A rapid and affordable point of care test for antibodies against SARS-CoV-2 based on hemagglutination and artificial intelligence interpretation

Abstract

Diagnostic tests that detect antibodies (AB) against SARS-CoV-2 for evaluation of seroprevalence and guidance of health care measures are important tools for managing the COVID-19 pandemic. Current tests have certain limitations with regard to turnaround time, costs and availability, particularly in point-of-care (POC) settings. We established a hemagglutination-based AB test that is based on bi-specific proteins which contain a dromedary-derived antibody (nanobody) binding red blood cells (RBD) and a SARS-CoV-2-derived antigen, such as the receptor-binding domain of the Spike protein (Spike-RBD). While the nanobody mediates swift binding to RBC, the antigen moiety directs instantaneous, visually apparent hemagglutination in the presence of SARS-CoV-2-specific AB generated in COVID-19 patients or vaccinated individuals. Method comparison studies with assays cleared by emergency use authorization demonstrate high specificity and sensitivity. To further increase objectivity of test interpretation, we developed an image analysis tool based on digital image acquisition (via a cell phone) and a machine learning algorithm based on defined sample-training and -validation datasets. Preliminary data, including a small clinical study, provides proof of principle for test performance in a POC setting. Together, the data support the interpretation that this AB test format, which we refer to as ‘NanoSpot.ai’, is suitable for POC testing, can be manufactured at very low costs and, based on its generic mode of action, can likely be adapted to a variety of other pathogens.

HAT-field: a cheap, robust and quantitative point-of-care serological test for Covid-19

“…Two recent reports have described that HAT could be performed on cards rather than in V-shaped wells, with semi-quantitative results being obtained in minutes, which was made possible by the use of much higher amounts of the IH4-RBD reagent than when HAT is performed in V-shaped well (Kruse et al, 2021; Redecke et al, 2021). Reliably quantitative card-based tests HAT test would unquestionably be a very attractive solution for performing the test in field settings.…”

Recent progress on rapid diagnosis of COVID-19 by point-of-care testing platforms

“…The abovementioned aspects make it unsuitable for detecting suspected cases promptly and quickly in controlling epidemic situations. Therefore, a specific and convenient method for diagnosing SARS-CoV-2 is urgently needed to protect public safety [22] , [23] , [24] , [25] . Thus, the real-time detection strategy by point-of-care testing (POCT) platforms is an excellent supplement for early diagnosis.…”

Modified Hemagglutination Tests for COVID-19 Serology in Resource-Poor Settings: Ready for Prime-Time?

“…Redecke et al developed NanoSpot.ai, a modified HAT that employed a dromedary-derived bispecific nanobody (H11-D4) binding RBCs and Spike RBD, and a smartphone tool for digital image acquisition and interpretation. The assay correlated well with both the Euroimmun ELISA and the Abbott CLIA assays [ 25 ].…”