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PLOS ONE logoLink to PLOS ONE
. 2022 May 11;17(5):e0267506. doi: 10.1371/journal.pone.0267506

Point of Care Lung Ultrasound Injury Score—A simple and reliable assessment tool in COVID-19 patients (PLIS I): A retrospective study

Lior Fuchs 1,2,3,*,#, Ori Galante 1,3,#, Yaniv Almog 1,3, Roy R Dayan 3,4, Alexander Smoliakov 3, Yuval Ullman 3, David Shamia 3,4, Ran Ben David Ohayon 3,4, Evgeny Golbets 3,4, Khaled El Haj 3,4, Jonathan Taylor 5, Itai Weissberg 3,4, Victor Novack 2,3, Leonid Barski 3,4, Eli Rosenberg 2,3, Eyal Gohar 3, Muhammad Abo Abed 3,4, Iftach Sagy 2,3
Editor: Jignesh K Patel6
PMCID: PMC9094523  PMID: 35544450

Abstract

Background

In COVID-19 patients, lung ultrasound is superior to chest radiograph and has good agreement with computerized tomography to diagnose lung pathologies. Most lung ultrasound protocols published to date are complex and time-consuming. We describe a new illustrative Point-of-care ultrasound Lung Injury Score (PLIS) to help guide the care of patients with COVID-19 and assess if the PLIS would be able to predict COVID-19 patients’ clinical course.

Methods

This retrospective study describing the novel PLIS was conducted in a large tertiary-level hospital. COVID-19 patients were included if they required any form of respiratory support and had at least one PLIS study during hospitalization. Data collected included PLIS on admission, demographics, Sequential Organ Failure Assessment (SOFA) scores, and patient outcomes. The primary outcome was the need for intensive care unit (ICU) admission.

Results

A total of 109 patients and 293 PLIS studies were included in our analysis. The mean age was 60.9, and overall mortality was 18.3%. Median PLIS score was 5.0 (3.0–6.0) vs. 2.0 (1.0–3.0) in ICU and non-ICU patients respectively (p<0.001). Total PLIS scores were directly associated with SOFA scores (inter-class correlation 0.63, p<0.001), and multivariate analysis showed that every increase in one PLIS point was associated with a higher risk for ICU admission (O.R 2.09, 95% C.I 1.59–2.75) and in-hospital mortality (O.R 1.54, 95% C.I 1.10–2.16).

Conclusions

The PLIS for COVID-19 patients is simple and associated with SOFA score, ICU admission, and in-hospital mortality. Further studies are needed to demonstrate whether the PLIS can improve outcomes and become an integral part of the management of COVID-19 patients.

Background

The novel coronavirus disease 2019 (COVID-19) pandemic is a global crisis, challenging healthcare systems worldwide. COVID-19 patients may present with profound hypoxemia without accompanying respiratory distress, also called "happy hypoxemia" [1]. The ambiguous clinical presentation, combined with the unpredictable course and potential for rapid deterioration, mandates an objective, quick, bedside lung assessment tool that helps assess illness severity and guide clinical decisions [2].

There is a direct association between the severity of COVID-19 pneumonia and computerized tomography (CT) findings. Ground glass opacities, lung consolidations, and peribronchial thickening are common [3]. CT scans may be unsafe and challenging to perform in severely hypoxemic patients that require meticulous isolation measures. In COVID-19 patients, lung ultrasound (LUS) was found superior to chest X-ray in detecting lung pathologies [4, 5] and has good agreement with chest CT, suggesting LUS may serve as a safe and convenient alternative that can be performed bedside [6, 7].

The characteristic LUS findings in COVID-19 involve B-lines, consolidations, and the pleura. B-lines can appear as focal, multifocal, or confluent, and consolidations present in various patterns, including multifocal, non-trans lobar, and trans-lobar with air bronchograms [3, 8, 9]. The pleural line appears thickened and irregular, and pleural effusions are uncommon. These findings collectively are associated with mortality and Intensive Care Unit (ICU) admission [10, 11]. Moreover, among COVID-19 patients, consolidations were specifically related to critical illness [12].

Most LUS protocols published to date are cumbersome and time-consuming. They typically involve screening at least 12 different lung areas, each graded from 0 to 3 points, thus generating scores ranging from zero to 36 [6, 1114]. While these scores are informative for research purposes, they are less practical during a pandemic when physicians need to assess many severely ill patients under restrictive personal protective equipment and time constraints. In addition, the simplistic single numerical score fails to illustrate the location of lung findings, denying spatial information from the clinical team. Moreover, in these previously reported systems, B-lines are graded and given the same final weight in nondependent lung fields as dependent areas, where the specificity of these findings is limited, while consolidations are only reported in a yes/no binary format without size or localizing information. These research-focused protocols restrict many of the LUS advantages and make LUS use for daily clinical care impractical. Therefore, our investigative group developed a fast and straightforward LUS score.

