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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Differential laboratory passaging of SARS-CoV-2 viral stocks impacts the in vitro assessment of neutralizing antibodies

Viral populations in natural infections can have a high degree of sequence diversity, which can directly impact immune escape. However, antibody potency is often tested in vitro with a relatively clonal viral populations, such as laboratory virus or pseudotyped virus stocks, which may not accurately represent the genetic diversity of circulating viral genotypes. This can affect the validity of viral phenotype assays, such as antibody neutralization assays. To address this issue, we tested whether recombinant virus carrying SARS-CoV-2 spike (VSV-SARS-CoV-2-S) stocks could be made more genetically diverse by passage, and if a stock passaged under selective pressure was more capable of escaping monoclonal antibody (mAb) neutralization than unpassaged stock or than viral stock passaged without selective pressures. We passaged VSV-SARS-CoV-2-S four times concurrently in three cell lines and then six times with or without polyclonal antiserum selection pressure. All three of the monoclonal antibodies tested neutralized the viral population present in the unpassaged stock. The viral inoculum derived from serial passage without antiserum selection pressure was neutralized by two of the three mAbs. However, the viral inoculum derived from serial passage under antiserum selection pressure escaped neutralization by all three mAbs. Deep sequencing revealed the rapid acquisition of multiple mutations associated with antibody escape in the VSV-SARS-CoV-2-S that had been passaged in the presence of antiserum, including key mutations present in currently circulating Omicron subvariants. These data indicate that viral stock that was generated under polyclonal antiserum selection pressure better reflects the natural environment of the circulating virus and may yield more biologically relevant outcomes in phenotypic assays. Thus, mAb assessment assays that utilize a more genetically diverse, biologically relevant, virus stock may yield data that are relevant for prediction of mAb efficacy and for enhancing biosurveillance.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6

Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (~30 kb). Here, we present a plasmid-based viral genome assembly and rescue strategy (pGLUE) that constructs complete infectious viruses or noninfectious subgenomic replicons in a single ligation reaction with >80% efficiency. Fully sequenced replicons and infectious viral stocks can be generated in 1 and 3 weeks, respectively. By testing a series of naturally occurring viruses as well as Delta-Omicron chimeric replicons, we show that Omicron nonstructural protein 6 harbors critical attenuating mutations, which dampen viral RNA replication and reduce lipid droplet consumption. Thus, pGLUE overcomes remaining barriers to broadly study SARS-CoV-2 replication and reveals deficits in nonstructural protein function underlying Omicron attenuation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Comparison of the Transcriptome Response within the Swine Tracheobronchial Lymphnode Following Infection with PRRSV, PCV-2 or IAV-S.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major respiratory pathogen of swine that has become extremely costly to the swine industry worldwide, often causing losses in production and animal life due to their ease of spread. However, the intracellular changes that occur in pigs following viral respiratory infections are still scantily understood for PRRSV, as well as other viral respiratory infections. The aim of this study was to acquire a better understanding of the PRRS disease by comparing gene expression changes that occur in tracheobronchial lymph nodes (TBLN) of pigs infected with either porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV-2), or swine influenza A virus (IAV-S) infections. The study identified and compared gene expression changes in the TBLN of 80 pigs following infection by PRRSV, PCV-2, IAV-S, or sham inoculation. Total RNA was pooled for each group and time-point (1, 3, 6, and 14 dpi) to make 16 libraries—analyses are by Digital Gene Expression Tag Profiling (DGETP). The data underwent standard filtering to generate a list of sequence tag raw counts that were then analyzed using multidimensional and differential expression statistical tests. The results showed that PRRSV, IAV-S and PCV-2 viral infections followed a clinical course in the pigs typical of experimental infection of young pigs with these viruses. Gene expression results echoed this course, as well as uncovered genes related to intersecting and unique host immune responses to the three viruses. By testing and observing the host response to other respiratory viruses, our study has elucidated similarities and differences that can assist in the development of vaccines and therapeutics that shorten or prevent a chronic PRRSV infection.

