OBJECTIVES: To identify genetic factors associated with severe COVID-19 infections, we used de-identified data sources from a commercial diagnostic laboratory merged with limited clinical annotation from a data aggregator.

METHODS: The study utilized limited clinical data from patients testing positive for SARS-CoV-2 by nucleic acid analysis within a year (median 1 month) of remnant whole-blood collection for clinical care. The remnant specimens, coded by a commercial laboratory (Quest Diagnostics) with study ID (QD-pID), had HIPAA identifiers removed. A Limited Use Data set, including zip code, State, gender, vital status, date of ascertainment, and SARS-CoV-2 results, and de-identified samples were sent to an academic center (MSKCC), which further de-identified specimens by replacing QD-pID with study participant ID (MSK-pID), and sent samples to the National Institutes of Health for germline whole genome SNP array genotyping. The research team used de-identified individual level data provided by HealthVerity, a data aggregator, to determine disease severity as represented by patient claims linked to the SARS-CoV-2 test accession ID and QD-pID. The study, reviewed by the Western Institutional Review Board, was deemed exempt from requirement for consent under 45 CFR § 46.104(d)(4).

RESULTS: Quest Diagnostics provided N=9,241 identifiers of SARS-CoV-2 positive samples, of which 4,644 samples from COVID-19 patients were sent for genotyping. Using HealthVerity’s data marketplace, of the 4,644 samples genotyped, 1,118 (24%) had comprehensive ICD codes for severity stratification, classified as: 914 mild, 10 moderate, and 194 severe COVID-19 positive cases; correlation with genotype is ongoing.

CONCLUSIONS: This design describes a human subject research compliant model for public health studies of the association of inherited genetic variations with COVID-19 severity, by linking remnant biospecimens from a commercial laboratory with clinical annotation provided by a data aggregator and de-identified genotyping by a third-party laboratory.