COVID-19 (Coronavirus Disease 2019) is an illness caused by the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) that mainly affects the breathing system.1 Last year COVID-19 affected individuals all over the world. In total, over 98 million cases of the disease and 2 million deaths have been recorded.2,3 The SARS-CoV-2 presents a 7% case fatality rate globally, however, it varies greatly in different countries of the world. The death rate of COVID-19 is not the best marker to estimate the severity of the illness, since its diagnosis is based on the Real Time Polymerase Chain Reaction (RT-PCR) and in many countries, like Brazil, the access to this resource is reduced due to lack of materials, equipment, transport logistics and laboratory staff to meet the demand for exams.4,5 Thus, many SARS-CoV-2 colonization asymptomatic cases or those presenting mild severity are not recorded by the health system.

The COVID-19 became a global challenge in 2020 due to the SARS-CoV-2 high virulence and the fact that it has been able to cross borders and reach populations all over the world, causing high demand on health services and the need for the action of multidisciplinary teams throughout the pandemic.5 Management of the disease requires the use of intensive care units; however, not all countries have been able to deal with the high number of individuals affected simultaneously and there has been a collapse in the health service of many countries that has resulted in the need for political interventions.6 In the global context, social distancing has been described as the most efficient mechanism for reducing virus spread and controlling the COVID-19 pandemic.7–9

The COVID-19 clinical variability is mainly dependent on underlying diseases and age.10 The literature reports alterations of the pulmonary function, and the use of lung high resolution computed tomography (HRCT) is advised to determine the extent of the damage.11 However, this examination presents high cost, difficult accessibility for the patients affected, necessity of physical structure and patient transportation to the tomography equipment, exposure to radiation and lack of applicability during hospitalization. Thus, among the image exams, the lung ultrasound (LU) stands out and might become a useful tool for use in the treatment and follow up of patients with COVID-19, mainly in more severe cases when intensive care is required. In this context, we carried out this systematic review of the use of LU in COVID-19 in 2019 and 2020.

The systematic review was carried out using the data base PubMed/Medline and according to the preferred reporting items for systematic review and meta-analysis (PRISMA) covering the period from December 2019 to October 2020. The following descriptors guided the search: ((Lung ultrasound OR ultrasound OR lung ultrasonography OR lung US) AND (coronavirus disease-19 OR coronavirus disease OR corona virus OR COVID-19 OR COVID19 OR SARS-CoV-2)) with the following filters: clinical study; clinical trial; clinical trial protocol; clinical trial, phase I; clinical trial, phase II; clinical trial, phase III; clinical trial, phase IV; comparative study; controlled clinical trial; guideline; journal article; observational study; practice guideline; and randomized controlled trial. Also, the filter for Humans and English language were used.

From the 1,691 studies found, the papers excluded were: (i) 10 in other languages (8 published in Chinese and 2 in Spanish); (ii) 77 reviews and guidelines; (iii) 969 papers that addressed other image exams such as HRCT, positron emission tomography combined with computed tomography and thorax radiography without the use of LU; (iv) 483 due to the approach of different themes that were related to LU or those that had been developed using animals; (v) 77 guidelines and systematic reviews without association with LU (Fig. 1).

Figure 1.

The systematic review flowchart. The systematic review was carried out using the data base PubMed/Medline and according to the preferred reporting items for systematic review and meta-analysis (PRISMA) covering the period from November 2019 to October 2020. The following descriptors guided the search: ((Lung ultrasound OR ultrasound OR lung ultrasonography OR lung US) AND (coronavirus disease-19 OR coronavirus disease OR corona virus OR COVID-19 OR COVID19 OR SARS-CoV-2)). LU = lung ultrasound; CT = computed tomography; CXR = chest X-ray; PET-CT = positron emission tomography combined with computed tomography; COVID-19 = coronavirus disease-2019.

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A total of 102 papers were evaluated, at least title and abstract, and some of these reports were selected to support this paper’s introduction and discussion and provide some theoretical-scientific basis of LU, from those, 57 addressed the LU role in COVID-19 without evaluating patients with that disease. Consequently, 45 papers were selected for the literature review. The inclusion criterion was the search for references to the application of LU in the investigation of SARS-CoV-2 infection. Three authors (AOP, RMC and RU) selected the titles and abstracts of the papers individually and there was no disagreement regarding this choice of material to produce the systematic review. Out of the 45 papers, one was excluded for lack of access to the full text even after contacting the corresponding author and one was dismissed because it appeared twice in the search, that is, the same study was published in the same journal, once as a short communication and another time as a letter to the editor.