Miller↗
DOE OSTI2022

The Evolution of Medical Countermeasures for Ebola Virus Disease: Lessons Learned and Next Steps

The Ebola virus disease outbreak that occurred in Western Africa from 2013–2016, and subsequent smaller but increasingly frequent outbreaks of Ebola virus disease in recent years, spurred an unprecedented effort to develop and deploy effective vaccines, therapeutics, and diagnostics. This effort led to the U.S. regulatory approval of a diagnostic test, two vaccines, and two therapeutics for Ebola virus disease indications. Moreover, the establishment of fieldable diagnostic tests improved the speed with which patients can be diagnosed and public health resources mobilized. The United States government has played and continues to play a key role in funding and coordinating these medical countermeasure efforts. Here, we describe the coordinated U.S. government response to develop medical countermeasures for Ebola virus disease and we identify lessons learned that may improve future efforts to develop and deploy effective countermeasures against other filoviruses, such as Sudan virus and Marburg virus.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Laboratory Infection of Novel Akhmeta Virus in CAST/EiJ Mice

Akhmeta virus is a zoonotic Orthopoxvirus first identified in 2013 in the country of Georgia. Subsequent ecological investigations in Georgia have found evidence that this virus is widespread in its geographic distribution within the country and in its host-range, with rodents likely involved in its circulation in the wild. Yet, little is known about the pathogenicity of this virus in rodents. We conducted the first laboratory infection of Akhmeta virus in CAST/EiJ Mus musculus to further characterize this novel virus. We found a dose-dependent effect on mortality and weight loss (p < 0.05). Anti-orthopoxvirus antibodies were detected in the second- and third-highest dose groups (5 × 104 pfu and 3 × 102 pfu) at euthanasia by day 10, and day 14 post-infection, respectively. Anti-orthopoxvirus antibodies were not detected in the highest dose group (3 × 106 pfu), which were euthanized at day 7 post-infection and had high viral load in tissues, suggesting they succumbed to disease prior to mounting an effective immune response. In order of highest burden, viable virus was detected in the nostril, lung, tail, liver and spleen. All individuals tested in the highest dose groups were DNAemic. Akhmeta virus was highly pathogenic in CAST/EiJ Mus musculus, causing 100% mortality when ≥3 × 102 pfu was administered.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Multiplex detection and identification of viral, bacterial, and protozoan pathogens in human blood and plasma using an expanded high-density resequencing microarray platform

Introduction: Nucleic acid tests for blood donor screening have improved the safety of the blood supply; however, increasing numbers of emerging pathogen tests are burdensome. Multiplex testing platforms are a potential solution. Methods: The Blood Borne Pathogen Resequencing Microarray Expanded (BBP-RMAv.2) can perform multiplex detection and identification of 80 viruses, bacteria and parasites. This study evaluated pathogen detection in human blood or plasma. Samples spiked with selected pathogens, each with one of 6 viruses, 2 bacteria and 5 protozoans were tested on this platform. The nucleic acids were extracted, amplified using multiplexed sets of primers, and hybridized to a microarray. The reported sequences were aligned to a database to identify the pathogen. To directly compare the microarray to an emerging molecular approach, the amplified nucleic acids were also submitted to nanopore next generation sequencing (NGS). Results: The BBP-RMAv.2 detected viral pathogens at a concentration as low as 100 copies/ml and a range of concentrations from 1,000 to 100,000 copies/ml for all the spiked pathogens. Coded specimens were identified correctly demonstrating the effectiveness of the platform. The nanopore sequencing correctly identified most samples and the results of the two platforms were compared. Discussion: These results indicated that the BBP-RMAv.2 could be employed for multiplex detection with potential for use in blood safety or disease diagnosis. The NGS was nearly as effective at identifying pathogens in blood and performed better than BBP-RMAv.2 at identifying pathogen-negative samples.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Detection of Apparent Early Rabies Infection by LN34 Pan-Lyssavirus Real-Time RT-PCR Assay in Pennsylvania

The Pennsylvania Department of Health Bureau of Laboratories (PABOL) tested 6855 animal samples for rabies using both the direct fluorescent antibody test (DFA) and LN34 pan-lyssavirus reverse transcriptase quantitative PCR (RT-qPCR) during 2017–2019. Only two samples (0.03%) were initially DFA negative but positive by LN34 RT-qPCR. Both cases were confirmed positive upon re-testing at PABOL and confirmatory testing at the Centers for Disease Control and Prevention by LN34 RT-qPCR and DFA. Rabies virus sequences from one sample were distinct from all positive samples processed at PABOL within two weeks, ruling out cross-contamination. Levels of rabies virus antigen and RNA were low in all brain structures tested, but were higher in brain stem and rostral spinal cord than in cerebellum, hippocampus or cortex. Taken together, the low level of rabies virus combined with higher abundance in more caudal brain structures suggest early infection. These cases highlight the increased sensitivity and ease of interpretation of LN34 RT-qPCR for low positive cases.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Nucleic Acid-Based Sensing Techniques for Diagnostics and Surveillance of Influenza