Here we present a novel Point-of-care ultrasound Lung Injury Score–called the PLIS—for COVID-19 patient assessment. PLIS involves only three scanning areas on each lung, based on the known BLUE protocol scanning points, and grade the lung pathologies on a 1–6 scale. This report is the first description and implementation of the PLIS. We hypothesized that using this focused clinical-sonographic score in admitted COVID-19 patients’ assessment would be associated with the need for ICU admission.

Methods

This is a retrospective study, data were collected during patients assesments and rounds. The PLIS protocol was taught and implemented in the COVID 19 wards and ICUs, and was part of the daily pateints’ assessment. PLIS was assessed multiple times among patients admitted with COVID-19 between April 1st and June 30th, 2020, to Soroka University Medical Center in Israel. The study period included the Alpha, and Beta SARS-CoV-2 variants.

The study was approved by the hospital’s ethics committee (IRB #0195–20). The PLIS protocol was developed by the authors at the beginning of the outbreak. Scans were carried out during most morning rounds and during clinical deterioration, as detailed below. The results of each PLIS study were documented in the electronic medical record. Patients were included in the analysis if they were admitted to the hospital, had a confirmed diagnosis of COVID-19, required any method of respiratory support (i.e., nasal cannula, non-invasive ventilation, invasive ventilation, etc.), and had at least one PLIS study. The ultrasound machines used were VENUE GO, GE Healthcare, R2 version. PLIS was conducted with the 3SC probe, using the manufacturer’s lung preset to detect B-lines and the cardiac preset to detect consolidations. The PLIS was assessed bedside by internal medicine residents and senior physicians. The residents, who already had a basic knowledge of performing point-of-care LUS, received two hours of hands-on training specifically on the PLIS protocol and its components. The senior physicians were all intensivists with over seven years of experience in LUS; all were the designers of this score. While in the non-ICU settings, PLIS was performed solely by internal medicine residents, the exam was conducted by both residents and senior physicians evenly within the ICU. Inter-observer reliability, calculated by comparing lung scan reads from 2 different operators on 16 different pateints, was assessed in a blinded manner and was found adequate (Cohen’s kappa 0.607, 0.750).

Data collected included the PLIS recorded on admission, when conducted during ward/ICU rounds, and when otherwise clinically indicated. As this is not a prospective study, the PLIS exams were not protocolized. Some patients could receive a PLIS study on regular ward admission, during the morning rounds, and also later, when admitted to the ICU. Some received ultrasound lung scan only during the ICU admission or only in the regular ward. Criteria for ICU admission included (1) patients who suffered respiratory failure and required mechanical ventilation or (2) those who needed non-invasive ventilation (high flow nasal cannula or bilevel positive pressure ventilation) and were assessed by an intensivist to potentially require mechanical ventilation in the next 24 hours potentially. Other variables included demographic characteristics, relevant laboratory tests, medical history, vital signs, and ventilation parameters. Outcomes measured included: daily SOFA score, length of admission, ICU admission, mortality, days of mechanical ventilation, and the ratio between arterial oxygen partial pressure and fractional inspired oxygen (PaO2/FiO2 ratio). The primary outcome was the requirement for ICU admission. Secondary outcomes were in-hospital mortality and a composite outcome composed of in-hospital mortality, prone position, and prolonged mechanical ventilation (>14 days). This study aimed to assess whether the PLIS is associated with the severity of illness, whether it is feasible to perform at the bedside in a short time, and if it may predict the clinical course of patients with COVID-19.

Lung ultrasound—The PLIS

Lung ultrasound was conducted on patients in the supine, semi-supine, or prone position in three areas; over the midclavicular line on the upper and lower thorax (zone 1, upper and lower regions) and above the diaphragm in the mid and posterior axillary line (zone 2, lower area) (Fig 1a). The total PLIS comprises three separate elements, labeled as the A, B, and C components of the PLIS (Table 1). Each is graded from 0 to 2. The PLIS was designed to combine the method of respiratory support (the A score) with a report of the two major COVID-19 ultrasonographic findings: the interstitial alveolar syndrome, diagnosed by bilateral B-lines (the B score), and lung consolidations (the C score). The final PLIS score comprises the sum of the three components, ranging from 0–6 points.

Fig 1.

