Dried blood spot specimens for SARS-CoV-2 antibody testing: A multi-site, multi-assay comparison

Abstract

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.

Monitoring of SARS-CoV-2 antibodies using dried blood spot for at-home collection

“…Since the start of the pandemic, many laboratories and researchers have investigated the use of DBS collection for both qualitative and quantitative detection of SARS-CoV-2 antibodies 10 , 15 – 21 . These assays have demonstrated high sensitivity and specificity when comparing DBS results to plasma or serum in proof-of-concept studies (Table 1 ).…”

Performance of Immunoglobulin G Serology on Finger Prick Capillary Dried Blood Spot Samples to Detect a SARS-CoV-2 Antibody Response

“…The diagnostic accuracy of MSD is comparable to that of the Roche Elecsys assay ( 16 ) and other commercial platforms ( 17 ) for surveillance of SARS-CoV-2 seroconversion in DBS-collected specimens. The MSD assay has the unique benefit of testing anti-S and anti-N IgG in a single multiplex reaction ( 18 ).…”

“…Public health agencies are challenged with simultaneously administering COVID-19 vaccines and measuring the elicited immune response. Addressing the latter requires a reliable and accessible method for detecting SARS-CoV-2 seropositivity ( 17 ). The logistic, economic, and demonstrated diagnostic accuracy of DBS-MSD testing make it a strong candidate for population-level investigation of SARS-CoV-2 antibody responses, especially in longitudinal study designs requiring repeated laboratory measures.…”

A scalable serology solution for profiling humoral immune responses to SARS‐CoV‐2 infection and vaccination

“…Samples were prepared at the National Microbiology Laboratory of Canada (NML) as in. 46 For panels 1–3, plasma from SARS‐CoV‐2 antibody‐positive COVID‐19 convalescent donors (MSH, Toronto) and SARS‐CoV‐2‐negative donors (NML, Winnipeg) were used to generate matched plasma and contrived DBS samples. For contrived DBS samples, fresh SARS‐CoV‐2 antibody‐negative blood was centrifuged, the plasma was removed, and the red blood cells were resuspended 1:1 in antibody‐positive plasma and spotted (5 × 75 µL) onto Whatman 903 Protein Saver Cards (GE Healthcare, Boston, MA, USA), which were dried at room temperature overnight, then stored with desiccant in gas‐impermeable bags at −80°C until testing.…”