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Negative antigen RDT and RT-PCR results do not rule out COVID-19 if clinical suspicion is strong

2021; Elsevier BV; Volume: 21; Issue: 9 Linguagem: Inglês

10.1016/s1473-3099(21)00271-1

1474-4457

Fernando Kemta Lekpa, Sylvain Raoul Simeni Njonnou, Eric V. Balti, Henry Namme Luma, Siméon Pierre Choukem,

SARS-CoV-2 and COVID-19 Research

We read with interest the Article by Yap Boum and colleagues,1Boom 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 Scopus (67) Google Scholar 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.1Boom 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 Scopus (67) Google Scholar 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.2Chen LD Li H Ye YM et al.A COVID-19 patient with multiple negative results for PCR assays outside Wuhan, China: a case report.BMC Infect Dis. 2020; 20: 517Crossref PubMed Scopus (24) Google Scholar These false-negative results could be explained by a number of factors: viral load, which is associated with disease course and disease severity; sputum or throat swab sample quality, which must contain sufficient cellular material for detection; kit performance; sample transportation and sample storage conditions; lack of standardised operating procedures; interpretation of results; and quality-control issues.2Chen LD Li H Ye YM et al.A COVID-19 patient with multiple negative results for PCR assays outside Wuhan, China: a case report.BMC Infect Dis. 2020; 20: 517Crossref PubMed Scopus (24) Google Scholar Moreover, patients with high platelet counts or C-reactive protein levels are at increased risk of having false-negative first RT-PCR results.3Lascarrou JB Colin G Le Thuaut A et al.Predictors of negative first SARS-CoV-2 RT-PCR despite final diagnosis of COVID-19 and association with outcome.Sci Rep. 2021; 112388Crossref Scopus (19) Google Scholar Finally, in the presence of a negative screening result for SARS-CoV-2, clinicians should not ignore potential differential diagnoses, which should be ruled out. As shown in the appendix, we propose in case of strong clinical suspicion but negative antigen rapid diagnostic tests or RT-PCR results that the patient is re-sampled by a different operator from the one who did the first test.4Challener DW Shah A O'Horo JC Berbari E Binnicker MJ Tande AJ Low utility of repeat real-time PCR testing for SARS-CoV-2 in clinical specimens.Mayo Clin Proc. 2020; 95: 1942-1945Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar Furthermore, adding antibody-based tests to the proposed armamentarium of diagnostic tools for COVID-19 in symptomatic individuals could improve the positive predictive value of the whole strategy. Also, in patients with a high clinical suspicion, performing up to three tests, as suggested by some authors,5Isikbay M Henry TS Frank JA Hope MD When to rule out COVID-19: how many negative RT-PCR tests are needed?.Respir Med Case Rep. 2020; 31101192PubMed Google Scholar would be wise before ruling out the diagnosis. Nevertheless, if clinical suspicion remains strong, chest CT imaging should be done, even in resource-limited settings, because of its reasonably good sensitivity and severity-grading role. Besides discussing strategies to improve the performance of the proposed algorithm, we would like to point out that the comparison of the different screening tests could have been improved by consideration of discrimination assessment methods. For instance, the authors report sensitivities and specificities of the various strategies in table 5. Assessing C-statistics, integrated discrimination improvement, and net reclassification indices could have given better insight to the data. However, the accuracy of these estimates requires an appropriate sample size, which is a prerequisite to their interpretation. We declare no competing interests. Download .pdf (.16 MB) Help with pdf files Supplementary appendix Negative antigen RDT and RT-PCR results do not rule out COVID-19 if clinical suspicion is strong – Authors' reply"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 Article1 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. 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