Zijie Shen1,2, Yan Xiao3, Lu Kang1,2, Wentai Ma1,2, Leisheng Shi1,2, Li Zhang1, Zhuo Zhou4, Jing Yang1,2, Jiaxin Zhong1,2, Donghong Yang5, Li Guo3, Guoliang Zhang6, Hongru Li7, Yu Xu5, Mingwei Chen8, Zhancheng Gao5, Jianwei Wang3, Lili Ren3, Mingkun Li1,9. 1. Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation, Beijing, China. 2. University of Chinese Academy of Sciences, Beijing, China. 3. National Health Commission of the People's Republic of China Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 4. Biomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. 5. Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, China. 6. National Clinical Research Center for Infectious Diseases, Guangdong Key Laboratory for Emerging Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China. 7. Fujian Provincial Hospital, Fujian, China. 8. Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. 9. Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China.
Abstract
BACKGROUND: A novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has infected >75 000 individuals and spread to >20 countries. It is still unclear how fast the virus evolved and how it interacts with other microorganisms in the lung. METHODS: We have conducted metatranscriptome sequencing for bronchoalveolar lavage fluid samples from 8 patients with SARS-CoV-2, and also analyzed data from 25 patients with community-acquired pneumonia (CAP), and 20 healthy controls for comparison. RESULTS: The median number of intrahost variants was 1-4 in SARS-CoV-2-infected patients, ranged from 0 to 51 in different samples. The distribution of variants on genes was similar to those observed in the population data. However, very few intrahost variants were observed in the population as polymorphisms, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intrahost variants in a possible person-to-person spread, the risk should not be overlooked. Microbiotas in SARS-CoV-2-infected patients were similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria. CONCLUSION: SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intrahost variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.
BACKGROUND: A novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has infected >75 000 individuals and spread to >20 countries. It is still unclear how fast the virus evolved and how it interacts with other microorganisms in the lung. METHODS: We have conducted metatranscriptome sequencing for bronchoalveolar lavage fluid samples from 8 patients with SARS-CoV-2, and also analyzed data from 25 patients with community-acquired pneumonia (CAP), and 20 healthy controls for comparison. RESULTS: The median number of intrahost variants was 1-4 in SARS-CoV-2-infectedpatients, ranged from 0 to 51 in different samples. The distribution of variants on genes was similar to those observed in the population data. However, very few intrahost variants were observed in the population as polymorphisms, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intrahost variants in a possible person-to-person spread, the risk should not be overlooked. Microbiotas in SARS-CoV-2-infectedpatients were similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria. CONCLUSION:SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intrahost variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.
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