skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Quantifying antibody kinetics and RNA detection during early-phase SARS-CoV-2 infection by time since symptom onset
Understanding and mitigating SARS-CoV-2 transmission hinges on antibody and viral RNA data that inform exposure and shedding, but extensive variation in assays, study group demographics and laboratory protocols across published studies confounds inference of true biological patterns. Our meta-analysis leverages 3214 datapoints from 516 individuals in 21 studies to reveal that seroconversion of both IgG and IgM occurs around 12 days post-symptom onset (range 1–40), with extensive individual variation that is not significantly associated with disease severity. IgG and IgM detection probabilities increase from roughly 10% at symptom onset to 98–100% by day 22, after which IgM wanes while IgG remains reliably detectable. RNA detection probability decreases from roughly 90% to zero by day 30, and is highest in feces and lower respiratory tract samples. Our findings provide a coherent evidence base for interpreting clinical diagnostics, and for the mathematical models and serological surveys that underpin public health policies.  more » « less
Award ID(s):
1557022
PAR ID:
10589606
Author(s) / Creator(s):
; ; ; ; ; ; ;
Publisher / Repository:
eLife
Date Published:
Journal Name:
eLife
Volume:
9
ISSN:
2050-084X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. To track COVID-19 immunity efficiently in point-of-care (POC) settings, we present a paper-based multiplexed vertical flow immunoassay (xVFA) along with a custom-designed serodiagnostic algorithm. During the development and testing of our algorithm, we utilized serum samples from individuals who had received mRNA-COVID-19 vaccines, tracking their antibody levels before and after each vaccine dose. By categorizing these samples based on their IgM and IgG levels into three categories (i.e., protected, unprotected, and infected), we trained and blindly evaluated a neural network-based algorithm for its inference accuracy. Leveraging this serodiagnostic algorithm, our cost-effective, paper-based xVFA platform swiftly measured the IgG and IgM levels from serum samples, facilitating the accurate monitoring of COVID-19 immunity levels. With its simple operation, scalability, and cost-effectiveness, our xVFA technology offers accessible COVID-19 serology testing to classify patients' immunity status rapidly. 
    more » « less
  2. Monitoring the level of COVID-19 immunity within populations is crucial for understanding the disease trend and guiding public health policies, as SARS-CoV-2 remains a threat. Serological testing is essential in assessing immunity by detecting antibodies, IgG, and IgM, the immune system's response developed against infection or after vaccination. To rapidly and cost-effectively monitor COVID-19 immunity levels, we developed a paper-based multiplexed vertical flow immunoassay (xVFA) which detects the IgG and IgM levels in less than 20 mins, aiming to monitor the COVID-19 immunity levels of individuals longitudinally and categorize immune levels into three groups: protected, unprotected, and infected. 
    more » « less
  3. Understanding protein adsorption behavior on rough and wrinkled surfaces is vital to applications including biosensors and flexible biomedical devices. Despite this, there is a dearth of study on protein interaction with regularly undulating surface topographies, particularly in regions of negative curvature. Here we report nanoscale adsorption behavior of immunoglobulin M (IgM) and immunoglobulin G (IgG) on wrinkled and crumpled surfaces via atomic force microscopy (AFM). Hydrophilic plasma treated poly(dimethylsiloxane) (PDMS) wrinkles with varying dimensions exhibit higher surface coverage of IgM on wrinkle peaks over valleys. Negative curvature in the valleys is determined to reduce protein surface coverage based both on an increase in geometric hindrance on concave surfaces, and reduced binding energy as calculated in coarse-grained molecular dynamics simulations. The smaller IgG molecule in contrast shows no observable effects on coverage from this degree of curvature. The same wrinkles with an overlayer of monolayer graphene show hydrophobic spreading and network formation, and inhomogeneous coverage across wrinkle peaks and valleys attributed to filament wetting and drying effects in the valleys. Additionally, adsorption onto uniaxial buckle delaminated graphene shows that when wrinkle features are on the length scale of the protein diameter, hydrophobic deformation and spreading do not occur and both IgM and IgG molecules retain their dimensions. These results demonstrate that undulating wrinkled surfaces characteristic of flexible substrates can have significant effects on protein surface distribution with potential implications for design of materials for biological applications. 
    more » « less
  4. Ovalbumin (OVA), one of the major allergens in hen egg, exhibits extensive structural heterogeneity due to a range of post-translational modifications (PTMs). However, analyzing the structural heterogeneity of native OVA is challenging, and the relationship between heterogeneity and IgG/IgE-binding of OVA remains unclear. In this work, ion exchange chromatography (IXC) with salt gradient elution and on-line detection by native electrospray ionization mass spectrometry (ESI MS) was used to assess the structural heterogeneity of OVA, while inhibition-ELISA was used to assess the IgG/IgE binding characteristics of OVA. Over 130 different OVA proteoforms (including glycan-free species and 32 pairs of isobaric species) were identified. Proteoforms with acetylation, phosphorylation, oxidation and succinimide modifications had reduced IgG/IgE binding capacities, whereas those with few structural modifications had higher IgG/IgE binding capacities. OVA isoforms with a sialic acid-containing glycan modification had the highest IgG/IgE binding capacity. Our results demonstrate that on-line native IXC/MS with salt gradient elution can be used for rapid assessment of the structural heterogeneity of proteins. An improved understanding of the relationship between IgG/IgE binding capacity and OVA structure provides a basis for developing biotechnology or food processing methods for reducing protein allergenicity reduction. 
    more » « less
  5. Abstract Novel methods that enable sensitive, accurate and rapid detection of RNA would not only benefit fundamental biological studies but also serve as diagnostic tools for various pathological conditions, including bacterial and viral infections and cancer. Although highly sensitive, existing methods for RNA detection involve long turn‐around time and extensive capital equipment. Here, an ultrasensitive and amplification‐free RNA quantification method is demonstrated by integrating CRISPR‐Cas13a system with an ultrabright fluorescent nanolabel, plasmonic fluor. This plasmonically enhanced CRISPR‐powered assay exhibits nearly 1000‐fold lower limit‐of‐detection compared to conventional assay relying on enzymatic reporters. Using a xenograft tumor mouse model, it is demonstrated that this novel bioassay can be used for ultrasensitive and quantitative monitoring of cancer biomarker (lncRNA H19). The novel biodetection approach described here provides a rapid, ultrasensitive, and amplification‐free strategy that can be broadly employed for detection of various RNA biomarkers, even in resource‐limited settings. 
    more » « less