Performance of Immunoglobulin G Serology on Finger Prick Capillary Dried Blood Spot Samples to Measure SARS-CoV-2 Humoral Immunogenicity
Authors: Nikiforuk Aidan M. , McMillan Brynn , Bartlett Sofia R. , Márquez Ana Citlali , Pidduck Tamara , Kustra Jesse , Goldfarb David M. , Barakauskas Vilte , Sinclair Graham , Patrick David M. , Sadarangani Manish , Ogilvie Gina S. , Morshed Muhammad , Sekirov Inna , Jassem Agatha N. 
Published: July 2021

Importance

Measuring humoral immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 vaccines and finding population-level correlates of protection against coronavirus disease presents an immediate challenge to public health practitioners.

Objective

To study the diagnostic accuracy and predictive value of finger prick capillary dried blood spot samples tested using an anti-immunoglobulin G (IgG) serology assay to measure SARS-CoV-2 seropositivity and the humoral immunogenicity of COVID-19 vaccination.

Design, Setting and Participants

This cross-sectional study enrolled participants (n= 644) who had paired DBS and serum samples collected by finger prick and venipuncture, respectively, in British Columbia, Canada between January 12th, 2020 and May 21st, 2021. Samples were tested by a multiplex electrochemiluminescence assay for SARS-CoV-2 anti-Spike (S), -Nucleocapsid (N) and -receptor binding domain (RBD) IgG reactivity using a Meso Scale Discovery (MSD) platform. Additionally, unpaired DBS samples (n= 6,706) that were collected in the province during the same time period were included for analysis of SARS-CoV-2 anti-N IgG reactivity.

Exposure

Collection of a capillary dried blood spot by finger prick alone or paired with serum by venipuncture.

Outcome

Humoral immune response to SARS-CoV-2 measured by detection of anti-S, -N or - RBD IgG.

Results

In comparison to a paired-serum reference, dried blood spot samples possess a sensitivity of 80% (95% CI: 61%-91%) and specificity of 97% (95% CI: 95%-98%). Receiver operator characteristic curve analysis (ROC) found that participant DBS samples tested for anti-SARS-CoV-2 IgG by MSD V-PLEX COVID-19 Coronavirus Panel 2 assay accurately classify SARS-CoV-2 seroconversion at an 88% percent rate, AUC= 88% (95% CI: 81%-96%). Modelling found that a dried blood spot-based testing approach has a high positive predictive value (98% [95% CI: 98%-99%]) in a theoretical population with seventy-five percent COVID-19 vaccine coverage. At lower vaccine coverages of fifteen and forty-five percent, the test’s positive predictive value decreased, and the negative predictive value increased.

Conclusion

We demonstrate that dried blood spot collected samples, when tested using an electrochemiluminescence assay, provide a valid alternative to traditional venipuncture and should be considered to reliably detect SARS-CoV-2 seropositivity.

Key Points

Question

What is the diagnostic accuracy and predictive value of immunoglobulin G serology on finger prick capillary dried blood spot samples to measure SARS-CoV-2 humoral immunogenicity?

Findings

In comparison to a paired-serum reference, dried blood spot samples tested for anti-SARS-CoV-2 IgG possess a sensitivity of 80% (95% CI: 61%-91%) and specificity of 97% (95% CI: 95%-98%). Dried blood spot testing has a positive predictive value of 98% (95% CI: 98%-99%) when modelled in a theoretical population with COVID-19 vaccine coverage of seventy-five percent.

Meaning

Dried blood spot samples have equal diagnostic accuracy to serum collected by venipuncture when tested by electrochemiluminescence assay and should be considered to reliably detect SARS-CoV-2 seropositivity.