The data collected from each study were: author (year of publication), type of study, number of patients with COVID-19 or number of participants, COVID-19 diagnostic method, clinical characteristics of the patients, LU findings, use of other imaging exams, scanning areas/LU technique/sort of equipment, patient treatment, the use of individual protection equipment by the professional carrying out the LU, machine cleaning and comments.

Forty-three studies reported lung impairment in COVID-19 evaluated by the LU propaedeutic. Those studies totaled 2,116 patients, including children, adults, elderly and pregnant women, 863 male and 1,210 female individuals, and 43 patients whose gender was not given, the age of the patients ranged from 0 to 106 years. The country with the highest number of reports on the use of this clinical tool was Italy with 15 studies,12,15,25,27,30,31,34,64,69,71,77,78,82,86,87 followed by China with 8 studies,29,38,62,67,70,73,76,83 Spain with 6 studies,35,72,79,80,85,89 France with 5 studies,32,33,65,68,88 Canada with 2 studies,18,19 Brazil,63 Bhutan81 Germany,84 Israel,75 South Korea,74 Turkey66 and USA26 with 1 study each.

The results of the characteristics of the studies investigating LU in COVID-19 are presented in Tables 1 and 2.

Among the articles included, 17 are case reports,15,18,19,29,30,32,33–35,73,74,80,81,84–86,89 12 are observational studies,25,26,27,31,63,65,71,76–78,87,88 5 are observational prospective,66,68,69,75,79 and 4 are observational retrospective64,67,70,83 studies, 1 is a short communication,72 and 1 is a protocol.12

Detection of SARS-Cov2 on RT-PCR assay from the nasopharyngeal swab was found in 34 studies19,26,27,29,30,31,32,34,35,38,62–75,77–82,85–88 while the infection diagnosis was not specified in the other studies.12,15,18,25,33,76,83,84

The clinical picture was described in 39 studies and despite the variability in the signs and symptoms of the disease, fever15,18,25,26,27,29,30,31,32,34,38,62,63,69,70,74,75,77,78,79,82,84–88 was the most common symptom reported, followed by cough and dyspnea with 6 studies.15,19,21,25,26,28,29,32 It has been noted that in child populations, from 27 patients evaluated, aged 0–17 years old, 14 (51.8%) had fever, 11 (40.7%) had dry cough, and less commonly 3 (11.1%) had dyspnea, 3 had headache, 3 had odynophagia, 3 had vomiting and diarrhea, 3 had arthralgia and 2 (7.4%) had anosmia.27,31,72,74,80,89 Among the children evaluated in the studies, 4 were asymptomatic. In the adult and elderly population analyzed, the most common symptoms were fever, cough, and dyspnea, followed by headache, myalgia, nausea, vomiting and abdominal pain. The less common symptomatology included rhinitis, pharyngitis, anosmia and ageusia. Finally, within the sample of pregnant women totaling 17 patients, 6 of them had cough, 5 had fever, 2 had dyspnea, 1 had anosmia, 1 had chest pain and lastly for 11 of them, although symptomatic, their symptoms were not specified.30,31,34,66

The results of the studies revealed that patients presenting a clinical condition of dyspnea and hypoxemia showed alterations in the pulmonary aeration evaluated by LU. The evolution of the A line pattern into the appearance of B lines and consolidations was associated with the worsening of the disease and, consequently, of the clinical signals and symptoms.

The related comorbidities reported included hypertension, obesity, asthma and dyslipidemia, obstructive sleep apnea, rheumatoid arthritis, systemic lupus erythematosus, atrial fibrillation, end-stage kidney disease, dementia, diabetes mellitus, cancer and immunosuppression, liver disease, coronary disease, transient ischemic attack and stroke, and chronic obstructive pulmonary disease.

