Patients with Initial Negative RT-PCR and Typical Imaging of COVID-19: Clinical Implications

Baicry, Florent; Borgne, Pierrick Le; Fabacher, Thibaut; Behr, Martin; Lemaitre, Elena Laura; Gayol, P.; Harscoat, Sébastien; Issur, Nirvan; Kepka, Sabrina; Ohana, Mickaël; Oberlin, M.

doi:10.3390/jcm9093014

“…The duration of the persistence of antibodies generated in response to SARS-CoV-2 infection and their effectiveness in offering protective immunity is still under study [ 31 , 32 ]. In our experience in Piedmont, it was not uncommon to have COVID-19-like patients that repeatedly tested negative at RT-PCR, as observed by other authors [ 17 , 33 , 34 ].…”

Section: Introductionsupporting

confidence: 80%

“…After Xie et al first described the case of five “false negative” patients [ 6 ] detected by chest computed tomography (CT), many other similar reports have been published [ 7 , 17 – 20 ]. Areas of ground-glass opacity (GGO) or a “crazy paving” pattern at chest CT [ 21 ] became the alternative gold-standard, or even the inclusion criteria as in the study by Baicry et al [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…After Xie et al first described the case of five “false negative” patients [ 6 ] detected by chest computed tomography (CT), many other similar reports have been published [ 7 , 17 – 20 ]. Areas of ground-glass opacity (GGO) or a “crazy paving” pattern at chest CT [ 21 ] became the alternative gold-standard, or even the inclusion criteria as in the study by Baicry et al [ 17 ]. Although the American College of Radiology reiterated the warning that a CT scan should not be used as a first-line test, their guidelines [ 22 ] specifically provided guidance to radiologists reporting CT findings that were potentially attributable to COVID-19 pneumonia and this classification has been widely used [ 7 , 17 – 19 , 21 – 23 ].…”

Section: Introductionmentioning

confidence: 99%

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The broad spectrum of COVID-like patients initially negative at RT-PCR testing: a cohort study

Caramello

¹

,

Macciotta

²

,

Bar

³

et al. 2022

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Background Patients that arrive in the emergency department (ED) with COVID-19-like syndromes testing negative at the first RT-PCR represent a clinical challenge because of the lack of evidence about their management available in the literature. Our first aim was to quantify the proportion of patients testing negative at the first RT-PCR performed in our Emergency Department (ED) that were confirmed as having COVID-19 at the end of hospitalization by clinical judgment or by any subsequent microbiological testing. Secondly, we wanted to identify which variables that were available in the first assessment (ED variables) would have been useful in predicting patients, who at the end of the hospital stay were confirmed as having COVID-19 (false-negative at the first RT-PCR). Methods We retrospectively collected data of 115 negative patients from2020, March 1st to 2020, May 15th. Three experts revised patients’ charts collecting information on the whole hospital stay and defining patients as COVID-19 or NOT-COVID-19. We compared ED variables in the two groups by univariate analysis and logistic regression. Results We classified 66 patients as COVID-19 and identified the other 49 as having a differential diagnosis (NOT-COVID), with a concordance between the three experts of 0.77 (95% confidence interval (95%CI) 0.66- 0.73). Only 15% of patients tested positive to a subsequent RT-PCR test, accounting for 25% of the clinically suspected. Having fever (odds ratio (OR) 3.32, (95%CI 0.97-12.31), p = 0.06), showing a typical pattern at the first lung ultrasound (OR 6.09, (95%CI 0.87-54.65), p = 0.08) or computed tomography scan (OR 4.18, (95%CI 1.11-17.86), p = 0.04) were associated with a higher probability of having COVID-19. Conclusions In patients admitted to ED with COVID-19 symptoms and negative RT-PCR a comprehensive clinical evaluation integrated with lung ultrasound and computed tomography could help to detect COVID-19 patients with a false negative RT-PCR result.

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“…First, we chose RT-PCR as the gold standard for both positive and negative definite diagnosis, which is a debatable position for cases with positive chest CT and negative RT-PCR (148 in our cohort), considering that the risk of false negative of RT-PCR is non-negligible is these cases [ 5 , 19 , 20 ]. However, 33.1 % of these 148 patients with a positive chest CT and an initially negative RT-PCR had a repeat RT-PCR assay (up to 6 times) that remained negative.…”

Section: Discussionmentioning

confidence: 99%

Temporal variations in the diagnostic performance of chest CT for Covid-19 depending on disease prevalence: Experience from North-Eastern France

