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Chi, J.

Publications and source records attributed to Chi, J..

At least 19 recordsLinked to original sources
bioRxiv2026

Akkermansia muciniphila prevents cadmium-induced cognitive impairment through gut microbiome mediated mechanisms

Akkermansia muciniphila has emerged as a promising next-generation probiotic with beneficial effects on learning and memory, but whether and how it can protect against environmental toxicant-induced cognitive impairment remains unknown. Cadmium (Cd) is a widespread environmental neurotoxicant that disrupts the gut-brain axis and impairs hippocampus-dependent learning and memory, yet effective preventive interventions are lacking. In this study, we discovered that oral supplementation with human fecal microbiome-derived A. muciniphila prevented Cd-induced cognitive impairment in mice throughout 9 weeks of oral Cd exposure at a human body burden-relevant concentration. Notably, brain Cd concentrations were not affected by A. muciniphila supplementation, indicating that cognitive protection was mediated through gut-brain signaling rather than affecting metal accumulation in the brain. Multi-omics characterization identified coordinated gut-brain pathways underlying this protective effect. A. muciniphila preserved Cd-suppressed Lactobacillus taxa (L. crispatus, L. intestinalis, L. taiwanensis), which positively correlated with cognitive performance, and restored intestinal tight-junction integrity across multiple intestinal sections, particularly the ileum. A. muciniphila also normalized Cd-induced cytokine dysregulation in the serum. In addition, colonic branched-chain fatty acids (BCFAs) emerged as candidate gut-brain mediators, with 2-methylpentanoic acid showing a robust negative correlation with cognitive performance. These A. muciniphila-mediated changes across gut microbiome, intestinal barrier, systemic cytokines, and microbial metabolites coincided with reversal of Cd-induced hippocampal transcriptional alterations regulating synaptic and vascular signaling. Together, this study identified A. muciniphila as a preventive microbiome-based strategy against environmental Cd neurotoxicity in mice, demonstrated that the gut microbial homeostasis can confer cognitive resilience independently of brain toxicant burden, and revealed distinct BCFAs as potential gut-brain mediators of heavy-metal-induced cognitive decline.

pharmacology and toxicology↗
bioRxiv2026

O-GlcNAcylation regulates PPAR-driven metabolic programming in intestinal stem cells

Diet deeply influences health and disease risk by reshaping cellular metabolism. In the intestine, dietary nutrients directly affect intestinal stem cell (ISC) behavior, yet the regulatory mechanisms linking metabolism to transcriptional control remain poorly defined. Because mitochondria function as central metabolic hubs, we focused on mitochondrial signaling to understand how nutrient utilization governs ISC function. Using the MITO-Tag mouse, we isolated metabolites specifically from ISC mitochondria and found that the sugar-derived metabolite UDP-GlcNAc was reduced in ISCs from mice fed a high-fat diet. Moreover, we identified that reducing O-GlcNAcylation (OGN) rapidly increased stem cell frequency, proliferation, regenerative capacity, and the abundance of PPAR target proteins. Mechanistically, these effects depend on PPAR signaling, as genetic loss of Ppar-d/a blocks the ISC phenotypes induced by reduced OGN. These results reveal an OGN-PPAR signaling axis that translates dietary metabolic cues into transcriptional programs governing fuel utilization and ISC behavior in the intestine. Collectively, our findings highlight that OGN is a previously unrecognized regulator of PPAR signaling in intestinal stem cells.

cell biology↗
bioRxiv2026

Erythropoietin Mediates Glycerophospholipid Remodeling During Human Early Erythropoiesis

