In search of out-of-the-box solutionsMay 9, 2020
India is stockpiling hundreds of thousands of COVID-19 test kits, but the effort is currently restricted to conventional tests such as RT-PCR and immune assays. However, what is most urgently needed is a simple, yet robust, diagnostic kit that can function independently without any laboratory equipment, much like a strip-based pregnancy test. This test should then be deployed at each and every port of entry, social gatherings, malls, schools and other places where people gather. RT-PCR and antibody tests cannot be used in the above-mentioned scenarios. It should be remembered that it takes only a few undetected people in public places for the virus to spread again.
The need for such a test becomes all the more apparent when we take into account the fact that a second lockdown will destroy our economy beyond repair. There is, therefore, both an urgent medical and economic need to develop such a diagnostic technology to prevent this disease from spreading. A simple, on-the-spot diagnostic kit will constitute a giant step towards tackling this pandemic. Such on-the-spot tests can be quickly used for random screening by regulatory and monitoring organizations like Indian Council for Medical Research (ICMR).
In this regard, approaches under development by GE Life Sciences and Neuome Technologies have focused on the molecular mechanism of viral attachment to epithelial cells and their entry into these cells. This is a novel approach where nanoparticle-tagged sensors have the capability to bind to virus proteins such as the S1 or S2 subunits of the spike protein. When such interactions happen, there will be color change, suggesting the presence of the virus.
Efforts are also on to evaluate the correlation between ACE2 gene single nucleotide polymorphisms (SNPs) to the severity of the infection, which can help in prioritising healthcare facilities for much-needed patients. Variant rs2285666 (also called G8790A) of ACE2 has been extensively studied as a risk for hypertension, type-2 diabetes and coronary artery disease. There is therefore a possibility that this variant also constitutes a predisposing factor for the comorbidities observed in COVID-19 patients. ACE2 is expressed in all tissues, with the highest levels of activity in the kidney and ileum, followed by the adipose tissue, heart, brain stem, lungs, stomach, liver, and nasal and oral mucosa. Comparison studies between SARS-CoV and COVID-19 (SARS-CoV-2) show the ACE2 binding domain is nearly identical between the two viruses, but small interaction differences indicate that convergent evolution may have occurred to improve COVID-19’s ACE2 receptor binding affinity. Differences in the ACE2 genes caused by single nucleotide polymorphisms may explain why younger people with no underlying conditions are succumbing to the virus. Other SNPs specific to the mannose-binding lectin structure in antigen-presenting cells (APCs) — immune cells that alert T-cells of invaders — have been cited as flagging an elevated risk in SARS-CoV infection. Another gene called TMPRSS2 is well known to oncologists as a fusion gene between TMPRSS2 and ERG, and is very common in prostate cancer patients. This gene has high expression levels in lungs too, suggesting its role in improving COVID-19 entry into lung cells. Three SNPs in this gene — rs2070788, rs9974589 and rs7364083 — seem to have an association with increased severity of the infection (Alsetta et al doi: https://doi.org/10.1101/2020.03.30.20047878). More studies, with a focus on genomics, are needed to help uncover the complexities of the viral interaction with the human body and to help in developing new therapies and provide an understanding of the genetic predisposition to the infection.
The author is a medical scientist and former director of SGRF, Bangalore