Regarding therapeutic measures, 19 studies did not mention the treatment employed. Some studies mentioned support measures, oxygen therapy and non-invasive ventilation19,25,26,29,35,67,69,70,74,76,78,80,87 or intubation with invasive mechanical ventilation19,33,36,67,69,70,76,80,81,86,89 and extracorporeal membrane oxygenation.67,70,74 The pharmacological interventions reported included the use of hydroxychloroquine, azithromycin, corticosteroids, oseltamivir, favipirapir, lopinavir/ritonavir, tolicizumab, sarilumab (anti-IL6), enoxaparin and broad-spectrum antibiotics,30,35,74,81,86,89 interferon inhalation therapy appeared in a single study,29 and another study reported the use of intravenous immunoglobulin.81

LU was implemented in the context of the SARS-CoV-2 infection in all studies and in 9 studies it was the only imaging test used in the propaedeutic of lung disease.12,34,64,67,71,72,77,80,82

Most of the studies under analysis had LU findings in common in the presence of SARS-CoV-2 infection. The most common finding was B lines, which had very distinct characteristics, 34 of which reported focal, diffuse and confluent B lines.12,15,18,19,25,26,27,29,30,31,32–35,38,62,67,68,70,72–74,77–88 Twenty-nine studies described consolidations of different types: small, large, linear, subpleural, multifocal and translobar,12,15,18,19,25,26,27,29,30,33,35,38,62,63,67,68,70,72,73,75,78–80,82–85,87,89 associated with white lung12,30 and with air bronchograms18,38. Nineteen studies described pleural irregularities,12,15,18,26,27,30,32,33,35,62,70,72,77,79,80,82,84,85,89 and 19 reported pleural and subpleural line alterations, such as thickening or shred sign.18,19,26,29,31,32,34,38,62,67,70,72,73,75,77,80,85 Ten studies referred to pleural effusion,38,62,67,70,72,75,77,82–84 8 reported bilateral findings15,34,63,79,82,86,87,88 and 3 revealed preponderance of compromise in posterior areas.79,80,89 Three studies associated appearance of A lines during recovery 35,67,80 and most of the papers reported the LU role in the serial evaluation of patients with COVID-19.27,29,30,33,35,67,68,70,71,72,74,75–77,80

Other characteristics found were the presence of glass rockets38 with or without the Birolleau variant,26 also known as white lung.61

Some studies reported radiological findings agreement between LU and HCRT.15,18,25,27,29,32,33,35,38,62,63,65,68,70,78,79,83,84,87,89 The main HCRT findings were ground glass opacities, “crazy-paving” pattern, consolidations, pulmonary infiltrates and pleural thickening as well as interlobular septal thickening.18,29,32,33,35,38,62,65,68,70,73,75,78,79,81,83–85,87,89 When comparing thorax HRCT features with those of LU in pneumonia resulting from COVID-19 the findings included (i) correlation of ground glass opacity with B lines (multifocal, discrete or confluent); (ii) presence of thickened pleura in HRCT with thickening of the pleural line in LU; (iii) pulmonary infiltrates as confluent B lines in LU; (iv) pulmonary consolidation in both techniques20 The finding “white lung” was also described as ground glass opacity in HRCT.15,18,26,27,38,62,78,87

The areas evaluated during LU presented varied results between studies; with the evaluation from 4 to 7 regions in each hemithorax depending on individual studies,12,15,30,31,34,35,62–72,74–77,79,80,82,83,87 totaling 8, 10, 12 and 14 assessment areas in these papers. Differences were found in relation to the type of transducer used, whose choice was related to the propaedeutic strategy of better evaluation of superficial regions or smaller thoraces such as in children, using the linear probe, or deeper regions and larger thoraces using the curved probe.12,15,25,31,34,35,38,62,66,67,69–72,74,76,77–80,82,87 Only one study employed sectorial probe in the pulmonary evaluation, since the institution protocols of that study advocated the point-of-care cardiac evaluation.75

