Evaluation of Dried Blood Spot Testing for SARS-CoV-2 Serology Using a Quantitative Commercial Assay.
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ABSTRACT:
SUBMITTER: Brinc D
PROVIDER: S-EPMC8224688 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The true severity of infection due to COVID-19 is under-represented because it is based on only those who are tested. Although nucleic acid amplifications tests (NAAT) are the gold standard for COVID-19 diagnostic testing, serological assays provide better population-level SARS-CoV-2 prevalence estimates. Implementing large sero-surveys present several logistical challenges within Canada due its unique geography including rural and remote communities. Dried blood spot (DBS) sampling is a practical solution but comparative performance data on SARS-CoV-2 serological tests using DBS is currently lacking. Here we present test performance data from a well-characterized SARS-CoV-2 DBS panel sent to laboratories across Canada representing 10 commercial and 2 in-house developed tests for SARS-CoV-2 antibodies. Three commercial assays identified all positive and negative DBS correctly corresponding to a sensitivity, specificity, positive predictive value, and negative predictive value of 100% (95% CI = 72.2, 100). Two in-house assays also performed equally well. In contrast, several commercial assays could not achieve a sensitivity greater than 40% or a negative predictive value greater than 60%. Our findings represent the foundation for future validation studies on DBS specimens that will play a central role in strengthening Canada's public health policy in response to COVID-19.
| S-EPMC8651133 | biostudies-literature
Project description:BackgroundSince 2020 SARS-CoV-2 spreads pandemically, infecting more than 119 million people, causing >2·6 million fatalities. Symptoms of SARS-CoV-2 infection vary greatly, ranging from asymptomatic to fatal. Different populations react differently to the disease, making it very hard to track the spread of the infection in a population. Measuring specific anti-SARS-CoV-2 antibodies is an important tool to assess the spread of the infection or successful vaccinations. To achieve sufficient sample numbers, alternatives to venous blood sampling are needed not requiring medical personnel or cold-chains. Dried-blood-spots (DBS) on filter-cards have been used for different studies, but not routinely for serology.MethodsWe developed a semi-automated protocol using self-sampled DBS for SARS-CoV-2 serology. It was validated in a cohort of matched DBS and venous-blood samples (n = 1710). Feasibility is demonstrated with two large serosurveys with 10247 company employees and a population cohort of 4465 participants.FindingsSensitivity and specificity reached 99·20% and 98·65%, respectively. Providing written instructions and video tutorials, 99·87% (4465/4471) of the unsupervised home sampling DBS cards could be analysed.InterpretationDBS-sampling is a valid and highly reliable tool for large scale serosurveys. We demonstrate feasibility and accuracy with a large validation cohort including unsupervised home sampling. This protocol might be of big importance for surveillance in resource-limited settings, providing low-cost highly accurate serology data.FundingProvided by Bavarian State Ministry of Science and the Arts, LMU University-Hospital; Helmholtz-Centre-Munich, German Ministry for Education and Research (project01KI20271); University of Bonn; University of Bielefeld; the Medical Biodefense Research Program of Bundeswehr-Medical-Service; Euroimmun, RocheDiagnostics provided discounted kits and machines.
