Performance of Immunoglobulin G Serology on Finger Prick Capillary Dried Blood Spot Samples to Measure SARS-CoV-2 Humoral Immunogenicity

Nikiforuk, A. M.; McMillan, B.; Bartlett, S. R.; Marquez, A. C.; Pidduck, T.; Kustra, J.; Goldfarb, D. M.; Barakauskas, V.; Sinclair, G.; Patrick, D. M.; Sadarangani, M.; Ogilvie, G. S.; Morshed, M.; Sekirov, I.; Jassem, A. N.

Abstract: Importance: Measuring humoral immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines and finding population-level correlates of protection against coronavirus disease (COVID-19) presents an immediate challenge to public health practitioners. Objective: To study the diagnostic accuracy and predictive value of finger prick capillary dried blood spot (DBS) 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 DBS 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, DBS samples possessed 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 DBS-based testing approach has a high positive predictive value (PPV) (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 PPV decreased and the negative predictive value increased. Conclusion: We demonstrate that DBS 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.