Eighteen studies used LU scores.12,38,62–64,67–71,74–77,79,80,82,87 One study proposed a unified approach to standardize the use of LU in the clinical management of patients with COVID-19,12 with a score system to classify the seriousness of the lung disease (score): (0 points) presence of A lines with continuous and regular pleural line; (1 point) presence of visible B lines and irregularities in the pleural line; (2 points) presence of discontinuous pleural line with dark areas under the pleura (consolidations) with associations of B lines; (3 points) presence of coalescent B lines with “white lung” aspect, dense and widely distributed, with or without consolidations. In that study, 14 thoracic regions were evaluated, using a LU score from 0 to 42 points, in which higher score represented higher severity. Another study38 applied an LU scoring method ranging from 0 to 36 points in which both hemithoraces were divided into six regions (totaling 12 areas) where: (0) points = presence of pleural line and A-line, <3 B-lines; (1) point = presence of more than 3 B-lines; (2) points = presence of coalescent B-lines; (3) points = presence of pulmonary consolidation signs. The same assay presented a classification of severity of lung lesions: none (0 points); mild (1–7 points); moderate (8–18 points), severe (≥19 points).40 A third assay showed a scoring system of three items: (a) pleural line involvement, where (0) points = normal; (1) point = thickening (≥0.5 mm) or irregular; (2) points = blurred; (3) points = discontinuous, fragmented; (b) lung parenchymal involvement, where (0) points = no B-line; (1) point = presence of B-line ≤3; (2) points = presence of B-lines ≥4 or partially merged; (3) points = presence of B-line fully integrated (white lung or waterfall sign); (4) points = presence of pulmonary consolidation or subpleural lesion; (c) complications, where (0) points = none; (4) points = am line (pulmonary balloon); (4) points = pneumothorax or empyema; (4) points = pleural effusion. Pleural line, pulmonary parenchyma and complications were observed and scored respectively in each of the 10 examined sections.62 Also, Zhao et al. proposed a scoring system from 0 to 4 points imputed to 10 lung sonographic areas, as described below: (0) points = presence of normal pattern with lung sliding, parallel A-lines and thin pleural line; (1) point =presence of B-lines pattern; (2) points = presence of ground glass sign with B-lines occupying the entire screen; (3) points = presence of shred sign suchlike small subpleural consolidations; (4) points = presence of consolidation/pulmonary tissue-like aspect or pleural effusion.67

Other particularities and LU scores found in the studies listed above are detailed in Table 2.

The description of individual protection equipment use during LU examinations was carried out in 14 studies only.12,15,18,26,27,38,64,66,67,72,74,75,77,87 The common strategy to minimize the risk of transmission was making a LU machine available exclusively for COVID-19 exams combined with the use of protective covers for the probe and equipment. The LU examination had to be carried out, if possible, by 2 professionals, one of whom would be in direct contact with the patient and the other with the screen, the keyboard and the image acquisition and recording.12,27,67 Another strategy employed to reduce the occupational risk when dealing with patients with COVID-19 was the use of portable wireless transducers, making it easier to clean and handle the equipment.12,27,31,62,69,73,77,79,80,82,88

Fig. 2 shows the main findings of the LU imaging described in the study.

Figure 2.

Findings of the LU imaging described in the study.

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In the COVID-19 pandemic, it is necessary to seek tools that enable the evaluation of lung impairment by the disease, minimizing the involvement of multiple teams and the exposure of professionals in the health area to the SARS-CoV-2. The LU examination is an alternative in the respiratory system propaedeutic as it is a low-cost technique, highly portable and allows for repetition of exams, and can be performed at the patient’s bedside.12–14,20,22,55 The LU may be used in several moments of the natural history of the SARS-CoV-2 colonization/infection as it can identify the pulmonary involvement and seriousness of the disease in patients with suspected or confirmed COVID-19. It can also help to reduce the use of X-ray and/or thorax HRCT.17,62,66,74,85 In addition, LU is a low-cost tool that can be used in low- and average-income countries where HRCT might not be available,12 however, specialization in the area is necessary to use this technique.

The application of LU in the screening of COVID-19 symptomatic patients in the pre-hospital phase through pneumonia evaluation was described.13,63,64,82 Dini et al. (2020) proposed a flowchart of the intervention carried out employing LU in the evaluation and triage of older individuals living in nursing homes that presented symptoms consistent with the SARS-CoV-2 infection and those exposed to the infection from having contact with patients with COVID-19. Those exposed to patients with COVID-19 were submitted to LU and when the result was negative, pneumonia was excluded. When the LU result was altered, nasopharyngeal material was collected for RT-PCR. Whenever the result was positive, isolation and treatment were started; in addition, LU was carried out every 5–7 days and if the symptoms worsened, hospital admission was indicated. Patients that presented clinical symptoms consistent with COVID-19 and whose LU showed altered results, were isolated, treated and their pulmonary condition was monitored with ultrasound. Those showing unaltered LU were subject to SARS-CoV-2 RT-PCR collection and when the result was negative, other etiologies were considered for a differential diagnosis.

