key: cord-1022081-23xljw4o
authors: Giovannetti, Guido; De Michele, Lucrezia; De Ceglie, Michele; Pierucci, Paola; Mirabile, Alessandra; Vita, Marco; Palmieri, Vincenzo Ostilio; Carpagnano, Elisiana; Scardapane, Arnaldo; D’Agostino, Carlo
title: Lung Ultrasonography for long-term follow-up of COVID-19 survivors compared to chest CT scan
date: 2021-03-31
journal: Respir Med
DOI: 10.1016/j.rmed.2021.106384
sha: 755fc8c04617225761796fcc1ce688a692b65e4e
doc_id: 1022081
cord_uid: 23xljw4o

BACKGROUND: While lung ultrasonography (LUS) has utility for the evaluation of the acute phase of COVID-19 related lung disease, its role in long-term follow-up of this condition has not been well described. The objective of this study is to compare LUS and chest computed tomography (CT) results in COVID-19 survivors with the intent of defining the utility of LUS for long-term follow-up of COVID-19 respiratory disease. METHODS: Prospective observational study that enrolled consecutive survivors of COVID-19 with acute hypoxemic respiratory failure (HARF) admitted to the Respiratory Intensive Care Unit. Three months following hospital discharge, patients underwent LUS, chest CT, body plethysmography and laboratory testing, the comparison of which forms the basis of this report. RESULTS: 38 patients were enrolled, with a total of 190 lobes analysed: men 27/38 (71.1%), mean age 60.6 y (SD 10.4). LUS findings and pulmonary function tests outcomes were compared between patients with and without ILD, showing a statistically significant difference in terms of LUS score (p: 0.0002), FEV1 (p: 0.0039) and FVC (p: 0.012). ROC curve both in lobe by lobe and in patient’s overall analysis revealed an outstanding ILD discrimination ability of LUS (AUC: 0.94 and 0.95 respectively) with a substantial Cohen’s coefficient (K: 0.74 and 0.69). CONCLUSIONS: LUS has an outstanding discrimination ability compared to CT in identifying an ILD of at least mild grade in the post COVID-19 follow-up. LUS should be considered as the first-line tool in follow-up programs, while chest CT could be performed based on LUS findings.

B ackground: While lung ultrasonography (L US) has utility for the evaluation of the acute phase of C OV ID -19 related lung disease, its role in long-term follow-up of this condition has not been well described. T he objective of this study is to compare L US and chest computed tomography (C T ) results in C OV ID -19 survivors with the intent of defining the utility of L US for long-term follow-up of C OV ID -19 respiratory disease.

Methods: Prospective observational study that enrolled consecutive survivors of C OV ID -19 with acute hypoxemic respiratory failure (HA R F) admitted to the R espiratory Intensive C are Unit. T hree months following hospital discharge, patients underwent L US, chest C T , body plethysmography and laboratory testing, the comparison of which forms the basis of this report. C orona V irus D isease 2019 (C OV ID -19) pandemic is the major current global health concern, due to its high rate of hypoxemic acute respiratory failure (HA R F) and the number of related deaths worldwide 1 .

T he long-term complications of C OV ID -19 pneumonia are starting to emerge but data from previous coronavirus outbreaks, such as S A R S and ME R S, suggest that some patients could experience long-term pulmonary complications such as IL D and pulmonary vascular disease 2 . Wang et al. 3 reported that 94% of the patients with C OV ID -19 pneumonia had residual C T findings after a median time from discharge of 25 days and ground glass opacities (GGO) have been identified as the most frequent residual pattern. On the contrary, the crazy-paving pattern was no longer observed after 14 days from the onset of initial symptoms, likely as a result of recovery 4 .

L ung ultrasonography has demonstrated utility for management of C OV ID -19 ( 5, 6, 7, 8, 9 ) and gives similar results as chest C T for the evaluation of lung involvement ( 10, 11 ) . Its ease of use, low cost, and lack of radiation has led to its well-defined use during the C OV ID -19 pandemic. T he role of L US in the recovery phase of C OV ID -19

following hospital discharge has not yet been defined. T o the best of our knowledge, this was the first long-term follow-up including a comparison between chest C T and L US, performed at the same time after at least 90 days after discharge at home.

T he aims of the present study were first, to assess the reliability of the L US compared to the gold standard chest C T in detecting the presence of IL D in patients survived to C OV ID -19 with H A R F, and second, to identify the L US role in the long-term follow-up of these patients. -severe disease's onset with at least one of the following criteria: HARF with respiratory rate >30 breaths/min, SpO2 <93% on room air in resting position, PaO2/FiO2 <300 mmHg, requiring Fio2>60% and non-invasive respiratory support (NRS); septic shock; multiple organ failure;

-no history of previous pulmonary fibrosis or pulmonary hypertension disease.

Two negative swabs and serology testing were required prior to be evaluated for the present study. A ll these findings were evaluated and graded and then compared to C T features. For the purpose of the study, HR C T images were analyzed to identify eventual presence of GGO and intra-lobular interstitial thickening. T he quantitative involvement of each lobe was recorded awarding a C T score from 0 to 5, depending on a visual assessment of the percentage of the parenchymal involved, as per the current literature 15 : score 0 as no involvement; 1 as <5% ; 2 as 5% -25% ; 3 as 26% -49% ; 4 as 50% -75% ; 5 as >75% . T he T otal Severity Score Ultrasonographic and radiographic findings were analysed both considering the final score of each method for each patient (L US score and T SS) and lobe by lobe, thus to increase the number of cases compared. Presence of disease was defined for C T and L US score cut-off of 1.