Influenza virus poses a threat to global health by causing seasonal outbreaks as well as three pandemics in the 20th century. In humans, disease is primarily caused by influenza A and B viruses, while influenza C virus causes mild disease mostly in children. Influenza D is an emerging virus found in cattle and pigs. To mitigate the morbidity and mortality associated with influenza, rapid and accurate diagnostic tests need to be deployed. However, the high genetic diversity displayed by influenza viruses presents a challenge to the development of a robust diagnostic test. Nucleic acid-based tests are more accurate than rapid antigen tests for influenza and are therefore better candidates to be used in both diagnostic and surveillance applications. We review various nucleic acid-based techniques that have been applied towards the detection of influenza viruses in order to evaluate their utility as both diagnostic and surveillance tools. We discuss both traditional as well as novel methods to detect influenza viruses by covering techniques that require nucleic acid amplification or direct detection of viral RNA as well as comparing advantages and limitations for each method. There has been substantial progress in the development of nucleic acid-based sensing techniques for the detection of influenza virus. However, there is still an urgent need for a rapid and reliable influenza diagnostic test that can be used at point-of-care in order to enhance responsiveness to both seasonal and pandemic influenza outbreaks.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Custom script used in 'Updated virophage taxonomy and distinction from polinton-like viruses' (Virophage_Scripts) v1

This is a script and the associated test input/output that will accompany a new manuscript (soon to be submitted for publication). It can be used to detect and classify virophage, a specific group of viruses. This script is released as documentation for the manuscript, but there is no specific invention, and most bioinformaticians would be able to recreate a comparable script in a matter of days (if not hours) based on the description in the manuscript.

Roux, Simon↗
DOE OSTI2023

classLog: Logistic regression for the classification of genetic sequences

Introduction Sequencing and phylogenetic classification have become a common task in human and animal diagnostic laboratories. It is routine to sequence pathogens to identify genetic variations of diagnostic significance and to use these data in realtime genomic contact tracing and surveillance. Under this paradigm, unprecedented volumes of data are generated that require rapid analysis to provide meaningful inference. Methods We present a machine learning logistic regression pipeline that can assign classifications to genetic sequence data. The pipeline implements an intuitive and customizable approach to developing a trained prediction model that runs in linear time complexity, generating accurate output rapidly, even with incomplete data. Our approach was benchmarked against porcine respiratory and reproductive syndrome virus (PRRSv) and swine H1 influenza A virus (IAV) datasets. Trained classifiers were tested against sequences and simulated datasets that artificially degraded sequence quality at 0, 10, 20, 30, and 40%. Results When applied to a poor-quality sequence data, the classifier achieved between >85% to 95% accuracy for the PRRSv and the swine H1 IAV HA dataset and this increased to near perfect accuracy when using the full dataset. The model also identifies amino acid positions used to determine genetic clade identity through a feature selection ranking within the model. These positions can be mapped onto a maximum-likelihood phylogenetic tree, allowing for the inference of clade defining mutations. Discussion Our approach is implemented as a python package with code available at https://github.com/flu-crew/classLog .

Zeller, Michael A.↗
DOE OSTI2022

Efficacy of an inactivated Senecavirus A vaccine in weaned pigs and mature sows

Senecavirus A (SVA), commonly known as Seneca Valley virus (SVV) is a causative agent for vesicular disease in swine. It has been found across the globe including the United States, Brazil, and China. Clinical disease caused by this virus is identical to foot-and-mouth disease virus (FMDV). Since FMDV has the potential to cause severe economic consequences in FMDV-free countries, those countries are on high alert for signs of vesicles in swine and an investigation is performed to rule out the presence of FMDV if observed. In countries where SVA cases have continued to occur, investigations and testing can cause a burden on personnel and resources. The objectives of this study were to test the efficacy of a whole-virus inactivated SVA vaccine against challenge in nursery-aged pigs, mature sows, and to assess the protection of passive maternal immunity generated by immunized dams. Animals were given two doses of the vaccine intramuscularly three weeks apart and challenged intranasally two weeks after the second dose. Non-vaccinated animals challenged with SVA developed clinical signs of disease, replicated virus, and developed a neutralizing antibody response. Vaccinated animals had robust neutralizing titers after two doses; and after challenge, did not develop vesicular disease and had limited rectal shedding. Piglets suckling immunized dams and challenged with SVA at 3–6 days-of-age had neutralizing titers prior to challenge and did not replicate or shed virus. An efficacious vaccine could improve swine welfare and reduce the economic consequences of continued foreign animal disease investigations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Simple Bioparticle Filtration Device Based on an Ultralow-Fouling Zwitterionic Polyurethane Membrane for Rapid Large-Volume Separation of Plasma and Viruses from Whole Blood