Other studies also showed LU applicability in the home assistance of older people and helping prevent unnecessary hospital admission, since LU integrated to the clinic and physical examination resulted in more accurate diagnosis of COVID-19 and other respiratory disease in older populations. In addition, due to the overload of the health service caused by the pandemic, some countries implemented home care for the older population whenever possible.64,82

Additionally, LU can be used in suspected diagnosis and in the prognostic stratification of individuals with pneumonia through the extension of specific patterns and their evolution to the consolidation phase in emergency assistance; it makes possible the management of patients in intensive care in relation to the mechanical ventilation and ventilator weaning; it can also monitor the effect of the therapeutic measures, like alveolar recruitment maneuvers, implemented in seriously affected patients submitted to invasive mechanical ventilation with orotracheal intubation.30,71,75

In clinical practice, when managing patients with acute hypoxemic respiratory failure due to COVID-19, deciding whether to proceed with the invasive mechanical ventilation and intubation might be a challenge; LU might be a helpful and accurate indicator of the ideal moment for intubation.76

Lu et al. investigated the role of LU role in the evaluation of the severity of the pulmonary aeration loss in intubated patients due to pneumonia by SARS-CoV-2 and those that were not intubated. The study carried out LU evaluations at different moments in the hospital care, within the period of one week after the patients had been admitted in the intensive care unit. The author pointed out that the LU could evaluate dynamically the ventilation condition of the two groups of patients in the study during the treatment and enable the prediction of the disease decline.76

Since a LU negative result, that is, without visible alterations, does not rule out a SARS-CoV-2 infection, LU cannot be considered a tool that substitutes the physical examination or the SARS-CoV-2 RT-PCR, but, it should be considered a complementary tool to be used in the screening of patients to detect mild symptoms and allow a fast and efficient decision.82 However, it has become clear that in the COVID-19 pandemic, the characteristics suggesting alterations provoked by the disease appearing in a LU or in the HRCT, even in the event of a negative SARS-CoV-2 RT-PCR test, might be highly suggestive of a SARS-CoV-2 infection.35

Antúnez-Montes et al. emphasized LU usefulness in the evaluation and triage of patients that presented respiratory complaints in the context of the SARS-CoV-2 pandemic.41 Abnormal LU findings would lead to a possible early admission into emergency units or intensive care units, while the identification of normal ultrasound patterns would categorize those patients as low risk patients. Fox et al. pointed out that LU presented a potential role in the triage of patients infected with the SARS-COV-2 and suggested an association between the more noticeable LU alterations and clinical deterioration.42,63,66,69

The existing literature suggests using of HRCT for the COVID-19 diagnosis and as a triage tool to identify SARS-CoV-2 infection, because, although the nasopharynx swab presents a definite etiological diagnosis, this test also presents limitations, mainly due to its low sensitivity,27,43 which is lower than HRCT.44 However, the HRCT is represents high cost, low availability, exposure to ionizing radiation that limits its use in some populations such as pregnant women, and the need for sedation in lower age groups.16,27,66 Therefore, LU becomes an important tool for the triage and evaluation of patients presenting COVID-19 symptoms.45,66,74

Pulmonary abnormalities might occur before clinical manifestations and some specialists recommend HRCT for patients with clinical suspicion of COVID-19.20,47 However, the high contagiousness of this virus and the risks of transporting patients in hemodynamically unstable and invasive mechanical ventilation to where radiography can be performed, results in the need for alternatives to evaluate lung damage. In such a context, LU is a positive choice as it provides similar results to those of the HRCT and is a more advanced method than thorax radiography for the evaluation of pneumonia and/or respiratory distress syndrome in adults, with the advantage of being an ionizing radiation free method.22,26,31 The LU findings in pneumonia and respiratory distress syndrome in adults caused by the SARS-CoV-2 are related to the illness phase, the seriousness of the pulmonary lesion and the presence of comorbidities. The predominant pattern is of varied degrees of interstitial syndrome and alveolar consolidations, related to the seriousness of the pulmonary lesion.20,26,30,82,83

