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1. Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting

Author

Keehner, Jocelyn, Abeles, Shira R, Longhurst, Christopher A, Horton, Lucy E, Myers, Frank E, Riggs-Rodriguez, Lindsay, Ahmad, Mohammed, Baxter, Sally, Boussina, Aaron, Cantrell, Kalen, Cardenas, Priscilla, De Hoff, Peter, El-Kareh, Robert, Holland, Jennifer, Ikeda, Daryn, Kurashige, Kirk, Laurent, Louise C, Aigner, Stefan, Andersen, Kristian G, Anderson, Catelyn, Baer, Nathan A, Barber, Tom, Bauk, Marco, Beck, Jennifer N, Belda-Ferre, Pedro, Betty, Maryann, Birmingham, Amanda, Castro-Martinez, Anelizze, Cheung, Willi, Fisch, Kathleen M, Gangavarapu, Karthik, Gargano, Isabella, Hakim, Abbas, Harsono, Shania, Henson, Benjamin, Hobbs, Charlotte, Holmes, Jacqueline, Jepsen, Kristen, Knight, Rob, Kurzban, Ezra, Marotz, Clarisse A, Matteson, Nathaniel L, Moshiri, Niema, Ngo, Toan T, Ostrander, Tyler R, Perkins, Sarah, Plascencia, Ashley, Rivera, Andrea, Rivera, Ariana, Salido, Rodolfo A, Sathe, Shashank, Seaver, Phoebe, Schwab, Madison, Veder, Anthony, Yeo, Gene W, Zeller, Mark, Lucas, Andrew, Pride, David, Tran, Allen R, Vasylyeva, Tetyana I, Yeo, Gene, Wertheim, Joel O, and Torriani, Francesca J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Pneumonia & Influenza, Clinical Research, Emerging Infectious Diseases, Infectious Diseases, Biodefense, Lung, Genetics, Vaccine Related, Prevention, Aetiology, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Humans, COVID-19, SARS-CoV-2, Retrospective Studies, Cross-Sectional Studies, Health Personnel, Male, Genome, Viral, Female, Adult, Middle Aged, Aged, Social Network Analysis, Contact Tracing, Genomics, Young Adult, Adolescent, Child, Aged, 80 and over, Cross Infection, Child, Preschool, SARS-CoV-2 pandemic, infection prevention precautions, healthcare transmission of SARS-CoV-2, whole-genome sequencing, social network analyses and contact tracing, SEARCH Alliance, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

BackgroundInfection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2.MethodsWe performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs.ResultsAmong 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001).ConclusionsIP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

Published
2024

2. Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics

Author

Matteson, Nathaniel L, Hassler, Gabriel W, Kurzban, Ezra, Schwab, Madison A, Perkins, Sarah A, Gangavarapu, Karthik, Levy, Joshua I, Parker, Edyth, Pride, David, Hakim, Abbas, De Hoff, Peter, Cheung, Willi, Castro-Martinez, Anelizze, Rivera, Andrea, Veder, Anthony, Rivera, Ariana, Wauer, Cassandra, Holmes, Jacqueline, Wilson, Jedediah, Ngo, Shayla N, Plascencia, Ashley, Lawrence, Elijah S, Smoot, Elizabeth W, Eisner, Emily R, Tsai, Rebecca, Chacón, Marisol, Baer, Nathan A, Seaver, Phoebe, Salido, Rodolfo A, Aigner, Stefan, Ngo, Toan T, Barber, Tom, Ostrander, Tyler, Fielding-Miller, Rebecca, Simmons, Elizabeth H, Zazueta, Oscar E, Serafin-Higuera, Idanya, Sanchez-Alavez, Manuel, Moreno-Camacho, Jose L, García-Gil, Abraham, Schafer, Ashleigh R Murphy, McDonald, Eric, Corrigan, Jeremy, Malone, John D, Stous, Sarah, Shah, Seema, Moshiri, Niema, Weiss, Alana, Anderson, Catelyn, Aceves, Christine M, Spencer, Emily G, Hufbauer, Emory C, Lee, Justin J, Ramesh, Karthik S, Nguyen, Kelly N, Saucedo, Kieran, Robles-Sikisaka, Refugio, Fisch, Kathleen M, Gonias, Steven L, Birmingham, Amanda, McDonald, Daniel, Karthikeyan, Smruthi, Martin, Natasha K, Schooley, Robert T, Negrete, Agustin J, Reyna, Horacio J, Chavez, Jose R, Garcia, Maria L, Cornejo-Bravo, Jose M, Becker, David, Isaksson, Magnus, Washington, Nicole L, Lee, William, Garfein, Richard S, Esparza, Marco A Luna-Ruiz, Alcántar-Fernández, Jonathan, Henson, Benjamin, Jepsen, Kristen, Olivares-Flores, Beatriz, Barrera-Badillo, Gisela, Lopez-Martínez, Irma, Ramírez-González, José E, Flores-León, Rita, Kingsmore, Stephen F, Sanders, Alison, Pradenas, Allorah, White, Benjamin, Matthews, Gary, Hale, Matt, McLawhon, Ronald W, Reed, Sharon L, Winbush, Terri, McHardy, Ian H, Fielding, Russel A, Nicholson, Laura, Quigley, Michael M, Harding, Aaron, Mendoza, Art, Bakhtar, Omid, and Browne, Sara H

