Lung ultrasound scan (LUS) vs nasopharyngeal airway polymerase chain reaction (NPA PCR) at diagnosis of COVID-19 Pneumonitis

Date First Published:
June 22, 2021
Last Updated:
July 4, 2021
Report by:
Johnathan Goves, Kirsten Goves, Nishant Cherian, Medical Student, Medical Student, Specialist Registrar in Emergency Medicine (University of Manchester)
Search checked by:
Johnathan Goves, University of Manchester
Three-Part Question:
[In adult patients presenting to the ED with respiratory symptoms suggestive of Covid-19][what is the sens and spec of lung ultrasound (LUS) by Emergency Practitioners at diagnosing Covid 19 pneumonitis][as confirmed by PCR]
Clinical Scenario:
A 65 year old male presents to the ED with a 3 day history of cough and breathlessness. You are unsure of whether this is likely to be COVID-19 or something else. You worry that sending this gentleman into the hot zone of the department will expose him to COVID-19.
You know that a nasopharyngeal swab will take a long time to come back, and wonder whether LUS will help you decide whether this gentleman is likely to have COVID-19 or not, in order to triage him safely.
Search Strategy:
Embase <1974 to 2021 May 13> , Ovid MEDLINE(R) ALL <1946 to May 13, 2021>
Other papers found via citation chaining of review articles, word of mouth from colleagues, social media and searching point-of-care ultrasound websites (eg. www.ultrasoundgel.org) and ahead-of-print databases (i.e. MedRxiv) were also included.

Inclusion criteria:
Studies comparing LUS as an index test to NPA-PCR as a reference standard.
Study outcome of diagnostic accuracy

Exclusion criteria:
Diagnostic case control studies
Case reports/case series
Not English language
Composite index test
Search Details:
1 (Ultraso* or Lung ultrasound or Thoracic ultrasound or Chest ultrasound).af. (1246516)
2 (Coronavirus or Covid* or SARS-CoV-2 or novel coronavirus or nCoV*).af. (313555)
3 (diagnostic accuracy or sensitivity or specificity).af. (3892619)
4 1 and 2 and 3 (445)
5 remove duplicates from 4 (309)
6 limit 5 to human (279)
7 limit 6 to yr="2019 -Current" (238)
8 limit 7 to covid-19 (223)
Outcome:
The most recent search was conducted 13/05/2021
The most recent search yielded 223 search results. 192 were eliminated based on title. Abstract and full text review eliminated a further 15 results, leaving 16 papers for inclusion.
Relevant Paper(s):
Study Title Patient Group Study type (level of evidence) Outcomes Key results Study Weaknesses
Diagnosing COVID-19 pneumonia in a pandemic setting: Lung Ultrasound versus CT (LUVCT) – a multicentre, prospective, observational study Lieveld A et al Oct-20 Netherlands 186 symptomatic patients admitted from ED.

Multicenter prospective observational study

Measures of Diagnostic accuracy of LUS Sensitivity= 91.9% Specificity= 71%. Positive Likelihood Ratio (PLR)=3.2 Negative Likelihood Ratio (NLR)=0.1 Positive Predictive Value (PPV)=73.2% Negative Predictive Value (NPV)=91.0% Area Under Receiver Operator Characteristic Curve (AUROC)=0.81. Multiplicity when working out the confidence interval width, has not been taken into account.

No blinding.
The role of lung ultrasound as a frontline diagnostic tool in the era of COVID-19 outbreak Sorlini C et al 22/10/2020 Italy 384 symptomatic ED patients.
Retrospective Cohort Study Diagnostic accuracy of LUS Sensitivity=92%, specificity=64.9% NPV=88.6% PPV=73.3% No protocol for relaying LUS findings. Therefore incomplete reports are not included.
Lung ultrasound for the early diagnosis of COVID-19 pneumonia: an international multicenter study Volpicelli G et al 20/03/2021 Germany 1462 symptomatic patients in 20 EDs, ICUs, and COVID units. International multicenter observational study The diagnostic accuracy of LUS findings and patient presentations. Patients were divided into 5 groups based on their phenotype. Within these groups high, intermediate, and low probability lung ultrasound patterns were used to create thresholds for positive diagnosis. In the overall population: High and Intermediate findings had a sensitivity=90.2%, specificity=52.5%. PPV=81.5% NPV=69.8% Accuracy=78.9 HighLUS findings only: sensitivity=60.3%, specificity=88.9%. Accuracy=68.9%. PPV=92.6% NPV=49.1% High prevalence of COVID-19
Diagnostic accuracy of point-of-care lung ultrasound in COVID-19 Haak et al 18/11/2020 Netherlands 100 symptomatic ED patients Prospective cohort study

Primary outcome Diagnostic accuracy of LUS compared to PCR Secondary Outcome Diagnostic accuracy in patients without prior pulmonary or cardiac disease. Sensitivity=96%, Specificity=59%, NLR=2.36 PLR=0.07 NPV=45% PPV=98% compared to PCR only as reference standard. In patients with no prior cardiopulmonary diseases(n=37): Sensitivity=100% Specificity=76% NPV=100% PPV=67% High incidence of COVID-19 at time of study. May cause overestimation of diagnostic accuracy.
Appropriateness of lung ultrasound for the diagnosis of COVID-19 pneumonia Bitar Z et al 24/05/2021 Kuwait 92 ICU patients with suspected COVID-19

observational single-center study 12 zone LUS used to assess sensitivity. Sensitivity=96.9 (95%CI 85-99.5) Diagnostic accuracy of LUS not primary objective.
High pre-test probability (77 COVID-19 positive)
Only severely ill patients included.
Feasibility of using point-of-care lung ultrasound for early triage of COVID-19 patients in the emergency room Narinx N et al 10/09/2020 Belgium 90 ED patients with suspected COVID-19.