Fig 1

a. Lung zones: The three scanning areas are marked with blue stars. b. Zone 1, PLIS B, c. Zone 2, PLIS C. The stars represent the area of the scan in each zone and not the exact place of the probe.

Table 1. The Point of Care Lung Ultrasound Injury Score (PLIS) grading system.

SCORE 0 1 2
A Room air/nasal prongs Any non-invasive support over nasal prongs Intubated or extracorporeal membrane oxygenation
B*
Zone 1 only -upper and lower areas
B-lines <3 B-lines 3–5 B-lines > 5
C
Zone 1—upper and lower areas
Zone 2- lower
No consolidation Small consolidation (either unilateral or bilateral) Large** consolidation (either unilateral or Bilateral)

* B-Lines contribute to the score only if located bilaterally (The higher number of B-lines from any side defined the grading of the B component)

**Large consolidation: over 4 cm measured from the largest diameter.

A score—The respiratory support

The “A” component reflects the method of respiratory support that the patient is receiving. It incorporates into the PLIS an objective, quantifiable measure of the severity of respiratory failure based on the modality needed to maintain appropriate oxygen levels. PLIS scores room air/nasal cannula as A0. More intensive support (e.g., non-rebreather mask, high-flow nasal cannula, or non-invasive positive-pressure ventilation) grades A1. The need for invasive mechanical ventilation, prone positioning, or the requirement for extracorporeal membrane oxygenation meets the criteria for A2.

B score- interstitial syndrome

Multifocal bilateral B-lines, either discrete or confluent, are predominant in COVID-19 [6, 9]. Up to 3–5 B-lines, known as septal rockets [1517], are graded as B1. The presence of either ground-glass rockets (i.e., > 5 B-Lines) or confluent and fused B-lines are graded as B2. In the PLIS, B-lines are counted only in the anterior thorax (midclavicular line, upper and lower zone 1, Fig 1b) as posterior interstitial changes can be found incidentally due to gravity alone. Additionally, B-lines only contribute to the score if located bilaterally to avoid consideration of artifacts [18]. The higher number of B-lines from any side defined the B component score of the PLIS.

C score- lung consolidations

As COVID-19 progresses, patients develop bilateral, peripheral-predominant ground-glass opacities, consolidations, or both [3, 9]. The majority of lung consolidations touch the pleura and are visible on LUS, with most cases localizing to the posterior-inferior lung areas [19]. The PLIS evaluates for consolidations over zone 1 and zone 2 (Fig 1a and 1c). A C-score between 0 to 2 is given by the extent of consolidations (Table 1) with a size cut-off set at 4 cm in the largest dimension. A score of 0 is assigned if no consolidation is appreciated. A score of 1 indicates smaller consolidations (< 4 cm), while a C-score of 2 describes a significant consolidation (≥ 4 cm). For localization purposes, unilateral consolidations, whether large or small, specifically received the letter "R" (for right-sided) or "L" (for left-sided) attached to the numerical score. Bilateral consolidations with at least one classifying as large are labeled as C2.

Putting it together

The total PLIS includes the sum of A, B, and C components. For example, the calculated PLIS for a patient on non-invasive ventilation, with more than five B-lines (located in zone 1 and bilaterally, Fig 1b-panel E) and small bilateral consolidations (situated in zone 1 or zone 2), is A1B2C1 with a total PLIS of 4. A patient receiving oxygen supplied by nasal cannula, with over five B-lines located only over the right lung and a right large consolidation situated in zone 2 (Fig 1c), will have a PLIS of A0B0C2R, resulting in a total PLIS of 2. In this second example, the B-lines did not confer any points to the PLIS B score, as they were not detected bilaterally and thus more likely reflected an artifact from consolidation and not from the COVID-19 lung interstitial syndrome. The PLIS is designed to provide clinicians with information on the severity of the respiratory failure (A score) along with an image of the pathologic findings (B and C scores), thereby integrating clinical, physiologic data into a visuospatial representation of the LUS extent of affected lung. Ultimately, the total PLIS results in an overall assessment of COVID-19 severity and risk for worsening disease course.

Statistical analysis

Data were analyzed using SPSS 25.0. Data were expressed as mean ± standard deviation (SD), median ± interquartile range (IQR), or number and percentage. The unit of analysis was a single LUS test per patient. Patient characteristics were compared between patients admitted to an ICU versus non-ICU patients using the t-test, chi-square, and non-parametric tests. Inter-observer reliability was assessed by comparing independent ratings of the PLIS B and C scores among 16 randomly selected patients in a blinded manner. The comparison was made between a senior physician with seven years of lung ultrasound experience (LF) and four rating residents. The PLIS was compared to the SOFA score to assess external validation of the former. SOFA score was calculated for the same day per each LUS test. Correlation between each patient’s PLIS and SOFA scores was calculated using Spearman’s rank correlation coefficient and inter-class correlation. To assess internal validation, Cohen’s Kappa was calculated for 16 random PLIS, evaluated by two experienced independent physicians. Multivariate generalized estimating equation (GEE) regression evaluated covariates associated with primary and secondary outcomes. The final model was selected based on the plausible clinical explanation, statistical significance, and goodness of fit using c-statistics.

