The Role of Proteins In Point-of-Care Serological Tests that Can Be Used to Manage SARS-Cov-2 (COVID-19)
Introduction. Severe acute respiratory syndrome 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and is responsible for causing a major health crisis with substantial morbidity and mortality¹. In general, coronaviruses are enveloped RNA viruses that can cause acute and chronic diseases¹. SARS-CoV-2 in particular uses the cellular receptor angiotensin-converting enzyme 2 (ACE2) for entry into cells¹. A key challenge faced by scientists has been tracking the highly replicative nature of SARS-CoV-2 and combating the rapid dissemination of infective and transmissible variants2. While nucleic acid amplification tests have been the gold standard for SARS-CoV-2 detection due to high sensitivity and specificity3, as the pandemic has raged onwards it has become more and more important to obtain a comprehensive immunological blueprint of patients. Resultantly there is an urgent need for point-of-care (POC) serological tests to detect antibodies and other biomarkers in SARS-CoV-2 patients. Methods. To address this need, several POC platforms have been established that target key portions of SARS-CoV-2: the nucleocapsid (N), spike S1 domain (S1), and the receptor-binding domain (RBD) regions. The Double antigen – Dispense, dissolve, diffuse, detect (DA-D4) platform uses capture antigens that are printed onto a non-fouling surface to target and detect the presence (or lack thereof) of antibodies within patients believed to be positive for SARS-CoV-23. Additionally, a modified DA-D4 platform utilizes capture antigens from SARS-CoV-2 variant strains to determine the degree of patient antibody neutralization against different SARS-CoV-2 variants4. An alternative approach creates a fusion protein consisting of the SARS-CoV-2 N-terminus RBD to induce hemagglutination when combined with the serum of a SARS-CoV-2 positive patient5. Results. The DA-D4 assay demonstrates high sensitivity and specificity, quantifies seroconversion in COVID-19 patients, can detect prognostic biomarkers indicative of disease severity, and can be converted into a microfluidic chip for rapid POC delivery3. Additionally, the modified DA-D4 assay is able to determine the antibody profile of a patient’s serum against SARS-CoV-2 variants of concern4. The alternative approach using a fusion protein demonstrates visible agglutination when used in conjunction with a SARS-CoV-2 seropositive patient5. Conclusion. Several studies have demonstrated that proteins (ie. antibodies) can and have been harnessed to be powerful tools in combating the spread of disease. In the tragic case that we see another pandemic in our lifetime, these low-cost devices will be critical in tracking seroconversion in infected patients, tracking serum neutralization in variants, tracking immunity of groups of individuals, and assisting healthcare providers in minimizing disease spread.
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