Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of ...government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses (
= 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.
Abstract
Background
Histo-blood group antigens (HBGAs) such as fucosyltransferase (FUT)2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their ...offspring to pediatric enteric infections.
Methods
In 3 community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. Quantitative polymerase chain reaction panels tested 3663 diarrheal and 18 148 asymptomatic stool samples for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child (n = 520) and mothers’ (n = 519) HBGA status and hazard ratios (HRs) derived for all-cause diarrhea and specific enteropathogens.
Results
Children of secretor (FUT2 positive) mothers had a 38% increased adjusted risk of all-cause diarrhea (HR = 1.38; 95% confidence interval (CI), 1.15–1.66) and significantly reduced time to first diarrheal episode. Child FUT2 and FUT3 positivity reduced the risk for all-cause diarrhea by 29% (HR = 0.81; 95% CI, 0.71–0.93) and 27% (HR = 0.83; 95% CI, 0.74–0.92), respectively. Strong associations between HBGAs and pathogen-specific infection and diarrhea were observed, particularly for noroviruses, rotaviruses, enterotoxigenic Escherichia coli, and Campylobacter jejuni/coli.
Conclusions
Histo-blood group antigens affect incidence of all-cause diarrhea and enteric infections at magnitudes comparable to many common disease control interventions. Studies measuring impacts of interventions on childhood enteric disease should account for both child and mothers’ HBGA status.
The histo-blood group antigens of children and their mothers are determinants of diarrhea in early childhood. This study estimates the innate immunity provided by HBGA for principal etiologies of diarrhea and demonstrates altered risk for bacterial and viral enteropathogens.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has emphasized the importance and challenges of correctly interpreting antibody test results. Identification of positive and ...negative samples requires a classification strategy with low error rates, which is hard to achieve when the corresponding measurement values overlap. Additional uncertainty arises when classification schemes fail to account for complicated structure in data. We address these problems through a mathematical framework that combines high dimensional data modeling and optimal decision theory. Specifically, we show that appropriately increasing the dimension of data better separates positive and negative populations and reveals nuanced structure that can be described in terms of mathematical models. We combine these models with optimal decision theory to yield a classification scheme that better separates positive and negative samples relative to traditional methods such as confidence intervals (CIs) and receiver operating characteristics. We validate the usefulness of this approach in the context of a multiplex salivary SARS-CoV-2 immunoglobulin G assay dataset. This example illustrates how our analysis: (i) improves the assay accuracy, (e.g. lowers classification errors by up to 42% compared to CI methods); (ii) reduces the number of indeterminate samples when an inconclusive class is permissible, (e.g. by 40% compared to the original analysis of the example multiplex dataset) and (iii) decreases the number of antigens needed to classify samples. Our work showcases the power of mathematical modeling in diagnostic classification and highlights a method that can be adopted broadly in public health and clinical settings.
BACKGROUND
Hepatitis E virus (HEV) can inapparently infect blood donors. To assess transfusion transmission of HEV in the United States, which has not been documented, a donor‐recipient repository ...was evaluated.
STUDY DESIGN AND METHODS
To identify donations that contained HEV RNA and were linked to patient‐recipients with antibody evidence of HEV exposure, we assayed samples from the Retrovirus Epidemiology Donor Study (REDS) Allogeneic Donor and Recipient repository that represents 13,201 linked donations and 3384 transfused patients. Posttransfusion samples, determined to contain IgG anti‐HEV by enzyme‐linked immunosorbent assay, were reassayed along with corresponding pretransfusion samples for seroconversion (incident exposure) or at least fourfold IgG anti‐HEV increase (reexposure). HEV‐exposed patients were linked to donations in which HEV RNA was then detected by reverse‐transcription quantitative polymerase chain reaction, confirmed by transcription‐mediated amplification, and phylogenetically analyzed as subgenomic cDNA sequences.
