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Authors: Kruse et al.

Link to paper: https://www.biorxiv.org/content/10.1101/2020.05.13.094490v1

Journal/ Pre-Print: bioRxiv

Tags: Clinical/ Diagnostics, Molecular Biology

Research Highlights 

1. Using hemagglutination assay to detect antibodies targeting SARS-CoV-2

2. Employing this method may present a cheap and time-efficient method for SARS-CoV-2 testing especially in a low-resource setting specially to monitor the disease progression

Summary

Kruse et al. tested the possibility of using the red blood cell agglutination assay to detect SARS-CoV-2 antibodies. They created a fusion protein consisting of the receptor-binding domain of the SARS-CoV-2 spike protein and scFv targeting the H antigen on red blood cells. The agglutination test was performed by mixing the fusion protein with red blood cells and the serum of a patient recovered from COVID-19 (specimen collected at least 28 days post symptoms and negative PCR testing upon discharge). Optimal agglutination yield observable by the naked eye was achieved at the highest fusion protein concentration (100%, 50% and 25%) within 5 minutes of the incubation.

Impact for SARS-CoV2/COVID19 research efforts

Develop diagnostic tools for SARS-CoV2/COVID19 – Use of fast and cheap hemagglutination assay for the detection of the antibodies against SARS-CoV-2

Study Type

Patient Case study

Strengths and limitations of the paper

Novelty: Using the hemagglutination assay for detection of antibodies against SARS-CoV-2

Standing in the field: Similar assays have been previously used to detect antibodies against HIV, West Nile virus etc. However, this technique has not been applied to SARS-CoV-2 so the validity of this technique for SARS-CoV-2 remained to be confirmed.

Appropriate statistics: No statistical test used (n=1)

Viral model used: SARS-CoV-2

Translatability: This method can be potentially used for routine testing, especially in low-resource settings as the authors reported that the price for one test was 25 U.S. cents.

Main limitations:

1) This detection was performed on 1 COVID-19 patient.

2) Data presented in the preprint (one WB and one agglutination assay) are not showing very convincing results.

3) Authors speculate that this method can be used in a low-resource setting from a finger prick, however, they performed their test on patient’s serum. For their suggested rapid use in low-resource setting, blood from finger prick should have been tested.

4) They used only a very small section of the spike protein for their antibody detection (AA 330-524).

5) They have not tested the stability of the fusion protein used in the assay. Authors themselves acknowledge this limitation.

6) Presence of IgM autoantibodies can cause false positive results in the agglutination assay.

7) Authors did not report the concentration of the RBD-scFv fusion protein used.