Earlier quantification of the severity of the pulmonary impairment in patients with COVID-19 might be obtained by estimating the total number of pulmonary areas detected as pathological in LU.48,83 In a prospective study with 10 patients during a 15-day investigation period, the author demonstrated the LU score as a bedside non-invasive monitor of the pneumonia evolution in the COVID-19 disease by the graphical description of the evolution of the scores in the LU. Successfully extubated patients showed lower scores than those found before the intubation. The scores tended to increase in deaths caused by refractory hypoxemia, as a result of the progressive component of the pulmonary aeration failure characteristic of COVID-19. In addition, the score enabled early diagnosis of pneumonia associated with mechanical ventilation through the increase in new consolidations. Good agreement was observed between the thorax HRCT and LU to detect the presence of consolidations.68

In an observational series, LU was shown to be a useful tool to evaluate and monitor lung impairment in pregnant women with COVID-19, playing an important role in the treatment decision. All the patients presented ultrasound characteristics indicating COVID-19 at admission and 3 patients obtained resolution of the ultrasound pulmonary alterations.30 The use of LU in the follow-up and evolution evaluation has been described in several studies.67,70,80 Zhao et al. evaluated 35 patients with different clinical conditions and divided them into two groups that were classified according to clinical severity. Patients feeling uncomfortable and with respiratory failure were called non-refractory, while those presenting refractory respiratory failure with PaO2 (oxygen partial pressure)/FiO2 (oxygen inspired fraction) ≤100 or patients treated with extracorporeal membrane oxygenation, were classified as refractory group. The ground-glass opacity pattern and the consolidations were more frequent in the refractory group. In the follow-up, B lines were seen to transform into A lines, with reduction in and disappearance of consolidations. Therefore, it seems relevant to emphasize that the presence of more consolidation areas and interstitial syndrome might imply disease worsening. In addition, the study showed one more use for the LU to spot, with high specificity (∼90%), patients that might need extracorporeal membrane oxygenation.

When evaluating the child population, a study with 8 individuals from 0 to 17 years old documented improvement of radiological alterations throughout clinical evolution and resolution of the pulmonary disease caused by the COVID-19. One of the patients that presented a severe clinical situation was examined repeatedly with LU on alternate days and a reduction was noticed in the B lines pattern bilaterally one day before the clinical and radiographic improvement. In the same study, LU repeated before the hospital discharge showed improvement in the resolution of consolidations and interstitial patterns, consistent with the concomitant radiologic findings.25 The reappearance of A lines was reported in the illness recovery phase.35,56,80

Gregorio-Hernández et al., described LU findings in newborns infected by SARS-CoV-2, carried out every 48 h in the first week after diagnosis, and ascribed a score according to the severity of the pulmonary sound involvement and applied the score (from 0 to 3 points) to the 6 anatomical regions under evaluation. Newborns with an initial score from 3 to 4 points presented some degree of interstitial alveolar syndrome, and the newborn with the highest score evolved with the worst respiratory outcome.

Dudea et al. proposed a severity classification through the evaluation of the pulmonary damage using LU, in which mild to moderate damage was seen as B lines in growing number and distribution, irregular pleural line with interruptions, heterogeneous mixture of B and A lines A and pleural areas with normal sliding and small subpleural consolidations (<1 cm); the severe damage involved several B lines, stretching in superior and anterior directions, with confluent areas and increase in the number and size of the subpleural consolidations, and critical damage presenting coalescent B lines, extensive damage to the anterior and superior pulmonary areas, numerous small consolidations, areas of bilateral alveolar filling syndrome with or without air bronchogram and rare pleural collections.46 The topographic analysis of lung regions by LU and the application of scores seem to be efficient strategies for patients that require intensive care. LU scores are important to evaluate the seriousness of the structural impairment and enable the establishment of correlations with clinical deterioration.12,17,38,67,69,70 A step-by-step approach to safely performing LUS was described in several studies and recommended a systematically scanning of different zones in both hemithoraces proposing a point-awarding system to the LU findings and their correlation to the severity of the lung impairment.17,49,69 Several studies reported scanning of three areas of the thorax: anterior, lateral and posterior segments and, next, superior and inferior. Thus, 6 regions were defined for each lung.15,17,34,38,63–65,68,71,74–76,79,83 Points were awarded according to the region and the distinct aeration patterns [point(s)]: [A lines] = 0 points; [B1 lines — are associated with an interstitial syndrome and diminished lung aeration] = 1 point; [B2 lines — confluent lines appearing as a “white lung” (called also glass-rockets), equivalent to computed tomography (CT) ground-glass opacities] = 2 points; [consolidations] = 3 points. Therefore, the LU score ranged from 0 (normal) to 36 (worst pulmonary aeration).17