RESULTS
Among all patients, 19 of 1036 (1.8%) who had IgG anti‐HEV before transfusion were reexposed; 40 of 2348 (1.7%) without pretransfusion IgG anti‐HEV seroconverted. These 59 patients were linked to 257 donations, 1 of which was positive by reverse‐transcription quantitative polymerase chain reaction and transcription‐mediated amplification. Plasma from this donation contained 5.5 log IU/mL of HEV RNA that grouped with HEV genotype 3, clade 3abchij. The patient‐recipient of RBCs from this donation had a greater than eightfold IgG increase; however, clinical data are unavailable.
CONCLUSIONS
This is the first report of probable HEV transmission via transfusion in the United States, although it has been frequently observed in Europe and Japan. Additional data on the magnitude of the risk in the United States are needed.
The optimal approach to COVID-19 surveillance in congregate populations remains unclear. Our study at the US Naval Academy in Annapolis, Maryland, USA, assessed the concordance of antibody prevalence ...in longitudinally collected dried blood spots and saliva in a setting of frequent PCR-based testing. Our findings highlight the utility of salivary-based surveillance.
North Carolina is the second leading state in pork production in the United States, with over 10 million swine. Swine manure in NC is typically collected and stored in open-pit lagoons before the ...liquid waste is sprayed onto agricultural fields for disposal. Components of this waste may be able to impact surface water quality with the potential for human exposure. This study examined viruses of public health concern in creeks adjacent to swine concentrated animal feeding operation (CAFO) spray fields. Surface water samples (n=154) were collected from public access waters in proximity to swine CAFO spray fields for six months and were tested for hepatitis E virus (HEV) and coliphages. HEV was detected in one sample. Somatic coliphages were detected in 98% of samples (geometric mean 24±4.1PFU per 100ml), and F+ coliphages were detected in 85% of samples (geometric mean 6.8±5.0PFU per 100ml). Only 3% (21) of the F+ coliphage isolates were RNA phage, and all of the F+ RNA coliphages belonged to genogroup I. Although the pervasiveness of swine CAFOs in this area prevented a comparison with samples from un-impacted sites, the near ubiquity of coliphages, as well as the presence of HEV, suggests that current waste management practices may be associated with the dissemination of viruses of public health concern in waters proximal to CAFO spray fields.
Display omitted
•Hepatitis E virus was detected in one sample.•Somatic coliphages were detected in 98% of samples.•F+ coliphages were detected in 85% of samples.•21 F+ coliphage isolates (3%) were RNA phage, which all belonged to genogroup I.
Swine production work is a risk factor for nasal carriage of livestock-associated (LA-) Staphylococcus aureus and also for skin and soft tissue infection (SSTI). However, whether LA-S. aureus nasal ...carriage is associated with increased risk of SSTI remains unclear. We aimed to examine S. aureus nasal carriage and recent (≤3 months prior to enrollment) SSTI symptoms among industrial hog operation (IHO) workers and their household contacts. IHO workers and their household contacts provided a nasal swab and responded to a questionnaire assessing self-reported personal and occupational exposures and recent SSTI symptoms. Nasal swabs were analyzed for S. aureus, including methicillin-resistant S. aureus (MRSA), multidrug-resistant-S. aureus (MDRSA), absence of scn (livestock association), and spa type. S. aureus with at least one indicator of LA was observed among 19% of 103 IHO workers and 6% of 80 household members. Prevalence of recent SSTI was 6% among IHO workers and 11% among 54 minor household members (0/26 adult household members reported SSTI). Among IHO workers, nasal carriers of MDRSA and scn-negative S. aureus were 8.8 (95% CI: 1.8, 43.9) and 5.1 (95% CI: 1.2, 22.2) times as likely to report recent SSTI as non-carriers, respectively. In one household, both an IHO worker and child reported recent SSTI and carried the same S. aureus spa type (t4976) intranasally. Prevalence of scn-negative S. aureus (PR: 5.0, 95% CI: 1.2, 21.4) was elevated among IHO workers who reported never versus always wearing a face mask at work. Although few SSTI were reported, this study of IHO workers and their household contacts is the first to characterize a relation between nasal carriage of antibiotic-resistant LA-S. aureus and SSTI. The direction and temporality of this relation and IHO workers' use of face masks to prevent nasal carriage of these bacteria warrant further investigation.