Ohana

¹

,

Müller

²

,

Séverac

³

et al. 2021

European Journal of Radiology

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The purpose of this work was to analyze temporal variations in the diagnostic performance of chest CT for Covid-19 throughout the first wave, depending on disease prevalence variations between the ascending, peak and descending phases of the epidemic in NorthEastern France. Materials and Methods: From March 6th to April 22nd 2020, all consecutive adult patients referred to the "Covid-19 clinic" of our Emergency Department with the availability of chest CT and of at least one RT-PCR result were retrospectively included in the present study. Chest CT was considered positive when typical Covid-19 lesions were observed (bilateral and predominantly peripheral and sub-pleural ground glass opacities and/or alveolar consolidations). RT-PCR results were considered as the reference standard. Ascending, peak and descending phases were determined based on the number of CT scans performed daily. CT diagnostic performance were calculated and variations between phases were tested for equivalence or difference using Bayesian methods. Results: 2194 consecutive chest CT were analyzed. Overall CT diagnostic performance was Se = 84.2 [82.0 ; 86.3], Sp = 86.6 [84.5 ; 88.5], PPV = 86.1 [84.0 ; 88.1], NPV = 84.7 [82.6 ; 86.7] and accuracy = 85.4 [83.9 ; 86.8], with no significant differences between chest and non-chest radiologists. Variations between the ascending (11 days, 281 chest CT, disease prevalence 37.0 %), the peak (18 days, 1167 chest CT, disease prevalence 64 %) and the descending phases (19 days, 746 chest CT, disease prevalence 32.2 %) were highest for PPV and NPV with a probability of difference >99.9 %, and smallest for accuracy and specificity with a probability of equivalence >98.8 %. Conclusion: In a homogenous cohort of 2194 consecutive chest CT performed over a 7-week epidemic wave, we observed significant variations of CT predictive values whereas CT specificity appeared marginally affected.

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“…All demographic, radiological, and virological characteristics showing a significantly different trend across PCT classes were considered as potential confounders in regression models. In particular, age, sex, positive RT-PCR test for SARS-CoV-2, and presence of consolidations on chest HRCT were considered as possible confounders, for their established influence on COVID-19 clinical presentation and prognosis [ 28 , 29 ].…”

Section: Methodsmentioning

confidence: 99%

The Clinical Significance of Procalcitonin Elevation in Patients over 75 Years Old Admitted for COVID-19 Pneumonia

Ticinesi

¹

,

Nouvenne

²

,

Prati

³

et al. 2021

Mediators of Inflammation

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Aim. To investigate the clinical significance of procalcitonin (PCT) elevation on hospital admission for coronavirus disease-19 (COVID-19) and its association with mortality in oldest old patients ( age > 75 years ). Methods. The clinical records of 1074 patients with chest high-resolution computed-tomography (HRCT) positive for interstitial pneumonia and symptoms compatible for COVID-19, hospitalized in medical wards during the first pandemic wave in a single academic center in Northern Italy, were retrospectively analyzed. All patients had serum PCT testing performed within six hours from admission. Information on COVID-19-related symptoms, comorbidities, drugs, autonomy in daily activities, respiratory exchanges, other routine lab tests, and outcomes were collected. Clinical characteristics were compared across different admission PCT levels and ages. The association of admission PCT with mortality was tested separately in participants aged > 75 and ≤75 years old by stepwise multivariate Cox regression model with forward selection. Results. With increasing classes of PCT levels (<0.05, 0.05-0.49, 0.5-1.99, and ≥2 ng/ml), there was a significant trend ( P < 0.0001 ) towards older age, male gender, wider extension of lung involvement on HRCT, worse respiratory exchanges, and several other laboratory abnormalities. Each incremental PCT class was associated with increased risk of hospital death at multivariate models in subjects older than 75 (hazard ratio for PCT ≥ 2 vs. <0.05 ng/ml: 30.629, 95% confidence interval 4.176-224.645, P = 0.001 ), but not in subjects aged 75 or younger. Conclusions. In patients admitted for COVID-19, PCT elevation was associated with several clinical, radiological, and laboratory characteristics of disease severity. However, PCT elevation was strongly associated with hospital mortality only in oldest old subjects ( age > 75 ).

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Patients with Initial Negative RT-PCR and Typical Imaging of COVID-19: Clinical Implications

Cited by 10 publications

References 33 publications

The broad spectrum of COVID-like patients initially negative at RT-PCR testing: a cohort study

The broad spectrum of COVID-like patients initially negative at RT-PCR testing: a cohort study

Temporal variations in the diagnostic performance of chest CT for Covid-19 depending on disease prevalence: Experience from North-Eastern France

The Clinical Significance of Procalcitonin Elevation in Patients over 75 Years Old Admitted for COVID-19 Pneumonia

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