The unique biconcave morphology and deformability of mature red blood cells (RBCs) require a specific membrane lipid composition. Disruption of this special lipid profile is seen in multiple types of anemia and bone marrow (BM) failure diseases, yet molecular mechanisms regulating lipid metabolism during normal erythroid differentiation remain poorly defined. Here, we identify a previously undescribed role for erythropoietin (Epo) in contributing to the appropriate lipid composition of differentiating human erythroid cells. Using single-cell transcriptomic profiling of ex vivo cultures of human BM-derived hematopoietic stem and progenitor cells cultured with or without Epo, we delineated transcriptional dynamics across differentiation stages, identifying the Epo-dependent transition of burst-forming unit erythroid (BFU-E) to colony-forming unit erythroid (CFU-E) progenitors. Comparative analysis revealed the activation of canonical erythroid programs involving heme biosynthesis, globin expression, and iron regulation, and additionally, uncovered a transient upregulation of lipid metabolic pathways during the BFU-E to CFU-E transition. Complementary untargeted lipidomics demonstrated Epo-dependent alterations in specific glycerophospholipid (GPL) species, consistent with differential expression of GPL biosynthesis genes in the single cell dataset. Intracellular flow cytometry further confirmed the requirement of Epo for maintaining enzymes critical for phosphatidylcholine and phosphatidylethanolamine synthesis in erythroid cells. Together, these multiomic findings reveal a new role for Epo in modulating lipid metabolism during early erythropoiesis and provide mechanistic insight into how membrane lipid composition is dynamically regulated to support normal red cell development.

cell biology↗
bioRxiv2025

Glucose and Oxygen Metabolism Coordinate Human Cortical Developmental Decisions

Defining metabolic regulation of neurodevelopmental programs is essential to approach developmental disorders and injuries driven by alterations in metabolism. In vitro cultures are the only available method to temporally perturb and study living human brain cells throughout neurogenesis, however most culture systems use supraphysiologic conditions of essential nutrients, glucose and oxygen. We probed how environmental exposure to endogenous-like concentrations impact metabolic state and developmental progression of cortical cell types using organoids. Nutrient accessibility globally impacted metabolic state, yet developmental responses to metabolic changes were cell type-specific. Metabolomic and transcriptomic datasets reveal increased TCA metabolites and amino acids and oxidative phosphorylation (OXPHOS) genes, under physiologic glucose conditions. Oxygen level had a modest, yet specific, molecular impact on deep layer excitatory neurons. We assessed consequences of metabolic changes on fate and observed that physiologic glucose expanded the human-enriched population of cortical stem cells, outer radial glia, and their progeny, upper layer excitatory neurons. Alterations in oxygen, instead, affected production of neurogenic progenitors and neuronal differentiation, with higher oxygen availability supporting shifts toward mitochondrial metabolism necessary for maturing cell types. We functionally tested this transition by inhibiting glycolysis; total inhibition promoted neuronal differentiation, whereas inhibition of anaerobic glycolysis/lactate production led to oRG expansion. Lactate signaling was sufficient to suppress oRG development and promote self-renewal of neurogenic progenitors. These data suggest that refined metabolic switches and decreased reliance on glucose are required for transition from stem cell self-renewal to more mature, diversified progenitor subtypes, where switch from anaerobic to aerobic metabolism discretely impacts progenitor diversification.

neuroscience↗
bioRxiv2025

Vagal volume receptors in the heart compensate for blood loss and posture change

Cranial nerves densely innervate the heart and vasculature, with sensory neurons reporting on blood pressure, respiratory gases, and tissue damage1. The roles of arterial baroreceptors in systemic physiology are well appreciated2, but the functions of vagal cardiac mechanoreceptors have been more difficult to parse, in part due to the closed-loop structure of the cardiovascular system. Here, we use genetic tools for isolated study of vagal mechanoreceptors in the heart, finding that they are acutely sensitive to circulating blood volume and play key roles in compensating for decreased filling of the heart that occurs in an upright posture and during hemorrhage. Vagal PIEZO2 neurons form characteristic end-net endings in the heart and display blood volume-dependent responses with every heartbeat that are timelocked to atrial and ventricular systole. Vagal PIEZO2 knockout eliminates heartbeatcoupled nerve activity, and compromises carotid blood pressure when mice on a tilttable are rotated to an upright position. Vagal PIEZO2 knockout mice also display a lethal failure to sustain blood pressure during trauma-induced blood loss. Together, these findings demonstrate an essential function for vagal cardiac mechanoreceptors in sustaining the constancy of blood circulation.

neuroscience↗
bioRxiv2025

Butyrate rescues chlorpyrifos-induced social deficits through inhibition of class I histone deacetylases