Results

A total of 109 patients and 293 PLIS studies were included in the analysis. Table 2 depicts the patient’s baseline characteristics and outcomes. The mean age was 60.9 years (±13.6). About two-thirds of cases (n = 76, 69%) were males, 32% (n = 34) suffered from diabetes mellitus, and the mean body mass index was 28 (±5.4). The median hospitalization length was nine days in total, and the overall mortality was 18.3%. The mean time of PLIS scan evaluation was 3:54 (±1:07) minutes. The Cohen’s kappa for inter-observer reliability was 0.607 for the B component and 0.750 for the C component.

Table 2. Patients’ characteristics.

Variable N = 109
Age (mean ± SD) 60.9 (13.6)
Males (n,%) 76 (69.7)
BMI (mean ± SD) 28.0 (5.4)
Smoking (n,%) 24 (22)
Diabetes (n,%) 35 (32.1)
Chronic obstructive pulmonary disease (n,%) 12 (11)
Malignancy (n,%) 10 (9.2)
Congestive heart failure (n,%) 2 (1.8)
Cerebrovascular disease (n,%) 9 (8.3)
Chronic kidney disease (n,%) 13 (11.9)
ICU admission (n,%) 36 (33)
ARDS (n,%) 27 (24.8)
Mechanical ventilation (n,%) 23 (21.1)
Composite outcome* 24 (22)
Vasopressors 23 (21.1)
Hospitalization days (median, interquartile range) 9 (6–17)
ICU days (median, interquartile range) 10 (4–21.7)
Mortality (n,%) 20 (18.3)

*Mechanical ventilation > 14 days, prone position or in-hospital mortality

ARDS- Acute Respiratory Distress Syndrome

BMI- Body Mass Index

ICU- Intensive Care Unit

A statistically significant direct association between each of the PLIS components (A, B, and C) and the SOFA score is shown in Fig 2A (PLIS A p<0.001, PLIS B p = 0.001, PLIS C p = 0.001). Fig 2B demonstrates a similar association between total PLIS (summation of A, B, and C) and the SOFA score (interclass correlation 0.63, p<0.001). Fig 3 further emphasizes the relation between PLIS and clinical outcomes by depicting an association between both higher initial and worst PLIS during hospitalization with ICU admission (A) and in-hospital mortality (B) (P<0.001 for all pairs).

Fig 2.

Fig 2

a: Presents the association between the SOFA score and each of the PLIS components: PLIS A (P<0.001), PLIS B (p = 0.001), and PLIS C (p = 0.001). b: Displays a boxplot diagram of median total PLIS and SOFA scores (interclass correlation 0.63, p<0.001).

Fig 3. Shows that both higher initial and worst PLIS during hospitalization are associated with intensive care unit (ICU) admission (A) and in-hospital mortality (B), respectively (P<0.001 for all pairs).

Fig 3

Table 3 depicts the differences in clinical characteristics between ICU and non-ICU patients. The mean number of PLIS studies conducted for ICU patients was 5.3 versus 1.4 for non-ICU patients. The SOFA score was predictably higher in the ICU group (median 0 versus 5, p<0.001). For all PLIS components, findings of A, B, and C, grade 0 (i.e., lower score) were significantly more prevalent among the non-ICU ward patients, while grades 1 and 2 were much more prevalent among scanned performed on ICU patients. The median total PLIS was 2.0 (1.0–3.0) and 5.0 (3.0–6.0) for non-ICU and ICU patients, respectively (p<0.001).

Table 3. Clinical characteristics during PLIS stratified by intensive care unit versus nonintensive care unit.