Plasma separation from whole blood is oftent required as an essential first step when performing blood tests with a viral assay. However, developing a point-of-care plasma extraction device with a large output and high virus recovery remains a significant obstacle to the success of on-site viral load tests. Here, we report a portable, easy-to-use, cost-efficient, membrane-filtration-based plasma separation device that enables rapid large-volume plasma extraction from whole blood, designed for point-of-care virus assays. The plasma separation is realized by a low-fouling zwitterionic polyurethane-modified cellulose acetate (PCBU-CA) membrane. The zwitterionic coating on the cellulose acetate membrane can decrease surface protein adsorption by 60% and increase plasma permeation by 46% compared with a pristine membrane. The PCBU-CA membrane, with its ultralow-fouling properties, enables rapid plasma separation. The device can yield a total of 1.33 mL plasma from 10 mL whole blood in 10 min. The extracted plasma is cell-free and exhibits a low hemoglobin level. In addition, our device demonstrated a 57.8% T7 phage recovery in the separated plasma. The results of real-time polymerase chain reaction analysis confirmed that the nucleic acid amplification curve of the plasma extracted by our device is comparable to that obtained by centrifugation. With its high plasma yield and good phage recovery, our plasma separation device provides an excellent replacement for traditional plasma separation protocols for point-of-care virus assays and a broad spectrum of clinical tests.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Integration of SARS-CoV-2 testing and genomic sequencing into influenza sentinel surveillance in Uganda, January to December 2022

The Uganda Virus Research Institute, National Influenza Center laboratory integrated SARS-CoV-2 polymerase chain reaction testing and genomic sequencing into the influenza surveillance program that was established in 2007. A total of 7,698 nasopharyngeal/oropharyngeal (NP/OP) swab samples were collected and analyzed from ILI/SARI sentinel sites across the country from January to December 2022. All samples were tested for influenza and SARS-CoV-2. Of these, 252 (3.3%), 162 (2.1%), and 589 (7.7%) were positive for influenza A, influenza B, and SARS-CoV-2, respectively. Out of 414 influenza-positive samples, 122 (29.5%) were AH1pdm09, 130 (31.4%) were AH3, and 162 (39.1%) were B-Victoria. All SARS-CoV-2 sequenced samples were of the Omicron variant, with subvariants of concern known to evade the immune system being detected, such as BQ.1 and XBB.2. Other SARS-CoV-2 positive samples collected from other health centers in the community outside the surveillance sites were included into SARS-CoV-2 genomic sequencing with similar patterns with respect to variants. In all, the ILI/SARI surveillance system has shown to be an efficient, cost-effective, and sustainable program, providing a ready platform to monitor the circulation of SARS-CoV-2 in communities at the national level while remaining vigilant for the persistent threat of influenza. The integration of SARS-CoV-2 detection and genomic surveillance into the influenza surveillance program will strengthen the laboratory response capacity, as well as facilitate the timely release of SARS-CoV-2 genomic information to be used to complement the multiple response strategies for COVID-19 pandemic mitigation.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2015