Subjects
Prevention, Human Genome, Genetics, Good Health and Well Being
Abstract

Summary: The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of SARS-CoV-2 lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of ‘local’ when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

Published
2023

3. Safer at school early alert: an observational study of wastewater and surface monitoring to detect COVID-19 in elementary schools

Author

Fielding-Miller, Rebecca, Karthikeyan, Smruthi, Gaines, Tommi, Garfein, Richard S, Salido, Rodolfo A, Cantu, Victor J, Kohn, Laura, Martin, Natasha K, Wynn, Adriane, Wijaya, Carrissa, Flores, Marlene, Omaleki, Vinton, Majnoonian, Araz, Gonzalez-Zuniga, Patricia, Nguyen, Megan, Vo, Anh V, Le, Tina, Duong, Dawn, Hassani, Ashkan, Tweeten, Samantha, Jepsen, Kristen, Henson, Benjamin, Hakim, Abbas, Birmingham, Amanda, De Hoff, Peter, Mark, Adam M, Nasamran, Chanond A, Rosenthal, Sara Brin, Moshiri, Niema, Fisch, Kathleen M, Humphrey, Greg, Farmer, Sawyer, Tubb, Helena M, Valles, Tommy, Morris, Justin, Kang, Jaeyoung, Khaleghi, Behnam, Young, Colin, Akel, Ameen D, Eilert, Sean, Eno, Justin, Curewitz, Ken, Laurent, Louise C, Rosing, Tajana, Knight, Rob, SEARCH, Baer, Nathan A, Barber, Tom, Castro-Martinez, Anelizze, Chacón, Marisol, Cheung, Willi, Crescini, Evelyn S, Eisner, Emily R, Vargas, Lizbeth Franco, Hobbs, Charlotte, Lastrella, Alma L, Lawrence, Elijah S, Matteson, Nathaniel L, Gangavarapu, Karthik, Ngo, Toan T, Seaver, Phoebe, Smoot, Elizabeth W, Tsai, Rebecca, Xia, Bing, Aigner, Stefan, Anderson, Catelyn, Belda-Ferre, Pedro, Sathe, Shashank, Zeller, Mark, Andersen, Kristian G, Yeo, Gene W, and Kurzban, Ezra

Subjects
Public Health, Health Sciences, Emerging Infectious Diseases, Infectious Diseases, Coronaviruses, Good Health and Well Being, Wastewater surveillance, SARS-CoV-2, COVID-19 in schools, SEARCH
Abstract

BackgroundSchools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown.MethodsThe objective of this study was to determine the effectiveness and accuracy of community-based passive wastewater and surface (environmental) surveillance to detect SARS-CoV-2 infection in neighborhood schools compared to weekly diagnostic (PCR) testing. We implemented an environmental surveillance system in nine elementary schools with 1700 regularly present staff and students in southern California. The system was validated from November 2020 to March 2021.FindingsIn 447 data collection days across the nine sites 89 individuals tested positive for COVID-19, and SARS-CoV-2 was detected in 374 surface samples and 133 wastewater samples. Ninety-three percent of identified cases were associated with an environmental sample (95% CI: 88%-98%); 67% were associated with a positive wastewater sample (95% CI: 57%-77%), and 40% were associated with a positive surface sample (95% CI: 29%-52%). The techniques we utilized allowed for near-complete genomic sequencing of wastewater and surface samples.InterpretationPassive environmental surveillance can detect the presence of COVID-19 cases in non-residential community school settings with a high degree of accuracy.FundingCounty of San Diego, Health and Human Services Agency, National Institutes of Health, National Science Foundation, Centers for Disease Control.