Chlorpyrifos (CPF) is a widely used organophosphate pesticide effective through inhibiting acetylcholinesterase, which leads to the accumulation of acetylcholine and continuous nerve stimulation. In addition to its well-known acute toxicity, exposure to CPF has also been linked to chronic conditions such as an increasing risk of autism spectrum disorder (ASD) and adverse effects on gut health, including disturbances to the gut microbiome and metabolism. However, the underlying mechanism of CPFs contribution to ASD remains unclear, and the roles of the gut microbiome and gut metabolites in CPF-induced neurodevelopmental toxicity remain elusive. Using a high-throughput social behavior assay, we found that embryonic exposure to CPF induced lasting social deficits in zebrafish. Through a small-scale screen of common health beneficial gut microbiome metabolites, we discovered that butyrate effectively rescued CPF-induced social deficits. RNA sequencing of zebrafish brain tissues revealed that early exposure to CPF induced a lasting suppression of neuronal genes, including many ASD risk genes, and elevated expression of circadian genes. Butyrate partially reversed the suppression of key neuronal genes. Butyrate is a non-selective inhibitor of histone deacetylases (HDACs). Through a series of loss-of-function experiments utilizing CRISPR-Cas9-induced knockouts and selective chemical inhibitors, we found that the class I HDAC, HDAC1, most likely mediates butyrates rescue effect. Metabolomics analysis detected changes in several nitrogen metabolism-related pathways in the zebrafish gut following CPF exposure. Metagenomics analysis revealed an increase in abundance of the denitrifying bacteria Pseudomonas and a reduction in the nitric oxide-sensitive bacteria Aeromonas in the CPF-exposed zebrafish gut microbiome. Our results connect CPF-exposure with changes in the gut microbiome, metabolome, epigenetics, gene expression, and behavior, inspiring a novel hypothesis for the underlying molecular mechanisms of CPF-induced neurodevelopmental toxicity. In the long run, our findings may help elucidate how CPF exposure contributes to autism risk and inspire therapeutic developments.

neuroscience↗
bioRxiv2025

In vivo exposure of mixed microplastic particles in mice and its impacts on the murine gut microbiome and metabolome

Microplastics (MPs) are emerging environmental contaminants due to increasing global plastic production and waste. Microplastics, defined as plastic particles less than 5 mm in diameter, are formed through degradation of larger plastics via sunlight, weathering, and microbes. These plastic compounds are widely detected in water, soil, food, as well as human stool and blood. The gut microbiome, often referred to as our second genome, is important in human health and is the primary point of contact for orally ingested microplastics. To investigate the impact of ingested MPs on the gut microbiome and the metabolome, 8 weeks-old male and female C57/BL6 mice were orally gavaged mixed plastic (5 um) exposure consisting of polystyrene, polyethylene, and the biodegradable/biocompatible plastic, poly-(lactic-co-glycolic acid) twice a week for 4 weeks at 0, 2, or 4 mg/week (n = 8/group). Fecal pellets were collected for bacterial DNA extraction and metagenomic shotgun sequencing, and serum was subjected to targeted and untargeted metabolomics. MPs exposure resulted in significant sex-specific and dose-dependent changes to the gut microbiome composition along with substantial regulation of the predicted metabolic pathways. Untargeted metabolomics in serum showed that a low MPs dose displayed a more prominent effect on key metabolic pathways such as amino acid metabolism, mitochondrial function, and inflammation. Additionally, SCFA-targeted metabolomics showed significant changes in neuroprotective SCFAs levels in both sexes by MPs exposure. In conclusion, our study has demonstrated that microplastics dysregulate the gut microbiome and serum metabolome, providing critical insights into potential human disease risks associated with microplastic contamination.

pharmacology and toxicology↗
bioRxiv2025

Exercise Conditioning Enhances Insulin Sensitivity with Metabolic and Glycemic Control Driven by Hepatic Silencing of HMGB1 in Type 2 Diabetic Mice