A retrospective study by Yan et al. analyzed 540 pulmonary regions of 29 patients with COVID-19 related pneumonia confirmed in China. The patients were submitted to simultaneous LU and HRCT in intervals of time under 12 h. That author defined two patterns of how the disease affected the pulmonary system: the interstitial alveolar pattern, defined by multiple B lines (≥3) within a region found in the LU or the presence of ground-glass opacity in the HRCT; and the Interstitial Alveolar Syndrome, defined by two or more regions with interstitial alveolar pattern per side, in which both should be found bilaterally. LU was seen to be highly sensitive to alterations in the air/pulmonary liquid interface, showing clearly the interstitial alveolar damage with inflammatory exudates and edema caused by the COVID-19. Therefore, LU showed higher sensitiveness than the thorax CT in the identification of alveolar and interstitial disorders, consolidations and pleural effusion.83

Another study adopted a new protocol called CLUE (COVID-19 Lung Ultrasound in Emergency) involving an anatomical parameter,49 a LU scoring system and oxygen requirement at the time of examination, in order to help the emergency clinician to make therapeutic decisions. The LU scoring system was reported as a valid tool for assessing regional and global lung aeration in Acute Respiratory Distress Syndrome in other studies,50,51 one that can be used in COVID-19 pneumonitis with several similar sonographic features.20 LU scoring system points ranged from 0 to 3 points, in each zone, totaling 12 zones, with higher points allocated to severe lung changes. The severity was classified as mild (score 1–5), moderate (6–15) and severe (>15). Employing the CLUE protocol could help risk-stratify suspected patients with COVID-19 and may decrease reliance on chest X-rays or HRCT chest during the initial clinical evaluation of suspected patients.

Two studies have evidenced LU accuracy in detecting acute illnesses and its non-inferiority in relation to thorax radiography in the differential diagnosis of pneumonias, pulmonary edema and pleural effusion;15,23 the use of this tool in chronic diseases such as cystic fibrosis was also evaluated.24 This demonstrates the advancement of ultrasound technology for pulmonary evaluation in the last few years and the relevance of this tool being disseminated in the management of COVID-19, not only for risk groups (elderly, pregnant women and adults with comorbidities) but also in the pediatric community.

When evaluating the findings of interstitial pneumonia in COVID-19, it is possible to obtain images that help the cardiovascular semiologic evaluation by providing information on the presence of morbidities such as cardiopathy and becoming a guide to fluid therapy and hemodynamic stability. Based on Point of Care Ultrasound (POCUS) findings in several organs, there are reports in which the patients received intravenous bolus injection of saline solution for hemodynamic resuscitation. The cardiac and inferior vena cava evaluations are easily obtained, and this approach aids determination of other dyspnea causes. Therefore, ultrasound might guide the amount of intravenous fluid to be used and also evaluate the right ventricular function when there is suspected cardiac insufficiency, in cases where COVID-19 might be co-occurring with cardiovascular comorbidities.57,65,72,75

POCUS can be used to quantify the illness course by counting the number of B lines in different lung regions, consolidation size or pleural effusion and development or resolution of any other lung abnormalities.53 Ji et al. used the B line count as a semi-quantitative index representing series of alterations in the pulmonary lesions before and after treatment,29,58,62 however, with some reservation, since B lines might be found in other cardiac and pleuropulmonary diseases.26,52 Other POCUS applications listed were the evaluation of deep venous thrombosis, assessment of endotracheal tube, mechanical ventilation weaning with evaluation of edema in the airways and diaphragm mobility, tracheostomy and sleep-guided deep vascular access.53,54,57,71,89