Published
2023

4. Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission

Author

Karthikeyan, Smruthi, Levy, Joshua I, De Hoff, Peter, Humphrey, Greg, Birmingham, Amanda, Jepsen, Kristen, Farmer, Sawyer, Tubb, Helena M, Valles, Tommy, Tribelhorn, Caitlin E, Tsai, Rebecca, Aigner, Stefan, Sathe, Shashank, Moshiri, Niema, Henson, Benjamin, Mark, Adam M, Hakim, Abbas, Baer, Nathan A, Barber, Tom, Belda-Ferre, Pedro, Chacón, Marisol, Cheung, Willi, Cresini, Evelyn S, Eisner, Emily R, Lastrella, Alma L, Lawrence, Elijah S, Marotz, Clarisse A, Ngo, Toan T, Ostrander, Tyler, Plascencia, Ashley, Salido, Rodolfo A, Seaver, Phoebe, Smoot, Elizabeth W, McDonald, Daniel, Neuhard, Robert M, Scioscia, Angela L, Satterlund, Alysson M, Simmons, Elizabeth H, Abelman, Dismas B, Brenner, David, Bruner, Judith C, Buckley, Anne, Ellison, Michael, Gattas, Jeffrey, Gonias, Steven L, Hale, Matt, Hawkins, Faith, Ikeda, Lydia, Jhaveri, Hemlata, Johnson, Ted, Kellen, Vince, Kremer, Brendan, Matthews, Gary, McLawhon, Ronald W, Ouillet, Pierre, Park, Daniel, Pradenas, Allorah, Reed, Sharon, Riggs, Lindsay, Sanders, Alison, Sollenberger, Bradley, Song, Angela, White, Benjamin, Winbush, Terri, Aceves, Christine M, Anderson, Catelyn, Gangavarapu, Karthik, Hufbauer, Emory, Kurzban, Ezra, Lee, Justin, Matteson, Nathaniel L, Parker, Edyth, Perkins, Sarah A, Ramesh, Karthik S, Robles-Sikisaka, Refugio, Schwab, Madison A, Spencer, Emily, Wohl, Shirlee, Nicholson, Laura, McHardy, Ian H, Dimmock, David P, Hobbs, Charlotte A, Bakhtar, Omid, Harding, Aaron, Mendoza, Art, Bolze, Alexandre, Becker, David, Cirulli, Elizabeth T, Isaksson, Magnus, Schiabor Barrett, Kelly M, Washington, Nicole L, Malone, John D, Schafer, Ashleigh Murphy, Gurfield, Nikos, Stous, Sarah, Fielding-Miller, Rebecca, Garfein, Richard S, Gaines, Tommi, Anderson, Cheryl, and Martin, Natasha K

Subjects
Biodefense, Human Genome, Lung, Emerging Infectious Diseases, Vaccine Related, Biotechnology, Genetics, Prevention, Infection, Good Health and Well Being, COVID-19, Humans, RNA, Viral, SARS-CoV-2, Sequence Analysis, RNA, Wastewater, Wastewater-Based Epidemiological Monitoring, General Science & Technology
Abstract

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing and/or sequencing capacity, which can also introduce biases1-3. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing4,5. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We developed and deployed improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detected emerging variants of concern up to 14 days earlier in wastewater samples, and identified multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Published
2022

5. Regional connectivity drove bidirectional transmission of SARS-CoV-2 in the Middle East during travel restrictions

Author

Parker, Edyth, Anderson, Catelyn, Zeller, Mark, Tibi, Ahmad, Havens, Jennifer L, Laroche, Geneviève, Benlarbi, Mehdi, Ariana, Ardeshir, Robles-Sikisaka, Refugio, Latif, Alaa Abdel, Watts, Alexander, Awidi, Abdalla, Jaradat, Saied A, Gangavarapu, Karthik, Ramesh, Karthik, Kurzban, Ezra, Matteson, Nathaniel L, Han, Alvin X, Hughes, Laura D, McGraw, Michelle, Spencer, Emily, Nicholson, Laura, Khan, Kamran, Suchard, Marc A, Wertheim, Joel O, Wohl, Shirlee, Côté, Marceline, Abdelnour, Amid, Andersen, Kristian G, and Abu-Dayyeh, Issa

Subjects
Life on Land, COVID-19, Humans, Middle East, Pandemics, SARS-CoV-2, Travel
Abstract

Regional connectivity and land travel have been identified as important drivers of SARS-CoV-2 transmission. However, the generalizability of this finding is understudied outside of well-sampled, highly connected regions. In this study, we investigated the relative contributions of regional and intercontinental connectivity to the source-sink dynamics of SARS-CoV-2 for Jordan and the Middle East. By integrating genomic, epidemiological and travel data we show that the source of introductions into Jordan was dynamic across 2020, shifting from intercontinental seeding in the early pandemic to more regional seeding for the travel restrictions period. We show that land travel, particularly freight transport, drove introduction risk during the travel restrictions period. High regional connectivity and land travel also drove Jordan's export risk. Our findings emphasize regional connectedness and land travel as drivers of transmission in the Middle East.

