The COVID-19 pandemic demonstrated the public health benefits of reliable and accessible point-of-care (POC) diagnostic tests for viral infections. Despite the rapid development of gold-standard reverse transcription polymerase chain reaction (RT-PCR) assays for SARS-CoV-2 only weeks into the pandemic, global demand created logistical challenges that delayed access to testing for months and helped fuel the spread of COVID-19. Additionally, the extreme sensitivity of RT-PCR had a costly downside as the tests could not differentiate between patients with active infection and those who were no longer infectious but still shedding viral genomes. To address these issues for the future, we propose a novel membrane-based sensor that only detects intact virions. The sensor combines affinity and size based detection on a membrane-based sensor and does not require external power to operate or read. Specifically, the presence of intact virions, but not viral debris, fouls the membrane and triggers a macroscopically visible hydraulic switch after injection of a 40 μL sample with a pipette. The device, which we call the μSiM-DX (microfluidic device featuring a silicon membrane for diagnostics), features a biotin-coated microslit membrane with pores ∼2–3× larger than the intact virus. Streptavidin-conjugated antibody recognizing viral surface proteins are incubated with the sample for ∼1 hour prior to injection into the device, and positive/negative results are obtained within ten seconds of sample injection. Proof-of-principle tests have been performed using preparations of vaccinia virus. After optimizing slit pore sizes and porous membrane area, the fouling-based sensor exhibits 100% specificity and 97% sensitivity for vaccinia virus ( n = 62). Moreover, the dynamic range of the sensor extends at least from 10 5.9 virions per mL to 10 10.4 virions per mL covering the range of mean viral loads in symptomatic COVID-19 patients (10 5.6 –10 7 RNA copies per mL). Forthcoming work will test the ability of our sensor to perform similarly in biological fluids and with SARS-CoV-2, to fully test the potential of a membrane fouling-based sensor to serve as a PCR-free alternative for POC containment efforts in the spread of infectious disease.
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SARS-CoV-2 Is Not Special, but the Pandemic Is: The Ecology, Evolution, Policy, and Future of the Deadliest Pandemic in Living Memory
The COVID-19 pandemic is extraordinary, but many ordinary events have contributed to its becoming and persistence. Here, we argue that the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, which has radically altered day-to-day life for people across the globe, was an inevitability of contemporary human ecology, presaged by spillovers past. We show the ways in which the emergence of this virus reiterates other infectious disease crises, from its origin via habitat encroachment and animal use by humans to its evolution of troublesome features, and we spotlight a long-running crisis of inequitable infectious disease incidence and death. We conclude by describing aspects of SARS-CoV-2 and the COVID-19 pandemic that present opportunities for disease control: spaces for intervention in infection and recovery that reduce transmission and impact. There are no more “before times”; therefore, we encourage embracing a future using old mitigation tactics and government support for ongoing disease control.
more » « less- Award ID(s):
- 1750675
- NSF-PAR ID:
- 10469148
- Publisher / Repository:
- Annual Reviews
- Date Published:
- Journal Name:
- Annual Review of Anthropology
- Volume:
- 51
- Issue:
- 1
- ISSN:
- 0084-6570
- Page Range / eLocation ID:
- 527 to 548
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Humans and viruses have been coevolving for millennia. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes COVID-19) has been particularly successful in evading our evolved defenses. The outcome has been tragic—across the globe, millions have been sickened and hundreds of thousands have died. Moreover, the quarantine has radically changed the structure of our lives, with devastating social and economic consequences that are likely to unfold for years. An evolutionary perspective can help us understand the progression and consequences of the pandemic. Here, a diverse group of scientists, with expertise from evolutionary medicine to cultural evolution, provide insights about the pandemic and its aftermath. At the most granular level, we consider how viruses might affect social behavior, and how quarantine, ironically, could make us susceptible to other maladies, due to a lack of microbial exposure. At the psychological level, we describe the ways in which the pandemic can affect mating behavior, cooperation (or the lack thereof), and gender norms, and how we can use disgust to better activate native “behavioral immunity” to combat disease spread. At the cultural level, we describe shifting cultural norms and how we might harness them to better combat disease and the negative social consequences of the pandemic. These insights can be used to craft solutions to problems produced by the pandemic and to lay the groundwork for a scientific agenda to capture and understand what has become, in effect, a worldwide social experiment.
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There is an ongoing debate on the different transmission modes of SARS-CoV-2 and their relative contributions to the pandemic. In this paper, we employ a simple mathematical model, which incorporates both the human-to-human and environment-to-human transmission routes, to study the transmission dynamics of COVID-19. We focus our attention on the role of airborne transmission in the spread of the disease in a university campus setting. We conduct both mathematical analysis and numerical simulation, and incorporate published experimental data for the viral concentration in the air to fit model parameters. Meanwhile, we compare the outcome to that of the standard SIR model, utilizing a perturbation analysis in the presence of multiple time scales. Our data fitting and numerical simulation results show that the risk of airborne transmission for SARS-CoV-2 strongly depends on how long the virus can remain viable in the air. If the time for this viability is short, the airborne transmission route would be inconsequential in shaping the overall transmission risk and the total infection size. On the other hand, if the infectious virus can persist in aerosols beyond a few hours, then airborne transmission could play a much more significant role in the spread of COVID-19.
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The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spurred unprecedented and concerted worldwide research to curtail and eradicate this pathogen. SARS-CoV-2 has four structural proteins: Envelope (E), Membrane (M), Nucleocapsid (N), and Spike (S), which self-assemble along with its RNA into the infectious virus by budding from intracellular lipid membranes. In this paper, we develop a model to explore the mechanisms of RNA condensation by structural proteins, protein oligomerization and cellular membrane–protein interactions that control the budding process and the ultimate virus structure. Using molecular dynamics simulations, we have deciphered how the positively charged N proteins interact and condense the very long genomic RNA resulting in its packaging by a lipid envelope decorated with structural proteins inside a host cell. Furthermore, considering the length of RNA and the size of the virus, we find that the intrinsic curvature of M proteins is essential for virus budding. While most current research has focused on the S protein, which is responsible for viral entry, and it has been motivated by the need to develop efficacious vaccines, the development of resistance through mutations in this crucial protein makes it essential to elucidate the details of the viral life cycle to identify other drug targets for future therapy. Our simulations will provide insight into the viral life cycle through the assembly of viral particles de novo and potentially identify therapeutic targets for future drug development.more » « less
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Abstract Viruses are infectious agents that pose significant threats to plants, animals, and humans. The current coronavirus disease 2019 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has spread globally and resulted in over 2 million deaths and immeasurable financial losses. Rapid and sensitive virus diagnostics become crucially important in controlling the spread of a pandemic before effective treatment and vaccines are available. Gold nanoparticle (AuNP)‐based testing holds great potential for this urgent unmet biomedical need. In this review, we describe the most recent advances in AuNP‐based viral detection applications. In addition, we discuss considerations for the design of AuNP‐based SARS‐CoV‐2 testings. Finally, we highlight and propose important parameters to consider for the future development of effective AuNP‐based testings that would be critical for not only this COVID‐19 pandemic, but also potential future outbreaks.
This article is categorized under:
Diagnostic Tools > Biosensing
Diagnostic Tools > In Vitro Nanoparticle‐Based Sensing
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1146/annurev-anthro-041420-100047
