Diagnosis of COVID-19 in Patients with Negative Nasopharyngeal Swabs: Reliability of Radiological and Clinical Diagnosis and Accuracy Versus Serology

Antonio Mirijello ,Giuseppe Miscio,Lazzaro Di Mauro,Giulia Castorani,Michele Zarrelli,Carmen Marciano,Massimo Carella,Massimiliano Copetti,Maurizio Leone,Gianluca Ciliberti,Cristina Borelli,Annabella Di Giorgio,Salvatore De Cosmo,Doriana Vergara,Pamela Piscitelli,Michele Inglese,Angela De Matthaeis,Cristiano Carbonelli,Annalisa Simeone ,Grazia Vittoria Orciulo ,The Css-Covid-Group

doi:10.3390/diagnostics11030386

Abstract

Background: The diagnosis of Coronavirus disease 2019 (COVID-19) relies on the positivity of nasopharyngeal swab. However, a significant percentage of symptomatic patients may test negative. We evaluated the reliability of COVID-19 diagnosis made by radiologists and clinicians and its accuracy versus serology in a sample of patients hospitalized for suspected COVID-19 with multiple negative swabs. Methods: Admission chest CT-scans and clinical records of swab-negative patients, treated according to the COVID-19 protocol or deceased during hospitalization, were retrospectively evaluated by two radiologists and two clinicians, respectively. Results: Of 254 patients, 169 swab-confirmed cases and one patient without chest CT-scan were excluded. A total of 84 patients were eligible for the reliability study. Of these, 21 patients died during hospitalization; the remaining 63 underwent serological testing and were eligible for the accuracy evaluation. Of the 63, 26 patients showed anti-Sars-Cov-2 antibodies, while 37 did not. The inter-rater agreement was “substantial” (kappa 0.683) between radiologists, “moderate” (kappa 0.454) between clinicians, and only “fair” (kappa 0.341) between radiologists and clinicians. Both radiologic and clinical evaluations showed good accuracy compared to serology. Conclusions: The radiologic and clinical diagnosis of COVID-19 for swab-negative patients proved to be sufficiently reliable and accurate to allow a diagnosis of COVID-19, which needs to be confirmed by serology and follow-up.

Highlights

The diagnosis of Coronavirus disease 2019 (COVID-19) stands on the positivity of real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) from nasopharyngeal swab [1,2], in addition to laboratory, clinical-epidemiological, and radiologic findings [1]
Initial CT findings of COVID-19 pneumonia are represented by bilateral ground glass opacities (GGO), with a predominantly subpleural location
In a sample of hospitalized patients with suspected COVID-19 and multiple negative molecular nasopharyngeal swabs, we aimed to ascertain the reliability of the diagnosis established by radiologists and clinicians and the accuracy of their diagnoses versus serology

Summary

Introduction

The diagnosis of Coronavirus disease 2019 (COVID-19) stands on the positivity of real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) from nasopharyngeal swab [1,2], in addition to laboratory, clinical-epidemiological, and radiologic findings [1]. We evaluated the reliability of COVID-19 diagnosis made by radiologists and clinicians and its accuracy versus serology in a sample of patients hospitalized for suspected COVID-19 with multiple negative swabs. The inter-rater agreement was “substantial” (kappa 0.683) between radiologists, “moderate” (kappa 0.454) between clinicians, and only “fair” (kappa 0.341) between radiologists and clinicians Both radiologic and clinical evaluations showed good accuracy compared to serology. Conclusions: The radiologic and clinical diagnosis of COVID-19 for swab-negative patients proved to be sufficiently reliable and accurate to allow a diagnosis of COVID-19, which needs to be confirmed by serology and follow-up

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