Published
2022

6. Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics

Author

Matteson, Nathaniel L., Hassler, Gabriel W., Kurzban, Ezra, Schwab, Madison A., Perkins, Sarah A., Gangavarapu, Karthik, Levy, Joshua I., Parker, Edyth, Pride, David, Hakim, Abbas, De Hoff, Peter, Cheung, Willi, Castro-Martinez, Anelizze, Rivera, Andrea, Veder, Anthony, Rivera, Ariana, Wauer, Cassandra, Holmes, Jacqueline, Wilson, Jedediah, Ngo, Shayla N., Plascencia, Ashley, Lawrence, Elijah S., Smoot, Elizabeth W., Eisner, Emily R., Tsai, Rebecca, Chacón, Marisol, Baer, Nathan A., Seaver, Phoebe, Salido, Rodolfo A., Aigner, Stefan, Ngo, Toan T., Barber, Tom, Ostrander, Tyler, Fielding-Miller, Rebecca, Simmons, Elizabeth H., Zazueta, Oscar E., Serafin-Higuera, Idanya, Sanchez-Alavez, Manuel, Moreno-Camacho, Jose L., García-Gil, Abraham, Murphy Schafer, Ashleigh R., McDonald, Eric, Corrigan, Jeremy, Malone, John D., Stous, Sarah, Shah, Seema, Moshiri, Niema, Weiss, Alana, Anderson, Catelyn, Aceves, Christine M., Spencer, Emily G., Hufbauer, Emory C., Lee, Justin J., King, Alison J., Ramesh, Karthik S., Nguyen, Kelly N., Saucedo, Kieran, Robles-Sikisaka, Refugio, Fisch, Kathleen M., Gonias, Steven L., Birmingham, Amanda, McDonald, Daniel, Karthikeyan, Smruthi, Martin, Natasha K., Schooley, Robert T., Negrete, Agustin J., Reyna, Horacio J., Chavez, Jose R., Garcia, Maria L., Cornejo-Bravo, Jose M., Becker, David, Isaksson, Magnus, Washington, Nicole L., Lee, William, Garfein, Richard S., Luna-Ruiz Esparza, Marco A., Alcántar-Fernández, Jonathan, Henson, Benjamin, Jepsen, Kristen, Olivares-Flores, Beatriz, Barrera-Badillo, Gisela, Lopez-Martínez, Irma, Ramírez-González, José E., Flores-León, Rita, Kingsmore, Stephen F., Sanders, Alison, Pradenas, Allorah, White, Benjamin, Matthews, Gary, Hale, Matt, McLawhon, Ronald W., Reed, Sharon L., Winbush, Terri, McHardy, Ian H., Fielding, Russel A., Nicholson, Laura, Quigley, Michael M., Harding, Aaron, Mendoza, Art, Bakhtar, Omid, Browne, Sara H., Olivas Flores, Jocelyn, Rincon Rodríguez, Diana G., Gonzalez Ibarra, Martin, Robles Ibarra, Luis C., Arellano Vera, Betsy J., Gonzalez Garcia, Jonathan, Harvey-Vera, Alicia, Knight, Rob, Laurent, Louise C., Yeo, Gene W., Wertheim, Joel O., Ji, Xiang, Worobey, Michael, Suchard, Marc A., Andersen, Kristian G., Campos-Romero, Abraham, Wohl, Shirlee, and Zeller, Mark

Published
2023
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7. Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

Author

Washington, Nicole L, Gangavarapu, Karthik, Zeller, Mark, Bolze, Alexandre, Cirulli, Elizabeth T, Schiabor Barrett, Kelly M, Larsen, Brendan B, Anderson, Catelyn, White, Simon, Cassens, Tyler, Jacobs, Sharoni, Levan, Geraint, Nguyen, Jason, Ramirez, Jimmy M, Rivera-Garcia, Charlotte, Sandoval, Efren, Wang, Xueqing, Wong, David, Spencer, Emily, Robles-Sikisaka, Refugio, Kurzban, Ezra, Hughes, Laura D, Deng, Xianding, Wang, Candace, Servellita, Venice, Valentine, Holly, De Hoff, Peter, Seaver, Phoebe, Sathe, Shashank, Gietzen, Kimberly, Sickler, Brad, Antico, Jay, Hoon, Kelly, Liu, Jingtao, Harding, Aaron, Bakhtar, Omid, Basler, Tracy, Austin, Brett, MacCannell, Duncan, Isaksson, Magnus, Febbo, Phillip G, Becker, David, Laurent, Marc, McDonald, Eric, Yeo, Gene W, Knight, Rob, Laurent, Louise C, de Feo, Eileen, Worobey, Michael, Chiu, Charles Y, Suchard, Marc A, Lu, James T, Lee, William, and Andersen, Kristian G

Subjects
Humans, Models, Biological, United States, Female, Male, COVID-19, SARS-CoV-2, 501Y.V1, B.1.1.7, VOC-202012/01, genomic epidemiology, variant of concern, Vaccine Related, Genetics, Human Genome, Biodefense, Prevention, Lung, Pneumonia, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Published
2021

8. Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

Author

Washington, Nicole L, Gangavarapu, Karthik, Zeller, Mark, Bolze, Alexandre, Cirulli, Elizabeth T, Barrett, Kelly M Schiabor, Larsen, Brendan B, Anderson, Catelyn, White, Simon, Cassens, Tyler, Jacobs, Sharoni, Levan, Geraint, Nguyen, Jason, Ramirez, Jimmy M, Rivera-Garcia, Charlotte, Sandoval, Efren, Wang, Xueqing, Wong, David, Spencer, Emily, Robles-Sikisaka, Refugio, Kurzban, Ezra, Hughes, Laura D, Deng, Xianding, Wang, Candace, Servellita, Venice, Valentine, Holly, De Hoff, Peter, Seaver, Phoebe, Sathe, Shashank, Gietzen, Kimberly, Sickler, Brad, Antico, Jay, Hoon, Kelly, Liu, Jingtao, Harding, Aaron, Bakhtar, Omid, Basler, Tracy, Austin, Brett, Isaksson, Magnus, Febbo, Phillip G, Becker, David, Laurent, Marc, McDonald, Eric, Yeo, Gene W, Knight, Rob, Laurent, Louise C, de Feo, Eileen, Worobey, Michael, Chiu, Charles, Suchard, Marc A, Lu, James T, Lee, William, and Andersen, Kristian G

Subjects
Vaccine Related, Prevention, Biodefense, Lung, Good Health and Well Being
Abstract

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Published
2021

9. Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission

Author

Karthikeyan, Smruthi, Levy, Joshua I, De Hoff, Peter, Humphrey, Greg, Birmingham, Amanda, Jepsen, Kristen, Farmer, Sawyer, Tubb, Helena M, Valles, Tommy, Tribelhorn, Caitlin E, Tsai, Rebecca, Aigner, Stefan, Sathe, Shashank, Moshiri, Niema, Henson, Benjamin, Mark, Adam M, Hakim, Abbas, Baer, Nathan A, Barber, Tom, Belda-Ferre, Pedro, Chacón, Marisol, Cheung, Willi, Cresini, Evelyn S, Eisner, Emily R, Lastrella, Alma L, Lawrence, Elijah S, Marotz, Clarisse A, Ngo, Toan T, Ostrander, Tyler, Plascencia, Ashley, Salido, Rodolfo A, Seaver, Phoebe, Smoot, Elizabeth W, McDonald, Daniel, Neuhard, Robert M, Scioscia, Angela L, Satterlund, Alysson M, Simmons, Elizabeth H, Abelman, Dismas B, Brenner, David, Bruner, Judith C, Buckley, Anne, Ellison, Michael, Gattas, Jeffrey, Gonias, Steven L, Hale, Matt, Hawkins, Faith, Ikeda, Lydia, Jhaveri, Hemlata, Johnson, Ted, Kellen, Vince, Kremer, Brendan, Matthews, Gary, McLawhon, Ronald W, Ouillet, Pierre, Park, Daniel, Pradenas, Allorah, Reed, Sharon, Riggs, Lindsay, Sanders, Alison, Sollenberger, Bradley, Song, Angela, White, Benjamin, Winbush, Terri, Aceves, Christine M, Anderson, Catelyn, Gangavarapu, Karthik, Hufbauer, Emory, Kurzban, Ezra, Lee, Justin, Matteson, Nathaniel L, Parker, Edyth, Perkins, Sarah A, Ramesh, Karthik S, Robles-Sikisaka, Refugio, Schwab, Madison A, Spencer, Emily, Wohl, Shirlee, Nicholson, Laura, Mchardy, Ian H, Dimmock, David P, Hobbs, Charlotte A, Bakhtar, Omid, Harding, Aaron, Mendoza, Art, Bolze, Alexandre, Becker, David, Cirulli, Elizabeth T, Isaksson, Magnus, Barrett, Kelly M Schiabor, Washington, Nicole L, Malone, John D, Schafer, Ashleigh Murphy, Gurfield, Nikos, Stous, Sarah, Fielding-Miller, Rebecca, Garfein, Richard S, Gaines, Tommi, Anderson, Cheryl, and Martin, Natasha K

Subjects
Vaccine Related, Infectious Diseases, Biodefense, Emerging Infectious Diseases, Lung, Genetics, Human Genome, Clinical Research, Prevention, Biotechnology, Infection, Good Health and Well Being
Abstract

