Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events

Lemieux, Jacob E.; Siddle, Katherine J.; Shaw, Bennett; Loreth, Christine; Schaffner, Stephen F.; Gladden-Young, Adrianne; Adams, Gordon; Fink, Timelia; Tomkins-Tinch, Christopher H.; Krasilnikova, Lydia A.; DeRuff, Katherine C.; Rudy, Melissa; Bauer, Matthew R.; Lagerborg, Kim A.; Normandin, Erica; Chapman, Sinéad B.; Reilly, Steven K.; Anahtar, Melis N.; Lin, Aaron E.; Carter, Amber; Myhrvold, Cameron; Kemball, Molly; Chaluvadi, Sushma; Cusick, Caroline; Flowers, Katelyn; Neumann, Anna; Cerrato, Felecia; Farhat, Maha; Slater, Damien; Harris, Jason B.; Branda, John A.; Hooper, David C.; Gaeta, Jessie M.; Baggett, Travis P.; O’Connell, James J.; Gnirke, Andreas; Lieberman, Tami D.; Philippakis, Anthony; Burns, Meagan; Brown, Catherine; Luban, Jeremy; Ryan, Edward T.; Turbett, Sarah E; LaRocque, Regina C.; Hanage, William P.; Gallagher, Glen R.; Madoff, Lawrence C.; Smole, Sandra; Pierce, Virginia; Rosenberg, Eric S.; Sabeti, Pardis C.; Park, Daniel J.; MacInnis, Bronwyn

doi:10.1126/science.abe3261

Cited by 250 publications

(245 citation statements)

References 33 publications

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“…As several pathogens and commensal microbes also utilize poly-adenylation for RNA intermediates, or contain poly-adenylated stretches of RNA within their genomes, they may also be represented within scRNA-seq libraries. First, to perform an unbiased search for co-detected viral, bacterial, and fungal genomic material, we used metatranscriptomic classification to assign reads according to a comprehensive reference database (previously described, see Methods ) 85,86 . As expected, the majority (28/38) of swabs from individuals with COVID-19 contain reads classified as SARS coronavirus species ( Figure 4A, Supplementary Figures 5A-5C ).…”

Section: Resultsmentioning

confidence: 99%

“…To identify co-detected microbial taxa present in the cell-associated or ambient RNA of nasopharyngeal swabs, we used the Kraken2 software implemented using the Broad Institute viral-ngs pipelines on Terra (https://github.com/broadinstitute/viral-pipelines/tree/master)86. A previously-published reference database included human, archaea, bacteria, plasmid, viral, fungi, and protozoa species and was constructed on May 5, 2020, therefore included sequences belonging to the novel SARS-CoV-2 virus 85 . Inputs to Kraken2 were: kraken2_db_tgz = “gs://pathogen-public-dbs/v1/kraken2-broad-20200505.tar.zst”, krona_taxonomy_db_kraken2_tgz = “gs://pathogen-public-dbs/v1/krona.taxonomy-20200505.tab.zst”, ncbi_taxdump_tgz = “gs://pathogen-public-dbs/v1/taxdump-20200505.tar.gz”, trim_clip_db = “gs://pathogen-public-dbs/v0/contaminants.clip_db.fasta” and spikein_db = “gs://pathogen-public-dbs/v0/ERCC_96_nopolyA.fasta”.…”

Section: Methodsmentioning

confidence: 99%

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Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

