These data demonstrate that lung POCUS provides rapid information regarding COVID-19 status that is consistent with results of the current gold standard RT-PCR test. In our patient cohort, there was also anecdotal evidence that lung POCUS could outperform the RT-PCR test. At least three patients in this study with initially negative RT-PCR testing but lung POCUS examinations suggestive of COVID-19 were subsequently diagnosed with SARS-CoV-2 infection through more invasive testing.
While descriptive studies of lung POCUS findings in COVID-19 are numerous [19, 22, 25], this is most thorough investigation of a quantitative lung POCUS score to diagnose COVID-19 with data allowing maximization of sensitivity, specificity, and discriminative ability. Other studies do provide information on the test characteristics of lung POCUS in the diagnosis of COVID-19, but are limited by much smaller cohorts and unable to demonstrate the performance in populations with various comorbidities [26, 27, 29, 31]. The present study provides a more comprehensive assessment of the diagnostic power of lung POCUS in a large heterogenous population, and provides vital information for properly applying lung POCUS in the diagnosis of COVID-19.
These data suggest that a Lung Ultrasound Score cutoff of 2 points maximizes sensitivity for use in screening of symptomatic patients. Using this approach, any POCUS examination with three or more discrete B-lines in two distinct lung fields, or any examination with confluent B-lines or subpleural consolidation in any single lung field is concerning for COVID-19, requires isolation, and may benefit from additional testing. Any lung POCUS examination with a Lung Ultrasound Score of 0 points or 1 point is very unlikely to be associated with COVID-19, and can be triaged out of PUI workflows and investigated for other etiologies of their symptoms. At any point during the examination, if the cumulative Lung Ultrasound Score is equal to or greater than 2 points, the clinician can stop and order confirmatory testing, and move on to the next patient. This approach deliberately maximizes the sensitivity and negative predictive value at the expense of the specificity and positive predictive value, and will need to be externally validated. Additionally, while this approach may be advantageous for efficiency, the secondary analysis strongly suggests that complete examinations with 12 lung fields have improved diagnostic power compared to abbreviated examinations. Other cutoffs maximizing specificity (8 points) or balancing between sensitivity and specificity (6 points) can be considered in the appropriate clinical contexts.
The accuracy of lung POCUS may be impacted by patient factors. Elevated BMI reduced the sensitivity of lung POCUS for COVID-19, consistent with prior studies that have reported similar effects of obesity [33]. Pre-existing interstitial lung disease reduced the specificity of lung POCUS for COVID-19. This confounder may be due to the pre-existing pathology of interstitial inflammation, scarring, and thickening leading to a similar ultrasonographic appearance. It is also challenging to differentiate between pulmonary edema due to heart failure [34] or end-stage renal disease and the interstitial inflammation caused by COVID-19. In patients with B-lines on lung POCUS, a concurrent cardiac POCUS may help differentiate between COVID-19 and cardiac etiologies [35]. Other tools such as M-mode evaluation for pleural irregularities [35] and the presence of "spared areas" [36] have been used to differentiate interstitial syndrome from pulmonary edema in the past, but have not been validated for use with COVID-19. Avoiding the use of lung POCUS in patients with these confounding comorbidities (morbid obesity, interstitial lung disease, heart failure) improves the diagnostic performance for COVID-19.
Study limitations
The retrospective design predisposes to recruitment bias. This study is somewhat insulated from this limitation since the RT-PCR testing often had not resulted when the POCUS images were acquired and when the patients were identified for inclusion in the review. The inclusion of patients with variable duration of symptoms and illness severity as well as in different practice environments raises concerns for spectrum bias, but also demonstrates the accuracy that can be expected with real-world application of this diagnostic test.
The majority (77%) of the patients evaluated in this study were admitted to the hospital, which may limit the applicability of these findings in patients who do not require hospitalization. Several factors contribute to this bias, including triage of less severe, outpatient-appropriate patients to a treatment tent without ultrasound equipment, absence of clear guidelines for safe discharge early in the pandemic, and the nature of the tertiary hospital study site as a transfer center for care of the majority of admitted COVID-19 patients in the health system. Despite the preponderance of hospitalized patients, the variable lengths of stay (interquartile range 1–11 days) hint at a wide spectrum of illness severity and resource requirement and suggest that the lung POCUS findings may be broadly generalizable.
Another limitation is the dependence on POCUS operator skill and experience. Less-experienced point-of-care ultrasonographers tended to more aggressively label mild abnormalities in a single lung field as evidence COVID-19 even though the data suggest that most patients with positive SARS-CoV-2 RT-PCR tests have bilateral pathological findings. Undergained or overgained images could also lead to false-negative or false-positive POCUS interpretations, although all images for this study were assessed for quality prior to inclusion. Mimics such as Z-lines (short, comet-tail artifacts arising from the pleural line that do not reach the distal end of the screen or erase A-lines) [37] and E-lines (long comet-tail artifacts that do erase A-lines but arise from the subcutaneous tissue rather than the pleura) [37] can easily be confused with B-lines and lead to false-positive diagnoses. The development of training resources will be crucial for widespread implementation of lung POCUS as a screening tool for COVID-19.
As this study only included PUI for COVID-19, it is unknown whether lung POCUS can be used as a screening tool for asymptomatic SARS-CoV-2 carriers. It is also unclear whether lung POCUS can be used for the diagnosis of COVID-19 in patients with primarily gastrointestinal [38] or neurological [39] symptoms. Additional studies will be necessary before lung POCUS can be applied for the screening and diagnosis of COVID-19 in these situations.
The results of this study are also applicable only during the current clinical environment, with high prevalence of SARS-CoV-2. In future periods with lower prevalence, lung POCUS may not perform well enough to use as a screening tool.
Finally, the use of RT-PCR as the reference standard is a significant limitation. Although RT-PCR is currently the gold standard for diagnosis, its sensitivity is known to be relatively limited [2]. Future, prospective studies will be needed to test whether lung POCUS provides improved sensitivity over RT-PCR testing in certain circumstances.