Summary As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Published
2021

10. Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics

Author

Matteson, Nathaniel L., primary, Hassler, Gabriel W., additional, Kurzban, Ezra, additional, Schwab, Madison A., additional, Perkins, Sarah A., additional, Gangavarapu, Karthik, additional, Levy, Joshua I., additional, Parker, Edyth, additional, Pride, David, additional, Hakim, Abbas, additional, Hoff, Peter De, additional, Cheung, Willi, additional, Castro-Martinez, Anelizze, additional, Rivera, Andrea, additional, Veder, Anthony, additional, Rivera, Ariana, additional, Wauer, Cassandra, additional, Holmes, Jacqueline, additional, Wilson, Jedediah, additional, Ngo, Shayla N., additional, Plascencia, Ashley, additional, Lawrence, Elijah S., additional, Smoot, Elizabeth W., additional, Eisner, Emily R., additional, Tsai, Rebecca, additional, Chacón, Marisol, additional, Baer, Nathan A., additional, Seaver, Phoebe, additional, Salido, Rodolfo A., additional, Aigner, Stefan, additional, Ngo, Toan T., additional, Barber, Tom, additional, Ostrander, Tyler, additional, Fielding-Miller, Rebecca, additional, Simmons, Elizabeth H., additional, Zazueta, Oscar E., additional, Serafin-Higuera, Idanya, additional, Sanchez-Alavez, Manuel, additional, Moreno-Camacho, Jose L., additional, García-Gil, Abraham, additional, Murphy Schafer, Ashleigh R., additional, McDonald, Eric, additional, Corrigan, Jeremy, additional, Malone, John D., additional, Stous, Sarah, additional, Shah, Seema, additional, Moshiri, Niema, additional, Weiss, Alana, additional, Anderson, Catelyn, additional, Aceves, Christine M., additional, Spencer, Emily G., additional, Hufbauer, Emory C., additional, Lee, Justin J., additional, Ramesh, Karthik S., additional, Nguyen, Kelly N., additional, Saucedo, Kieran, additional, Robles-Sikisaka, Refugio, additional, Fisch, Kathleen M., additional, Gonias, Steven L., additional, Birmingham, Amanda, additional, McDonald, Daniel, additional, Karthikeyan, Smruthi, additional, Martin, Natasha K., additional, Schooley, Robert T., additional, Negrete, Agustin J., additional, Reyna, Horacio J., additional, Chavez, Jose R., additional, Garcia, Maria L., additional, Cornejo-Bravo, Jose M., additional, Becker, David, additional, Isaksson, Magnus, additional, Washington, Nicole L., additional, Lee, William, additional, Garfein, Richard S., additional, Luna-Ruiz Esparza, Marco A., additional, Alcántar-Fernández, Jonathan, additional, Henson, Benjamin, additional, Jepsen, Kristen, additional, Olivares-Flores, Beatriz, additional, Barrera-Badillo, Gisela, additional, Lopez-Martínez, Irma, additional, Ramírez-González, José E., additional, Flores-León, Rita, additional, Kingsmore, Stephen F., additional, Sanders, Alison, additional, Pradenas, Allorah, additional, White, Benjamin, additional, Matthews, Gary, additional, Hale, Matt, additional, McLawhon, Ronald W., additional, Reed, Sharon L., additional, Winbush, Terri, additional, McHardy, Ian H., additional, Fielding, Russel A., additional, Nicholson, Laura, additional, Quigley, Michael M., additional, Harding, Aaron, additional, Mendoza, Art, additional, Bakhtar, Omid, additional, Browne, Sara H., additional, Flores, Jocelyn Olivas, additional, Rincon Rodríguez, Diana G., additional, Ibarra, Martin Gonzalez, additional, Robles Ibarra, Luis C., additional, Arellano Vera, Betsy J., additional, Garcia, Jonathan Gonzalez, additional, Harvey-Vera, Alicia, additional, Knight, Rob, additional, Laurent, Louise C., additional, Yeo, Gene W., additional, Wertheim, Joel O., additional, Ji, Xiang, additional, Worobey, Michael, additional, Suchard, Marc A., additional, Andersen, Kristian G., additional, Campos-Romero, Abraham, additional, Wohl, Shirlee, additional, and Zeller, Mark, additional

Published
2023
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11. Safer at school early alert: an observational study of wastewater and surface monitoring to detect COVID-19 in elementary schools

Author

Fielding-Miller, Rebecca, primary, Karthikeyan, Smruthi, additional, Gaines, Tommi, additional, Garfein, Richard S., additional, Salido, Rodolfo A., additional, Cantu, Victor J., additional, Kohn, Laura, additional, Martin, Natasha K., additional, Wynn, Adriane, additional, Wijaya, Carrissa, additional, Flores, Marlene, additional, Omaleki, Vinton, additional, Majnoonian, Araz, additional, Gonzalez-Zuniga, Patricia, additional, Nguyen, Megan, additional, Vo, Anh V., additional, Le, Tina, additional, Duong, Dawn, additional, Hassani, Ashkan, additional, Tweeten, Samantha, additional, Jepsen, Kristen, additional, Henson, Benjamin, additional, Hakim, Abbas, additional, Birmingham, Amanda, additional, De Hoff, Peter, additional, Mark, Adam M., additional, Nasamran, Chanond A., additional, Rosenthal, Sara Brin, additional, Moshiri, Niema, additional, Fisch, Kathleen M., additional, Humphrey, Greg, additional, Farmer, Sawyer, additional, Tubb, Helena M., additional, Valles, Tommy, additional, Morris, Justin, additional, Kang, Jaeyoung, additional, Khaleghi, Behnam, additional, Young, Colin, additional, Akel, Ameen D., additional, Eilert, Sean, additional, Eno, Justin, additional, Curewitz, Ken, additional, Laurent, Louise C., additional, Rosing, Tajana, additional, Knight, Rob, additional, Baer, Nathan A., additional, Barber, Tom, additional, Castro-Martinez, Anelizze, additional, Chacón, Marisol, additional, Cheung, Willi, additional, Crescini, Evelyn S., additional, Eisner, Emily R., additional, Franco Vargas, Lizbeth, additional, Hobbs, Charlotte, additional, Lastrella, Alma L., additional, Lawrence, Elijah S., additional, Matteson, Nathaniel L., additional, Gangavarapu, Karthik, additional, Ngo, Toan T., additional, Seaver, Phoebe, additional, Smoot, Elizabeth W., additional, Tsai, Rebecca, additional, Xia, Bing, additional, Aigner, Stefan, additional, Anderson, Catelyn, additional, Belda-Ferre, Pedro, additional, Sathe, Shashank, additional, Zeller, Mark, additional, Andersen, Kristian G., additional, Yeo, Gene W., additional, and Kurzban, Ezra, additional

