key: cord-0979854-7gzx6ljt
authors: Vigneshwar, Navin G.; Krause, Martin; Bartels, Karsten
title: Positive tracheal SARS-CoV-2 RNA test after three negative SARS-CoV-2 RNA tests in a patient with COVID-19
date: 2020-06-12
journal: Can J Anaesth
DOI: 10.1007/s12630-020-01742-0
sha: c4675c2cb741d75a1f9fed8d0f2aee5eea1c5c93
doc_id: 979854
cord_uid: 7gzx6ljt

nan

Perioperative guidelines for patients with suspected coronavirus disease (COVID-19) often rely on nasopharyngeal swab testing for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Herein, we report the case of a patient with three consecutive negative nasopharyngeal swab tests followed by a positive tracheal aspirate test for SARS-CoV-2 RNA (Figure 1 ). Consent for this report was given by the patient's healthcare power of attorney.

A 78-yr-old male with a history of smoking, chronic obstructive pulmonary disease, and anemia presented with respiratory insufficiency. Two weeks prior, the patient was diagnosed at an outside hospital with COVID-19 through a positive real-time polymerase chain reaction test (RT-PCR). He continued to decompensate at his skilled nursing facility, eventually presenting to our emergency department. On admission, a viral respiratory panel and two nasopharyngeal swab SARS-CoV-2 RT-PCR tests separated by four hours were negative. With an increasing oxygen requirement and a chest radiograph revealing multifocal opacities, the patient was admitted to the inpatient COVID service.

On hospital day 1, the patient's hypoxia improved, and results from a repeat SARS-CoV-2 RT-PCR test from a nasopharyngeal swab were negative. On the morning of hospital day 2, the patient developed worsening hypoxia requiring 100% fraction of inspired oxygen delivered via high flow nasal cannula, and a repeat chest radiograph showed worsening patchy infiltrates. As he was presumed SARS-CoV-2-negative, levofloxacin and doxycycline were started for community-acquired pneumonia. As his oxygenation worsened, he was trialed on bi-level positive airway pressure ventilation but ultimately required endotracheal intubation. His post-intubation PaO 2 /FiO 2 fraction was 85. A tracheal aspirate sample was collected for a repeat SARS-CoV-2 RT-PCR test. By hospital day 3, results of the fourth SARS-CoV-2 test were positive.

Negative RT-PCR results in SARS-CoV-2-positive patients range from 20% to 70%. This variability in RT-PCR results is attributed to the anatomic location and viral load of the sample, RNA stability, the duration of viral shedding, and technical limitations within the assay itself. 1-3 Particularly relevant to our experience, the highest positive test rates have been seen in bronchoalveolar lavage specimens (93%), followed by sputum (72%), and nasopharyngeal swabs (63%), indicating that lower respiratory tract sampling may be optimal for serial testing in critically ill patients. 1 For this patient, the outside hospital used a commercially available RT-PCR kit that tested for a combination of gene targets. These included SARS-CoV-2 replicase complex (ORF 1 ab), spike, and nucleocapsid genes. Our institution's clinical laboratory used several different assays to test for SARS-CoV-2. The first negative test resulted from a commercial assay that targeted the ORF 1 ab gene. The second and third negative tests utilized a commercial assay that targets both the ORF 1 ab gene and the protein envelope E gene. The final positive test resulted from a laboratory-developed test that targeted the ORF 1 ab gene. Early reports of SARS-CoV-2 testing indicate that different gene targets may have varying sensitivities and specificities. 4 It is possible that this variability in testing kits may have impacted the yield of our nasopharyngeal samples.

Variability in testing is not limited to SARS-CoV-2, and, in part, can be explained by the viral load of the sample. During the novel influenza A (H1N1) pandemic, approximately 10% of patients showed positive RT-PCR test results in respiratory secretions after intubation when prior tests on nasopharyngeal swab gave negative results. 5 Additionally, as we have seen during the SARS pandemic, RT-PCR is very susceptible to poor sample collection and degradation of the viral RNA sample.

The incidence of negative RT-PCR results in SARS-CoV-2-positive patients is likely under-reported. An initial negative nasopharyngeal swab test should not alter clinical management in a patient showing the constellation of symptoms consistent with COVID-19. When feasible, serial lower respiratory tract samples should be collected to help confirm the diagnosis.

Disclosures None.

Editorial responsibility This submission was handled by Dr. Hilary P. Grocott, Editor-in-Chief, Canadian Journal of Anesthesia. Figure 1 Timeline for the SARS-CoV-2 RNA testing in a patient with COVID-19. After testing positive for SARS-CoV-2 RNA from a nasopharyngeal sample two weeks prior to hospital admission, three negative nasopharyngeal SARS-CoV-2 RT-PCR tests were obtained. Following further deterioration of the patient's respiratory status and endotracheal intubation, a tracheal sample was positive for SARS-CoV-2 RNA. COVID-19 = coronavirus disease; FIO 2 = fraction of inspired oxygen; E = protein envelope; HFNC = high-flow nasal cannula; N = nucleocapsid; NC = nasal cannula; PaO 2 = arterial oxygen partial pressure; RT-PCR = real-time polymerase chain reaction; S = spike; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; ORF1ab = SARS-CoV-2 replicase complex.

Detection of SARS-CoV-2 in different types of clinical specimens

Virological assessment of hospitalized patients with COVID-2019

Influenza A viral loads in respiratory samples collected from patients infected with pandemic H1N1, seasonal H1N1 and H3N2 viruses

Comparative Performance of SARS-CoV-2 detection assays using seven different primerprobe sets and one assay kit

Intensive care adult patients with severe respiratory failure caused by influenza A (H1N1)v in Spain

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations