Clinical, Laboratory, and Radiologic Characteristics of Patients With Initial False-Negative Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid Amplification Test Results

Abstract

Concerns about false-negative (FN) SARS-CoV-2 nucleic acid amplification tests (NAATs) have prompted recommendations for repeat testing if suspicion for COVID-19 infection is moderate to high. However, the frequency of FNs and patient characteristics associated with FNs are poorly understood. We retrospectively reviewed test results from 15,011 adults who underwent ≥1 SARS-CoV-2 NAATs; 2,699 had an initial negative NAAT and repeat testing. We defined FNs as ≥1 negative NAATs followed by a positive NAAT within 14 days during the same episode of illness. We stratified subjects with FNs by duration of symptoms prior to the initial FN test (≤5 days versus >5 days) and examined their clinical, radiologic, and laboratory characteristics. Sixty of 2,699 subjects (2.2%) had a FN result during the study period. The weekly frequency of FNs among subjects with repeat testing peaked at 4.4%, coinciding with peak NAAT positivity (38%). Most subjects with FNs had symptoms (52/60; 87%) and chest radiography (19/32; 59%) consistent with COVID-19. Of the FN NAATs, 18/60 (30%) were performed early (i.e., ≤1 day of symptom onset), and 18/60 (30%) were performed late (i.e., >7 days after symptom onset) in disease. Among 17 subjects with two consecutive FNs on NP NAATs, 9 (53%) provided lower respiratory tract (LRT) specimens for testing, all of which were positive. Our findings support repeated NAATs among symptomatic patients, particularly during periods of higher COVID-19 incidence. LRT testing should be prioritized to increase yield among patients with high clinical suspicion for COVID-19.