A Data-Driven Strategy for Identifying Individuals Resistant to SARS-CoV-2 Virus under In-Household Exposure
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Introduction
Since the SARS-CoV-2 pandemic outbreak, susceptibility to the virus has been widely investigated from both genetic and clinical aspects. Genome-wide association studies have identified an association between the ABO locus and innate resistance to infection, though the protective effect is small. In vitro studies have pointed to several other candidate genes that might provide protection, such as a rare variant in the ACE2 receptor. Other multi-OMICs (such as proteomics and metabolomics studies) have yet to be published on this subject.
A different approach to susceptibility explores the sub-clinical infection hypothesis. These studies examined whether in some individuals, exposure leads to a subclinical infection without seroconversion, that is, without a positive reverse transcription polymerase
chain reaction (RT-PCR) or antibody measurement; and whether this results in clinical resistance, rather than a ‘complete’, or measurable, infection. Based on this hypothesis, we aimed to develop a feasible and modifiable approach for identifying TEFLONs, an acronym for Timely Exposed to Family members Leaving One Not infected. TEFLONs’ high probability of clinical resistance to a SARS-CoV-2 infection is based on their not contracting SARS-CoV-2 infection, despite residence in a household in which at least one resident had a confirmed infection. We used the household unit for the measure of exposure as it has demonstrated efficiency in assessing close contact to infected persons, and has confirmed exposure to SARS-CoV-2 infections with a high degree of certainty.
We expect our approach to be suitable for global implementation, regardless of the accessibility to genetic or other OMIC testing. This study describes the application of the approach to identifying TEFLONs, in a database of one million anonymized electronic medical records (EMR). We searched for possible commonalities and similar patient journeys of the TEFLONs, which could elucidate their potential non-genetic resistance to SARS-CoV-2.
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