Suboptimal Biological Sampling as a Probable Cause of False-Negative COVID-19 Diagnostic Test Results

Can you provide a brief overview of your lab’s current research focus?

Before the pandemic, our lab studied HIV genetic diversity at the within-host and population levels, towards the ultimate goal of designing preventive (e.g. vaccine) or curative strategies. After COVID-19 emerged however, we, like other virology laboratories across the globe, pivoted our research programme to SARS-CoV-2.

What is the significance of the findings in this publication?

The study is important because it investigates possible causes of false-negative SARS-CoV-2 diagnostic test results, which can negatively impact the clinical and public health response to COVID-19. Current COVID-19 diagnostic tests employ molecular technologies to detect the virus’ genetic material, and nasopharyngeal swabs have been the preferred sample for testing to date. Although nasopharyngeal swabs are routinely ordered for respiratory viruses, the collection of a high quality specimen requires training and expertise, and it was long speculated that improper sample collection – among other factors – could cause false-negative results. To investigate this, we quantified human DNA levels recovered on nasopharyngeal swabs submitted to a single laboratory for COVID-19 testing, hypothesizing that human DNA could serve as a stable molecular marker of specimen collection quality. In support of this, we found that human DNA levels were significantly lower in samples from 40 confirmed or suspected COVID-19 cases that yielded negative diagnostic test results (i.e. suspected false-negative test results) compared to a representative pool of specimens submitted for COVID-19 testing to the same lab. Our results support suboptimal biological sampling as a contributor to false-negative COVID-19 test results and underscore the importance of proper training and technique in the collection of nasopharyngeal specimens.