Retrospective study Diagnostic accuracy of LUS Sensitivity=93.3% Specificity=21.3% NPV=94.1 PPV=19.2 Accuracy=33.3% Retrospective design

Small incidence rate of COVID-19 in the study
Diagnostic accuracy of lung ultrasound for SARS-CoV-2: a retrospective cohort study Brenner D et al 01/03/2021 USA 174 symptomatic or exposed ED and inpatients Retrospective Cohort LUS scans given a quantified score, and measures of diagnostic accuracy taken using ROC curve analysis derived cutoff. Sensitivity=86% Specificity=71.6% NPV=81.7% PPV=77.7% AUROC=0.84(95%CI 0.78-0.9) When using complete scans, Sensitivity=90.9% Specificity=75.6% NPV=87.2% PPV=82.0% AUROC=0.89(95%CI 0.83-0.96) High variation in symptom severity and duration, and patient setting may have introduced spectrum bias.

One author consults for the equipment manufacturer. However, EchoNous was not involved in the production of this study.
Lung ultrasound in the emergency department - a valuable tool in the management of patients presenting with respiratory symptoms during the SARS-CoV-2 pandemic Schmid B et al 07/12/2020 Germany 135 symptomatic ED patients

Retrospective cohort study Diagnostic accuracy of LUS Sensitivity=76.9% Specificity=77.1% PPV=57.7% NPV=89.2% Funded by multiple external sources. Authors claim no conflict of interest.
Lung Ultrasound in the Emergency Department for Early Identification of COVID-19 Pneumonia Zanforlin A et al 07/12/2020 Italy 111 ED patients with suspected COVID-19
Retrospective single center Diagnostic accuracy of scored LUS results was assessed using ROC curve analysis. AUROC=0.837 (95%CI 0.75-0.92) using a cutoff score of 3 yielded sensitivity=90% specificity=75% Composite reference standard of PCR, ABG, and clinical judgement.

Point-of-care Lung Ultrasound Is More Sensitive than Chest Radiograph for Evaluation of COVID-19 Pare J et al 19/06/2020 USA 43 symptomatic ED patients Retrospective cohort study Sensitivity of LUS vs Chest X ray with PCR reference standard Sensitivity: LUS=88.9%(95%CI 71.1-97) CXR=51.9%(95%CI 34-69.3) Predictive values calculated as: PPV 77.4% NPV=75.0% Small sample size, retrospective study, prone to selection bias.

The physicians blinded only to RT-PCR results.

High prevalence of COVID-19 in testing group.
Accuracy of Emergency Department Clinical Findings for Diagnosis of Coronavirus Disease 2019 Peyrony O et al 21/05/2020 France 87 ED patients
Prospective observational study

Diagnostic accuracy of symptoms, clinical judgement and Bilateral B lines on LUS. Diagnostic accuracy of LUS Sensitivity=77% (95%CI 62-88) Specificity=89% (95%CI 75-97 PPV=0.9 (95%CI 0.76-0.97) NPV=0.75 (95%CI 0.60-0.87) PLR=7.09 (95%CI 2.77-18.12) NLR=0.26 (95%CI 0.15-0.45) High prevalence (57.6%) of COVID-19 in the sample population.

LUS was only performed in the most unwell patients.
Lung Assessment with Point-of-Care Ultrasound in Respiratory Coronavirus Disease (COVID-19): A Prospective Cohort Study Speidel V et al Apr-21 Switzerland 49 hospital patients with suspected COVID-19.

Prospective cohort study LUS were quantified using a score out of 36 points. Diagnostic accuracy was measured using ROC curve analysis AUROC=0.85 The odds ratio was 1.30 per point. With a cutoff of 8/36 points: sensitivity=91%, specificity=76%, PLR=3.84 NLR=0.12. LUS all carried out by a single physician

Values derived from ROC curve analysis from small sample size.

Higher Accuracy of Lung Ultrasound over Chest X-ray for Early Diagnosis of COVID-19 Pneumonia Redondo J et al 27/03/2021 Spain 212 symptomatic ED patients Observational descriptive study. Evaluate diagnostic accuracy of LUS when categorised as ‘pathologic’ or ‘non pathologic’ Sensitivity=82.75 Specificity=71% When detecting interstitial disease. Confirmation bias potentially introduced as other radiological findings evaluated by the same unblinded clinician.
Comparison of admission chest computed tomography and lung ultrasound performance for diagnosis of COVID-19 pneumonia in populations with different disease prevalence Colombi D et al 08/10/2020 Italy 486 consecutively admitted ED patients.

