key: cord-0828395-q8qsu81z
authors: Poitevineau, Thibaud; Chassagnon, Guillaume; Bouam, Samir; Jaubert, Paul; Cheurfa, Chérifa; Regard, Lucile; Canniff, Emma; Dinh-Xuan, Anh Tuan; Revel, Marie-Pierre
title: Computed tomography after severe COVID-19 pneumonia: findings at 6 months and beyond
date: 2021-09-24
journal: ERJ Open Res
DOI: 10.1183/23120541.00488-2021
sha: 848a5c9723bb0dfd14842ed9018a17c1f702b0d4
doc_id: 828395
cord_uid: q8qsu81z

SARS-Cov-2 infects the alveolar epithelial cells causing COVID-19 pneumonia of varying severity [1, 2]. Fifteen to 30% of patients develop acute respiratory distress syndrome (ARDS) requiring hospitalisation in intensive care units (ICU) and mechanical ventilation [2, 3]. At 3 months, there are persisting CT abnormalities in 17 to 91% of discharged COVID-19 patients [4–8], mainly consistent with an organising pneumonia pattern. These anomalies are more frequently reported in patients who were admitted to ICU [9]. Pulmonary fibrosis has been reported at autopsy of patients deceased from COVID-19 pneumonia, along with pulmonary microvascular thrombosis [10]. Fibrotic-like changes have also been reported at 6-month CT follow-up in COVID-19 survivors [11]. A proportion of survivors from the first SARS-Cov outbreak of 2003 had residual impairment of lung function and abnormal chest radiograph (CXR) findings at 6 months [12]. However, little is known about long-term changes on CT following severe SARS-Cov-2 pneumonia, or after ARDS in general, most descriptions being limited to CXR.

SARS-Cov-2 infects the alveolar epithelial cells causing COVID-19 pneumonia of varying severity [1, 2] . Fifteen to 30% of patients develop acute respiratory distress syndrome (ARDS) requiring hospitalization in intensive care units (ICU) and mechanical ventilation [2, 3] . At 3 months, there are persisting CT abnormalities in 17 to 91% of discharged COVID-19 patients [4] [5] [6] [7] [8] , mainly consistent with an organizing pneumonia pattern. These anomalies are more frequently reported in patients who were admitted to ICU [9] . Pulmonary fibrosis has been reported at autopsy of patients deceased from COVID-19 pneumonia, along with pulmonary microvascular thrombosis [10] . Fibrotic-like changes have also been reported at 6month CT follow-up in COVID-19 survivors [11] . A proportion of survivors from the first SARS-Cov outbreak of 2003 had residual impairment of lung function and abnormal chest radiograph (CXR) findings at 6 months [12] . However, little is known about long-term changes on CT following severe SARS-Cov-2 pneumonia, or after ARDS in general, most descriptions being limited to CXR.

There are ongoing studies evaluating the role of antifibrotic drugs for the prevention of lung fibrosis after SARS-CoV-2 infection [13] . However, the exact proportion of patients who will develop irreversible lung fibrosis remains unknown. The aim of this study was to describe chest CT abnormalities persisting at 6 months and beyond, in patients who were admitted to ICU for severe COVID-19 pneumonia.

This single center retrospective study was approved by our local ethics committee, which waived the need for patients' consent. All patients admitted to ICU between March 1 st and April 30 th for COVID-19 pneumonia were eligible. Inclusion criteria were a positive RT-PCR for SARS-CoV-2 and the availability of a long-term chest-CT scan follow-up, performed at least 6 months after ICU admission.

Follow-up chest CT scans-all performed on multi detector CT units allowing acquiring high-resolution images-were reviewed in consensus by 2 chest radiologists (GC and MPR) with 7 and 20-year experience in chest imaging, respectively. Images were analyzed for the presence of residual ground glass opacities, parenchymal bands, traction bronchiectasis, reticulations, or honeycombing, the latter three being considered to define fibrotic changes. CT scans were then categorized into three different radiological patterns: no residual anomalies, residual ground glass and parenchymal bands defining a pattern of late organizing pneumonia (OP), and lastly fibrotic lung changes if traction bronchiectasis, reticulations or honeycombing were observed, regardless of other anomalies.

Additionally, demographic characteristics, comorbidities and pulmonary function tests (PFTs) closest to the long-term chest CT scan were collected from medical charts. Chest CT scans performed at ICU admission, when available, were also reviewed for visual quantification of initial lung disease extent.

