The use of dried blood spots for the serological evaluation of SARS-CoV-2 antibodies

Abstract

Background To determine if dried blood spot specimens (DBS) can reliably detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, we compared the SARS-CoV-2 IgG antibody response in paired serum and eluates from DBS specimens. Methods A total of 95 paired DBS and serum samples were collected from 74 participants (aged 1–63 years) as part of a household cohort study in Melbourne, Australia. SARS-CoV-2 IgG antibodies specific for the receptor-binding domain (RBD) and S1 proteins between serum and eluates from DBS specimens were compared using an FDA-approved ELISA method. Results Among the 74 participants, 42% (31/74) were children and the rest were adults. A total of 16 children and 13 adults were SARS-CoV-2 positive by polymerase chain reaction. The IgG seropositivity rate was similar between serum and DBS specimens (18.9% (18/95) versus 16.8% (16/95)), respectively. Similar RBD and S1-specific IgG levels were detected between serum and DBS specimens. Serum IgG levels strongly correlated with DBS IgG levels (r = 0.99, P < 0.0001) for both SARS-CoV-2 proteins. Furthermore, antibodies remained stable in DBS specimens for >3 months. Conclusions DBS specimens can be reliably used as an alternative to serum samples for SARS-CoV-2 antibody measurement. The use of DBS specimens would facilitate serosurveillance efforts particularly in hard-to-reach populations and inform public health responses including COVID-19 vaccination strategies.

SARS-CoV-2 antibody binding and neutralization in dried blood spot eluates and paired plasma

“…For SARS-CoV-2 studies, adoption of DBS may reduce frontline worker demand, improve sampling in resource-limited areas, and increase study enrollment. Though prior work with DBS and plasma pairs has supported the suitability of DBS for SARS-CoV-2 antibody binding assays (27)(28)(29)(30)(31)(32)(33)(34)(35)(36), important gaps remained that prevented the broad implementation of this sample type. For example, most studies used DBS with venous (27,30) or fingerstick blood collected at the clinic with the assistance of a phlebotomist (29,(31)(32)(33)35), which does not account for variables introduced with self-sampling or ambient shipping.…”

“…Though prior work with DBS and plasma pairs has supported the suitability of DBS for SARS-CoV-2 antibody binding assays (27)(28)(29)(30)(31)(32)(33)(34)(35)(36), important gaps remained that prevented the broad implementation of this sample type. For example, most studies used DBS with venous (27,30) or fingerstick blood collected at the clinic with the assistance of a phlebotomist (29,(31)(32)(33)35), which does not account for variables introduced with self-sampling or ambient shipping. One study did utilize self-collected fingerstick cards (28), but only evaluated four sample pairs via an agglutination-PCR assay.…”

“…The DBS cards used so far in this study were prepared with venous blood, similar to prior studies (27,30,(42)(43)(44), and were thus informative intermediates to understand antibody features that can be captured and preserved on filter paper. However, the ideal DBS sample for broad field application would be fingerstick DBS cards (FS DBS) self-collected by individuals at home and mailed to the clinic for storage, processing, and evaluation.…”

“…Therefore, when the current pandemic began, several groups sought to verify the use of DBS eluates for SARS-CoV-2 antibody assays. The most robust of these studies compared antibody binding measurements between paired DBS eluates and plasma or sera from COVID-19 convalescent individuals (27)(28)(29)(30)(31)(32)(33)(34)(35)(36) and, impressively, all have found strong agreement between sample types. Despite this supportive evidence, the majority of these reports did not use self-collected, mailed-in fingerstick DBS cards and the compatibility of DBS with other assay formats, including neutralization, has not been carefully examined for SARS-CoV-2.…”

Lessons Learned From the Implementation of a Participant-Collected, Mail-Based SARS-CoV-2 Serological Survey in Massachusetts, USA

“…3 Athome serosurvey sampling using DBS from a mailed testing kit has been validated and found to be a reliable alternative to serum samples for detecting SARS-CoV-2 antibodies. 11,12 Additionally, there is evidence that collecting venous blood either in-person or at home might be less acceptable to participants than an at-home dried blood spot (DBS) collection. 3,9,10,13,14 While simpler to use a convenience sample of serology measures, this might reduce validity and generalizability of results.…”