Transmission of livestock-associated Staphylococcus aureus clonal complex 9 (LA-SA CC9) between pigs raised on industrial hog operations (IHOs) and humans in the United States is poorly understood. ...We analyzed whole-genome sequences from 32 international S. aureus CC9 isolates and 49 LA-SA CC9 isolates from IHO pigs and humans who work on or live near IHOs in 10 pig-producing counties in North Carolina, USA. Bioinformatic analysis of sequence data from the 81 isolates demonstrated 3 major LA-SA CC9 clades. North Carolina isolates all fell within a single clade (C3). High-resolution phylogenetic analysis of C3 revealed 2 subclades of intermingled IHO pig and human isolates differing by 0-34 single-nucleotide polymorphisms. Our findings suggest that LA-SA CC9 from pigs and humans share a common source and provide evidence of transmission of antimicrobial-resistant LA-SA CC9 between IHO pigs and humans who work on or live near IHOs in North Carolina.
Industrial livestock operations (ILOs), particularly processing facilities, emerged as centers of coronavirus disease 2019 (COVID-19) outbreaks in spring 2020. Confirmed cases of COVID-19 ...underestimate true prevalence. To investigate the prevalence of antibodies against SARS-CoV-2, we enrolled 279 participants in North Carolina from February 2021 to July 2022: 90 from households with at least one ILO worker (ILO), 97 from high-ILO intensity areas (ILO neighbors ILON), and 92 from metropolitan areas (metro). More metro (55.4%) compared to ILO (51.6%) and ILON participants (48.4%) completed the COVID-19 primary vaccination series; the median completion date was more than 4 months later for ILO compared to ILON and metro participants, although neither difference was statistically significant. Participants provided a saliva swab we analyzed for SARS-CoV-2 IgG using a multiplex immunoassay. The prevalence of infection-induced IgG (positive for nucleocapsid and receptor binding domain) was higher among ILO (63%) than ILON (42.9%) and metro (48.7%) participants (prevalence ratio PR, 1.38; 95% confidence interval CI, 1.06 to 1.80; reference category ILON and metro combined). The prevalence of infection-induced IgG was also higher among ILO participants than among an Atlanta health care worker cohort (PR, 2.45; 95% CI, 1.80 to 3.33) and a general population cohort in North Carolina (PRs, 6.37 to 10.67). The infection-induced IgG prevalence increased over the study period. Participants reporting not masking in public in the past 2 weeks had higher infection-induced IgG prevalence (78.6%) than participants reporting masking (49.3%) (PR, 1.59; 95% CI, 1.19 to 2.13). Lower education, more people per bedroom, Hispanic/Latino ethnicity, and more contact with people outside the home were also associated with higher infection-induced IgG prevalence.
Few studies have measured COVID-19 seroprevalence in North Carolina, especially among rural, Black, and Hispanic/Latino communities that have been heavily affected. Antibody results show high rates of COVID-19 among industrial livestock operation workers and their household members. Antibody results add to evidence of health disparities related to COVID-19 by socioeconomic status and ethnicity. Associations between masking and physical distancing with antibody results also add to evidence of the effectiveness of these prevention strategies. Delays in the timing of receipt of COVID-19 vaccination reinforce the importance of dismantling vaccination barriers, especially for industrial livestock operation workers and their household members.
Antinucleocapsid (anti-N) immunoglobulin G antibody responses were lower in plasma and oral fluid after severe acute respiratory syndrome coronavirus 2 infection in vaccinated patients compared with ...patients infected before vaccination or infected without vaccination. This raises questions about the long-term use of anti-N antibodies as a marker for natural infection for surveillance.
PDF
