COVID 19 Testing Cannot Replace Clinical Judgement

Since the onset of the coronavirus disease 2019 (COVID-19) due to the SARS-CoV-2 virus, recommendations for diagnostics and therapeutics have rapidly evolved. The World Health Organization recommends nucleic acid amplification testing (NAAT) such as reverse transcriptase PCR (RT-PCR) as the standard for COVID-19, with a sensitivity of 95%. However, many factors can affect the results including timing of test, specimen quality, specimen handling, pooling specimens, and other technical reasons, resulting in false negatives. The case below describes a patient with a clinical presentation concerning for COVID-19 despite three negative RT-PCR tests and highlights the importance of treating patients based on their entire clinical impression rather than a single data point. A 53-year-old Hispanic male with no medical history presented to the hospital with 4 days of dyspnea and cough. He was admitted to the intensive care unit with acute hypoxemic respiratory failure requiring heated high flow nasal cannula. No associated fever, myalgias, anosmia, diarrhea, and he denied any known ill contacts, inhalation exposures or prior smoking history. Laboratory workup was notable for thrombocytosis, lymphopenia, elevated ferritin, C-reactive protein, D-dimer and lactate dehydrogenase as commonly seen with COVID-19. Infectious screen resulted with negative SARS-CoV-2 PCR by nasal swab, negative respiratory viral panel, negative HIV PCR, and negative fungal pneumonia screen. Imaging showed bilateral ground-glass opacities consistent with multifocal pneumonia (figure). He was started on a 5-day course of antibiotics for community acquired pneumonia and given high suspicion for COVID-19 pneumonia was started on dexamethasone 6mg daily with a plan to repeat SARS-CoV-2 testing. Repeat SARS-CoV-2 PCR was negative on hospital day 2 and 4 but SARS-CoV-2 antibody was positive on hospital day 6 (10 days after symptom onset). Given the positive antibody test and clinical course consistent with COVID-19 pneumonia, he was continued on dexamethasone for a total of 10 days, completed a 5-day course of remdesivir, and received 1 unit of convalescent plasma with clinical improvement. He was discharged home on hospital day 15 with supplemental oxygen. With increasing rates of infection with the SARS-CoV-2 virus, it becomes critically important to quickly and accurately diagnose patients. While RT-PCR has high sensitivity, there are still several factors that affect the accuracy and may result in false-negative results with potential implications such as delay in treatment and failure to quarantine. This case highlights the importance to treat patients based on a comprehensive clinical impression rather than a single test result.