False negative SARS-CoV-2 PCR - A case report and literature review

Abstract

The first case of the novel Coronavirus Diseases (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was detected in Wuhan, China in December 2019. On January 30, 2020, the World Health Organization declared a global health emergency. Countries around the world advised social distancing, businesses and schools closed, while health care workers faced a viral war. With the declaration of a global emergency, a test to rapidly detect the SARS-CoV-2 was developed to ensure swift isolation of infected persons to prevent spread of disease. Currently, the gold standard for test is Reverse Transcriptase Polymerase Chain Reaction (RT-PCR); however, patients with a high clinical suspicion for COVID-19 can sometimes have multiple negative tests. We discuss a patient under investigation (PUI) who had classic findings of COVID-19 but repeatedly tested negative from nasopharyngeal swabs until a fifth sample obtained from a deep suctioning was tested.

Management of severe COVID-19 patient with negative RT-PCR for SARS-CoV-2: Role of clinical, radiological, and serological diagnosis

“…Real-Time Polymerase Chain Reaction is the gold standard for detecting SARS-CoV-2 infection,[ 3 , 4 ] which relies on sufficient viral levels for gene amplification. [6] SARS-CoV-2 infection poses several diagnostic challenges, especially when negative RT-PCR was obtained but clinical and radiographic findings showed a high suspicion and consistent with COVID-19. False-negative RT-PCR results have been attracted significant attention recently in many reports.…”

“…False-negative RT-PCR results have been attracted significant attention recently in many reports. [ 6 , 7 , 10 , 17 ] The sensitivity of the RT-PCR assay is dependent on viral load with peak levels occurring on day 4 based on virological studies. The reliability of the test is limited by the timing of sample collection with regards to symptom onset and user technique with nasopharyngeal swabs.…”

“…The reliability of the test is limited by the timing of sample collection with regards to symptom onset and user technique with nasopharyngeal swabs. [6] RT-PCR method heavily relies on the presence of the viral genome in sufficient amounts at the site of sample collection that can be amplified. Missing the time window of viral replication can provide false-negative results.…”

“… [5] Patients with a high clinical suspicion for COVID-19 can sometimes have multiple negative tests. [6] The false-negative PCR result has been pushed significant attention and confused the clinicians as final diagnosis relies on RT-PCR positivity for the presence of SARS-CoV-2 in sufficient quantify. [ 7 , 8 , 9 ]…”

Specific and Rapid SARS-CoV-2 Identification Based on LC-MS/MS Analysis

“…However, due to the high sensitivity of these nucleic acid-based methods (limit of detection is estimated as 1-10 PFU/ml 14,15 ), they are prone to false positive results 10,16 . On the other hand, nucleic acid tests are susceptible inhibition by substances in clinical samples, leading to possible false negative results [16][17][18] . Thus in some cases, a positive result might immediately follow repeated negative tests 16 .…”