Retrospective analysis Diagnostic accuracy of LUS calculated for high and medium prevalence groups. High prevalence n=247 Sensitivity=94% Specificity=7% PPV=94% NPV=7% AUROC=0.51 Medium prevalence n=239 Sensitivity=93% Specificity=31% PPV=52% NPV=83% AUROC=0.62 No evaluation of interobserver agreement.

Inconsistency in the number of RT-PCR tests carried out on each patient.
Outcomes of universal SARS-CoV-2 testing program in pregnant women admitted to hospital and the adjuvant role of lung ultrasound in screening: a prospective cohort study Yassa M et al 28/07/2020 Turkey 296 women admitted to an obstetric unit.

Prospective observational study

Diagnostic accuracy of LUS in screening pregnant women of any gestation. LUS results: 73.91% sensitive, 94.14% specific. PPV=51.52% NPV=97.72% PLR=12.61 NLR=0.28 Diagnostic accuracy was 92.57%. AUROC=0.799 (Standard error=0.064, 95%CI 0.674-0.923) Only includes women of child bearing age.

No description of any blinding processes.
Is Lung Ultrasound Imaging a Worthwhile Procedure for Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia Detection? Fonsi GB et al 07/09/2020 Italy 63 symptomatic patients admitted that underwent haematological tests, CT, LUS and RT-PCR. Prospective observational study

Diagnostic accuracy of LUS, and measure of interobserver agreement. Sensitivity=68% Specificity=79% PPV=88% NPV=52% AUROC=0.745 (95%CI 0.606-0.884) Interobserver agreement k value = 0.877 Only used patients who were symptomatic for COVID-19

Inclusion criteria selected more seriously ill patients.
Author Commentary:
The sensitivity and specificity of LUS at detecting COVID-19 pneumonitis ranged from 68-96.9% and 7-94.4% respectively.
However, ten studies reported sensitivities of over 90%, and 9 reported specificities of over 70%.
LUS demonstrates variable but potentially formidable diagnostic capabilities. High variability is likely due to the qualitative nature of imaging and issues from inter-observer agreement, though some studies described methods of quantification of pathological findings to create diagnostic thresholds. Lack of standardised LUS techniques also likely contributed, although the 12-zone and BLUE techniques were common.
Spectrum bias, varying pre-test probability, and high incidence of COVID-19 was commented upon in several studies.Authors commented this may have led to overestimation of the diagnostic accuracy of LUS.
Bottom Line:
[In adult patients presenting to the ED with respiratory symptoms suggestive of Covid-19][the sensitivity and specificity of LUS ranged between 68-96.9% and 7-94.4%, though the majority of papers reported >90% and >70% ][as confirmed by NPA]
References:
  1. Lieveld A et al. Diagnosing COVID-19 pneumonia in a pandemic setting: Lung Ultrasound versus CT (LUVCT) – a multicentre, prospective, observational study
  2. Sorlini C et al. The role of lung ultrasound as a frontline diagnostic tool in the era of COVID-19 outbreak
  3. Volpicelli G et al. Lung ultrasound for the early diagnosis of COVID-19 pneumonia: an international multicenter study
  4. Haak et al. Diagnostic accuracy of point-of-care lung ultrasound in COVID-19
  5. Bitar Z et al. Appropriateness of lung ultrasound for the diagnosis of COVID-19 pneumonia
  6. Narinx N et al. Feasibility of using point-of-care lung ultrasound for early triage of COVID-19 patients in the emergency room
  7. Brenner D et al. Diagnostic accuracy of lung ultrasound for SARS-CoV-2: a retrospective cohort study
  8. Schmid B et al. Lung ultrasound in the emergency department - a valuable tool in the management of patients presenting with respiratory symptoms during the SARS-CoV-2 pandemic
  9. Zanforlin A et al. Lung Ultrasound in the Emergency Department for Early Identification of COVID-19 Pneumonia
  10. Pare J et al. Point-of-care Lung Ultrasound Is More Sensitive than Chest Radiograph for Evaluation of COVID-19
  11. Peyrony O et al. Accuracy of Emergency Department Clinical Findings for Diagnosis of Coronavirus Disease 2019
  12. Speidel V et al. Lung Assessment with Point-of-Care Ultrasound in Respiratory Coronavirus Disease (COVID-19): A Prospective Cohort Study
  13. Redondo J et al. Higher Accuracy of Lung Ultrasound over Chest X-ray for Early Diagnosis of COVID-19 Pneumonia
  14. Colombi D et al. Comparison of admission chest computed tomography and lung ultrasound performance for diagnosis of COVID-19 pneumonia in populations with different disease prevalence
  15. Yassa M et al. Outcomes of universal SARS-CoV-2 testing program in pregnant women admitted to hospital and the adjuvant role of lung ultrasound in screening: a prospective cohort study
  16. Fonsi GB et al. Is Lung Ultrasound Imaging a Worthwhile Procedure for Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia Detection?