Sensitive Detection of SARS-CoV-2–Specific Antibodies in Dried Blood Spot Samples

Morley, Gabriella L; Taylor, Stephen; Jossi, Sian; Pérez-Toledo, Marisol; Faustini, Sian; Marcial‐Juárez, Edith; Shields, Adrian; Goodall, Margaret; Allen, Joel D.; Watanabe, Yasunori; Newby, Maddy L.; Crispin, Max; Drayson, Mark T.; Cunningham, Adam F.; Richter, Alex; O’Shea, Matthew K.

doi:10.3201/eid2612.203309

Cited by 85 publications

(85 citation statements)

References 13 publications

(12 reference statements)

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“…Our results confirm previous findings on the utility of DBS for SARS-CoV-2 antibody measurements, 5 , 8 , 9 but also extend these findings in several ways by (1) demonstrating the stability of DBS specimens, (2) using an established assay that has been granted Food and Drug Administration Emergency Use Authorization status, (3) using a standardized reference panel serum provided by National Institute for Biological Standards and Controls (UK) and the World Health Organization Solidarity II group and (4) including paediatric samples.…”

Section: Discussionsupporting

confidence: 92%

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

Toh

Higgins

Anderson

et al. 2021

Journal of Public Health

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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.

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Section: Discussionsupporting

confidence: 92%

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

Toh

Higgins

Anderson

et al. 2021

Journal of Public Health

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“…Several studies have recently examined the utility of DBS SARS-CoV-2 antibody testing. 12 – 17 However, many of these studies suffer from small sample sizes 12 , 14 , 15 or use sample punching/sample extraction procedures that do not make the assay amenable for rapid high-throughput testing. 12 , 15 , 16 Furthermore, none of these studies have linked testing with the established newborn DBS screening laboratory infrastructure.…”

Section: Discussionmentioning

confidence: 99%

“…This finding confirms that of Morley and colleagues, using a similar ELISA format. 16 To further characterise the performance of our DBS assay, we compared the OD values obtained for DBS specimens analysed using the ELISA to the results from paired serum results obtained using the Healgen Scientific PoCT (IgG &IgM) lateral flow device (detects antibodies to both the spike and nucleocapsid proteins). The results demonstrated good concordance between paired specimens.…”

Section: Dbs Specimen Stability Studiesmentioning

confidence: 99%

Development of a high-throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens

et al. 2020

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Background: Serologic assays for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have roles in seroepidemiology, convalescent plasma-testing, antibody durability and vaccine studies. Currently, SARS-CoV-2 serology is performed using serum/plasma collected by venepuncture. Dried bloodspot (DBS) testing offers significant advantages; as it is minimally invasive, avoids venepuncture with specimens being mailed to the laboratory. Methods: A pathway utilising a newborn screening laboratory infrastructure was developed using an Enzyme-Linked Immunosorbent assay (ELISA) to detect IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in DBS specimens. Paired plasma and DBS specimens from SARS-CoV-2 antibody positive and negative subjects and PCR positive subjects were tested. DBS specimen stability, effect of blood volume and punch location were also evaluated. Results: DBS from antibody-negative (n=85) and positive (n=35) subjects and PCR positive subjects (n=11) had a mean (SD; range) optical density (OD) of 0.14 (0.046; 0.03-0.27), 0.98 (0.41; 0.31-1.64) and 1.12 (0.37; 0.49-1.54), respectively. An action value OD >0.28 correctly assigned all cases. The weighted Deming regression for comparison of the DBS and the plasma assay yielded: y=0.004041+1.005x, r=0.991, Sy/x 0.171, n=82. Extraction efficiency of antibodies from DBS was >99%. DBS were stable for at least 28 days at ambient room temperature and humidity. Conclusions: SARS-CoV-2 IgG RBD antibodies can be reliably detected in DBS. DBS serological testing offers lower costs than either point of care or serum/plasma assays that require patient travel, phlebotomy and hospital/clinic resources; the development of a DBS assay may be particularly important for resource poor settings.

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“…Thirty-two (89%) reported the methodology used to elute the DBS samples [14,15,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][35][36][37][39][40][41][42][44][45][46][47][48][49][50][51][52]. The shortest incubation period of the DBS in elution buffer (50 μl 0.05% PBS/Tween-20) was 30 minutes [42] and the longest incubation period of the DBS in elution buffer (700 μl and 300 μl PBS/0.05% BSA) was 18-24 hours [17]) ( Table 2).…”

Section: Elution Methodsmentioning

confidence: 99%

“…Twelve papers reported on Chagas disease [35], Epstein-Barr virus [36], HPV, H. pylori, hepatitis C and polyomavirus [37], Strongyloidiasis [39], pertussis [41], hepatitis E [56], Vibrio cholera [2], measles, mumps and rubella [42], tuberculosis and cytomegalovirus [43], toxoplasmosis [44], trypanosoma [45], Covid-19 [52], respectively. Twelve studies were conducted in Europe [14,18,21,27,29,30,35,[41][42][43]50,52], four in North America [19,20,32,36], eleven in South America [15][16][17]22,24,34,38,39,48,49,51], seven in Africa [23,25,26,31,40,44,45] and five in Asia [28,33,…”

Section: Study Characteristicsmentioning

confidence: 99%

Reliability of dried blood spot (DBS) cards in antibody measurement: A systematic review

et al. 2021

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Background Increasingly, vaccine efficacy studies are being recommended in low-and-middle-income countries (LMIC), yet often facilities are unavailable to take and store infant blood samples correctly. Dried blood spots (DBS), are useful for collecting blood from infants for diagnostic purposes, especially in low-income settings, as the amount of blood required is miniscule and no refrigeration is required. Little is known about their utility for antibody studies in children. This systematic review aims to investigate the correlation of antibody concentrations against infectious diseases in DBS in comparison to serum or plasma samples that might inform their use in vaccine clinical trials. Methods and findings We searched MEDLINE, Embase and the Cochrane library for relevant studies between January 1990 to October 2020 with no language restriction, using PRISMA guidelines, investigating the correlation between antibody concentrations in DBS and serum or plasma samples, and the effect of storage temperature on DBS diagnostic performance. We included 40 studies in this systematic review. The antibody concentration in DBS and serum/plasma samples reported a good pooled correlation, (r2 = 0.86 (ranged 0.43 to 1.00)). Ten studies described a decline of antibody after 28 days at room temperature compared to optimal storage at -20°C, where antibodies were stable for up to 200 days. There were only five studies of anti-bacterial antibodies. Conclusions There is a good correlation between antibody concentrations in DBS and serum/plasma samples, supporting the wider use of DBS in vaccine and sero-epidemiological studies, but there is limited data on anti-bacterial antibodies. The correct storage of DBS is critical and may be a consideration for longer term storage.

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Sensitive Detection of SARS-CoV-2–Specific Antibodies in Dried Blood Spot Samples

Cited by 85 publications

References 13 publications

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

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

Development of a high-throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens

Reliability of dried blood spot (DBS) cards in antibody measurement: A systematic review

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