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.
【저자키워드】 SARS-CoV-2, COVID-19 severity, Nonsynonymous mutations, virus quasispecies, within-host diversity, 【초록키워드】 COVID-19, pandemic, intensive care, severity, disease severity, variant, outcome, virus, RNA, Prevalence, Asymptomatic, SARS-CoV-2 genome, Patient, severe cases, Mild, age, genetic diversity, platform, mild symptoms, association, Evidence, Analysis, severe disease, COVID-19 patient, observation, Consensus, Factor, significant difference, Illumina Miseq, mild cases, sequence, coding, P -value, Severe case, MOST, different clinical manifestations, sequence identity, nasopharyngeal sample, sequenced, significantly, investigated, the disease, required, eight, provided, exhibited, characterized, majority, significantly higher, severe symptom, severe complication, mild case, non-coding region, 【제목키워드】 COVID-19, Diversity, variable,