Revealing fine-scale spatiotemporal differences in SARS-CoV-2 introduction and spread

Moreno, Gage K.; Braun, Katarina M.; Riemersma, Kasen K.; Martin, Michael; Halfmann, Peter; Crooks, Chelsea M.; Prall, Trent M.; Baker, David; Baczenas, John J.; Heffron, Anna S.; Ramuta, Mitchell D.; Khubbar, Manjeet; Weiler, Andrea M.; Accola, Molly A.; Rehrauer, William M.; O’Connor, Shelby L.; Safdar, Nasia; Pepperell, Caitlin S.; Dasu, Trivikram; Bhattacharyya, Sanjib; Kawaoka, Yoshihiro; Koelle, Katia; O’Connor, David H.; Friedrich, Thomas C.

doi:10.1038/s41467-020-19346-z

Cited by 42 publications

(50 citation statements)

References 62 publications

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“…Recent studies have also suggested that the intra-host heterogeneity of SARS-CoV-2 genome in individuals may be transferable (53)(54)(55), and given that a minuscule percent of population is responsible for most of the local transmission of SARS-CoV-2 infection (56-58), there arises a possibility of iSNVs harbouring genome to be passed through a super-spreading event. This, in an isolated population, might also lead to an altered haplotype with some unique variations leading to fixation or removal of alleles from the population (59). By temporally capturing iSNVs and the consequential variant appearance in the population, we could determine iSNV sites in the East Indian population which possibly transitioned into an SNV (Supplementary Figure S5).…”

Section: Discussionmentioning

confidence: 99%

Spatio-temporal dynamics of intra-host variability in SARS-CoV-2 genomes

Pathak

Fatihi

Abbas

et al. 2020

Preprint

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Since its zoonotic transmission in the human host, the SARS-CoV-2 virus has infected millions and has diversified extensively. A hallmark feature of viral system survival is their continuous evolution and adaptation within the host. RNA editing via APOBEC and ADAR family of enzymes has been recently implicated as the major driver of intra-host variability of the SARS-CoV-2 genomes. Analysis of the intra-host single-nucleotide variations (iSNVs) in SARS-CoV-2 genomes at spatio-temporal scales can provide insights on the consequence of RNA editing on the establishment, spread and functional outcomes of the virus. In this study, using 1,347 transcriptomes of COVID-19 infected patients across various populations, we find variable prevalence of iSNVs with distinctly higher levels in Indian population. Our results also suggest that iSNVs can likely establish variants in a population. These iSNVs may also contribute to key structural and functional changes in the Spike protein that confer antibody resistance.

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Section: Discussionmentioning

confidence: 99%

Spatio-temporal dynamics of intra-host variability in SARS-CoV-2 genomes

Pathak

Fatihi

Abbas

et al. 2020

Preprint

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“…All consensus-level surveillance sequencing of SARS-CoV-2 was performed using Oxford Nanopore sequencing (n = 3,351) as described previously [ 51 ].…”

Section: Methodsmentioning

confidence: 99%

Acute SARS-CoV-2 infections harbor limited within-host diversity and transmit via tight transmission bottlenecks

et al. 2021

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The emergence of divergent SARS-CoV-2 lineages has raised concern that novel variants eliciting immune escape or the ability to displace circulating lineages could emerge within individual hosts. Though growing evidence suggests that novel variants arise during prolonged infections, most infections are acute. Understanding how efficiently variants emerge and transmit among acutely-infected hosts is therefore critical for predicting the pace of long-term SARS-CoV-2 evolution. To characterize how within-host diversity is generated and propagated, we combine extensive laboratory and bioinformatic controls with metrics of within- and between-host diversity to 133 SARS-CoV-2 genomes from acutely-infected individuals. We find that within-host diversity is low and transmission bottlenecks are narrow, with very few viruses founding most infections. Within-host variants are rarely transmitted, even among individuals within the same household, and are rarely detected along phylogenetically linked infections in the broader community. These findings suggest that most variation generated within-host is lost during transmission.

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“…We found that 24 (92%) of these 26 genomic sequences cluster tightly in the Nextstrain 20A clade on a time-resolved tree and are separated by 0-2 fixed consensus nucleotide differences (Figure 3). The limited diversity of viruses detected in the 24 individuals suggests sustained transmission of SARS-CoV-2 following a single introduction [20][21][22].Viruses from Athletics-3 and Athletics-26 did not appear to be part of the primary transmission cluster. As of 1-day-40, there was no evidence for onward spread within the program originating from Athletics-3 or Athletics-26.…”

Section: Resultsmentioning

confidence: 88%

“…All eight virus sequences (four from each team) clustered tightly in the 20G clade on a time-resolved tree and were separated by 0-2 fixed consensus nucleotide differences (Figure 4). Given the known epidemiological associations between these teams, this likely represented a single transmission cluster [20][21][22].…”

Section: Outbreak 2: Sars-cov-2 Transmission During Intercollegiate Cmentioning

confidence: 99%

SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing

Moreno

Braun

Pray

et al. 2021

Preprint

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Background High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing. Methods During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel's Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks. Results In Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during intercollegiate competition. Conclusions These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlights the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings.

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Revealing fine-scale spatiotemporal differences in SARS-CoV-2 introduction and spread

Cited by 42 publications

References 62 publications

Spatio-temporal dynamics of intra-host variability in SARS-CoV-2 genomes

Spatio-temporal dynamics of intra-host variability in SARS-CoV-2 genomes

Acute SARS-CoV-2 infections harbor limited within-host diversity and transmit via tight transmission bottlenecks

SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing

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