False-positive and false-negative COVID-19 cases: respiratory prevention and management strategies, vaccination, and further perspectives

ABSTRACT

Introduction: A novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was reported via nucleic acid identification in December, 2019. Accuracy of SARS-CoV-2 diagnostic assays has emerged as a major barrier to COVID-19 diagnosis, particularly in cases requiring urgent or emergent treatment.

Areas covered: In this review, we explore the major reasons for false-positive and false-negative SARS-CoV-2 test results. How clinical characteristics, specific respiratory comorbidities and SARS-CoV-2 vaccination impact on existing diagnostic assays are highlighted. Different COVID-19 management algorithms based on each test and limitations are thoroughly presented.

Expert opinion: The diagnostic accuracy and the capacity of every available assay, which need to be interpreted in the light of the background incidence of SARS-CoV-2 infection in the communities in which they are used, are essential in order to minimize the number of falsely tested cases. Automated testing platforms may enhance diagnostic accuracy by minimizing the potential for human error in assays’ performance. Prior immunization against SARS-CoV-2 impairs the utility of serologic testing of suspected COVID-19 cases. Future avenues of research to evaluate lung tissue innate immune responses hold promise as a target for research to optimize SARS-CoV-2 and future infections’ testing accuracy.

KEYWORDS:

• COVID-19
• false-negative
• false-positive
• management
• respiratory
• vaccination

Article highlights

• False-positive COVID-19 cases occur in erroneous testing and cross-reactions, and place patients at risk through cohorting with other COVID-19 cases.

• False-negative COVID-19 cases occur through sample deficiency, concurrent respiratory infection, or test inhibitors, and place healthcare workers, other patients, and the general public at risk for infection from an undiagnosed source case.

• SARS-CoV-2 vaccination produces an antibody response, which renders serologic testing for COVID-19 less reliable.

• prevailing community incidence of covid-19, together with diagnostic test accuracy, must be considered in the management of all suspected covid-19 cases

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.