Rapid point-of-care tests to detect SARS-CoV-2 antibodies are promising, but field results are not ideal

CITF Leadership Group member Dr. Mel Krajden and Muhammad Morshed who receives support from the CITF for another project, along with their team at the British Columbia Centre for Disease Control Public Health Laboratory, recently evaluated the sensitivity of rapid tests to detect antibodies to SARS-CoV-2 in blood samples under different testing settings. The team concluded that while in the laboratory setting using venous blood samples these tests were very sensitive (almost 100%) when compared to other commercial tests, their sensitivity dramatically dropped when testing was performed using finger prick collected samples.

The number of COVID-19 cases continues to increase worldwide. Likewise, the urgency to develop fast, easy-to-use, and accurate antibody testing tools that people could even use at home has increased proportionally. Rapid point-of-care lateral flow cassettes resemble pregnancy tests but take a blood sample instead and measure antibodies that recognize SARS-CoV-2 proteins. A number of these are currently available in Canada. When a drop of blood is added to the cassette, a visual read out identifying the presence of SARS-CoV-2-specific IgM and IgG antibodies quickly shows up.

The team used four commercial ELISA-type assays to first confirm if the samples were positive or negative, as a control for their main experiment which involved three cassette-type rapid tests. They collected samples from individuals who had COVID-19, confirmed by a positive PCR result (swab test). These samples were collected at least 14 days after symptom onset to ensure that sufficient antibodies were present for testing. They also collected samples from individuals who were never tested or who tested negative by PCR. These were labeled as ‘presumed positive’ if SARS-CoV-2 antibodies were detected by several commercial high-throughput automated serology platforms simultaneously. Likewise, samples were dubbed ‘presumed negative’ if they gave negative results in all high-throughput automated platforms. Any samples with discrepant results on any of the platforms were excluded from the analysis.

The authors then tested these samples using three rapid point-of-care cassettes referred to in their manuscript as Artron, BioCan and BTNX. All three yielded very promising analytical performance with high sensitivity and specificity in their initial validation under laboratory conditions.

As rapid point-of-care cassettes are meant to be used in the field, the Artron cassettes were selected for field trials. The field trials were conducted in two long-term care facilities with confirmed COVID-19 outbreaks. In these facilities, the tests were performed by laboratory technologists who were trained in conducting finger prick tests. The sensitivity of the assay dropped significantly in the field trials. When the blood samples taken in the field were tested with the rapid test cassettes in the laboratory, the sensitivity did improve but still did not reach that which was observed in the initial validation study.

The authors concluded that these assays have a lower performance in the field than in the laboratory. They proposed several reasons for this issue: 1) It would be difficult to standardize the volume of blood added to the cassette using blood from a finger prick in the field, 2) The nature of capillary blood collection also predisposes the red blood cells in the sample to rupture, affecting quality of the read-outs, 3) The level of training of the field operators, poor cassette readability, and possible quality issues from different batches of the products may further compound these effects. The research team concluded that these tests can be useful for surveillance purposes in hard-to-reach populations that have no easy access to laboratories, but their readout should be analyzed with caution.