In a retrospective cohort study, researchers in Umeå University, Karolinska Institute and Xerum AB in Sweden found that home sampling with Capitainer’s quantitative DBS device Capitainer®B increased accessibility to COVID-19 antibody testing in a large sparsely populated region of Northern Sweden, compared to regular blood sampling at health clinics. This study is the first to demonstrate the impact of increased access to diagnostics with home sampling versus traditional venous blood sampling in a western country.
Since the COVID-19 pandemic was declared by the World Health Organization in March 2020, real-time monitoring of SARS-CoV-2 transmission, serological monitoring of previously infected individuals and population-wide serology surveillance have been critical tools in the assessment of public health risk, to help inform and support governing and health authorities in decision-making, and to develop effective vaccines by monitoring vaccine-induced humoral immune responses.
While SARS-CoV-2 infection is typically diagnosed in sputum, saliva or nasopharyngeal swabs, venipuncture has been the main sampling approach for SARS-CoV-2 serological testing. Venipuncture requires trained personnel to take blood samples, which besides being resource-demanding, can reduce accessibility to diagnostics in remote or sparsely populated areas that may be located long distances from healthcare centres. Moreover, diagnostic tests that rely on venipuncture may introduce bias when used in population studies, by excluding weak, elderly or otherwise vulnerable individuals who cannot travel the distance to a clinic for testing.
Exploring dried blood spot home sampling for serology testing
Since its emergence in the 1960s, dried blood spot (DBS) testing has become the predominant sampling method in newborn screening and monitoring of individuals with metabolic disorders such as phenylketonuria.
More recently, a role for volumetric DBS sampling in other applications has become apparent, with studies demonstrating its potential in therapeutic drug monitoring of lithium within psychiatry, anti-epileptics, and immunosuppressive drugs (1,2 and references therein). However, despite increased attention towards DBS testing in recent years, it has been used surprisingly rarely in the context of public health.
Recognising the limitations in venous blood sampling for serology surveillance studies in the pandemic era, as well as the potential of quantitative DBS (qDBS) for large scale serology surveillance in sparsely populated areas, researchers from Umeå University, Karolinska Institute and Xerum AB developed and implemented a strategy for home sampling for COVID-19 serology testing in a rural area of Sweden in 2021, and evaluated its role in providing equal healthcare access for its inhabitants.
Their findings, which were recently published in the high-impact journal Eurosurveillance, demonstrate that test results for seroconversion to SARS-CoV-2 following at-home sampling with Capitainer’s qDBS device Capitainer®B are comparable to results obtained by regular venous blood sampling performed at a healthcare clinic, and that qDBS elutes were minimally affected by conditions that mimic climate variations in northern Sweden. Importantly, they show that home sampling gives individuals living in rural areas equal access to the diagnostic test as urban dwellers (3).
Strong correlation between qDBS home sampling and venous sampling in clinical setting
The researchers sought to track which individuals harbour antibodies against SARS-CoV-2 in a large human population. To this end, they compared SARS-CoV-2 seroconversion (i.e., the presence of anti-SARS-CoV-2 antibodies) results following DBS home sampling or regular venous sampling in individuals inhabiting a sparsely populated area in Northern Sweden. The area in question, called Region Västerbotten, measures 55,185 square kilometres and had a population of around 275,000 during the testing period, which lasted approximately four months between November 2020 and May 2021.
Venous blood samples were taken over a two-month period during November 2020 and January 2021. This was performed by phlebotomists at select sites in the two most urban areas within Region Västerbotten, or at mobile travelling health centres outside of these areas. Capillary blood samples were collected by home sampling with Capitainer®B self-sampling kits, which were sent by mail to the individuals’ homes in a two-month period during March and May 2021.
In total, 3,559 qDBS and 8,002 venous blood samples were analysed in the Clinical Microbiology Laboratory at the University Hospital of Umeå, following an in-house developed ELISA method to detect IgG antibodies against the SARS-CoV-2 spike (S) protein. This assay was previously found to be more sensitive and specific than 11 commercially available SARS-CoV-2 assays, in a comparative study undertaken by the Swedish Public Health Agency (4). Incorporation of capillary samples into the ELISA workflow was validated using paired serum and qDBS samples that were previously collected for clinical purposes by the University Hospital of Umeå.
