SARS-CoV-2 Detection Sensitivity: Digital vs Quantitative PCR

The use of digital polymerase chain reaction (dPCR) to measure plasma levels of SARS-CoV-2 RNA (RNAemia) provides greater sensitivity than quantitative PCR (qPCR) for predicting disease severity, clinical deterioration, and extrapulmonary complications (EPCs) associated with COVID-19, according to study results published in Clinical Infectious Diseases.

A team of researchers from Stanford University measured SARS-CoV-2 RNA in the plasma of 191 patients who presented to an emergency department with COVID-19 with dPCR and  qPCR. Patient symptoms, laboratory markers, and clinical outcomes were evaluated. Longitudinal plasma samples (n=27) were also collected from a subset of patients. The investigators also evaluated the role of RNAemia in the prediction of clinical severity and EPCs.

RNAemia was detected in plasma at a higher rate with dPCR compared with qPCR at baseline (23.0% vs 1.4%, respectively). The dPCR modality also featured a greater sensitivity than qPCR in detecting RNAemia on day 3 (13.3%) and on day 7 (6.8%). 

The majority of patients who underwent serial measurements showed undetectable plasma RNA within a 10-day period from symptom onset and reached a maximum clinical severity within a 16-day period. Most patients with serial measurements had symptom resolution within 33 days. 

Patients with RNAemia were significantly more likely to show signs of severe disease (odds ratio [OR], 6.72; 95% CI, 2.45-19.79), worsening of disease severity (OR, 2.43; 95% CI, 1.07-5.38), and EPCs (OR, 2.81; 95% CI, 1.26-6.36). There was also an association between RNA load and maximum disease severity (r=0.47; 95% CI, 0.20-0.67).

Limitations of the study included the small number of patient samples as well as the single-center design, which may limit the generalizability of the findings. 

The investigators noted “RNAemia on presentation might serve to direct early initiation of appropriate therapies to the patients most likely to deteriorate,” emphasizing the clinical utility of dPCR in this population.

Reference

Ram-Mohan N, Kim D, Zudock EJ, et al. SARS-CoV-2 RNAemia predicts clinical deterioration and extrapulmonary complications from COVID-19. Clin Infect Dis. Published online May 5, 2021. doi:10.1093/cid/ciab394