Nathan D Grubaugh

Nathan D Grubaugh
Yale University | YU · Department of Epidemiology of Microbial Diseases

Ph.D., M.S.

About

180
Publications
60,415
Reads
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11,799
Citations
Introduction
Track the emergence and spread of mosquito-borne viruses. Assess how natural selection shapes the mutational landscapes of RNA virus populations within ecologically relevant hosts. Develop novel methods for surveillance and discovery of viral pathogens.
Additional affiliations
June 2016 - present
The Scripps Research Institute
Position
  • PostDoc Position
Description
  • Zika virus evolution during the South American outbreak www.andersen-lab.com
August 2012 - March 2016
Colorado State University
Position
  • PhD Student
September 2010 - September 2012
United States Army Medical Research Institute for Infectious Diseases
Position
  • ORISE Fellow
Education
August 2012 - May 2016
Colorado State University
Field of study
  • Microbiology, Immunology, Pathology
September 2009 - June 2011
Johns Hopkins University
Field of study
  • Biotechnology
September 2001 - June 2005
Western Michigan University
Field of study
  • Biomedical Sciences

Publications

Publications (180)
Article
Full-text available
Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV intro...
Article
Full-text available
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 frequ...
Article
The magnitude of the 2013–2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP)...
Article
The emergence of mosquito-borne RNA viruses, such as West Nile virus (WNV), is facilitated by the formation of genetically complex populations. Mosquito-borne transmission imposes unique evolutionary pressures on WNV: diversification in mosquitoes and selective constraint in birds. We sought to determine whether important enzootic (Culex tarsalis,...
Preprint
Full-text available
How viruses evolves within hosts can dictate infection outcomes; however, accurately reconstructing this process is challenging from samples with low virus concentrations. We evaluated our highly multiplexed amplicon approach - PrimalSeq - to enrich for viral RNA and demonstrate how virus concentration, sequencing coverage depth, primer mismatches,...
Preprint
The chronic infection hypothesis for novel 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...
Article
Background During August–September 2021, a Connecticut college experienced a large SARS-CoV-2 Delta outbreak despite high (99%) vaccination coverage, indoor masking policies, and twice weekly reverse transcription-polymerase chain reaction (RT-PCR) testing. The Connecticut Department of Public Health investigated characteristics associated with inf...
Article
Full-text available
The Omicron variant of SARS-CoV-2 recently swept the globe and showed high level of immune evasion. Here, we generate an Omicron-specific lipid nanoparticle (LNP) mRNA vaccine candidate, and test its activity in animals, both alone and as a heterologous booster to WT mRNA vaccine. Our Omicron-specific LNP-mRNA vaccine elicits strong antibody respon...
Article
Full-text available
Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 as...
Preprint
Though instances of arthropod-borne (arbo)virus co-infection have been documented clinically, the overall incidence of arbovirus co-infection and its drivers are not well understood. Now that dengue, Zika, and chikungunya viruses are all in circulation across tropical and subtropical regions of the Americas, it is important to understand the enviro...
Article
Full-text available
SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surve...
Preprint
Background While considerable attention was placed on SARS-CoV-2 testing and surveillance programs in the K-12 setting, younger age groups in childcare centers were largely overlooked. Childcare facilities are vital to communities, allowing parents/guardians to remain at work and providing safe environments for both children and staff. Therefore, e...
Article
Full-text available
As the biomedical community produces datasets that are increasingly complex and high dimensional, there is a need for more sophisticated computational tools to extract biological insights. We present Multiscale PHATE, a method that sweeps through all levels of data granularity to learn abstracted biological features directly predictive of disease o...
Preprint
Full-text available
Mutations in the viral genome of SARS-CoV-2 can impact the performance of molecular diagnostic assays. In some cases, such as S gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here we describe partial ORF1ab gene target failure (pOGTF) on the cobas® SARS-Co...
Article
Background The SARS-CoV-2 Omicron variant became a global concern due to its rapid spread and displacement of the dominant Delta variant. We hypothesized that part of Omicron’s rapid rise was based on its increased ability to cause infections in persons that are vaccinated compared to Delta. Methods We analyzed nasal swab PCR tests for samples coll...
Article
6 years ago, I published a Cell Host and Microbe paper that described randomization of virus genetic populations during mosquito infection. From within the evolutionary chaos, however, there is an order that can reveal a virus’ past. Using these insights, I forged a career harnessing virus evolution to understand epidemiological patterns.
Article
Full-text available
Background There is an urgent need to expand testing for SARS-CoV-2 and other respiratory pathogens as the global community struggles to control the COVID-19 pandemic. Current diagnostic methods can be affected by supply chain bottlenecks and require the assistance of medical professionals, impeding the implementation of large-scale testing. Self-c...