The researchers observed a strong correlation between the qDBS and venous sampling methods when eluates of either sample type were applied to the ELISA microplate (r2 = 0.96; p < 0.0001).
Access to SARS-CoV-2 serological testing in Region Västerbotten, Sweden, by venous blood sampling, November 2020–January 2021 (n = 8,002) and dried blood spot self-sampling, March−May 2021 (n = 4,122). The map inset of Sweden shows Västerbotten subdivided in geographical area codes. The colour distribution shows the over or under representation of at-home testing using quantitative dried blood spots (qDBS) compared to venous testing for serology. The two urban areas of Umeå and Skellefteå are indicated. The large map is subdivided in major administrative regions (3).
The image is republished from the paper (3) where the work is licensed under a Creative Commons Attribution 4.0 International License.
Home sampling increased access to diagnostic test in rural areas
Upon comparing the geographical distribution of venous blood sampling with at-home sampling, the researchers found that 26.3% (n = 2,107) and 44.4% (n = 1,831) of the SARs-CoV-2-positive venous or capillary samples, respectively, originated from individuals inhabiting rural areas of Västerbotten. Based on those figures, they could conclude that the home sampling strategy with qDBS resulted in an increased proportion of tests in rural areas, while the strategy of venous blood sampling was skewed towards the two major urban areas of Region Västerbotten.
This study by Byström et al. is, to the best of our knowledge, the first to demonstrate the power of home sampling to increase access to diagnostics in a western country. Additional benefits of the qDBS home sampling approach include reduced risk of infectious disease transmission (during regular testing at healthcare centres), scalability, and potential cost savings because of the reduced demand for phlebotomists and outreach to geographically distant areas.
Recognising the potential of a home sampling approach to COVID-19 serology surveillance studies, the Public Health Agency of Sweden already implemented the same strategy in clinical practice, in a national point seroprevalence study to determine country-wide exposure to or vaccination against SARS-CoV-2 in Sweden during 2021 and 2022 (5).
Home sampling for serology surveillance testing – a blueprint for future public health studies
Although COVID-19 is the focus of the current study, a testing strategy that includes home sampling should allow public health agencies to obtain rapid and unbiased information about immunity within a population to any infectious disease, even in remote areas. The findings also highlight untapped opportunities to include home sampling with qDBS more broadly in therapeutic drug monitoring, drug screening and public surveillance diagnostic studies, without the risk of bias related to geographic constraints. In summary, home sampling is expected to promote equality in healthcare access for individuals living in remote areas.
References
- Wikström F, Olsson C, Palm B, Roxhed N, Backlund L, Schalling M, Beck O. Determination of lithium concentration in capillary blood using volumetric dried blood spots. J Pharm Biomed Anal. 2023. 1;227:115269. doi: 10.1016/j.jpba.2023.115269.
- Deprez S, Stove C. Application of a Fully Automated Dried Blood Spot Method for Therapeutic Drug Monitoring of Immunosuppressants. Arch Pathol Lab Med. 2022. doi: 10.5858/arpa.2021-0533-OA.
- Byström JW, Vikström L, Rosendal E, et al. At-home sampling to meet geographical challenges for serological assessment of SARS-CoV-2 exposure in a rural region of northern Sweden, March to May 2021: a retrospective cohort study. Euro Surveill. 2023. 28(13):2200432. doi: 10.2807/1560-7917.ES.2023.28.13.2200432.
- Lagerqvist N, Maleki KT, Verner-Carlsson J, et al. Evaluation of 11 SARS-CoV-2 antibody tests by using samples from patients with defined IgG antibody titers. Sci Rep. 2021. 7;11(1):7614. doi: 10.1038/s41598-021-87289-6.
- Beser J, Galanis I, Enkirch T, et al. Seroprevalence of SARS-CoV-2 in Sweden, April 26 to May 9, 2021. Sci Rep. 2022. 25;12(1):10816. doi: 10.1038/s41598-022-15183-w.
- Beyerl J, Rubio-Acero R, Castelletti N, Paunovic I, Kroidl I, Khan ZN, Bakuli A, Tautz A, Oft J, Hoelscher M, Wieser A. A dried blood spot protocol for high throughput analysis of SARS-CoV-2 serology based on the Roche Elecsys anti-N assay. EBioMedicine. 2021. 70:103502. doi: 10.1016/j.ebiom.2021.103502.