Ziegler

Miao

Owings

et al. 2021

Preprint

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Infection with SARS-CoV-2, the virus that causes COVID-19, can lead to severe lower respiratory illness including pneumonia and acute respiratory distress syndrome, which can result in profound morbidity and mortality. However, many infected individuals are either asymptomatic or have isolated upper respiratory symptoms, which suggests that the upper airways represent the initial site of viral infection, and that some individuals are able to largely constrain viral pathology to the nasal and oropharyngeal tissues. Which cell types in the human nasopharynx are the primary targets of SARS-CoV-2 infection, and how infection influences the cellular organization of the respiratory epithelium remains incompletely understood. Here, we present nasopharyngeal samples from a cohort of 35 individuals with COVID-19, representing a wide spectrum of disease states from ambulatory to critically ill, as well as 23 healthy and intubated patients without COVID-19. Using standard nasopharyngeal swabs, we collected viable cells and performed single-cell RNA-sequencing (scRNA-seq), simultaneously profiling both host and viral RNA. We find that following infection with SARS-CoV-2, the upper respiratory epithelium undergoes massive reorganization: secretory cells diversify and expand, and mature epithelial cells are preferentially lost. Further, we observe evidence for deuterosomal cell and immature ciliated cell expansion, potentially representing active repopulation of lost ciliated cells through coupled secretory cell differentiation. Epithelial cells from participants with mild/moderate COVID-19 show extensive induction of genes associated with anti-viral and type I interferon responses. In contrast, cells from participants with severe lower respiratory symptoms appear globally muted in their anti-viral capacity, despite substantially higher local inflammatory myeloid populations and equivalent nasal viral loads. This suggests an essential role for intrinsic, local epithelial immunity in curbing and constraining viral-induced pathology. Using a custom computational pipeline, we characterized cell-associated SARS-CoV-2 RNA and identified rare cells with RNA intermediates strongly suggestive of active replication. Both within and across individuals, we find remarkable diversity and heterogeneity among SARS-CoV-2 RNA+ host cells, including developing/immature and interferon-responsive ciliated cells, KRT13+ "hillock"-like cells, and unique subsets of secretory, goblet, and squamous cells. Finally, SARS-CoV-2 RNA+ cells, as compared to uninfected bystanders, are enriched for genes involved in susceptibility (e.g., CTSL, TMPRSS2) or response (e.g., MX1, IFITM3, EIF2AK2) to infection. Together, this work defines both protective and detrimental host responses to SARS-CoV-2, determines the direct viral targets of infection, and suggests that failed anti-viral epithelial immunity in the nasal mucosa may underlie the progression to severe COVID-19.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

Ziegler

Miao

Owings

et al. 2021

Preprint

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“…The combination of several mutations and phylogenetic associations provides information that helps to determine the origin of the viral genotypes, and so theoretically, if we know the origin of the genotypes, both local and imported cases can be detected allowing us to track the dynamics of viral spread at a local and global level. Thanks to molecular epidemiology, it has been possible to detect the emergence, introduction and transmission of new variants of the virus in different regions during this current pandemic [10,[31][32][33][34]. This information is vital for developing public health interventions and policy to control viral spread.…”

Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology Surveillance of SARS-CoV-2: Mutations and Genetic Diversity One Year after Emerging

et al. 2021

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In December 2019, the first cases of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified in the city of Wuhan, China. Since then, it has spread worldwide with new mutations being reported. The aim of the present study was to monitor the changes in genetic diversity and track non-synonymous substitutions (dN) that could be implicated in the fitness of SARS-CoV-2 and its spread in different regions between December 2019 and November 2020. We analyzed 2213 complete genomes from six geographical regions worldwide, which were downloaded from GenBank and GISAID databases. Although SARS-CoV-2 presented low genetic diversity, there has been an increase over time, with the presence of several hotspot mutations throughout its genome. We identified seven frequent mutations that resulted in dN substitutions. Two of them, C14408T>P323L and A23403G>D614G, located in the nsp12 and Spike protein, respectively, emerged early in the pandemic and showed a considerable increase in frequency over time. Two other mutations, A1163T>I120F in nsp2 and G22992A>S477N in the Spike protein, emerged recently and have spread in Oceania and Europe. There were associations of P323L, D614G, R203K and G204R substitutions with disease severity. Continuous molecular surveillance of SARS-CoV-2 will be necessary to detect and describe the transmission dynamics of new variants of the virus with clinical relevance. This information is important to improve programs to control the virus.

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“…SARS-CoV-2 superspreading events can dramatically change the course of local outbreaks and have long-lasting effects. Previously, superspreading during a biotech conference in Boston in early 2020 25 and a motorcycle rally in Sturgeon, South Dakota in August, 2020 26 have been estimated to have resulted in more than 250,000 SARS-CoV-2 infections. Although we did not attempt to estimate the exact magnitude of the Mardi Gras superspreading event, given the lack of genetic diversity of SARS-CoV-2 within Louisiana, it seems likely that the majority of the ~50,000 confirmed COVID-19 cases during the first wave 27 can be traced back to Mardi Gras.…”

Section: Discussionmentioning

confidence: 99%

Emergence of an early SARS-CoV-2 epidemic in the United States

Zeller

Gangavarapu

Anderson

et al. 2021

Preprint

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The emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the annual Mardi Gras festival, which went ahead without precautions. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large, crowded events may have accelerated early transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana initially had limited sequence diversity compared to other U.S. states, and that one successful introduction of SARS-CoV-2 led to almost all of the early SARS-CoV-2 transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras and that the festival dramatically accelerated transmission, eventually leading to secondary localized COVID-19 epidemics throughout the Southern U.S.. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate COVID-19 epidemics on a local and regional scale.

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Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events

Cited by 250 publications

References 33 publications

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

Molecular Epidemiology Surveillance of SARS-CoV-2: Mutations and Genetic Diversity One Year after Emerging

Emergence of an early SARS-CoV-2 epidemic in the United States

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