Published
2023
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12. Regional connectivity drove bidirectional transmission of SARS-CoV-2 in the Middle East during travel restrictions

Author

Parker, Edyth, primary, Anderson, Catelyn, additional, Zeller, Mark, additional, Tibi, Ahmad, additional, Havens, Jennifer L., additional, Laroche, Genevieve, additional, Benlarbi, Mehdi, additional, Ariana, Ardeshir, additional, Robles-Sikisaka, Refugio, additional, Latif, Alaa, additional, Watts, Alexander, additional, Awidi, Abdalla, additional, Jaradat, Saied A., additional, Gangavarapu, Karthik, additional, Kurzban, Ezra, additional, Matteson, Nathaniel L., additional, Han, Alvin X., additional, Hughes, Laura D., additional, McGraw, Michelle, additional, Spencer, Emily, additional, Nicholson, Laura, additional, Khan, Kamran, additional, Suchard, Marc A., additional, Wertheim, Joel O., additional, Wohl, Shirlee, additional, Cote, Marceline, additional, Abdelnour, Amid, additional, Andersen, Kristian G., additional, and Abu-Dayyeh, Issa, additional

Published
2022
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13. Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission

Author

Karthikeyan, Smruthi, primary, Levy, Joshua I, additional, De Hoff, Peter, additional, Humphrey, Greg, additional, Birmingham, Amanda, additional, Jepsen, Kristen, additional, Farmer, Sawyer, additional, Tubb, Helena M., additional, Valles, Tommy, additional, Tribelhorn, Caitlin E, additional, Tsai, Rebecca, additional, Aigner, Stefan, additional, Sathe, Shashank, additional, Moshiri, Niema, additional, Henson, Benjamin, additional, Mark, Adam M., additional, Hakim, Abbas, additional, Baer, Nathan A, additional, Barber, Tom, additional, Belda-Ferre, Pedro, additional, Chacón, Marisol, additional, Cheung, Willi, additional, Cresini, Evelyn S, additional, Eisner, Emily R, additional, Lastrella, Alma L, additional, Lawrence, Elijah S, additional, Marotz, Clarisse A, additional, Ngo, Toan T, additional, Ostrander, Tyler, additional, Plascencia, Ashley, additional, Salido, Rodolfo A, additional, Seaver, Phoebe, additional, Smoot, Elizabeth W, additional, McDonald, Daniel, additional, Neuhard, Robert M, additional, Scioscia, Angela L, additional, Satterlund, Alysson M., additional, Simmons, Elizabeth H, additional, Abelman, Dismas B., additional, Brenner, David, additional, Bruner, Judith C., additional, Buckley, Anne, additional, Ellison, Michael, additional, Gattas, Jeffrey, additional, Gonias, Steven L., additional, Hale, Matt, additional, Hawkins, Faith, additional, Ikeda, Lydia, additional, Jhaveri, Hemlata, additional, Johnson, Ted, additional, Kellen, Vince, additional, Kremer, Brendan, additional, Matthews, Gary, additional, McLawhon, Ronald W., additional, Ouillet, Pierre, additional, Park, Daniel, additional, Pradenas, Allorah, additional, Reed, Sharon, additional, Riggs, Lindsay, additional, Sanders, Alison, additional, Sollenberger, Bradley, additional, Song, Angela, additional, White, Benjamin, additional, Winbush, Terri, additional, Aceves, Christine M, additional, Anderson, Catelyn, additional, Gangavarapu, Karthik, additional, Hufbauer, Emory, additional, Kurzban, Ezra, additional, Lee, Justin, additional, Matteson, Nathaniel L, additional, Parker, Edyth, additional, Perkins, Sarah A, additional, Ramesh, Karthik S, additional, Robles-Sikisaka, Refugio, additional, Schwab, Madison A, additional, Spencer, Emily, additional, Wohl, Shirlee, additional, Nicholson, Laura, additional, Mchardy, Ian H, additional, Dimmock, David P, additional, Hobbs, Charlotte A, additional, Bakhtar, Omid, additional, Harding, Aaron, additional, Mendoza, Art, additional, Bolze, Alexandre, additional, Becker, David, additional, Cirulli, Elizabeth T, additional, Isaksson, Magnus, additional, Schiabor Barrett, Kelly M, additional, Washington, Nicole L, additional, Malone, John D, additional, Schafer, Ashleigh Murphy, additional, Gurfield, Nikos, additional, Stous, Sarah, additional, Fielding-Miller, Rebecca, additional, Garfein, Richard S., additional, Gaines, Tommi, additional, Anderson, Cheryl, additional, Martin, Natasha K., additional, Schooley, Robert, additional, Austin, Brett, additional, MacCannell, Duncan R., additional, Kingsmore, Stephen F, additional, Lee, William, additional, Shah, Seema, additional, McDonald, Eric, additional, Yu, Alexander T., additional, Zeller, Mark, additional, Fisch, Kathleen M, additional, Longhurst, Christopher, additional, Maysent, Patty, additional, Pride, David, additional, Khosla, Pradeep K., additional, Laurent, Louise C., additional, Yeo, Gene W, additional, Andersen, Kristian G, additional, and Knight, Rob, additional