Preprint
Importance The suitability of the currently recommended 5-day COVID-19 isolation period remains unclear in an Omicron-dominant landscape. Early data suggest high positivity via rapid antigen test beyond day 5, but evidence gaps remain regarding optimal isolation duration and the best use of limited RATs to exit isolation. Objective To determine th...
Article
Importance: The emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2 has led to increases in both infections and hospitalizations among adolescents. Little is known about the effectiveness of the BNT162b2 vaccine in adolescents in the general population, as opposed to a clinical trial population. Objective: To estimate the effectiveness of t...
Article
Full-text available
The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and by its numerous spike mutations with potential to evade neutralizing antibodies elicited by COVID-19 vaccines. Here, we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants...
Article
Full-text available
The SARS-CoV-2 Delta variant rose to dominance in mid-2021, likely propelled by an estimated 40-80% increased transmissibility over Alpha. To investigate if this ostensible difference in transmissibility is uniform across populations, we partner with public health programs from all six states in New England, USA. We compare logistic growth rates du...
Preprint
Full-text available
RNA viruses have short generation times and high mutation rates, allowing them to undergo rapid molecular evolution during epidemics. However, the extent of RNA virus phenotypic evolution within epidemics and the resulting effects on fitness and virulence remain mostly unknown. Here, we screened the 2015-2016 Zika epidemic in the Americas for linea...
Preprint
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continues to shape the coronavirus disease 2019 (Covid-19) pandemic. The detection and rapid spread of the SARS-CoV-2 Omicron variant (lineage B.1.1.529) in Botswana and South Africa became a global concern because it contained 15 mutations in the spike protein i...
Article
Full-text available
Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J...
Preprint
Full-text available
Background. The Omicron SARS-CoV-2 variant is responsible for a major wave of COVID-19, with record case counts reflecting high transmissibility and escape from prior immunity. Defining the time course of Omicron viral proliferation and clearance is crucial to inform isolation protocols aiming to minimize disease spread. Methods. We obtained longit...
Preprint
Full-text available
The frequency of SARS-CoV-2 breakthrough infections in fully vaccinated individuals increased with the emergence of the Delta variant, particularly with longer time from vaccine completion. However, whether breakthrough infections lead to onward transmission remains unclear. Here, we conducted a study involving 125 patients comprised of 72 vaccinat...
Article
Full-text available
Genomic sequencing is crucial to understanding the epidemiology and evolution of SARS-CoV-2. Often, genomic studies rely on remnant diagnostic material, typically nasopharyngeal swabs, as input into whole genome SARS-CoV-2 next-generation sequencing pipelines. Saliva has proven to be a safe and stable specimen for the detection of SARS-CoV-2 RNA vi...
Article
Solid organ transplant recipients are at increased risk of COVID-19 associated morbidity and mortality. We describe the first nosocomial outbreak investigation on an immunocompromised inpatient unit aided by SARS-CoV-2 whole genome sequencing. Two patients were identified as potential index cases; one presented with diarrhea and the other tested po...
Preprint
The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and by its numerous spike mutations with potential to evade neutralizing antibodies elicited by COVID-19 vaccines. The Dominican Republic was among the first countries in recommending the administration of a third dose COVID-19 vacci...
Article
Full-text available
The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1–6. We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV...
Article
Full-text available
Background Streptococcus pneumoniae (pneumococcus) is a common colonizer of the upper respiratory tract and can progress to cause invasive and mucosal disease. Additionally, infection with pneumococcus can complicate respiratory viral infections (influenza, respiratory syncytial virus, etc.) by exacerbating the initial disease. Limited data exist d...
Article
Full-text available
Background Quickly detecting and isolating individuals positive for SARS-CoV-2 is essential for limiting virus spread. Policy makers rely on the number of active cases to make decisions, and individuals use this information to evaluate risk should they return to public spaces. Robust testing strategies have been plagued with limited authorized diag...
Article
In this issue of Cell, Bushman et al. show how more transmissible variants, even if they do not escape immunity, can be strongly selected during the early pandemic. This explains the dynamics of past SARS-CoV-2 variants, but as immunity increases, it is difficult to predict what will emerge next.
Article
Full-text available
As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mous...
Article
We reconstructed the 2016–2017 Zika virus epidemic in Puerto Rico by using complete genomes to uncover the epidemic’s origin, spread, and evolutionary dynamics. Our study revealed that the epidemic was propelled by multiple introductions that spread across the island, intricate evolutionary patterns, and ≈10 months of cryptic transmission.
Article