Type 2 Diabetes (T2D) is characterized by chronic insulin resistance and inflammation. Exercise induces hyperglycemia control in T2D more than pharmacologic therapies alone. High Mobility Group Box 1 (HMGB1) is a ubiquitous nuclear factor for T2D progression. We hypothesize that hepatic silencing of HMGB1 in T2D and exercise will increase insulin sensitivity and shift metabolic routes, decrease liver damage and improve metabolic health in T2D mice. MethodsLiver HMGB1 KO (HMGB1{Delta}) was induced with AAV8-TBG in HMGB1 flox mice (AAV8-EGFP was used as wildtype controls). T2D mice were induced with a low-dose STZ and a high-fat diet. T2D mice ran for four weeks (1hr daily). Dual Energy X-Ray Absorptiometry (DEXA), A1C, glycemia, HMGB1, metabolomics and metabolic cage analysis were performed pre- and post-exercise. RT-PCR, immunoblotting and immunohistochemistry for glucose metabolism markers were performed in tissue samples. ResultsT2D HMGB1{Delta} mice show 20% less hyperglycemia compared to controls with a strong correlation between reduced HMGB1 levels and lower A1C following exercise. Additionally, fat percentage, liver damage, and glycogen storage were significantly reduced. These findings highlight the high potential effect of exercise potentiated has via HMGB1 governed mechanisms and highlights HMGB1 as a therapeutic target for managing hyperglycemia in T2D. ARTICLE HIGHLIGHTSHMGB1 hepatic silencing in Type 2 Diabetic mice is a promising therapeutic target for enhancing Insulin sensitivity. Combination of hepatic HMGB1 silencing and exercise potentiates the metabolic benefits and liver protection in Type 2 Diabetic mice. Shift in metabolic routes and carbohydrate metabolism due to regulation of hepatic HMGB1 expression makes HMGB1 an ideal target for pharmacologic intervention. However, our study also underscores the value of exercise as the primary focus of diabetic glucose control aided by enhanced therapeutic targeting of HMGB1 for chronic inflammation and hyperglycemia.

molecular biology↗
bioRxiv2025

CD2 expression is co-regulated with stemness- and exhaustion-associated factors in human T cells

The CD2-CD58 pathway has been highlighted as a major player in anti-tumour T cell immunity. Our study reveals that CD2 costimulation strength significantly correlates with T cell activation, the average number of cell divisions, fold expansion, and IFN-{gamma} production. Our findings suggest that the correlation of CD2 strength with the level of CD25 expression is a potential regulatory mechanism by which CD2 strength enhances above proliferation parameters. We find that human brain cancer tumour-infiltrating CD8+ and CD4+ T cells exhibit reduced levels of CD2, suggestive of a compromised CD2 strength upon CD2 engagement. Through a genome-wide CRISPR-Cas9 knockout screen, we identified two epigenetic regulators, SUZ12 and BAP1, as positive modulators of CD2 expression. We demonstrate that BAP1 is crucial for the upregulation and sustained high expression of CD2 following T cell activation. We reveal that CD2 is co-regulated with other co-stimulatory/inhibitory receptors, and factors associated with T cell stemness and exhaustion, in a dose-dependent manner. Importantly, we rescue the loss of CD2 due to BAP1 knockout by pharmacological inhibition of histone deacetylases making this a harnessable regulatory pathway. The insight from our study enhance our understanding of CD2-mediated T cell regulation and identify essential regulators of this pathway.

immunology↗
bioRxiv2024

Maternal dietary deficiencies in folic acid and choline change metabolites levels in offspring after ischemic stroke

Ischemic stroke is a debilitating disease, with nutrition being a modifiable risk factor. Changes in levels of metabolites can be used to measure the alterations in the gut, a significant marker for the etiology of diseases. This study utilized untargeted metabolomics to investigate changes in fecal samples of offspring in response to maternal dietary deficiencies and ischemic stroke. Female mice were placed on control (CD), folic acid- (FADD), or choline-deficient (ChDD) diets prior to, during pregnancy, and lactation. Offspring were weaned on to CD and at 2 months of age an ischemic stroke was induced. Fecal samples were collected prior to ischemic stroke, and at 1- and 4-weeks post-stroke for analysis. Sex and maternal dietary differences in metabolites were observed at both the 1- and 4-week post-stroke timepoints. At the 1-week post-stroke, female FADD offspring had more changes in metabolites than males. Comparatively, at the 4-week post-stroke timepoint, female offspring on either FADD or ChDD demonstrated metabolite changes. This study demonstrates a long-lasting impact of maternal dietary deficiencies on central nervous system and gut microbiome function after ischemic stroke. Summary StatementOur study investigated metabolite changes in female and male offspring fecal samples from mothers maintained on folic acid or choline deficient diet. We report that female offspring metabolite levels were impacted.

neuroscience↗
bioRxiv2024

Interplay of IGF1R and estrogen signaling regulates hematopoietic stem and progenitor cells