Variable Non-ICU (n = 103) ICU (n = 190) P value
Temperature (mean ± SD) (Celsius) 36.8 (0.5) 37.1 (0.7) <0.001
Oxygen saturation % (mean ± SD) 94.6 (4.5) 91.4 (4.8) <0.001
Mean arterial pressure (mean ± SD) (mmHg) 89.2 (12.9) 82.3 (34.7) 0.02
PaO2/FiO2 (median, interquartile range) * 137.1 (95–212.5) ___
White blood count (median, interquartile range) (K/μL) 6.4 (5–9.5) 12 (8.2–17.7) <0.001
Platelets (median, interquartile range) (K/μL) 207 (162–281.5) 320 (230–399) <0.001
Creatinine (median, interquartile range) (mg/dl) 0.88 (0.74–1.05) 0.62 (0.49–1.14) <0.001
Bilirubin (median, interquartile range) (mg/dl) 0.53 (0.33–0.67) 0.40 (0.28–0.61) 0.03
SOFA score (median, interquartile range) 0 (0–1) 5 (4–7) <0.001
AKI stage (median, interquartile range) 0 (0–0) 0 (0–1) <0.001
PLIS A (n, %)
0 72 (69.9) 27 (14.2) <0.001
1 31 (30.1) 63 (66.2)
2 0 (0) 100 (34.1)
PLIS B (n, %)
0 31 (30.1) 21 (11.1) <0.001
1 36 (35.0) 53 (27.9)
2 36 (35.0) 116 (61.1)
PLIS C (n, %)
0 56 (54.4) 44 (23.2) <0.001
1 34 (33) 41 (21.6)
2 13 (12.6) 105 (55.3)
PLIS score (median, interquartile range) 2 (1–3) 5 (3–6) <0.001

AKI- Acute Kidney Injury

ICU- Intensive Care Unit

FiO2- Fractional inspired oxygen

PaO2- Partial pressure of oxygen in arterial blood

PLIS- Point of Care Lung Ultrasound Injury Score

An initial PLIS of 0–2 was found in 81% (n = 60) of patients who had a relatively benign course, did not require ICU care, and remained in a non-ICU ward throughout their hospitalization. In contrast, A first PLIS of 3 or more was found in 68.6% (n = 21) of those patients who ultimately clinically deteriorated during their hospital stay requiring ICU hospitalization (Fig 4).

Fig 4. Presents the results of the initial PLIS stratified by the decision of intensive care unit (ICU) vs. non-ICU admissions (p<0.001).

Fig 4

Multivariate GEE models for the study outcomes are presented in Table 4. Model 1 and 2 show that every increase in one PLIS point was associated with a higher risk for ICU admission (O.R 2.09, 95% C.I 1.59–2.75) and in-hospital mortality (O.R 1.54, 95% C.I 1.10–2.16), respectively.

Table 4. Multivariate Generalized Estimating Equation (GEE) regression for study outcomes.

Variable P value O.R 95% C.I
Model 1—ICU admission Age 0.15 1.03 0.98–1.09
Diabetes 0.03 3.49 1.12–10.86
Saturation 0.01 0.88 0.8–0.97
PLIS score <0.001 2.09 1.59–2.75
Model 2—in-hospital mortality Age 0.01 1.09 1.02–1.17
Malignancy 0.10 6.18 0.68–55.77
PLIS score 0.01 1.54 1.1–2.16
Model 3—composite outcome* Age 0.36 1.03 0.96–1.11
Saturation 0.01 0.88 0.81–0.96
AKI <0.001 3.58 1.76–7.3
PLIS score 0.001 1.72 1.24–2.39

*Mechanical ventilation > 14 days, prone position or in-hospital mortality

AKI- Acute Kidney Injury

ICU- Intensive Care Unit

PLIS- Point of Care Lung Ultrasound Injury Score

The increase in PLIS point was also associated with increased risk for the composite outcome, composed of prolonged mechanical ventilation over two weeks, prone positioning, or in-hospital mortality (O.R 1.72, 95% C.I 1.24–2.39) (Model 3).

Discussion

Here we present a new simple clinical-sonographic LUS score that is quick and easy to perform. The PLIS incorporates the level of respiratory support, the extent of the pulmonary interstitial syndrome, and the severity and progression of the consolidation burden in a single and intuitive score. Our main findings illustrate that the PLIS is associated with the patient’s clinical status and disease severity. Furthermore, our data suggest that higher PLIS predicts ICU admission and in-hospital death. This method has been efficiently implemented in real-life clinical settings to facilitate daily assessment and follow-up of COVID-19 patients and may predict further patient outcomes and appropriate triage.

COVID-19 patients manifest relative comfort in the face of severe hypoxia, thus masking the severity of their lung injury. However, these patients may rapidly deteriorate without warning. The PLIS offers a straightforward bedside tool that can be done daily as part of the regular follow-up and may help recognize imminent deterioration and pending intubation. The PLIS is a more "friendly" scoring system than those previously referenced, which involves scanning only three fields per lung and a maximal 6 points for ultrasound findings. The PLIS is simple enough to perform in any setting by a lone operator and takes about three minutes to complete by a resident. Six residents and three senior physicians conducted the PLIS after short training with good inter-observer correlation.

