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Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis.
Microorganisms. 2020 Aug 26; 8(9)M

Abstract

We report whole-genome and intra-host variability of SARS-Cov-2 assessed by next generation sequencing (NGS) in upper (URT) and lower respiratory tract (LRT) from COVID-19 patients. The aim was to identify possible tissue-specific patterns and signatures of variant selection for each respiratory compartment. Six patients, admitted to the Intensive Care Unit, were included in the study. Thirteen URT and LRT were analyzed by NGS amplicon-based approach on Ion Torrent Platform. Bioinformatic analysis was performed using both realized in-house and supplied by ThermoFisher programs. Phylogenesis showed clade V clustering of the first patients diagnosed in Italy, and clade G for later strains. The presence of quasispecies was observed, with variants uniformly distributed along the genome and frequency of minority variants spanning from 1% to ~30%. For each patient, the patterns of variants in URT and LRT were profoundly different, indicating compartmentalized virus replication. No clear variant signature and no significant difference in nucleotide diversity between LRT and URT were observed. SARS-CoV-2 presents genetic heterogeneity and quasispecies compartmentalization in URT and LRT. Intra-patient diversity was low. The pattern of minority variants was highly heterogeneous and no specific district signature could be identified, nevertheless, analysis of samples, longitudinally collected in patients, supported quasispecies evolution.

Authors+Show Affiliations

National Institute for Infectious Diseases, L'Istituto Nazionale per le Malattie Infettive (INMI), "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00149 Rome, Italy.National Institute for Infectious Diseases, L'Istituto Nazionale per le Malattie Infettive (INMI), "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00149 Rome, Italy.National Institute for Infectious Diseases, L'Istituto Nazionale per le Malattie Infettive (INMI), "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00149 Rome, Italy.Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, Università Degli Studi di Pavia, 27100 Pavia, Italy.National Institute for Infectious Diseases, L'Istituto Nazionale per le Malattie Infettive (INMI), "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00149 Rome, Italy.National Institute for Infectious Diseases, L'Istituto Nazionale per le Malattie Infettive (INMI), "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00149 Rome, Italy.National Institute for Infectious Diseases, L'Istituto Nazionale per le Malattie Infettive (INMI), "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00149 Rome, Italy.National Institute for Infectious Diseases, L'Istituto Nazionale per le Malattie Infettive (INMI), "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00149 Rome, Italy.National Institute for Infectious Diseases, L'Istituto Nazionale per le Malattie Infettive (INMI), "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00149 Rome, Italy.National Institute for Infectious Diseases, L'Istituto Nazionale per le Malattie Infettive (INMI), "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00149 Rome, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32858978

Citation

Rueca, Martina, et al. "Compartmentalized Replication of SARS-Cov-2 in Upper Vs. Lower Respiratory Tract Assessed By Whole Genome Quasispecies Analysis." Microorganisms, vol. 8, no. 9, 2020.
Rueca M, Bartolini B, Gruber CEM, et al. Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis. Microorganisms. 2020;8(9).
Rueca, M., Bartolini, B., Gruber, C. E. M., Piralla, A., Baldanti, F., Giombini, E., Messina, F., Marchioni, L., Ippolito, G., Di Caro, A., & Capobianchi, M. R. (2020). Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis. Microorganisms, 8(9). https://doi.org/10.3390/microorganisms8091302
Rueca M, et al. Compartmentalized Replication of SARS-Cov-2 in Upper Vs. Lower Respiratory Tract Assessed By Whole Genome Quasispecies Analysis. Microorganisms. 2020 Aug 26;8(9) PubMed PMID: 32858978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis. AU - Rueca,Martina, AU - Bartolini,Barbara, AU - Gruber,Cesare Ernesto Maria, AU - Piralla,Antonio, AU - Baldanti,Fausto, AU - Giombini,Emanuela, AU - Messina,Francesco, AU - Marchioni,Luisa, AU - Ippolito,Giuseppe, AU - Di Caro,Antonino, AU - Capobianchi,Maria Rosaria, Y1 - 2020/08/26/ PY - 2020/07/17/received PY - 2020/08/22/revised PY - 2020/08/24/accepted PY - 2020/8/30/entrez PY - 2020/8/30/pubmed PY - 2020/8/30/medline KW - COVID-19 KW - SARS-COV-2 KW - coronavirus KW - quasispecies KW - variability JF - Microorganisms JO - Microorganisms VL - 8 IS - 9 N2 - We report whole-genome and intra-host variability of SARS-Cov-2 assessed by next generation sequencing (NGS) in upper (URT) and lower respiratory tract (LRT) from COVID-19 patients. The aim was to identify possible tissue-specific patterns and signatures of variant selection for each respiratory compartment. Six patients, admitted to the Intensive Care Unit, were included in the study. Thirteen URT and LRT were analyzed by NGS amplicon-based approach on Ion Torrent Platform. Bioinformatic analysis was performed using both realized in-house and supplied by ThermoFisher programs. Phylogenesis showed clade V clustering of the first patients diagnosed in Italy, and clade G for later strains. The presence of quasispecies was observed, with variants uniformly distributed along the genome and frequency of minority variants spanning from 1% to ~30%. For each patient, the patterns of variants in URT and LRT were profoundly different, indicating compartmentalized virus replication. No clear variant signature and no significant difference in nucleotide diversity between LRT and URT were observed. SARS-CoV-2 presents genetic heterogeneity and quasispecies compartmentalization in URT and LRT. Intra-patient diversity was low. The pattern of minority variants was highly heterogeneous and no specific district signature could be identified, nevertheless, analysis of samples, longitudinally collected in patients, supported quasispecies evolution. SN - 2076-2607 UR - https://www.unboundmedicine.com/medline/citation/32858978/Compartmentalized_Replication_of_SARS_Cov_2_in_Upper_vs__Lower_Respiratory_Tract_Assessed_by_Whole_Genome_Quasispecies_Analysis_ L2 - https://www.mdpi.com/resolver?pii=microorganisms8091302 DB - PRIME DP - Unbound Medicine ER -
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