Diagnostic accuracy of RT-PCR for detection of SARS-CoV-2 compared to a composite reference standard in hospitalized patients

Stefanovic, A.; Reich, N.; Lowe, C. F.; Puddicombe, D.; Matic, N.; Greiner, J.; Simons, J.; Leung, V.; Chu, T.; Naik, H.; Myles, N.; Burns, L.; Romney, M. G.; Ritchie, G.; Champagne, S.; Dooley, K.; Sekirov, I.

Background: COVID 19 caused by the novel coronavirus SARS CoV 2 has caused the greatest public health emergency of our time. Accurate laboratory detection of the virus is critical in order to contain the spread. Although real time polymerase chain reaction (PCR) has been the cornerstone of laboratory diagnosis, there have been conflicting reports on the diagnostic accuracy of this method. Methods: A retrospective review was performed on all hospitalized patients tested for SARS CoV 2 (at St. Pauls Hospital in Vancouver, BC) from March 13 to April 12, 2020. Diagnostic accuracy of initial PCR on nasopharyngeal (NP) swabs was determined against a composite reference standard which included a clinical assessment of the likelihood of COVID 19 by medical experts, initial and repeat PCR, and post-hoc serological testing. Results: A total of 323 patients were included in the study, 33 (10.2%) tested positive and 290 (89.8%) tested negative by initial PCR. Patients testing positive were more likely to exhibit features of cough (66.7% vs 39.3%), shortness of breath (63.6% vs 35.9%), fever (72.7% vs 27.6%), radiographic findings (83.3% vs 39.6%) and severe outcomes including ICU admission (24.2% vs 9.7%) and mortality (21.2% vs 6.2%) compared to patients testing negative. Serology was performed on 90 patients and correlation between serology and PCR was 98.9%. There were 90 patients included in the composite reference standard. Compared to the composite reference standard, initial PCR had sensitivity of 94.7% (95% CI 74.0 to 99.9%), specificity of 100% (95% CI 94.9 to 100%), positive predictive value of 100% (95% CI 81.5 to 100%) and a negative predictive value of 98.6% (95% CI 92.5 to 100%). Discussion: Our study showed high sensitivity of PCR on NP swab specimens when compared to composite reference standard in hospitalized patients. High correlation of PCR with serological testing further increased confidence in the diagnostic reliability of properly collected NP swabs.