Medicine and Health Sciences Commons^™

Accelerated Sars-Cov-2 Intrahost Evolution Leading To Distinct Genotypes During Chronic Infection, Chrispin Chaguza, Anne M. Hahn, Mary E. Petrone, Shuntai Zhou, David Ferguson, Mallery I. Breban, Kien Pham, Mario A. Peña-Hernández, Christopher Castaldi, Verity Hill, Yale Sars-Cov-2 Genomic Surveillance Initiative, Wade Schulz, Ronald I. Swanstrom, Scott C. Roberts, Nathan D. Grubaugh, Kendall Billig, Rebecca Earnest, Joseph R. Fauver, Chaney C. Kalinch, Nicholas Kerantzas, Tobias R. Koch, Bony De Kumar, Marie L. Landry, Isabel M. Ott, David Peaper, Irina R. Tikhonova, Chantal B. F. Vogels

Journal Articles: Epidemiology

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting …

Lineage Abundance Estimation For Sars-Cov-2 In Wastewater Using Transcriptome Quantification Techniques, Jasmijn A. Baaijens, Alessandro Zulli, Isabel M. Ott, Ioanna Nika, Mart J. Van Der Lugt, Mary E. Petrone, Tara Alpert, Joseph R. Fauver, Chaney C. Kalinich, Chantal B. F. Vogels, Mallery I. Breban, Claire Duvallet, Kyle A. Mcelroy, Newsha Ghaeli, Maxim Imakaev, Malaika F. Mckenzie-Bennett, Keith Robison, Alex Plocik, Rebecca Schilling, Martha Pierson, Rebecca Littlefield, Michelle L. Spencer, Birgitte B. Simen, Yale Sars-Cov-2 Genomic Surveillance Initiative, William P. Hanage, Nathan D. Grubaugh, Jordan Peccia, Michael Baym

Journal Articles: Epidemiology

Effectively monitoring the spread of SARS-CoV-2 mutants is essential to efforts to counter the ongoing pandemic. Predicting lineage abundance from wastewater, however, is technically challenging. We show that by sequencing SARS-CoV-2 RNA in wastewater and applying algorithms initially used for transcriptome quantification, we can estimate lineage abundance in wastewater samples. We find high variability in signal among individual samples, but the overall trends match those observed from sequencing clinical samples. Thus, while clinical sequencing remains a more sensitive technique for population surveillance, wastewater sequencing can be used to monitor trends in mutant prevalence in situations where clinical sequencing is unavailable.

Quantifying The Impact Of Immune History And Variant On Sars-Cov-2 Viral Kinetics And Infection Rebound: A Retrospective Cohort Study, James A. Hay, Stephen M. Kissler, Joseph R. Fauver, Christina Mack, Caroline G. Tai, Radhika M. Samant, Sarah Connolly, Deverick J. Anderson, Gaurav Khullar, Matthew Mackay, Miral Patel, Shannan Kelly, April Manhertz, Isaac Eiter, Daisy Salgado, Tim Baker, Ben Howard, Joel T. Dudley, Christopher E. Mason, Manoj Nair, Yaoxing Huang, John Difiori, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad

Journal Articles: Epidemiology

BACKGROUND: The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear.

METHODS: We characterized 1,280 infections from the National Basketball Association occupational health cohort identified between June 2020 and January 2022 using serial RT-qPCR testing. Logistic regression and semi-mechanistic viral RNA kinetics models were used to quantify the effect of age, variant, symptom status, infection history, vaccination status and antibody titer to the founder SARS-CoV-2 strain on the duration of potential infectiousness and overall viral kinetics. The frequency of viral rebounds was quantified under multiple cycle threshold (Ct) value-based definitions.

RESULTS: Among individuals detected …

Viral Dynamics Of Acute Sars-Cov-2 Infection And Applications To Diagnostic And Public Health Strategies, Stephen M. Kissler, Joseph R. Fauver, Christina Mack, Scott W. Olesen, Caroline Tai, Kristin Y. Shiue, Chaney C. Kalinich, Sarah Jednak, Isabel M. Ott, Chantal B. F. Vogels, Jay Wohlgemuth, James Weisberger, John Difiori, Deverick J. Anderson, Jimmie Mancell, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad

Journal Articles: Epidemiology

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found …

Isolation And Characterization Of A Novel Bacteriophage Wo From Allonemobius Socius Crickets In Missouri, Jonah Kupritz, John Martin, Kerstin Fischer, Kurt C. Curtis, Joseph R. Fauver, Yuefang Huang, Young-Jun Choi, Wandy L. Beatty, Makedonka Mitreva, Peter U. Fischer

Journal Articles: Epidemiology

Wolbachia are endosymbionts of numerous arthropod and some nematode species, are important for their development and if present can cause distinct phenotypes of their hosts. Prophage DNA has been frequently detected in Wolbachia, but particles of Wolbachia bacteriophages (phage WO) have been only occasionally isolated. Here, we report the characterization and isolation of a phage WO of the southern ground cricket, Allonemobius socius, and provided the first whole-genome sequence of phage WO from this arthropod family outside of Asia. We screened A. socius abdomen DNA extracts from a cricket population in eastern Missouri by quantitative PCR for Wolbachia surface protein …

Lying In Wait: The Resurgence Of Dengue Virus After The Zika Epidemic In Brazil, Anderson Fernandes Brito, Lais Ceschini Machado, Rachel J. Oidtman, Márcio Junio Lima Siconelli, Quan Minh Tran, Joseph R. Fauver, Rodrigo Dias De Oliveira Carvalho, Filipe Zimmer Dezordi, Mylena Ribeiro Pereira, Luiza Antunes De Castro-Jorge, Elaine Cristina Manini Minto, Luzia Márcia Romanholi Passos, Chaney C. Kalinich, Mary E. Petrone, Emma Allen, Guido Camargo España, Angkana T. Huang, Derek A. T. Cummings, Guy Baele, Rafael Freitas Oliveira Franca, Benedito Antônio Lopes Da Fonseca, T. Alex Perkins, Gabriel Luz Wallau, Nathan D. Grubaugh

Journal Articles: Epidemiology

After the Zika virus (ZIKV) epidemic in the Americas in 2016, both Zika and dengue incidence declined to record lows in many countries in 2017-2018, but in 2019 dengue resurged in Brazil, causing ~2.1 million cases. In this study we use epidemiological, climatological and genomic data to investigate dengue dynamics in recent years in Brazil. First, we estimate dengue virus force of infection (FOI) and model mosquito-borne transmission suitability since the early 2000s. Our estimates reveal that DENV transmission was low in 2017-2018, despite conditions being suitable for viral spread. Our study also shows a marked decline in dengue susceptibility …

Real-Time Public Health Communication Of Local Sars-Cov-2 Genomic Epidemiology, Chaney C. Kalinich, Cole G. Jensen, Peter Neugebauer, Mary E. Petrone, Mario Peña-Hernández, Isabel M. Ott, Anne L. Wyllie, Tara Alpert, Chantal B. F. Vogels, Joseph R. Fauver, Nathan D. Grubaugh, Anderson F. Brito

Journal Articles: Epidemiology

Genomic epidemiology can provide a unique, real-time understanding of SARS-CoV-2 transmission patterns. Yet the potential for genomic analyses to guide local policy and community-based behavioral decisions is limited because they are often oriented towards specially trained scientists and conducted on a national or global scale. Here, we propose a new paradigm: Phylogenetic analyses performed on a local level (municipal, county, or state), with results communicated in a clear, timely, and actionable manner to strengthen public health responses. We believe that presenting results rapidly, and tailored to a non-expert audience, can serve as a template for effective public health response to …

Acute Encephalopathy With Elevated Csf Inflammatory Markers As The Initial Presentation Of Covid-19, Shelli Farhadian, Laura R. Glick, Chantal B. F. Vogels, Jared Thomas, Jennifer Chiarella, Arnau Casanovas-Massana, Jing Zhou, Camila Odio, Pavithra Vijayakumar, Bertie Geng, John Fournier, Santos Bermejo, Joseph R. Fauver, Tara Alpert, Anne L. Wyllie, Cynthia Turcotte, Matthew Steinle, Patrick Paczkowski, Charles Dela Cruz, Craig Wilen, Albert I. Ko, Sean Mackay, Nathan D. Grubaugh, Serena Spudich, Lydia Aoun Barakat

Journal Articles: Epidemiology

BACKGROUND: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients.

CASE PRESENTATION: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion.

CONCLUSION: Our findings …

The Covid-19 Response In Nebraska: How Students Answered The Call, Sabrine Chengane, Anlan Cheney, Sierra Garth, Sharon J. Medcalf

Journal Articles: Epidemiology

The Student Response Team at the University of Nebraska Medical Center answered the statewide call to assist local health departments during the coronavirus disease 2019 (COVID-19) pandemic. As a voluntary student-led effort, the SRT assisted health departments to conduct contact tracing, monitor social media, and educate the public. Their experience demonstrates how students can increase the public health surge capacity of local health departments while gaining applied experience during public health emergencies. This call-to-action commentary proposes that SRTs should be formed, trained, and deployed through academic institutions across the nation and the globe, during and beyond the current pandemic.