Despite the LU nonspecific findings that can occur in other illnesses including other viral pneumonias and a broad spectrum of non-infectious diseases (chronic obstructive pulmonary disease, neoplastic lymphangitis, pulmonary fibrosis and interstitial pulmonary disease), the homogeneous interstitial pattern seems to suggest the cardiogenic edema diagnosis, while a heterogeneous interstitial pattern, mainly in combination with subpleural consolidation and/or pleural thickening might suggest, in the pandemic clinical and epidemiological environment, pneumonia caused by the SARS-CoV-2.59 One study investigated ultrasound particularities that could help the distinction of bacterial pneumonia and the pneumonia caused by SARS-CoV-2. The differentiation by LU between viral and bacterial pneumonia is a challenge, however, in that assay the finding of B line artifacts, or partial or confluent B lines, small consolidations and pleural alterations was suggestive of the COVID-19. These findings are described in other interstitial pneumonic processes of viral etiology.62 Isolated large lobar consolidation with or without pleural effusion and with dynamic air bronchograms indicates bacterial infection.60

Some studies used the contrast-enhanced ultrasound to evaluate lungs regarding the presence of an underlying thrombosis process. Bedside contrast-enhanced ultrasound was indicated due to the presence of small and cuneiform pulmonary consolidations with a central echogenic point (signal described in pulmonary embolism patients) associated to the discovery of high levels of d-dimer and the impossibility of performing contrast-enhanced HRCT. Large delimited perfusion defects were demonstrated in relation to the normally perfused parenchyma. These areas were solved with the clinical improvement.37,39,46

The point of the disease development at which the ultrasound evaluation is performed is extremely important since the structural damage might precede clinical alterations.

The observation studies were seen to present small samples and experimental clinical studies were scarce.

Besides the high number of studies, the use of LU as a triage tool still lacks specific protocols, operator experience as well as reproducibility and inter-operator agreement.42,45,46 Further studies are needed to determine the role of LU as a triage tool and its use in the prognostic and monitoring of hospital patients.47

Due to the model of register of papers on the PubMed, some studies that might possibly include data collected from patients might have been overlooked in the filter analysis.

LU findings presented correlation with HRCT images.

LU can be used in respiratory system propaedeutics as an alternative to the “stethoscope use”. Special clothing and individual protection equipment are indispensable, since the manipulation of the stethoscope in pulmonary evaluation might create contamination risks for the health professionals and patients.

COVID-19 normally induces a bilateral and diffuse interstitial pneumonia with asymmetric lesions and uneven distribution, mainly involving the lung periphery, which makes it particularly suitable for investigation using LU.60

Studies have identified potential correlation between the LU patterns and the patients’ clinical outcome. One of the assays in this study reported that each pulmonary area could be in a different stage of the disease, therefore, the global evaluation of the lungs is fundamental.69

The POCUS allows for hemodynamic, cardiac and vascular evaluations (thromboembolic phenomena — deep venous thrombosis).

LU should be associated to the multisystem point-of-care exam, since the SARS-CoV-2 infection might be linked to myocarditis and a high incidence of thromboembolic events. Thus, multiorgan ultrasound evaluation in early treatment is useful to screening these complications at the bedside.

More studies on LU application in the pediatric population are necessary.

LU in COVID-19 score standardization.

Improvement of reading/automatic identification of B line software, as reported in this study is still needed.74

The advancement of the remote robotic ultrasound scanning technology assisted by the 5G network in real time by the use of big data, cloud storage and artificial intelligence must be improved.73

LU can be employed in different age groups to evaluate the seriousness and the response to treatment for the COVID-19 control. The main characteristics of LU in COVID-19 are focal, multifocal and/or confluent B lines, corresponding to the ground glass opacity of the thorax HRCT, in addition to the evidence of pleural thickening and irregularities. The fact that findings correspond shows the potential of LU as a radiation free, low cost, safe, reproducible method, with easy-to-sanitize equipment. Another advantage is the reduced need to manipulate the patient compared to the HRCT, avoiding transportation of the patient to the X-ray room and reducing the risk of contamination of other patients and the health professionals directly or indirectly involved with the patient. With the increase in the number of studies on the application of ultrasound, LU has been shown to be a useful tool for evaluating the progression, therapeutic response and follow-up of pulmonary disease in COVID-19.

The authors have no conflicts of interest to declare.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

[AOP, RMC, RU and FALM] participated in data collection; [AMAF, JDR and FALM] supervised, performed and validated data based on reproducibility. All authors conducted the writing and critical review of this study. Also, all authors read and approved the latest version of the manuscript prior to submission.