Respiratory tract microbiome is closely related to respiratory tract infections, while characterization of oropharyngeal microbiome in recovered coronavirus disease 2019 (COVID-19) patients is not studied. Herein, oropharyngeal swabs are collected from confirmed cases (CCs) with COVID-19 (73 subjects), suspected cases (SCs) (36), confirmed cases who recovered (21), suspected cases who recovered (36), and healthy controls (Hs) (140) and then completed MiSeq sequencing. Oropharyngeal microbial 𝜶-diversity is markedly reduced in CCs versus Hs. Opportunistic pathogens are increased, while butyrate-producing genera are decreased in CCs versus Hs. The classifier based on eight optimal microbial markers is constructed through a random forest model and reached great diagnostic efficacy in both discovery and validation cohorts. Notably, the classifier successfully diagnosed SCs with positive IgG antibody as CCs and is demonstrated from the perspective of the microbiome. Importantly, several genera with significant differences gradually increase and decrease along with recovery from COVID-19. Forty-four oropharyngeal operational taxonomy units (OTUs) are closely correlated with 11 clinical indicators of SARS-CoV-2 infection and Hs based on Spearman correlation analysis. Together, this research is the first to characterize oropharyngeal microbiota in recovered COVID-19 cases and suspected cases, to successfully construct and validate the diagnostic model for COVID-19 and to depict the correlations between microbial OTUs and clinical indicators.

The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the World Health Organization statistics, more than 500 million individuals have been infected and more than 6 million deaths have resulted worldwide. Although COVID-19 mainly affects the respiratory system, considerable evidence shows that the digestive, cardiovascular, nervous, and reproductive systems can all be involved. Angiotensin-converting enzyme 2 (AEC2), the target of SARS-CoV-2 invasion of the host is mainly distributed in the respiratory and gastrointestinal tract. Studies found that microbiota contributes to the onset and progression of many diseases, including COVID-19. Here, we firstly conclude the characterization of respiratory, gut, and oral microbial dysbiosis, including bacteria, fungi, and viruses. Then we explore the potential mechanisms of microbial involvement in COVID-19. Microbial dysbiosis could influence COVID-19 by complex interactions with SARS-CoV-2 and host immunity. Moreover, microbiota may have an impact on COVID-19 through their metabolites or modulation of ACE2 expression. Subsequently, we generalize the potential of microbiota as diagnostic markers for COVID-19 patients and its possible association with post-acute COVID-19 syndrome (PACS) and relapse after recovery. Finally, we proposed directed microbiota-targeted treatments from the perspective of gut microecology such as probiotics and prebiotics, fecal transplantation and antibiotics, and other interventions such as traditional Chinese medicine, COVID-19 vaccines, and ACE2-based treatments.