Serological testing is being carried out extensively in order to help understand the prevalence of COVID-19 in both observational studies and the community. These can identify both specific antibodies against the virus, including various isotypes like Immunoglobulin M (IgM) and Immunoglobulin G (IgG).
Some evidence suggests that IgGs appear at 6-15 days after infection and may persist for months. However, large-scale testing over time is required to understand the immunological response to COVID-19 with greater accuracy. A recent pilot study published on the preprint server medRxiv* in September 2020 reports the use of self-collected capillary blood for serology, with highly promising results.
The Problem with Venepuncture
Many current tests use serum or plasma from blood samples that are obtained by venepuncture. This is a laborious and skilled procedure and requires significant investment in terms of personnel, facilities, personal protective equipment (PPE), and time. The patient must also attend a healthcare facility of some sort for collection of the sample, which increases the risk to both the patient and others at the facility.
The cost and infrastructural demands make this type of study unrealistic in many low and middle-income countries (LMICs). In order to overcome this obstacle, scientists have developed rapid lateral flow immunoassays (LFIAs). Their variable performance has made this unreliable, however, even in a laboratory setting, and also by finger prick at home, as demonstrated by a UK study.
Why Not Capillary Blood?
Venous blood is a suitable sample for ELISA testing, and so is capillary blood, but the latter has not been tested for SARS-CoV-2 detection. However, pending its validation, the self-collection of capillary blood at home, with the sample being posted to a reference laboratory, could reduce the costs and risks associated with inpatient sampling. This, in turn, would facilitate large-scale surveillance.
A Question of Stability
The researchers investigated the suitability of capillary blood collected by self-sampling, comparing the COVID-19 IgG ELISA results with those obtained by venepuncture. Of the 39 participants, over 56% were female, and the median age was 37 years. Only one person failed to get enough blood by self-sampling.
They looked at the stability of these samples first, after storing it at room temperature for 7 days, and dried blood spots (DBS). Secondly, they examined the performance of both types of blood samples.
The storage of the blood at room temperature for 7 days did not alter the results.
Highly Concordant Results
There were 209 samples matched for venous and capillary blood results, of which only five were discordant, indicating ~2% discordance. The researchers found high agreement between capillary and venous blood samples, at over 94%, concerning detectable anti- SARS-CoV-2 IgG antibodies by ELISA.
In statistical terms, this is a near-perfect agreement, and the discrepancy was, in fact, only observed for samples where the values were near the cut-off, with a positive reference venous blood sample and indeterminate capillary blood sample.
The results were strongly correlated across all types of samples. The study thus shows that IgG ELISA against COVID-19 is equally detectable from capillary blood compared to venous blood.
Implications and Future Directions
This finding could revolutionize current antibody testing for COVID-19 by widening access to blood samples across almost the entire population. If capillary blood, self-collected, can provide valid results, it obviates the need for skilled personnel with dedicated facilities to do venepuncture. It is important to note that only one of the participants was unable to collect enough blood for the test by capillary self-sampling, “which indicates self-sampling is a feasible alternative to venepuncture,” according to the researchers.
Another important finding is that storage at room temperatures between 21 – 25°C does not alter the validity of the test by leaving the stability of the antibodies unimpaired. This is again highly useful because the need for cold chain transport conditions is avoided, and there is no additional urgency placed on the role of the postal and laboratory staff to expedite the transport and testing of the samples.
Not only did the venous blood samples match the capillary blood samples concerning the ELISA results, but the type of capillary blood did not appear to make any significant difference. That is, whether collected in lithium heparin-treated capillary tubes or as DBS on filter paper, the capillary blood provided results with high equivalency.
Since DBS requires more manual steps before ELISA can be done, this can take more time. On the other hand, DBS samples are more easily transported and do not present a significant biohazard risk. They are both highly portable and robust to normal handling, while the antibodies in DBS can remain stable for weeks at room temperature. This latter finding requires experimental validation for COVID-19 antibodies.
Both methods of self-sampling of capillary blood are cheap and straightforward and should be seriously considered by LMICs to overcome a potential shortage of skilled workers or when the population is dispersed over a large area.
The researchers suggest that if the results are discordant due to indeterminate capillary blood samples, such individuals could be re-tested using venepuncture. Even so, this will provide enormous relief to laboratory personnel by reducing the amount of blood sampling they need to carry out, as well as significantly reducing the risk of transmission.
Earlier studies have already established the equivalence of DBS and venous blood samples in serologic testing for COVID-19. The current study showed that it is relatively easy to collect one’s own capillary blood sample. However, the degree of acceptability and personal preference for this method in the population at large remains to be investigated.
The investigators consider this a proof of concept study, and say, “We plan to validate this method in future studies of large patient cohorts.” If so, it would be very useful in large-scale surveillance as well as to follow up and understand the dynamics of the immunological response in COVID-19 over time.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.