterations of oropharyngeal microbiome is associated with disease severity in patients with COVID-19, and whether interferences in microbiome composition, if any, eliminate with clearance of the SARS-CoV-2 virus. We employed metatranscriptomic sequencing to analyse oropharyngeal swabs collected within a week of diagnosis COVID-19 (period of disease group: PDG) and two months after clearance of the SARS-CoV-2 virus (convalescent group: CG) from 47 patients with COVID-19. Meanwhile, oropharyngeal swabs from 40 healthy subjects were analyzed as healthy control group (HCG). Results: Oropharyngeal microbial composition was significantly altered in patients with COVID-19 compared with healthy controls even two months after clearance of the SARS-CoV-2 virus. Little changes in α-diversity among HCG, PDG and CG ( P ＞0.05), but obviously changes in β-diversity among them. Notably, Prevotella increased significantly in PDG than that in HCG (Wilcoxon rank-sum test, P ＜0.001) and increased gradually along with the severity of patients with COVID-19 aggravated. There was a positive correlation between Prevotella and the elevation of Neutrophil percentage (R = 0.301, P = 0.040). Similarly, SARS-CoV-2 and Aspergillus increased remarkably in critical Patients with COVID-19. There was a negative correlation between SARS-CoV-2 viral load and platelet counts (R = −0.330, P = 0.022). Conclusions: The oropharyngeal microbiome in patients with COVID-19 present persistent dysbiosis even two months after clearance of the SARS-CoV-2 virus. Furthermore, alterations in oropharyngeal microbial composition reflected the severity of disease in patients with COVID-19. Our findings underscore that there is an urgent need to understand the specific roles of oropharyngeal microorganisms in COVID-19 disease progression and rehabilitation.