Negative antigen RDT and RT-PCR results do not rule out COVID-19 if clinical suspicion is strong – Authors' reply
Authors: Nadia Mandeng, Karl Njuwa Fai, Lisa M Bebell, Yap Boum
Journal: The Lancet Infectious Diseases (2021)

"One hand cannot tie up a bundle of wood." This African proverb highlights the need for complementary efforts to achieve important tasks. The comments from Fernando Kemta Lekpa and colleagues on our Article1Boum Y Fai KN Nicolay B et al.Performance and operational feasibility of antigen and antibody rapid diagnostic tests for COVID-19 in symptomatic and asymptomatic patients in Cameroon: a clinical, prospective, diagnostic accuracy study.Lancet Infect Dis. 2021; (published online March 25.)https://doi.org/10.1016/S1473-3099(21)00132-8Summary Full Text Full Text PDF PubMed Scopus (67) Google Scholar underscore the challenge of COVID-19 diagnosis in symptomatic people testing negative for SARS-CoV-2 by both antigenic rapid diagnostic tests (RDTs) and RT-PCR. The authors suggest integrating clinical and radiographical features into the COVID-19 diagnostic algorithm for low-resource settings. Specifically, they believe chest CT could have an added screening value when there is strong clinical suspicion of COVID-19 but negative RT-PCR or RDT results. The use of chest CT for COVID-19 diagnosis has been extensively assessed and is reported to have 87% sensitivity and 43% specificity—test characteristics no better than most RT-PCR assays and RDTs.2Khatami F Saatchi M Zadeh SST et al.A meta-analysis of accuracy and sensitivity of chest CT and RT-PCR in COVID-19 diagnosis.Sci Rep. 2020; 10: 1-12Crossref PubMed Scopus (77) Google Scholar Although chest CT could potentially detect lower respiratory tract disease in symptomatic patients with negative upper respiratory tract testing, it is better used to help classify COVID-19 disease as mild, moderate, or severe. Because of its low specificity, ionising radiation, and limited availability, we do not believe chest CT should be added to COVID-19 screening and diagnostic algorithms in low-resource settings. However, we agree with Lekpa and colleagues that COVID-19 antibody tests have an important place in screening algorithms for people testing negative by RDT and RT-PCR, and we included antibody testing in our algorithm for asymptomatic patients.1Boum Y Fai KN Nicolay B et al.Performance and operational feasibility of antigen and antibody rapid diagnostic tests for COVID-19 in symptomatic and asymptomatic patients in Cameroon: a clinical, prospective, diagnostic accuracy study.Lancet Infect Dis. 2021; (published online March 25.)https://doi.org/10.1016/S1473-3099(21)00132-8Summary Full Text Full Text PDF PubMed Scopus (67) Google Scholar We also agree that if there is ongoing strong suspicion for COVID-19, clinicians can request up to three RDTs or RT-PCR tests to increase the probability of detecting SARS-CoV-2, especially in patients with low viral load in very early or later phases of the disease. If subsequent tests are negative and strong clinical suspicion for COVID-19 disease remains, we believe these patients should be treated as though they have COVID-19. Treatment should then be adapted to symptom severity based on pulse oximeter readings or chest CT findings, where available. Pulse oximetry is a proxy measure of arterial oxygenation, a prognostic indicator, and recommended for inpatient and remote monitoring of patients with confirmed or possible COVID-19 to identify silent hypoxaemia and limit risk of significant deterioration.3Greenhalgh T Knight M Inda-Kim M Fulop NJ Leach J Vindrola-Padros C Remote management of COVID-19 using home pulse oximetry and virtual ward support.BMJ. 2021; 372: n677Crossref PubMed Scopus (97) Google Scholar We believe pulse oximetry is a more practical risk-stratification tool for confirmed or possible COVID-19 patients, especially in low-resource settings. Those with pulse oximetry levels lower than 92% should be managed as severe COVID-19 disease, per WHO guidelines.4WHOCOVID-19 clinical management: living guidance. World Health Organization, GenevaJanuary, 2021Google Scholar Low-cost pulse oximeters could supplement management of patients with negative RDT and RT-PCR results in low-income and middle-income countries, with added prognostic and monitoring value, higher availability, and lower cost than chest CT. We declare no competing interests. Negative antigen RDT and RT-PCR results do not rule out COVID-19 if clinical suspicion is strongWe read with interest the Article by Yap Boum and colleagues,1 which brought significant insight into the importance of rapid diagnostic tests for SARS-CoV-2. Boum and colleagues provided useful information about the patterns of patient presentation. However, some important considerations lead us to suggest an improvement to the algorithm they describe in figure 2A.1 Our feeling is that the clinical context for the suspicion of COVID-19 warrants consideration. Indeed, it is not unusual to see patients with a suggestive clinical presentation, with or without chest CT imaging features suggestive of COVID-19, but negative rapid diagnostic or RT-PCR test results. Full-Text PDF Performance and operational feasibility of antigen and antibody rapid diagnostic tests for COVID-19 in symptomatic and asymptomatic patients in Cameroon: a clinical, prospective, diagnostic accuracy studyRapid diagnostic tests had good overall sensitivity for diagnosing SARS-CoV-2 infection. Rapid diagnostic tests could be incorporated into efficient testing algorithms as an alternative to PCR to decrease diagnostic delays and onward viral transmission. Full-Text PDF