Background The underlying immunologic deficiencies enabling SARS-CoV-2 reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for COVID-19. Methods A 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVI...
Preprint
Full-text available
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant quickly rose to dominance in mid-2021, displacing other variants, including Alpha. Studies using data from the United Kingdom and India estimated that Delta was 40-80% more transmissible than Alpha, allowing Delta to become the globally dominant variant. However, it was...
Article
Full-text available
In fall 2020, a coronavirus disease cluster comprising 16 cases occurred in Connecticut, USA. Epidemiologic and genomic evidence supported transmission among persons at a school and fitness center but not a workplace. The multiple transmission chains identified within this cluster highlight the necessity of a combined investigatory approach.
Article
Full-text available
Infection with Zika virus (ZIKV), a member of the Flavivirus genus of the Flaviviridae family, typically results in mild self-limited illness, but severe neurological disease occurs in a limited subset of patients. In contrast, serious outcomes commonly occur in pregnancy that affect the developing fetus, including microcephaly and other major birt...
Preprint
Full-text available
Effectively monitoring the spread of SARS-CoV-2 variants is essential to efforts to counter the ongoing pandemic. Wastewater monitoring of SARS-CoV-2 RNA has proven an effective and efficient technique to approximate COVID-19 case rates in the population. Predicting variant abundances from wastewater, however, is technically challenging. Here we sh...
Article
As the SARS-CoV-2 pandemic evolves, new variants continue to emerge. Some highly transmissible variants, such as Delta, also raised concerns about the effectiveness provided by current vaccines. Understanding immunological correlates of protection and how laboratory findings correspond to clinical effectiveness is imperative to shape future vaccina...
Article
Full-text available
Seven cases of COVID-19 SARS-CoV-2 reinfection from the NBA 2020-2021 occupational testing cohort are described including clinical details, antibody test results, genomic sequencing, and longitudinal RT-PCR results. Reinfections were infrequent and varied in clinical presentation, viral dynamics, and immune response.
Preprint
Full-text available
The COVID-19 pandemic has revealed the importance of virus genome sequencing to guide public health interventions to control virus transmission and understand SARS-CoV-2 evolution. As of July 20th, 2021, >2 million SARS-CoV-2 genomes have been submitted to GISAID, 94% from high income and 6% from low and middle income countries. Here, we analyse th...
Preprint
Full-text available
Infection with Zika virus (ZIKV), a member of the Flavivirus genus of the Flaviviridae family, typically results in mild self-limited illness, but severe neurological disease occurs in a limited subset of patients. In contrast, serious outcomes commonly occur in pregnancy that affect the developing fetus, including microcephaly and other major birt...
Preprint
The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination (1-6). We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-...
Article
Full-text available
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 quan...
Article
Full-text available
COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1–6. While pathological innate immune activation is well documented in severe disease¹, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody (AAb) disc...
Preprint
Full-text available
Emerging SARS-CoV-2 variants have shaped the second year of the COVID-19 pandemic and the public health discourse around effective control measures. Evaluating the public health threat posed by a new variant is essential for appropriately adapting response efforts when community transmission is detected. However, this assessment requires that a tru...
Article
Full-text available
Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over...
Article
The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequence...
Preprint
Full-text available
Genomic sequencing is crucial to understanding the epidemiology and evolution of SARS-CoV-2. Often, genomic studies rely on remnant diagnostic material, typically nasopharyngeal swabs, as input into whole genome SARS-CoV-2 next-generation sequencing pipelines. Saliva has proven to be a safe and stable specimen for the detection of SARS-CoV-2 RNA vi...
Preprint
BACKGROUND Clinical and virologic characteristics of COVID-19 infections in veterans in New England have not been described. OBJECTIVE To evaluate clinical and virologic factors impacting COVID-19 outcomes. METHODS We reviewed charts and sequenced virus from nasopharyngeal specimens with confirmed SARS-CoV-2 from 426 veterans in six New England s...
Article
Background Clinical and virologic characteristics of COVID-19 infections in veterans in New England have not been described. The average US veteran is a male older than the general US population. SARS-CoV-2 infection is known to cause poorer outcomes among men and older adults, making the veteran population an especially vulnerable group for COVID-...
Article
Full-text available
Background SARS-CoV-2 infection has, as of April 2021, affected >133 million people worldwide, causing >2.5 million deaths. Because the large majority of individuals infected with SARS-CoV-2 are asymptomatic, major concerns have been raised about possible long-term consequences of the infection. Methods Wedeveloped an antigen capture assay to dete...
Preprint
Full-text available
As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mous...