The PLIS combines information from patients’ LUS findings (B and C scores) with the extent of respiratory support (A score). Similar to the Berlin criteria for Adult Respiratory Distress Syndrome (ARDS), by using the level of hypoxemia for the grading of severity, we believe that combining the extent of respiratory support (PLIS A) with the ultrasonographic score provides another level of information in communicating the patient’s health while improving the LUS’s ability to predict outcomes and prognosis. This is one of the first LUS scores associated with the SOFA score, predicting ICU hospitalization and in-hospital mortality. Multivariate data analysis suggests that for every increase in a single point in the PLIS, ICU admission, in-hospital mortality, and the composite outcome (prolonged mechanical ventilation over two weeks, prone positioning, or in-hospital mortality) increases with odds ratio 2.09, 1.54, and 1.72 respectively.

Furthermore, though this study did not evaluate the use of the PLIS in the outpatient and Emergency Department settings, it is easily conceivable how it can be of value in these settings while guiding triage, referrals, and admitting decisions. In our experience, most non-ICU patients who required hospitalization had a PLIS of 2 or less (Fig 4), suggesting that patients with either a combination of mild interstitial disease with a small consolidation (B1, C1), diffuse severe interstitial disease (B2), or large consolidation (C2), represent disease presentations that warrant careful observation beyond focusing solely on oxygen requirements. Moreover, most non-ICU patients with a relatively benign course that did not necessitate ICU transfer had a PLIS of 2 or less (81%). Conversely, a significant majority of those who did suffer a deleterious course requiring ICU admission had a PLIS of 3 or more (68.6%) (Fig 4). This suggests that the PLIS can serve as a prognostic marker and facilitate triage decisions.

The PLIS offers a simple and intuitive three-letter score that illustrates almost graphically an easily conveyable conceptual imaging of the extent of illness within the lungs. While our study did not directly assess the ability of the PLIS to obviate the need for chest X-ray in the management of these patients, well-established literature suggests that in COVID-19 patients, PLIS may diminish the need for frequent chest imaging. Beyond its simplicity, the PLIS addresses an additional limitation of previous LUS scores by providing spatial information as opposed to summing all LUS data into a single discreet number.

The limitations of this report are mainly due to the sample size and its observational nature. Though almost 300 PLIS exams were included, only 109 patients were enrolled; of those, only 36 were in the ICU, all from one tertiary care medical center. Not all patients with COVID-19 admitted to medicine floors (i.e., outside the ICU) received a PLIS, depending on the availability of the trained physicians on call, which could result in unintentional sampling bias. A larger, multicenter study is needed to better validate generalizability and PLIS prediction power for outcomes. We did not evaluate the association between the PLIS phenotype and the potential for lung recruitment, a topic ripe for future study. Could a specific disease pattern, such as a higher B score with a low C score, suggest positive end-expiratory pressure, prone positioning, or inhaled nitric oxide responsiveness? Such data is essential if this score is to be a dynamic, daily management tool that can aid in clinical decisions. Lastly, the studied group may not reflect the prevalence of underlying diseases in other countries or ethnicities. For example, CKD or CHF may be more prevalent in certain populations which potentially can affect the lung sonographic profile.

Conclusions

We introduce a novel lung ultrasound score for COVID-19 patients that is simple, illustrative, and associated with SOFA score, ICU admission, and in-hospital mortality. Further studies are needed to demonstrate if PLIS can become an integral part of the daily assessment and management of COVID 19 patients and ARDS patients in general.

Abbreviations

AKI

Acute kidney injury

ARDS

Adult respiratory life support

COVID19

coronavirus disease 2019 (COVID-19)

CT

Computed Tomography

Fio2

Fractional inspired oxygen

ICU

Intensive Care Unit

LUS

Lung Ultrasound

PaO2

Partial pressure of oxygen in arterial blood

PLIS

Point of Care Lung Ultrasound Injury Score

SOFA

Sequential Organ Failure Assessment

Data Availability

Data access is restricted as the data relevant to this study contains potentially identifying and sensitive patient information. The data are owned by the Clalit Health Services and these restrictions are imposed by the local ethics committee. For further details and to request access to the data please contact NaomiAm@clalit.org.il, the head of the research unit at Soroka University Medical Centre.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

Jignesh K Patel

17 Mar 2022

PONE-D-21-38198

Point of Care Lung Ultrasound Injury Score - a Simple and Reliable Assessment Tool in COVID-19 Patients (PLIS I): A Retrospective Study

PLOS ONE

Dear Dr. Fuchs,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Jignesh K. Patel

Academic Editor

PLOS ONE

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Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

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We will update your Data Availability statement to reflect the information you provide in your cover letter.