Advanced Preparation Makes Research In Emergencies And Isolation Care Possible: The Case Of Novel Coronavirus Disease (Covid-19), David Brett-Major, Elizabeth R. Schnaubelt, Hannah M. Creager, Abigail Lowe, Theodore J. Cieslak, Jacob M. Dahlke, Daniel W. Johnson, Paul D. Fey, Keith F. Hansen, Angela L. Hewlett, Bruce G. Gordon, Andre C. Kalil, Ali S. Khan, Mark G. Kortepeter, Christopher J. Kratochvil, Luann Larson, Deborah A. Levy, James Linder, Sharon J. Medcalf, Mark E. Rupp, Michelle M. Schwedhelm, James N. Sullivan Md, Angela M. Vasa, Michael C. Wadman, Rachel E. Lookadoo, John-Martin J. Lowe, James V. Lawler, M. Jana Broadhurst

Journal Articles: Epidemiology

The optimal time to initiate research on emergencies is before they occur. However, timely initiation of high-quality research may launch during an emergency under the right conditions. These include an appropriate context, clarity in scientific aims, preexisting resources, strong operational and research structures that are facile, and good governance. Here, Nebraskan rapid research efforts early during the 2020 coronavirus disease pandemic, while participating in the first use of U.S. federal quarantine in 50 years, are described from these aspects, as the global experience with this severe emerging infection grew apace. The experience has lessons in purpose, structure, function, and performance …

Mitigating A Covid-19 Outbreak Among Major League Baseball Players - United States, 2020, Meghan T. Murray, Margaret A. Riggs, David M. Engelthaler, Caroline Johnson, Sharon Watkins, Allison Longenberger, David Brett-Major, John Lowe, M. Jana Broadhurst, Chandresh N. Ladva, Julie M. Villanueva, Adam Macneil, Shoukat Qari, Hannah L. Kirking, Michael Cherry, Ali S. Khan

Journal Articles: Epidemiology

Mass gatherings have been implicated in higher rates of transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), and many sporting events have been restricted or canceled to limit disease spread (1). Based on current CDC COVID-19 mitigation recommendations related to events and gatherings (2), Major League Baseball (MLB) developed new health and safety protocols before the July 24 start of the 2020 season. In addition, MLB made the decision that games would be played without spectators. Before a three-game series between teams A and B, the Philadelphia Department of Public Health was notified of a team A …

Aerosol And Surface Contamination Of Sars-Cov-2 Observed In Quarantine And Isolation Care, Joshua L. Santarpia, Danielle N. Rivera, Vicki L. Herrera, M. Jane Morwitzer, Hannah M. Creager, George W. Santarpia, Kevin K. Crown, David Brett-Major, Elizabeth R. Schnaubelt, M. Jana Broadhurst, James V. Lawler, St. Patrick Reid, John Lowe

Journal Articles: Epidemiology

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in late 2019, and its resulting coronavirus disease, COVID-19, was declared a pandemic by the World Health Organization on March 11, 2020. The rapid global spread of COVID-19 represents perhaps the most significant public health emergency in a century. As the pandemic progressed, a continued paucity of evidence on routes of SARS-CoV-2 transmission has resulted in shifting infection prevention and control guidelines between classically-defined airborne and droplet precautions. During the initial isolation of 13 individuals with COVID-19 at the University of Nebraska Medical Center, we collected air …

Mosquitoes Transmit Unique West Nile Virus Populations During Each Feeding Episode, Nathan D. Grubaugh, Joseph R. Fauver, Claudia Rückert, James Weger-Lucarelli, Selene Garcia-Luna, Reyes A. Murrieta, Alex Gendernalik, Darci R. Smith, Doug E. Brackney, Gregory D. Ebel

Journal Articles: Epidemiology

Arthropod-borne viruses (arboviruses), such as Zika virus, chikungunya virus, and West Nile virus (WNV), pose continuous threats to emerge and cause large epidemics. Often, these events are associated with novel virus variants optimized for local transmission that first arise as minorities within a host. Thus, the conditions that regulate the frequency of intrahost variants are important determinants of emergence. Here, we describe the dynamics of WNV genetic diversity during its transmission cycle. By temporally sampling saliva from individual mosquitoes, we demonstrate that virus populations expectorated by mosquitoes are highly diverse and unique to each feeding episode. After transmission to birds, …