| S-EPMC8320407 | biostudies-literature
Project description:Numerous sero-epidemiological studies have been initiated to investigate the spread and dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To address the concomitant need for serological high-throughput assays, a bead-based multiplex serology assay, specific for SARS-CoV-2, had been developed. SARS-CoV-2 serolomics allows for measuring antibody responses to almost the entire SARS-CoV-2 proteome in up to 2000 serum samples per day. To enlarge the pool of eligible sample collection methods, we here test the compatibility of serolomics with dried blood spot (DBS)-derived eluates. Antibody levels of nine SARS-CoV-2 antigens, including the nucleocapsid (N) and receptor-binding domain of the spike protein (S1-RBD), were measured in 142 paired DBS and serum samples. The numeric correlation between the two sample types was high, with a Pearson's r of 0.88 for both S1-RBD and N and intraclass correlation coefficients of 0.93 and 0.92, respectively. Systematically reduced antibody levels in DBS eluates were compensated by lowering the cutoffs for seropositivity accordingly. This enabled the concordant classification of SARS-CoV-2 seropositivity, without loss in sensitivity. Antibody levels against accessory SARS-CoV-2 antigens also showed a high concordance, demonstrating that DBS-derived eluates are eligible for SARS-CoV-2 serolomics. DBS cards facilitate the collection of blood samples, as they obviate the need for medically trained personnel and can be shipped at room temperature. In combination with SARS-CoV-2 serolomics, DBS cards enable powerful sero-epidemiological studies, thus allowing for the monitoring of patients and epidemiological analyses in resource-poor settings.
| S-EPMC9322257 | biostudies-literature
Project description:ObjectiveSerological testing is needed to investigate the extent of transmission of SARS-CoV-2 from front-line essential workers to their household members. However, the requirement for serum/plasma limits serological testing to clinical settings where it is feasible to collect and process venous blood. To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of finger stick capillary whole blood, collected in the home and dried on filter paper (dried blood spot, DBS). We describe assay performance and demonstrate its utility for remote sampling with results from a community-based study.MethodsAn ELISA to the receptor binding domain of the SARS-CoV-2 spike protein was optimized to quantify IgG antibodies in DBS. Samples were self-collected from a community sample of 232 participants enriched with health care workers, including 30 known COVID-19 cases and their household members.ResultsAmong 30 individuals sharing a household with a virus-confirmed case of COVID-19, 80% were seropositive. Of 202 community individuals without prior confirmed acute COVID-19 diagnoses, 36% were seropositive. Of documented convalescent COVID-19 cases from the community, 29 of 30 (97%) were seropositive for IgG antibodies to the receptor binding domain.ConclusionDBS ELISA provides a minimally-invasive alternative to venous blood collection. Early analysis suggests a high rate of transmission among household members. High rates of seroconversion were also noted following recovery from infection. Serological testing for SARS-CoV-2 IgG antibodies in DBS samples can facilitate seroprevalence assessment in community settings to address epidemiological questions, monitor duration of antibody responses, and assess if antibodies against the spike protein correlate with protection from reinfection.
| S-EPMC7428174 | biostudies-literature
Project description:Dried blood spot (DBS) samples can be used for the detection of severe acute respiratory syndrome coronavirus 2 spike antibodies. DBS sampling is comparable to matched serum samples with a relative 98.1% sensitivity and 100% specificity. Thus, DBS sampling offers an alternative for population-wide serologic testing in the coronavirus pandemic.
| S-EPMC7706975 | biostudies-literature
Project description:We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.
| S-EPMC8007057 | biostudies-literature
Project description:We examined the usefulness of dried spot blood and saliva samples in SARS-CoV-2 antibody analyses. We analyzed 1231 self-collected dried spot blood and saliva samples from healthcare workers. Participants filled in a questionnaire on their COVID-19 exposures, infections, and vaccinations. Anti-SARS-CoV-2 IgG, IgA, and IgM levels were determined from both samples using the GSP/DELFIA method. The level of exposure was the strongest determinant of all blood antibody classes and saliva IgG, increasing as follows: (1) no exposure (healthy, non-vaccinated), (2) exposed, (3) former COVID-19 infection, (4) one vaccination, (5) two vaccinations, and (6) vaccination and former infection. While the blood IgG assay had a 99.5% sensitivity and 75.3% specificity to distinguish participants with two vaccinations from all other types of exposure, the corresponding percentages for saliva IgG were 85.3% and 65.7%. Both blood and saliva IgG-seropositivity proportions followed similar trends to the exposures reported in the questionnaires. Self-collected dry blood and saliva spot samples combined with the GSP/DELFIA technique comprise a valuable tool to investigate an individual's immune response to SARS-CoV-2 exposure or vaccination. Saliva IgG has high potential to monitor vaccination response wane, since the sample is non-invasive and easy to collect.