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7. Please upload a new copy of Figures 2 and 3 as the detail is not clear. Please follow the link for more information: https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/" https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/

8. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

********** 

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

********** 

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

********** 

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

********** 

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thanks for this interesting paper on the use of ultrasound in COVID patients.

My comments are :

Background : could you provide some references to “There is a direct association between the severity of COVID-19 pneumonia and computerized tomography (CT) findings”

Could you add something about the predominant COVID variant in your hospital during the study?

Could you please address this comment: This is a retrospective study, although data were prospectively collected.

Was the study designed prospectively?? Was it registered? Could you discuss how the study was designed?

An important question is the timing of the data collection. The COVID time course is useful in understanding deterioration, and I am not sure from the manuscript whether the measures on patients reflect – paired measurements (ED or ward then ICU, or in some patients were single measurements, or in others, multiple measurements on the same patient). It just states “on admission” – not sure whether that is to hospital or the ward or to ICU.

P 5 “were assessed by an intensivist to require mechanical ventilation in the next 24 hours potentially. “

Were assessed by an intensivist to potentially require …

Figure 1: why are the stars in a different position to the probe?

For the “putting it together” could you create a figure that shows perhaps the different components with the ultrasound images ?

Interobserver variability – how many scans were repeated by different operators?

Table 4 Did you run the model just with PLIS A? Just wanting to understand the added benefit of the U/S scan in predictions.

Reviewer #2: This is a interesting paper which validates some of our regular utility of sonography in the ICU during the pandemic. We have already appreciated that CT scan findings with higher "scores" i.e. worse diseases, likely have a poorer outcomes. This essentially is also shown in this paper where the authors evaluate the lung parenchyma.

Using PLIS in their group is sound however this group may not reflect the prevalence of underlying diseases in other countries and so this should be taken with a grain of salt. For example, CKD or CHF may be more prevalent in certain populations which would affect the lung sonographic profile.

********** 

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Kinner Patel

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2022 May 11;17(5):e0267506. doi: 10.1371/journal.pone.0267506.r002

Author response to Decision Letter 0


2 Apr 2022

Answer letter to:

PONE-D-21-38198

Point of Care Lung Ultrasound Injury Score - a Simple and Reliable Assessment Tool in COVID-19 Patients (PLIS I): A Retrospective Study

PLOS ONE

Dear Editor,

Thank to you and to the reviewers, we believe that the manuscript now is better, more clear to the readers, and improved:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Answer: Done

2. answer: “The authors received no specific funding for this work.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

Answer: Done

3. Thank you for stating the following in the Competing Interests section: "Lior Fuchs is a consultant for GE Healthcare."

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

Answer: I – Lior Fuchs, declare that: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.”

It is updated in the cover letter.

4. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

Answer: unfortunately, there are ethical and legal restrictions to sharing our data publicly:

Based on Clalit Health Services regulations, the study data set maintain only at Clalit Health Services servers. Researchers are not allowed to upload or share the data set with other sources.

5. Please amend the manuscript submission data (via Edit Submission) to include author Khaled el haj, MD:

Answer: Done

6. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

Answer: Done

7. Please upload a new copy of Figures 2 and 3 as the detail is not clear. Please follow the link for more information: https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/" https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/

Answer: Done

8. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Answer: Sorry for the inconsistency with the references. There was a technical problem with the order of the references. I have reviewed the reference list and corrected it. No references were retracted. All original references are labeled by the PLOS one font instructions.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thanks for this interesting paper on the use of ultrasound in COVID patients.

My comments are :

Background : could you provide some references to “There is a direct association between the severity of COVID-19 pneumonia and computerized tomography (CT) findings.”

Answer: there were errors with the references labels – now we provide the right references at the right place, as well as the one in your comment.

Could you add something about the predominant COVID variant in your hospital during the study?

Answer: The study period included the Alpha, and Beta SARS-CoV-2 variants.

We added this sentence to the first paragraph of the Methods.

Could you please address this comment: This is a retrospective study, although data were prospectively collected.

Was the study designed prospectively?? Was it registered? Could you discuss how the study was designed?

Answer: we agree that the term “prospectively collected “ is confusing. This is a retrospective study that analyses retrospectively a new clinical lung US score that was implemented during the COVID 19 outbreak. We removed the term prospectively collected and added it to the methods section:

“This is a retrospective study; data were collected during patients assessments and rounds. The PLIS protocol was taught and implemented in the COVID 19 wards and ICUs and was part of the daily patients assessment.”