West African Anopheles Gambiae Mosquitoes Harbor A Taxonomically Diverse Virome Including New Insect-Specific Flaviviruses, Mononegaviruses, And Totiviruses, Joseph R. Fauver, Nathan D. Grubaugh, Benjamin J. Krajacich, James Weger-Lucarelli, Steven M. Lakin, Lawrence S. Fakoli, Fatorma K. Bolay, Joseph W. Diclaro, Kounbobr Roch Dabiré, Brian D. Foy, Doug E. Brackney, Gregory D. Ebel, Mark D. Stenglein

Journal Articles: Epidemiology

Anopheles gambiae are a major vector of malaria in sub-Saharan Africa. Viruses that naturally infect these mosquitoes may impact their physiology and ability to transmit pathogens. We therefore used metagenomics sequencing to search for viruses in adult Anopheles mosquitoes collected from Liberia, Senegal, and Burkina Faso. We identified a number of virus and virus-like sequences from mosquito midgut contents, including 14 coding-complete genome segments and 26 partial sequences. The coding-complete sequences define new viruses in the order Mononegavirales, and the families Flaviviridae, and Totiviridae. The identification of a flavivirus infecting Anopheles mosquitoes broadens our understanding of the evolution and host …

Maporal Hantavirus Causes Mild Pathology In Deer Mice (Peromyscus Maniculatus), Amanda Mcguire, Kaitlyn Miedema, Joseph R. Fauver, Amber Rico, Tawfik Aboellail, Sandra L. Quackenbush, Ann Hawkinson, Tony Schountz

Journal Articles: Epidemiology

Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the …

Molecular Epidemiology Of Early And Acute Hiv Type 1 Infections In The United States Navy And Marine Corps, 2005–2010, Richard A. Heipertz, Eric Sanders-Buell, Gustavo Kijak, Shana Howell, Michelle Lazzaro, Linda L. Jagodzinski, John Eggleston, Sheila Peel, Jennifer Malia, Adam Armstrong, Nelson L. Michael, Jerome H. Kim, Robert J. O'Connell, Paul T. Scott, David Brett-Major, Sodsai Tovanabutra

Journal Articles: Epidemiology

The U.S. military represents a unique population within the human immunodeficiency virus 1 (HIV-1) pandemic. The last comprehensive study of HIV-1 in members of the U.S. Navy and Marine Corps (Sea Services) was completed in 2000, before large-scale combat operations were taking place. Here, we present molecular characterization of HIV-1 from 40 Sea Services personnel who were identified during their seroconversion window and initially classified as HIV-1 negative during screening. Protease/reverse transcriptase (pro/rt) and envelope (env) sequences were obtained from each member of the cohort. Phylogenetic analyses were carried out on these regions to determine relatedness within the cohort and …

Growth, Immune And Viral Responses In Hiv Infected African Children Receiving Highly Active Antiretroviral Therapy: A Prospective Cohort Study., Philippa M. Musoke, Peter Mudiope, Linda N. Barlow-Mosha, Patrick Ajuna, Danstan Bagenda, Michael M. Mubiru, Thorkild Tylleskar, Mary G. Fowler

Journal Articles: Epidemiology

BACKGROUND: Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes.

METHODS: A prospective cohort of HIV infected children were initiated on HAART and followed for 48 weeks. Body mass index for age z scores(BAZ), weight and height-for-age z scores (WAZ & HAZ) were calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12 weeks. Treatment outcomes were classified according to; both …

Sars Surveillance During Emergency Public Health Response, United States, March-July 2003, Stephanie J. Schrag, John T. Brooks, Chris Van Beneden, Umesh D. Parashar, Patricia M. Griffin, Larry J. Anderson, William J. Bellini, Robert F. Benson, Dean D. Erdman, Alexander Klimov, Thomas G. Ksiazek, Teresa C. T. Peret, Deborah F. Talkington, W. Lanier Thacker, Maria L. Tondella, Jacquelyn S. Sampson, Allen W. Hightower, Dale F. Nordenberg, Brian D. Plikaytis, Ali S. Khan, Nancy E. Rosenstein, Tracee A. Treadwell, Cynthia G. Whitney, Anthony E. Fiore, Tonji M. Durant, Joseph F. Perz, Annemarie Wasley, Daniel Feikin, Joy L. Herndon, William A. Bower, Barbara W. Klibourn, Deborah A. Levy, Victor G. Coronado, Joanna Buffington, Clare A. Dykewicz, Rima F. Khabbaz, Mary E. Chamberland

Journal Articles: Epidemiology

In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of …