key: cord-0965457-bbr53elj
authors: Fogante, Marco; Cavagna, Enrico; Rinaldi, Giovanni
title: COVID-19 follow-up: chest X-ray findings with clinical and radiological relationship three months after recovery
date: 2021-10-22
journal: Radiography (Lond)
DOI: 10.1016/j.radi.2021.10.012
sha: f2e627b272df956175f22373771f8de9d94c120b
doc_id: 965457
cord_uid: bbr53elj

Introduction To evaluate the radiological sequelae of coronavirus disease (COVID-19) in a mid-term follow-up and investigate their relationship with clinical-radiological findings. Methods This prospective study included COVID-19 patients who underwent a CXR three months after discharge. The relationship between CXR score at three months after discharge and clinical findings and previous CXR scores, at admission and before the discharge, were evaluated. Then, based on mid-term follow-up CXR score, patients were divided in Group A (score=0) and Group B (score≥1), and clinical-radiological findings were compared between two Groups. Finally, we calculated the CXR scores at admission and before the discharge with the highest sensitivity and specificity to predict normal and abnormal CXR score at mid-term follow-up. Results The study included 119 patients, mean age 65.9±14.6 years. The oxygen saturation (SaO2) (p=0.0006), the days of hospitalization (p<0.0001) and the CXR score before the discharge (p=0.0091) were independent factors to predict the mid-term follow-up CXR score. The Group A, 59 (49.6%) patients, had CXR scores at admission and before the discharge lower than Group B. The CXR scores at admission and before the discharge with the highest sensitivity and specificity to predict normal and abnormal CXR score at mid-term follow-up were, respectively, 3 and 2 (p<0.0001). Conclusions The radiological abnormalities were present in about half patients three months after discharge, which had higher age, previous CXR scores and longer hospitalization. The SO2, days of hospitalization and previous CXR scores were independent factors for predicting the CXR at three months. Implications for practice The radiologist with CXR could play a central role in mid to long-term follow-up of COVID-19, assessing the radiological sequelae of patients and identifying those who might require a closer follow-up.

Coronavirus disease 2019 is caused by a novel coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1, 2] . Though most symptomatic patients have mild flu-like symptoms, a significant minority develop acute respiratory distress syndrome, leading to considerable morbidity and mortality [3] . Despite chest computed tomography (CT) is the best modality to detect lung abnormalities [4] , in case of a high number of hospitalized patients chest Xray (CXR) is the most common radiological method to monitor the rapid course of COVID-19 [5, 6] .

Moreover, some CXR scoring systems, including the Brixia Score, were developed to rate pulmonary involvement according to the type and the extension of lung abnormalities [7] .

Despite several previous studies reporting radiological temporal changes of COVID-19 in-patients until four weeks after the disease onset, most patients who have recovered still have residual abnormalities on CXR: a close follow-up during the hospitalization is essential but may not be enough [8 -10] . Indeed, some studies concluded that long-term follow-up is needed to evaluate the development of irreversible fibrosis [11 -13] . However, the optimal time for follow-up imaging is unknown; the American Thoracic Society does not recommend routine follow-up imaging for patients recovering satisfactorily from community-acquired pneumonia [14, 15] . Trying to solve this problem, George et al. [14] provided a structure for long-term follow-up in COVID-19 patients.

Therefore, the aim of this study is to evaluate the radiological sequelae of COVID-19 patients in a mid-term follow-up (3 months) and to investigate their relationship with clinical and radiological findings.

All procedures on studies involving human participants were performed in accordance with the ethical standards of the Institutional and National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

The Institutional Review Board of our Hospital approved the study protocol (013087S). Written informed consent was obtained from all the patients.

In this prospective study from May 01 to June 31, 2021 we enrolled 122 consecutive patients with previous COVID-19 who underwent a follow-up with CXR three months after Hospital discharge.

The inclusion criteria were: COVID-19 infection at admission and COVID-19 resolution at discharge, confirmed by real-time reverse transcription polymerase chain reaction test using nasal and oropharyngeal swab specimens; the execution of a CXR exam at admission and before discharge.

The exclusion criteria were: inaccessible clinical data and CXRs images (n=3).

The final study population was composed by 119 patients.

For each patient sex, age and medical history (comorbidities and smoking) were collected.

Moreover, we retrospectively collected the clinical (fever, cough, dyspnea, myalgia, diarrhea, ambient air oxygen saturation, type of ventilation support during hospitalization) and laboratory data (value of lactate dehydrogenase, number of lymphocytes) at hospital admission, the number of days between disease onset and hospital admission, and the number of days of hospitalization.

The date of disease onset was defined as the day when the first symptoms were noticed.

For each patient, two radiologists in consensus evaluated the CXR at admission, at discharge and at mid-term follow-up (3 months), using an 18-points score system.

In each CXR, lungs were divided into three equal parts: upper, middle and lower, for a total of six zones. A score (from 0 to 3) was assigned to each zone based on lung abnormalities detected on a frontal view, as follow: 0 -no abnormalities; 1 -interstitial infiltrates; defined as septal thickenings and focal or extensive opacity, with the evidence of extravascular structure;

2 -interstitial and alveolar infiltrates (interstitial predominance);

3 -interstitial and alveolar infiltrates (alveolar predominance).

The single scores of the six lung zones were added to obtain an overall CXR score ranging from 0 to 18. To minimize bias, two radiologists were blinded to patient histories.

The mid-term follow-up CXR score was correlated with age, ambient air oxygen saturation (SO2), days from disease onset to hospital admission, days of hospitalization, CXR scores at admission and before discharge.

Based on mid-term follow-up CXR score, the patients were divided in two Groups: Group A, with radiological complete recovery (CXR score = 0) and Group B, with radiological abnormalities (CXR score ≥ 1). Age, sex, oxygen saturation (SO2), days from disease onset to hospital admission, days of J o u r n a l P r e -p r o o f hospitalization, CXR scores at admission and before discharge, were compared between the two Groups.

Then we calculated the cut-off CXR score at admission and before discharge with the highest sensitivity and specificity to distinguish patients with normal (score=0) and abnormal (score ≥ 1) CXR at mid-term follow-up.

A dedicated statistical software was used (MedCalc v19.1.6, MedCalc Software, Ostend, Belgium).

Continuous variables were displayed as mean ± standard deviation and categorical variables were reported as counts and percentages.

CXR score was evaluated at admission, before discharge and in a mid-term follow-up (three months after the discharge). Regression analysis was used to study the independent covariates for the midterm follow-up CXR score. Regression coefficient (b) and partial regression coefficient (r) were calculated.

Mann-Whitney U test and χ2 test were used to compare, respectively, continuous and categorical variables between the two Groups A and B. A receiving operating characteristic (ROC) curve with area under the curve (AUC) and the Youden's index were used to calculate the cut-off CXR score at admission and before discharge with the highest sensitivity and specificity to distinguish patients with normal (score=0) and abnormal (score ≥ 1) CXR at mid-term follow-up.

p<0.05 was defined as statistically significant.

J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f 6.9 ± 3.1 (95% CI: 6.1 -7.7)

<0.0001 The cut-off CXR score at admission with the highest sensitivity and specificity to distinguish normal and abnormal CXR at mid-term follow-up was 3 (A). The cut-off CXR score before discharge with the highest sensitivity and specificity to distinguish normal and abnormal CXR at mid-term follow-up was 2 (B).

The figure shows the examples of patient with a CXR score of 3 at admission and CXR scores of 0 before the discharge and at three months follow-up.

The figure shows the examples of patient with a CXR score of 6 at admission and CXR scores of 4

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