Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have been emerging. However, knowledge of temporal and spatial dynamics of SARS-CoV-2 is limited. This study characterized SARS-CoV-2 evolution in immunosuppressed patients with long-term SARS-CoV-2 shedding for 73-250 days, without specific treatment. We conducted whole-genome sequencing of 27 serial samples, including 26 serial samples collected from various anatomic sites of two patients and the first positive sample from patient 2’s mother. We analysed the intrahost temporal dynamics and genomic diversity of the viral population within different sample types. Intrahost variants emerging during infection showed diversity between individual hosts. Remarkably, N501Y, P681R, and E484K, key substitutions within spike protein, emerged in vivo during infection and became the dominant population. P681R, which had not yet been detected in the publicly available genome in Korea, appeared within patient 1 during infection. Mutually exclusive substitutions at residues R346 (R346S and R346I) and E484 (E484K and E484A) of spike protein and continuous turnover of these substitutions occurred. Unique genetic changes were observed in urine samples. A household transmission from patient 2 to his mother, at least 38 days after the diagnosis, was characterized. Viruses may differently mutate and adjust to the host selective pressure, which could enable the virus to replicate efficiently for fitness in each host. Intrahost variants could be candidate variants likely to spread to the population eventually. Our findings may provide new insights into the dynamics of SARS-CoV-2 in response to interactions between the virus and host.
Keywords: SARS-CoV-2; long-term viral shedding; mutation dynamics; variant of concern; whole genome sequencing.
【저자키워드】 SARS-CoV-2, variant of concern, whole genome sequencing., long-term viral shedding, mutation dynamics, 【초록키워드】 severe acute respiratory syndrome coronavirus 2, whole-genome sequencing, coronavirus, Mutation, knowledge, Sequencing, Genome, variant, Infection, variants of concern, Diagnosis, severe acute respiratory syndrome Coronavirus, virus, variants, Spike protein, Whole genome sequencing, N501Y, Patient, Urine, household transmission, SARS-CoV-2 evolution, E484K, fitness, P681R, temporal dynamics, in vivo, genomic, immunosuppressed patients, mother, Interaction, Diversity, Immunosuppressed, in urine, acute respiratory syndrome, acute respiratory syndrome coronavirus, two patients, residue, hosts, Substitution, residues, specific treatment, selective, whole genome, genetic change, dominant, Host, first positive, collected, occurred, spread to, conducted, replicate, analysed, characterized, mutate, adjust, anatomic site, immunosuppressed patient, 【제목키워드】 Transmission, immunosuppressed patient,