Tissue stem cells often exhibit developmental stage-specific and sexually dimorphic properties, but the underlying mechanism remains largely elusive. By characterizing IGF1R signaling in hematopoietic cells, here we report that its disruption exerts sex-specific effects in adult hematopoietic stem and progenitor cells (HSPCs). Loss of IGF1R decreases the HSPC population in females but not in males, in part due to a reduction in HSPC proliferation induced by estrogen. In addition, the adult female microenvironment enhances engraftment of wild-type but not Igf1r-null HSPCs. In contrast, during gestation, when both female and male fetuses are exposed to placental estrogens, loss of IGF1R reduces the numbers of their fetal liver HSPCs regardless of sex. Collectively, these data support the interplay of IGF1R and estrogen pathways in HSPCs and suggest that the proliferation-promoting effect of estrogen on HSPCs is in part mediated via IGF1R signaling.

cell biology↗
bioRxiv2022

Control of lipolysis by a population of oxytocinergic sympathetic neurons

Oxytocin (OXT), a nine amino acid peptide produced in the hypothalamus and released by the posterior pituitary, has well-known actions in parturition, lactation, and social behavior1, and has become an intriguing therapeutic target for diseases like autism and schizophrenia2. Exogenous OXT has also been shown to promote weight loss, among other beneficial metabolic effects1,3, suggesting that its therapeutic potential may extend to diabetes and obesity1,4. It is unclear, however, whether endogenous OXT participates in metabolic homeostasis. Here we show that OXT is a critical regulator of adipose tissue lipolysis in both mice and humans. In addition, OXT serves to license the ability of {beta}- adrenergic agonists to fully promote lipolysis. Most surprisingly, the relevant source of OXT in these metabolic actions is a previously unidentified subpopulation of tyrosine hydroxylase (TH)-positive sympathetic neurons. Our data reveal that OXT from the peripheral nervous system is an endogenous regulator of adipose and systemic metabolism.

physiology↗
bioRxiv2022

Yeast U6 snRNA made by RNA polymerase II is less stable but functional

U6 small nuclear (sn)RNA is the shortest and most conserved snRNA in the spliceosome and forms a substantial portion of its active site. Unlike the other four spliceosomal snRNAs, which are synthesized by RNA polymerase (RNAP) II, U6 is made by RNAP III. To determine if some aspect of U6 function is incompatible with synthesis by RNAP II, we created a U6 snRNA gene with RNAP II promoter and terminator sequences. This "U6-II" gene is functional as the sole source of U6 snRNA in yeast, but its transcript is much less stable than U6 snRNA made by RNAP III. Addition of the U4 snRNA Sm protein binding site to U6-II increased its stability and led to formation of U6-II*Sm complexes. We conclude that synthesis of U6 snRNA by RNAP III is not required for its function and that U6 snRNPs containing the Sm complex can form in vivo. The ability to synthesize U6 snRNA with RNAP II relaxes sequence restraints imposed by intragenic RNAP III promoter and terminator elements and allows facile control of U6 levels via regulators of RNAP II transcription.

molecular biology↗
bioRxiv2021

Fine-grained, nonlinear image registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes

We present an application of non-linear Image registration that allows spatiotemporal analysis of extremely noisy and diffuse molecular processes across the entire cell. To produce meaningful local tracking of the spatially coherent portion of diffuse protein dynamics, we improved upon existing non-linear image registration to compensate for cell movement and deformation. The registration relies on a subcellular fiducial marker, a cell motion mask, and a topological regularization that enforces diffeomorphism on the registration without significant loss of granularity. We demonstrate the potential of this approach in conjunction with stochastic time-series analysis through the discovery of distinct zones of coherent Profillin dynamics in symmetry-breaking U2OS cells. Further analysis of the resulting Profilin dynamics revealed strong relationships with the underlying actin organization. This study thus provides a framework for extracting functional interactions between cell morphodynamics, protein distributions, and signaling in cells undergoing continuous shape changes. Author SummaryBy adapting optical flow based nonlinear image registration we created a method specific for live cell movies that preserves the dynamics of a signal of interest by remapping using a separate measurable subcellular location fiducial. This is an extension as well on our labs previously published method of cell edge-based referencing of subcellular locations that was incapable of extracting interpretable subcellular time series more than a few microns away from the cell edge. We showed that our method overcomes this key limitation and allows sampling of subcellular time series from every subcellular location through our discovery of organized profilin dynamics in moving cell and that these profilin dynamics are related to actin dynamics due to their ability to bind growing actin structures likely through actin polymerizing factors. Most importantly, our method is applicable to discovering subcellular organization and coordination in a widely used form of live cell microscopy data that hitherto has been largely limited to anecdotal analysis.