Published
2021
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14. Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States

Author

Washington, Nicole L., primary, Gangavarapu, Karthik, additional, Zeller, Mark, additional, Bolze, Alexandre, additional, Cirulli, Elizabeth T., additional, Barrett, Kelly M. Schiabor, additional, Larsen, Brendan B., additional, Anderson, Catelyn, additional, White, Simon, additional, Cassens, Tyler, additional, Jacobs, Sharoni, additional, Levan, Geraint, additional, Nguyen, Jason, additional, Ramirez, Jimmy M., additional, Rivera-Garcia, Charlotte, additional, Sandoval, Efren, additional, Wang, Xueqing, additional, Wong, David, additional, Spencer, Emily, additional, Robles-Sikisaka, Refugio, additional, Kurzban, Ezra, additional, Hughes, Laura D., additional, Deng, Xianding, additional, Wang, Candace, additional, Servellita, Venice, additional, Valentine, Holly, additional, De Hoff, Peter, additional, Seaver, Phoebe, additional, Sathe, Shashank, additional, Gietzen, Kimberly, additional, Sickler, Brad, additional, Antico, Jay, additional, Hoon, Kelly, additional, Liu, Jingtao, additional, Harding, Aaron, additional, Bakhtar, Omid, additional, Basler, Tracy, additional, Austin, Brett, additional, Isaksson, Magnus, additional, Febbo, Phillip G., additional, Becker, David, additional, Laurent, Marc, additional, McDonald, Eric, additional, Yeo, Gene W., additional, Knight, Rob, additional, Laurent, Louise C., additional, de Feo, Eileen, additional, Worobey, Michael, additional, Chiu, Charles, additional, Suchard, Marc A., additional, Lu, James T., additional, Lee, William, additional, and Andersen, Kristian G., additional

Published
2021
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15. Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission.

Author

Karthikeyan S, Levy JI, De Hoff P, Humphrey G, Birmingham A, Jepsen K, Farmer S, Tubb HM, Valles T, Tribelhorn CE, Tsai R, Aigner S, Sathe S, Moshiri N, Henson B, Mark AM, Hakim A, Baer NA, Barber T, Belda-Ferre P, Chacón M, Cheung W, Cresini ES, Eisner ER, Lastrella AL, Lawrence ES, Marotz CA, Ngo TT, Ostrander T, Plascencia A, Salido RA, Seaver P, Smoot EW, McDonald D, Neuhard RM, Scioscia AL, Satterlund AM, Simmons EH, Abelman DB, Brenner D, Bruner JC, Buckley A, Ellison M, Gattas J, Gonias SL, Hale M, Hawkins F, Ikeda L, Jhaveri H, Johnson T, Kellen V, Kremer B, Matthews G, McLawhon RW, Ouillet P, Park D, Pradenas A, Reed S, Riggs L, Sanders A, Sollenberger B, Song A, White B, Winbush T, Aceves CM, Anderson C, Gangavarapu K, Hufbauer E, Kurzban E, Lee J, Matteson NL, Parker E, Perkins SA, Ramesh KS, Robles-Sikisaka R, Schwab MA, Spencer E, Wohl S, Nicholson L, Mchardy IH, Dimmock DP, Hobbs CA, Bakhtar O, Harding A, Mendoza A, Bolze A, Becker D, Cirulli ET, Isaksson M, Barrett KMS, Washington NL, Malone JD, Schafer AM, Gurfield N, Stous S, Fielding-Miller R, Garfein RS, Gaines T, Anderson C, Martin NK, Schooley R, Austin B, MacCannell DR, Kingsmore SF, Lee W, Shah S, McDonald E, Yu AT, Zeller M, Fisch KM, Longhurst C, Maysent P, Pride D, Khosla PK, Laurent LC, Yeo GW, Andersen KG, and Knight R

Abstract

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Published
2022
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