Risk of Crew Adverse Health Event Due to Altered Immune Response

Determining the effect of space travel on the human immune system has proven to be extremely challenging. Limited opportunities for in-flight studies, varying mission durations, technical and logistical obstacles, small subject numbers, and a broad range of potential assays have contributed to this problem. Additionally, the inherent complexity of the immune system, with its vast array of cell populations, sub-populations, diverse regulatory molecules, and broad interactions with other physiological systems, makes determining precise variables to measure very difficult. There is also the challenge of determining the clinical significance of any observed immune alterations. Will such a change lead to disease, or is it a transient subclinical observation related to short-term stress? The effect of this problem may be observed by scanning publications associated with immunity and spaceflight, which began to appear during the 1970s. Although individually they are each valid studies, the comprehensive literature to date suffers from widely varying sampling methods and assay techniques, low subject counts, and sometimes a disparate focus on narrow aspects of immunity. The most clinically relevant data are derived from in-flight human studies, which have demonstrated altered cell-mediated immunity and reactivation of latent herpes viruses. Much more data are available from post-flight testing of humans, with clear evidence of altered cytokine production patterns, altered leukocyte distribution, continued latent viral reactivation, and evidence of dramatically altered virus-specific immunity. It is unknown if post-flight assessments relate to the in-flight condition or are a response to landing stress and readaptation. In-flight culture of cells has clearly demonstrated that immune cells are gravity-sensitive and display altered functional characteristics. It is unknown if these data are related to in vivo immune cell function or are an artifact of microgravity culture. Ground analog testing of humans and animals, as well as microgravity-analog cell culture, has demonstrated utility. However, in all cases, it is not known with certainty if these data would reflect similar testing during space travel. Given their ready availability, ground analogs may be extremely useful for assay development and the evaluation of potential countermeasures. In general, the evidence base suffers from widely disparate studies on small numbers of subjects that do not directly correlate well with each other or spaceflight itself. Also lacking are investigations of the effect of gender on adaption to spaceflight. This results in significant knowledge 'gaps' that must be filled by future studies to completely determine any clinical risk related to immunity for human exploration-class space missions. These gaps include a significant lack of in-flight data, particularly during long-duration space missions. The International Space Station represents an excellent science platform with which to address this knowledge gap. Other knowledge gaps include lack of a single validated ground analog for the phenomenon and a lack of flight-compatible laboratory equipment capable of monitoring astronauts (for either clinical or research purposes). However, enough significant data exist, as described in this manuscript, to warrant addressing this phenomenon during the utilization phase of the ISS. A recent Space Shuttle investigation has confirmed the 31 in-flight nature of immune dysregulation, demonstrating that it is not merely a post-flight phenomenon. Several current studies are ongoing onboard the ISS that should thoroughly characterize the phenomenon. NASA recognizes that if spaceflight-associated immune dysregulation persists during exploration flights in conjunction with other dangers, such as high-energy radiation, the result may be a significant clinical risk. This emphasizes the need for a continued integrated comprehensive approach to determining the effect of prolonged spaceflight, separated from transient launch and landing stresses, on human immunity. After such studies, the phenomenon will be understood, and, hopefully, a monitoring strategy will have been developed that could be used to monitor the effectiveness of countermeasure

Crucian, Brian↗
DOE OSTI2023

MArVD2: a machine learning enhanced tool to discriminate between archaeal and bacterial viruses in viral datasets

Abstract Our knowledge of viral sequence space has exploded with advancing sequencing technologies and large-scale sampling and analytical efforts. Though archaea are important and abundant prokaryotes in many systems, our knowledge of archaeal viruses outside of extreme environments is limited. This largely stems from the lack of a robust, high-throughput, and systematic way to distinguish between bacterial and archaeal viruses in datasets of curated viruses. Here we upgrade our prior text-based tool (MArVD) via training and testing a random forest machine learning algorithm against a newly curated dataset of archaeal viruses. After optimization, MArVD2 presented a significant improvement over its predecessor in terms of scalability, usability, and flexibility, and will allow user-defined custom training datasets as archaeal virus discovery progresses. Benchmarking showed that a model trained with viral sequences from the hypersaline, marine, and hot spring environments correctly classified 85% of the archaeal viruses with a false detection rate below 2% using a random forest prediction threshold of 80% in a separate benchmarking dataset from the same habitats.

Vik, Dean (ORCID:000000027546899X)↗
NASA NTRS2010

Latent Virus Reactivation in Astronauts and Shingles Patients

Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpesviruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpes viruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

Mehta, Satish K.↗
NASA NTRS2010

Salivary Varicella Zoster Virus in Astronauts and in Patients of Herpes Zoster

Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpes viruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpesviruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors? offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

Mehta, Satish↗
DOE OSTI2021

Agent-based Disease Surveillance and Transmission Model

The SARS-CoV-2 pandemic has driven a need for models that can predict transmission among populations and test the effectiveness of proposed interventions to control it such as testing, quarantining, vaccinations, and nonpharmaceutical interventions. Some questions of interest include:1. How rapidly will the virus spread if no action is taken? 2. How frequently should people be tested and quarantined if necessary? 3. Should unvaccinated persons be tested more frequently than the vaccinated? 4. If test results are delayed, how will that affect the spread? 5. How do test false negative rates affect the overall efficacy of testing programs? 6. How do constraints on testing resources impact the overall efficacy of testing programs? 7. How does the patient’s failure to recognize COVID symptoms and quarantine affect the spread? 8. What level of vaccination coverage is needed to suppress the epidemic? 9. What is the risk of a large outbreak (probability exceeding x infections)? 10. What is the cost effectiveness of interventions (dollars per avoided infection)? This report describes the structure of a discrete event simulation model that provides actionable information to address these questions. Parameter inputs and results of analyses have been reported in briefings provided to LLNL management and are not discussed here.

59 BASIC BIOLOGICAL SCIENCES↗