Biobanks could identify medically actionable findings relevant for COVID-19 clinical care

To the Editor — DNA biobanks have the potential to provide real-time clinical utility during this COVID-19 pandemic by identifying patients with underlying genetic conditions that could result in a higher risk for COVID-19-related morbidity or mortality. Medically actionable genetic findings are generally considered to be genetic changes that reveal or predict a genetic condition for which preventive measures and/or treatments are available^1,2. In 2013, the American College of Medical Genetics and Genomics (ACMG) recommended the reporting of medically actionable secondary findings identified during routine clinical exome and genome sequencing¹, and in 2016 the ACMG updated this list to include 59 genes for genetic conditions they deemed to meet criteria for medical actionability (i.e., ACMG59)³. Although these ACMG recommendations were not intended to become a definitive statement on genetic conditions that are or are not medically actionable, the ACMG59 list has become a default standard across multiple DNA biobanks, in which sequencing has identified that roughly 3% of the population harbors a deleterious variant in one of these genes⁴. While the overall clinical impact of returning unanticipated genomic findings is still being studied, early findings in some categories indicate evidence of its potential impact on improving patient outcomes⁵.

More recently, ongoing efforts from the Clinical Genome Resource Actionability Working Group have highlighted over 150 medically actionable genetic conditions². Using the ACMG59 and Clinical Genome Resource actionability curations as a reference, we have identified over 70 genetic conditions that could be relevant to making clinical decisions for patients who have developed COVID-19 (Table 1). These genetic conditions can broadly be split into three main categories: (1) conditions associated with an increased susceptibility to medications commonly used in managing COVID-19 and respiratory failure; (2) conditions that cause reversible metabolic or thrombotic crises that are often induced by severe illnesses such as COVID-19; and (3) conditions that cause reversible cardiopulmonary complications that can be exacerbated during severe illnesses such as COVID-19. Although knowledge of a patient’s status for one of these conditions will not protect them from developing COVID-19, it may indicate potential complexity and allow clinicians to anticipate and mitigate morbidity or mortality associated with their clinical management.

Table 1 Potential COVID-19-related medically actionable genetic conditions

Academic and national biobanks are well positioned to quickly initiate a clinical workflow for returning these medically actionable findings, as many have already accrued a critical mass of genotyping and sequencing data, and many of these biobanks already have in place the governance infrastructure for returning clinically actionable genetic findings to patients.