bioinformatics↗
bioRxiv2021

Inference of Granger-causal relations in molecular systems -- a case study of the functional hierarchy among actin regulators in lamellipodia

Many cell regulatory systems implicate nonlinearity and redundancy among components. The regulatory network governing lamellipodial and lamellar actin structures is prototypical of such a system, containing tens of actin-nucleating and -modulating molecules with functional overlap and feedback loops. Due to instantaneous and long-term compensation, phenotyping the system response to perturbation provides limited information on the roles the targeted component plays in the unperturbed system. Accordingly, how individual actin regulators contribute to lamellipodial dynamics remains ambiguous. Here, we present a perturbation-free reconstruction of cause-effect relations among actin regulators by applying Granger-causal inference to constitutive image fluctuations that indicate regulator recruitment as a proxy for activity. Our analysis identifies distinct zones of actin regulator activation and of causal effects on filament assembly and delineates actin-dependent and actin-independent regulator roles in controlling edge motion. We propose that edge motion is driven by assembly of two independently operating actin filament systems. A record of this papers Transparent Peer Review process is included in the Supplemental Information.

cell biology↗
bioRxiv2021

Blebs Promote Cell Survival by Assembling Oncogenic Signaling Hubs

Most human cells require anchorage for survival. Cell-substrate adhesion activates diverse signaling pathways, without which cells undergo anoikis - a form of programmed cell death1. Acquisition of anoikis resistance is a pivotal step in cancer disease progression, as metastasizing cancer cells often lose firm attachment to surrounding tissue2-5. In these poorly attached states, cells adopt rounded morphologies and form small hemispherical plasma membrane protrusions called blebs6-13. Bleb function has been thoroughly investigated in the context of amoeboid migration but is far less examined in other scenarios14-19. Here we show by quantitative subcellular 3D imaging and manipulation of cell morphological states that blebbing triggers the formation of plasma membrane-proximal signaling hubs that confer anoikis resistance. Specifically, we discovered in melanoma cells that blebbing generates plasma membrane contours, which recruit curvature-sensing septin proteins as scaffolds for constitutively active mutant NRAS and effectors. These signaling hubs activate ERK and PI3K - canonical promoters of pro-survival pathways. Inhibition of blebs or septins has little effect on the survival of well-adhered cells, but in detached cells causes NRAS mislocalization, reduced MAPK and PI3K activity, and ultimately, death. This unveils an unanticipated morphological requirement for mutant NRAS to operate as an effective oncoprotein. Moreover, we find that though some BRAF mutant melanoma do not rely on this survival pathway in a basal state, BRAF/MEK inhibition strongly sensitizes them to both bleb and septin inhibition. Importantly, we demonstrate that fibroblasts engineered to sustain blebbing acquire the same anoikis resistance as cancer cells even without harboring oncogenic mutations. These data define a role for blebs as potent signaling organelles capable of integrating myriad cellular information flows into concerted cellular responses, in this case granting robust anoikis resistance.

cell biology↗
bioRxiv2021

Antibody Conversion rates to SARS-CoV-2 in Saliva from Children Attending Summer Schools in Barcelona, Spain

Surveillance tools to estimate infection rates in young populations are essential to guide recommendations for school reopening and management during viral epidemics. Ideally, field-deployable non-invasive, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We determined SARS-CoV-2 antibody conversion by high-throughput Luminex assays in saliva samples collected weekly in 1,509 children and 396 adults in 22 Summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st 2020, between the first and second COVID-19 pandemic waves. Saliva antibody conversion defined as [≥]4-fold increase in IgM, IgA and/or IgG levels to SARS-CoV-2 antigens between two visits over a 5-week period was 3.22% (49/1518), or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. To conclude, saliva antibody profiling including three isotypes and multiplexing antigens is a useful and more user-friendly tool for screening pediatric populations to determine SARS-CoV-2 exposure and guide public health policies during pandemics.

immunology↗