| S-EPMC9191541 | biostudies-literature
Project description:The utilization of vaccines to fight the spread of SARS-CoV-2 has led to a growing need for expansive serological testing. To address this, an EUA approved immunoassay for detection of antibodies to SARS-CoV-2 in venous serum samples was investigated for use with dried blood spot (DBS) samples. Results from self-collected DBS samples demonstrated a 98.1% categorical agreement to venous serum with a correlation (R) of 0.9600 while professionally collected DBS samples demonstrated a categorical agreement of 100.0% with a correlation of 0.9888 to venous serum. Additional studies were performed to stress different aspects of at-home DBS collection, including shipping stability, effects of interferences, and other sample-specific robustness studies. These studies demonstrated a categorical agreement of at least 95.0% and a mean bias less than ± 20.0%. Furthermore, the ability to track antibody levels following vaccination with the BioNTech/Pfizer vaccine was demonstrated with serial self-collected DBS samples from pre-dose (Day 0) out to 19 weeks.
| S-EPMC8985748 | biostudies-literature
Project description:Measurement of telomere length is crucial for the study of telomere maintenance and its role in molecular pathophysiology of diseases and in aging. Several methods are used to measure telomere length, the choice of which usually depends on the type and size of sample to be assayed, as well as cost and throughput considerations. The goal of this study was to investigate the factors that may influence the reliability of qPCR-based relative telomere length measurements in whole blood. Day to day intra-individual variability, types of blood anticoagulant, sample storage conditions, processing and site of blood draw were investigated. Two qPCR-based methods to measure telomere length (monoplex vs. multiplex) were also investigated and showed a strong correlation between them. Freezing and thawing of the blood and storage of the blood at 4°C for up to 4 days did not affect telomere length values. Telomere lengths in dried blood spots were significantly higher than both whole blood and peripheral mononuclear blood cells, and were highly correlated with both. We found that telomere length measurements were significantly higher in dried blood spots collected directly from fingertip prick compared to dried blood spots prepared with anticoagulated whole blood collected from the finger, and non-blotted whole blood taken from both finger and arm venipuncture. This suggests that DNA from cells blotted on paper is not equivalent to that collected from venipuncture whole blood, and caution should be taken when comparing between blood sample types.
| S-EPMC3581490 | biostudies-literature
Project description:BackgroundIt is unknown whether a positive serology result correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value of SARS-CoV-2 serology tests, especially when testing populations with low disease prevalence.MethodsA neutralization assay was validated in a set of PCR-confirmed positive specimens and in a negative cohort. In addition, 9530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N = 164 individuals) were reanalyzed using the neutralization assay, the Roche total immunoglobin assay, and the Abbott IgG assay. The relationship between the magnitude of a positive SARS-CoV-2 serology result and neutralizing activity was determined. Neutralizing antibody titers (50% inhibitory dilution, ID50) were also longitudinally monitored in patients confirmed to have SARS-CoV-2 by PCR.ResultsThe SARS-CoV-2 neutralization assay had a positive percentage agreement (PPA) of 96.6% with a SARS-CoV-2 PCR test and a negative percentage agreement (NPA) of 98.0% across 100 negative control individuals. ID50 neutralization titers positively correlated with all 3 clinical serology platforms. Longitudinal monitoring of hospitalized PCR-confirmed patients with COVID-19 demonstrated they made high neutralization titers against SARS-CoV-2. PPA between the Diazyme IgG assay alone and the neutralization assay was 50.6%, while combining the Diazyme IgG assay with either the Roche or Abbott platforms increased the PPA to 79.2 and 78.4%, respectively.ConclusionsThese 3 clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in patients with COVID-19. All patients confirmed SARS-CoV-2 positive by PCR develop neutralizing antibodies.
| S-EPMC7665417 | biostudies-literature