Later in Methods, we further explain the way we collected the data: “Data collected included the PLIS recorded on admission, when conducted during ward/ICU rounds, and when otherwise clinically indicated.”

This was a routine lung assessment for all. All about it is a retrospective analysis.

An important question is the timing of the data collection. The COVID time course is useful in understanding deterioration, and I am not sure from the manuscript whether the measures on patients reflect – paired measurements (ED or ward then ICU, or in some patients were single measurements, or in others, multiple measurements on the same patient). It just states “on admission” – not sure whether that is to hospital or the ward or to ICU.

Answer: Thank you for the important comment. For clarification: this is not a prospective study, and PLIS exams were not protocolized. Some of the patients received only ward PLIS assessments as they were never admitted to the ICU. Some received only in the ICU and not in the ward. Some were received in both locations. The studies were not paired.

We added the following sentence to the second paragraph in the Methods:

“As this is not a prospective study, the PLIS exams were not protocolized. Some patients could receive a PLIS study on regular ward admission, during the morning rounds, and also later, when admitted to the ICU. Some received ultrasound lung scan only during the ICU admission or only in the regular ward.”

P 5 “were assessed by an intensivist to require mechanical ventilation in the next 24 hours potentially. “

Were assessed by an intensivist to potentially require …

Answer: Thanks, we have added “potentially”.

Figure 1: why are the stars in a different position to the probe?

Answer:The stars represent the area of scan in each zone and not the exact place of the probe. This comment was added to the Figure 1 legend.

For the “putting it together,” could you create a figure that shows perhaps the different components with the ultrasound images ?

Answer: Thank you for an excellent idea. Figures 1b and 1c with b lines and consolidation were added and referred to in the putting it together paragraph.

Interobserver variability – how many scans were repeated by different operators?

Answer: Inter-observer reliability was assessed by comparing independent ratings of the PLIS B and C scores among 16 randomly selected patients in a blinded manner by two physicians. Please see the Statistical Analysis section for more details.

Table 4 Did you run the model just with PLIS A? Just wanting to understand the added benefit of the U/S scan in predictions.

Answer: PLIS A is connected to the prognosis, as we know from previous data regarding the outcomes of SARS- 2 ventilated patients. This is the reason we present Figure 2, which shows the association between the SOFA, PLIS B and PLIS C. We also analyzed the association between these lung ultrasound scores (PLIS B and C, independently from PLIS A) and other outcomes, as the risk for mechanical ventilation. We found OR of over 4 and over 10 for PLIS B2 and PLIS C2, respectively, compared to PLIS B0 and C0. So, we do know that the ultrasound score is a predictor and associated with bad outcomes, regardless of the PLIS A score. We chose to publish these specific associations in PLIS II report.

Reviewer #2: This is an interesting paper which validates some of our regular utility of sonography in the ICU during the pandemic. We have already appreciated that CT scan findings with higher "scores" i.e. worse diseases, likely have a poorer outcomes. This essentially is also shown in this paper where the authors evaluate the lung parenchyma.

Using PLIS in their group is sound however this group may not reflect the prevalence of underlying diseases in other countries and so this should be taken with a grain of salt. For example, CKD or CHF may be more prevalent in certain populations which would affect the lung sonographic profile.

Answer: I strongly concur. We have added this sentence to the Limitations paragraph.

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Kinner Patel

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: PONE- answering letter .docx

Decision Letter 1

Jignesh K Patel

11 Apr 2022

Point of Care Lung Ultrasound Injury Score - a Simple and Reliable Assessment Tool in COVID-19 Patients (PLIS I): A Retrospective Study

PONE-D-21-38198R1

Dear Dr. Fuchs,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Jignesh K. Patel

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

author's have appropriately answer and modify the manuscript accordingly.

Reviewers' comments:

Acceptance letter

Jignesh K Patel

14 Apr 2022

PONE-D-21-38198R1

Point of Care Lung Ultrasound Injury Score - a Simple and Reliable Assessment Tool in COVID-19 Patients (PLIS I): A Retrospective Study

Dear Dr. Fuchs:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Jignesh K. Patel

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: PONE- answering letter .docx

    Data Availability Statement

    Data access is restricted as the data relevant to this study contains potentially identifying and sensitive patient information. The data are owned by the Clalit Health Services and these restrictions are imposed by the local ethics committee. For further details and to request access to the data please contact NaomiAm@clalit.org.il, the head of the research unit at Soroka University Medical Centre.


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