bioRxiv Science⌕ Search

bioRxiv · 10.1101/2020.05.29.124776

Validation and Performance Comparison of Three SARS-CoV-2 Antibody Assays

Abstract

Serology testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increasingly being used during the current pandemic of Coronavirus Disease 2019 (COVID-19). The clinical and epidemiologic utilities of antibody-based SARS-CoV-2 testing are under debate. Characterizing these assays helps to understand the disease and provides scientific basis for deciding how to best use these assays. The study assessed one chemiluminescent assay (Abbott COVID-2 IgG) and two lateral flow assays (STANDARD Q [SQ] IgM/IgG Duo and Wondfo Total Antibody Test). Validation included 113 blood samples from 71 PCR-confirmed COVID-19 patients and 1182 samples from negative controls with potential interferences/cross-reactions, including 1063 pre-pandemic samples. IgM antibodies against SARS-CoV-2 were detected as early as post-symptom onset days 3-4. IgG antibodies were first detected post-onset days 5-6 by SQ assays. The detection rates increased gradually, and SQ IgG, Abbott IgG and Wondfo Total detected antibodies from all the PCR-confirmed patients 14 days after symptom onset. Overall agreements between SQ IgM/IgG and Wondfo Total was 88.5% and between SQ IgG and Abbott IgG was 94.6% (Kappa = 0.75, 0.89). No cross-reaction with other endemic coronavirus infections were identified. Viral hepatitis and autoimmune samples were the main cross-reactions observed. However, the interferences/cross-reactions were low. The specificities were 100% for SQ IgG and Wondfo Total and 99.62% for Abbott IgG and 98.87% for SQ IgM. These findings demonstrate high sensitivity and specificity of appropriately validated antibody-based SARS-CoV-2 assays with implications for clinical use and epidemiological seroprevalence studies.View Full Text

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lu, S., Paiva, K. J., Grisson, R. D., Chan, P. A., Lonks, J., King, E., Huard, R. C., Pytel-Parenteau, D. L., Nam, G. H., Yakirevich, E.. 2020-05-30. Validation and Performance Comparison of Three SARS-CoV-2 Antibody Assays. https://doi.org/10.1101/2020.05.29.124776

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Relative expression of THY1 and PDGFRA in equine endometrosis in relation to severity, histopathological features and endometrial transcripts

Equine endometrosis is a degenerative uterine disease characterized by periglandular fibrosis and represents a major cause of subfertility in mares. While stromal cell activation results in pathological tissue remodeling, the involvement of cell-surface integrators (THY1) and growth factor receptors (PDGFRA) was not researched. This study evaluated the relative mRNA expression of THY1 and PDGFRA across Kenney and Doig (KD) endometrosis categories and specific histopathological features. Additionally, transcriptomic correlation profiles between target genes and markers of myofibroblast differentiation (ACTA2), cellular proliferation (MKI67), and steroid hormone receptors (ESR1, PGR) were analyzed. Endometrial samples (n = 47) were quantified using RT-qPCR. Relative mRNA expression of THY1 differed significantly across KD categories (p = 0.014), exhibiting a transient upregulation in category IIA compared with category I (p = 0.009) and category IIB (p = 0.002). Furthermore, THY1 relative mRNA expression was significantly elevated in tissues with glandular basal lamina disruption (p = 0.022). Conversely, PDGFRA relative mRNA expression remained stable across disease categories (p > 0.05). THY1 relative mRNA expression correlated very strongly with ACTA2 ({rho} = 0.875, p < 0.001) and strongly with ESR1 ({rho} = 0.652, p < 0.001). PDGFRA relative mRNA expression exhibited a very strong positive correlation with ESR1 ({rho} = 0.864, p < 0.001) and a strong positive correlation with MKI67 ({rho} = 0.674, p < 0.001). These results indicate that THY1 transcription is transiently induced during early stromal remodeling and basal lamina loss, whereas PDGFRA maintains constitutive transcript stability. Observed co-expression profiles reflect statistical co-variation among stromal remodeling, proliferative, and steroid-responsive cell populations in bulk tissue.

pathology↗

sPLA2 inhibitor-loaded nanoparticles mitigate spontaneous osteoarthritis in guinea pigs

Osteoarthritis (OA) is a prevalent degenerative joint disease lacking effective disease-modifying therapies. Secreted phospholipase A2 (sPLA2), a key upstream regulator of inflammatory lipid mediators, has been implicated in OA pathogenesis, but its therapeutic potential in age-related OA remains unclear. Here, we evaluated the role of sPLA2 and the efficacy of nanoparticle-mediated sPLA2 inhibition in a spontaneous OA model using female Dunkin-Hartley (DH) guinea pigs. We first characterized OA progression and observed age-dependent increases in cartilage degeneration, synovitis, oxidative stress, and sPLA2 expression and enzymatic activity. We then developed sPLA2 inhibitor (thioetheramide-PC)-loaded nanoparticles (sPLA2i-NPs) and demonstrated their superior ability, compared to free inhibitor, to prevent IL-1{beta}-induced cartilage degeneration in guinea pig cartilage explants. In vivo, intra-articular administration of sPLA2i-NPs from 3 months of age significantly attenuated cartilage destruction, synovial inflammation, and osteophyte formation in 7- and 10-month-old guinea pigs. These structural improvements were accompanied by normalization of anabolic and catabolic gene expression and a marked reduction in synovial fluid sPLA2 activity. Importantly, longitudinal gait analysis revealed that sPLA2i-NP treatment preserved limb loading, propulsion, and locomotor performance, demonstrating functional recovery. No systemic toxicity was observed following long-term treatment. Collectively, our findings identify sPLA2 as a key driver of spontaneous OA and establish nanoparticle-mediated sPLA2 inhibition as a promising disease-modifying strategy for age-related OA.

pathology↗

Midlife nonlinearities across scale in Biondi body amyloid formation in the human choroid plexus

Human choroid plexus epithelial cells (CPECs), which produce cerebrospinal fluid and form the blood-cerebrospinal fluid barrier, accumulate discrete intracellular amyloid inclusions called Biondi bodies (BBs). Using systematic manual and machine learning approaches on the choroid plexus glomus, we determined the percentages of CPECs containing thioflavin S-stained BBs as well as BB load and spatial distributions in whole slide images from 77 cases across the human lifespan. On average, BB prevalence was near zero until age 40, rose steeply in the 5th and 6th decades, and exceeded 50% after age 70. As prevalence plateaued, BB load continued to rise with age. Accelerated BB accumulation was seen in two cases of diabetic ketoacidosis, including a 16-year-old, while an 85-year-old with the relatively rare APOE2/E2 genotype had fewer BBs than expected. BB prevalence in the choroid plexus glomus was not associated with Alzheimer's disease, but was lower in females than males. Notably, spatial clustering of BBs was universal across cases while nearest-neighbor analyses suggested cell-to-cell, prion-like BB spread that can account for the nonlinearities seen at tissue and population scales. The abrupt, nonlinear BB accumulation during midlife coincides with or precedes other common aging-associated neuropathologies of the human brain, consistent with broad BB and choroid plexus contributions to brain aging and disease.

pathology↗