Statistical analysis was performed using the statistical software package "R" (version 3.2.1, R Foundation, Vienna, Austria). Quantitative data is presented as median [interquartile range (IQR)] and was compared using a Kruskal-Wallis test by ranks. Qualitative data was compared using a Fisher exact test. A p-value less than 0.05 was considered as statistically significant.

A total of 126 COVID-19 patients were admitted to ICU during the study period.

Management of ARDS was standardized, in accordance with the guidelines from the French Intensive Care Society [14] . Of these patients, 20% (26/126) died. Of the remaining 100 patients, 51 were transferred outside the institution after ICU and lost to follow-up. Six patients had CT scan normalization during the 6-month period post ICU discharge and were not re-evaluated afterwards. The remaining 43 patients had a late follow-up chest CT scan and composed the study sample. Their characteristics are summarized in the Table. The study sample was mostly composed of men (32/43, 74%) and the median age was 56.0 years [IQR= 50. 5 Nine of these 12 patients had DLCO measurements which were abnormal in one third (3/9), despite apparent CT normalization. A late OP pattern, with a variable association of residual ground glass and parenchymal bands but no fibrotic changes was observed in 44% (19/43) of the patients. Lastly, fibrotic changes were found in 28% of patients (12/43) overall and were of limited extent, involving less than 10% of lung parenchyma on visual assessment. They consisted of traction bronchiectasis within residual ground glass opacities in all 12 patients (100%), associated with reticulations in 5 patients (42%). Ten patients also had parenchymal bands (83%). (73%) vs 6/13 (46%) for patients with late OP and 0/9 (0%) for patients with CT normalization, p=0.003.

The strength of this retrospective study was to focus on severe COVID-19 patients who were admitted to ICU. The proportion of patients with residual abnormalities at 6 months in our cohort is in line with other reports from China [11, 15] . However, despite focusing on a population admitted to ICU, we found a lower proportion of patients with late fibrotic changes (28 vs up to 35%) and these changes were of limited extent. The difference may be related to a more restrictive definition of fibrotic changes in our study. Indeed, parenchymal bands were considered as fibrotic-like changes in the studies by Han et al. [11] and Liu et al. [15] , whereas we considered them as residual signs of organizing pneumonia, observed from the early phase of the disease and improving over time, unlike traction bronchiectasis [16] .

Our study has several limitations. Firstly, owing to its retrospective design, late chest CT scan and PFT follow-up were not available for all COVID-19 patients admitted to ICU during the study period. Patients transferred to other hospitals were lost to follow-up.

However, for those followed-up onsite, late fibrotic changes were of limited extent, when observed, which is worth noting. Secondly, patients in the early phase of the pandemic were more often intubated and the beneficial effect of dexamethasone was not established at that time. Our result may not thus be applicable to patients managed in the subsequent waves of the pandemic. However, long-term sequelae affecting the patients of the first wave of the pandemic will have to be managed in the coming years, justifying the report of late findings in these patients.

In conclusion, a late organizing pneumonia pattern is common 6 months after severe COVID-19 pneumonia, whereas fibrotic changes of limited extent are only seen in one third of patients. DLCO remains abnormal in the vast majority of patients, including a subset with apparent CT normalization, possibly due to residual microvascular obstruction. 

Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19)

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Integrative respiratory follow-up of severe COVID-19 reveals common functional and lung imaging sequelae

lung function and CT findings 3 months after hospital admission for COVID-19

Post-discharge chest CT findings and pulmonary function tests in severe COVID-19 patients

Comprehensive health assessment three months after recovery from acute COVID-19

Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery

Pulmonary Function and Radiologic Features in Survivors of Critical COVID-19

The Pathology of Severe COVID-19-Related Lung Damage

Sixmonth Follow-up Chest CT Findings after Severe COVID-19 Pneumonia

The 1-Year Impact of Severe Acute Respiratory Syndrome on Pulmonary Function, Exercise Capacity, and Quality of Life in a Cohort of Survivors

Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy

Formal guidelines: management of acute respiratory distress syndrome

Follow-Up Study of the Chest CT Characteristics of COVID-19 Survivors Seven Months After Recovery

COVID-19 pneumonia: A review of typical CT findings and differential diagnosis

Note: Quantitative data are presented as median

OP: organizing pneumonia; ICU: intensive care unit; PFTs: pulmonary function tests; FVC: forced vital capacity; TLC: total lung capacity DLCO: diffusing capacity for the lung monoxide