AUTHOR=Al Khatib Hebah A. , Benslimane Fatiha M. , Elbashir Israa E. , Coyle Peter V. , Al Maslamani Muna A. , Al-Khal Abdullatif , Al Thani Asmaa A. , Yassine Hadi M.
TITLE=Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities
JOURNAL=Frontiers in Cellular and Infection Microbiology
VOLUME=10
YEAR=2020
URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.575613
DOI=10.3389/fcimb.2020.575613
ISSN=2235-2988
ABSTRACT=Background: The ongoing pandemic of SARS-COV-2 has already infected more than eight million people worldwide. The majority of COVID-19 patients either are asymptomatic or have mild symptoms. Yet, about 15% of the cases experience severe complications and require intensive care. Factors determining disease severity are not yet fully characterized.
Aim: Here, we investigated the within-host virus diversity in COVID-19 patients with different clinical manifestations.
Methods: We compared SARS-COV-2 genetic diversity in 19 mild and 27 severe cases. Viral RNA was extracted from nasopharyngeal samples and sequenced using the Illumina MiSeq platform. This was followed by deep-sequencing analyses of SARS-CoV-2 genomes at both consensus and sub-consensus sequence levels.
Results: Consensus sequences of all viruses were very similar, showing more than 99.8% sequence identity regardless of the disease severity. However, the sub-consensus analysis revealed significant differences in within-host diversity between mild and severe cases. Patients with severe symptoms exhibited a significantly (p-value 0.001) higher number of variants in coding and non-coding regions compared to mild cases. Analysis also revealed higher prevalence of some variants among severe cases. Most importantly, severe cases exhibited significantly higher within-host diversity (mean = 13) compared to mild cases (mean = 6). Further, higher within-host diversity was observed in patients above the age of 60 compared to the younger age group.
Conclusion: These observations provided evidence that within-host diversity might play a role in the development of severe disease outcomes in COVID-19 patients; however, further investigations are required to elucidate this association.