The best way to estimate the actual prevalence of COVID-19 in the population is by antibody testing. A new study by scientists at Enable Biosciences and published on the preprint server medRxiv* in May 2020 reports the development of fast and sensitive antibody testing kits designed for at-home use. This could significantly boost the measurement of population prevalence of this infection and help understand whether it confers immunity to reinfection.
While the gold standard remains the PCR or antigen test for the virus, antibody tests have their own place for several reasons. Firstly, they can improve the yield of cases. Secondly, they can help detected false-negative cases. Thirdly, antibody testing can help evaluate the prevalence of infection and of neutralizing antibodies.
Image Credit: Enable Biosciences
However, serological testing is currently dependent on healthcare workers who need to come and physically collect the blood sample. This limits the reach of the test for persons with restricted mobility and increases the need for labor and the costs associated with testing, which means money flows away from the care of ill people. It also exposes more people on both sides of the collection process to the risk of infection and requires the use of large quantities of personal protective equipment (PPE).
Presently available tests that may potentially be modifiable for at-home testing, like lateral flow assays, are too unreliable for such use. The current study thus offers a viable alternative.
The researchers first created standardized dried blood spot collection kits, which could be mailed safely to and from residential addresses. These include lancets for blood collection, with cards to dry and preserve the blood samples for transport to a central laboratory for analysis. The advantages of such an approach are the home-based collection, which avoids risk to laboratory workers and patients, an extensive reach, and the availability of a high-quality serological test for reliable findings.
The study included all individuals who tested positive between March to April 2020, recruited via social media. Healthy donors without SARS-CoV-2 symptoms were enrolled as negative controls. Each individual was asked to give 2-5 dried blood spots, which were returned by standard United States Postal Service (USPS) blue drop boxes for ground return shipment to Enable Biosciences.
There were 56 specimens, with 31 from patients and 25 from donors. Plasma samples were also collected from 4 patients and 4 healthy donors.
All positive samples tested positive for antibodies to COVID-19, and all negative samples tested negative. Thus, the test results showed 100% sensitivity and specificity, with preliminary results. The study is being expanded for future results.
The use of self-collection techniques by untrained participants could cause dilution of the blood by other tissue fluids, but no such effect was seen when comparing the results of the dried blood spots against the plasma samples. There was also no variation with the distance the test had to travel to reach the laboratory.
The researchers thus commend this approach for widespread population testing for COVID-19. The reasons are many:
RT-PCR is associated with a significant false-negative rate, especially with a low viral load. This could partly be corrected using complementary antibody testing in the early and recovery phases of the illness.
The ability to detect antibodies in the blood is important as an indicator of historical exposure to the virus. This helps evaluate the immune or infection status of the whole population, which is essential for basic measures such as the fatality rate and the basic reproduction number R0.
The use of convalescent plasma is a promising approach for treating the gravely ill. Serologic testing could help pick up more donors who can be tested for neutralizing antibodies, which are necessary for such treatment to be fruitful.
It overcomes the need for a vein-drawn sample, replacing it with a molecular self-collected finger prick test. This will complement the at-home RT-PCR tests now being approved for viral detection.
This method is faster, more rapid, more accessible, and saves resources as well as reducing the burden on the healthcare workers to collect samples for testing.
The use of dried blood spots makes the samples stable at room temperature without a cold chain.
The use of a mailer-based self-collected sample model may increase participation and thus reduce the bias of such serologic studies by making it more possible for poor, discriminated, or isolated communities to take part, even more than via drive-through testing.
The method used in this assay uses up microscopic amounts of reagent, and this allows the samples to be conserved for further testing using appropriate algorithms to refine the accuracy of the test. A high specificity is mandatory for extensive screening tests.
The researchers conclude: “If proven successful at large scale, this method can greatly facilitate the conduct of unbiased serosurveys within hard to reach population populations and help reduce the sample collection burden of serological testing on both health care systems and individuals alike.”
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.