SARS-CoV-2 Variant Testing: AMP Guidance and Recommendations

The Association for Molecular Pathology (AMP), Infectious Disease Society of America, and Pan American Society for Clinical Virology have released new guidance for laboratories on sequencing and identifying SARS-CoV-2 variants in clinical specimens (1). The document contains information on the importance of sequencing variants, when sequencing should be used, and what samples are used for next-generation sequencing (NGS) to identify SARS-CoV-2 variants.

“Timely diagnostic testing is foundational to an effective response to any emerging communicable disease – and there are several situations in which genetic variants might be suspected and testing positive samples might be prioritized,” says Blake W. Buchan of the AMP Clinical Practice Committee. “For example, samples collected from: patients with reinfection(s); patients who develop breakthrough infections; hospitalized patients with reinfection or vaccine escape; and patients with treatment failure.”

However, Buchan highlights several technical barriers that can prevent labs from routinely screening SARS-CoV-2 samples. “Variant identification can only be conducted on positive specimens collected in viral transport media and cannot be performed from the dry swabs used in some point-of-care testing methods; likewise, certain test methods use transport media that may interfere with sequencing reactions. Pooled samples also cannot be used for NGS analysis.”

He continues, “Clinical specimens used for strain identification should be the same strong-positive SARS-CoV-2 specimens identified by target-based detection assays. Requiring a relatively high viral load means that many PCR-positive specimens fail to yield adequate sequence data to enable variant identification.” This limitation has led to the development of target-specific assays for variants of concern. “These tests provide rapid and simplified identification of select known variants; however, full sequencing is required to identify novel mutations in strong positive samples. Currently, regardless of the method used, viral strain identification remains most useful for epidemiology purposes.”

Molecular pathology’s role in the pandemic is constantly expanding as new SARS-CoV-2 variants emerge. “As molecular diagnostic procedures become increasingly complex and the value and need for testing continues to grow, so too does the demand for the services of qualified molecular laboratory professionals,” he says. “As such, the AMP will continue to share expertise, assess laboratory needs, engage key stakeholders, and provide recommendations for improving future pandemic responses to ensure more patients have access to high-quality testing procedures.”