• 
• 

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
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)

Search 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)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Lieveld et al 10/2020 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.
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.
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
Haak S 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.
Bitar 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.
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
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.
Schmid 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.
Zanforlin 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.
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.
Peyroni 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.
Speidel V et al 04/2021 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.
Redondo et al 27/03/21 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.
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.
Yassa 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.
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.

Comment(s)

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.

Clinical 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 ERJ 10/2020
2. Sorlini C et al The role of lung ultrasound as a frontline diagnostic tool in the era of COVID-19 outbreak Internal and Emergency Medicine 22/10/2020
3. Volpicelli G et al Lung ultrasound for the early diagnosis of COVID-19 pneumonia: an international multicenter study Intensive Care Medicine 20/03/2021
4. Haak et al Diagnostic accuracy of point-of-care lung ultrasound in COVID-19 Emergency Medicine Journal 18/11/2020
5. Bitar Z et al Appropriateness of lung ultrasound for the diagnosis of COVID-19 pneumonia Health Science Reports
6. Narinx N et al Feasibility of using point-of-care lung ultrasound for early triage of COVID-19 patients in the emergency room Emergency Radiology 10/09/2021
7. Brenner D et al Diagnostic accuracy of lung ultrasound for SARS-CoV-2: a retrospective cohort study The Ultrasound Journal
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 BMC Emergency medicine
9. Zanforlin A et al Lung Ultrasound in the Emergency Department for Early Identification of COVID-19 Pneumonia Respiration
10. Pare J et al Point-of-care Lung Ultrasound Is More Sensitive than Chest Radiograph for Evaluation of COVID-19 Western Journal of Emergency Medicine
11. Peyrony O et al Accuracy of Emergency Department Clinical Findings for Diagnosis of Coronavirus Disease 2019 Annals of Emergency Medicine
12. Speidel V et al Lung Assessment with Point-of-Care Ultrasound in Respiratory Coronavirus Disease (COVID-19): A Prospective Cohort Study Ultrasound in Medicine and Biology
13. Redondo J et al Higher Accuracy of Lung Ultrasound over Chest X-ray for Early Diagnosis of COVID-19 Pneumonia International Journal of Environmental Research and Public Health 27/03/21
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 European Journal of Radiology 08/10/2020
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 The Journal of Maternal-Fetal and Neonatal Medicine 28/07/2020
16. Fonsi GB et al Is Lung Ultrasound Imaging a Worthwhile Procedure for Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia Detection? Journal of Ultrasound in Medicine 07/09/2020