Further statistical analysis was performed in order to confirm LUS ability to identify ILD affecting <5% in each lobe. This was reached applying a mixed cut-off which considered a CT score of 1 (i.e. <5% lobe parenchymal involvement) both in the case of minimal presence or in absence of disease at LUS.

Sunburst diagram was also used for visual representation of CT and LUS concordance. It shows the hierarchical relation between the central circle which represents the CT scan findings and the outer ring which represents the LUS findings.

Chest CT and LUS outcomes were compared using X 2 test. Pulmonary function tests (PFTs) outcomes were compared in patients with and without signs of ILD using student's t test and X 2 test between variables. P-value None of the patients included in our study population had pleural effusion nor were consolidations on LUS examination, and these data were confirmed on chest CT scan.

According to Yang et al. 6 , ultrasound scanning areas were grouped to identify corresponding lobes, thus to perform a lobe by lobe analysis between LUS and CT findings, with cut-off value of 1 ( fig. 2 

Conversely, applying the mixed cut-off ( fig. 2.B) , the AUC in the lobe by lobe analysis raised to 0.94 (outstanding discrimination ability) and Cohen's K coefficient raised to 0.74 (substantial correlation). Similarly, in the comparison between the TSS and L US score in the patient's overall analysis ( fig. 2 .D) the AUC raised to 0.95 (outstanding discrimination ability) and Cohen's K coefficient raised to 0.69 (substantial correlation).

A good visual representation of CT and L US concordance was reached through the Sunburst chart (e- figure) . In the patient's overall analysis, the presence of a TSS score >5 correlated with high L US score in each patient. In Conclusions:

This study proved that LUS has an outstanding discrimination ability and a substantial agreement rate compared to the chest CT scan in the assessment and grading of ILD in patients at 3 months after COVID-19 severe lung infection with HARF. Therefore, LUS should be considered as the first-line tool in the follow-up of COVID 19

survivors looking for ILD, and it may guide the physician towards an effective treatment plan.

Further studies are required to provide evidence of the correct timing for LUS to be performed after discharge and how it may precisely influence the pharmacological therapy management.

J o u r n a l P r e -p r o o f 13 S tatem ents:

A cknowledgments:

T he authors would like to thank all the patients who participated in the study, D r S. C ascella, D r P. C olonna, Mrs Francesca C agnetta, Mrs A nna Maria C aldarola and all physicians and nurses of the C ardiothoracic D epartment, C ardiovascular and R espiratory and C ritical care unit of the B ari Policlinic University hospital.

Statement of E thics T his study was conducted ethically in accordance with the World Medical A ssociation D eclaration of Helsinki.

It was approved by the E thic C ommittee of University Hospital Policlinico of B ari (study number 6380, 12th

May 2020) and all patients involved signed an informed and written consent before being enrolled.

A ll the authors have no conflicts of interest to declare. 

Imaging and PFTs outcomes in the follow-up of COVID-19 survivors after 3 months from discharge at home. P values statistically significant are in bold font (p value ≤0.05). No signs of ILD corresponding to CT score=0 and LUS score=0. Signs of ILD corresponding to CT score=1-25 and LUS score=1-36

Severe ILD corresponding to CT score 13-25 and LUS score 19-36. *No ILD is defined as CT score = 0. † ILD is defined as CT score ≥1. Abbreviations: PFTs: Pulmonary function tests; ILD: interstitial lung disease; TSS: total severity score; LUS: lung ultrasound

partial arterial pressure of oxygen/fraction of inspired oxygen ratio; 6MWT: six minutes walking test; HR: heart rate; FVC: forced vital capacity

FEV1: forced expiratory volume in 1 second; TLC: total lung capacity; DLCO: Diffusing capacity of the lung for carbon monoxide

T able 2 Imag ing and P F T s outc omes of patients inc luded

-19 D ashboard by the centre for systems science and engineering

R espiratory follow-up of patients with C OV ID -19 pneumonia

T emporal C hanges of C T Findings in 90 Patients with C OV ID -19 Pneumonia: A L ongitudinal Study. R adiology

T ime C ourse of L ung C hanges at C hest C T during R ecovery from C oronavirus D isease 2019 (C OV ID -19). R adiology

L ung ultrasonography versus chest C T in C OV ID -19 pneumonia: a two-centered retrospective comparison study from C hina

T he emerging role of lung ultrasound in C OV ID -19 pneumonia

Point-of-care lung ultrasound in patients with C OV ID -19 -a narrative review. A naesthesia

L ung ultrasound score to monitor C OV ID -19 pneumonia progression in patients with A R D S

L ung Ultrasound in C OV ID -19 Pneumonia: C orrelations with C hest C T on Hospital admission. R espiration

Is T here a R ole for L ung Ultrasound D uring the C OV ID -19 Pandemic?

E SC /E R S G uidelines for the diagnosis and treatment of pulmonary hypertension: T he Joint T ask Force for the D iagnosis and T reatment of Pulmonary H ypertension of the E uropean Society of C ardiology (E SC ) and the E uropean R espiratory Society (E R S): E ndorsed by: A ssociation for E uropean Paediatric and C ongenital C ardiology (A E PC

Findings of lung ultrasonography of novel corona virus pneumonia during the 2019-2020 epidemic

D iaphragmatic and lung ultrasound application as new predictive indices for the weaning process in IC U patients. E gypt. J. R adiol