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Thin-Section Computed Tomography Manifestations During Convalescence and Long-Term Follow-Up of Patients with Severe Acute Respiratory Syndrome (SARS)

Authors:

Abstract

Background SARS is not only an acute disease, but also leads to long-term impaired lung diffusing capacity in some survivors. However, there is a paucity of data regarding long-term CT findings in survivors after SARS. The aim of this study was to assess the changes in lung function and lung thin-section computed tomography (CT) features in patients recovering from severe acute respiratory syndrome (SARS), especially the dynamic changes in ground-glass opacity (GGO). Material/Methods Clinical and radiological data from 11 patients with SARS were collected. The serial follow-up thin-section CTs were evaluated at 3, 6, and 84 months after SARS presentation. The distribution and predominant thin-section CT findings of lesions were evaluated. Results The extent of the lesions on the CT scans of the 11 patients decreased at 6 and 84 months compared to 3 months. The number of segments involved on 84-month follow-up CTs was less than those at 6 months (P<0.05). The predominant thin-section CT manifestation at 84 months (intralobular and interlobular septal thickening) was different than that at 6 months, at which GGO was predominant. Conclusions During convalescence after SARS, GGO and intralobular and interlobular septal thickening were the main thin-section CT manifestation. Intralobular and interlobular septal thickening predominated over GGO at 84 months.
Received: 2015.12.04
Accepted: 2016.01.12
Published: 2016.08.08
2367 2 3 31
Thin-Section Computed Tomography
Manifestations During Convalescence and Long-
Term Follow-Up of Patients with Severe Acute
Respiratory Syndrome (SARS)
ABC 1 Xiaohua Wu
CD 2 Dawei Dong
DE 1 Daqing Ma
Corresponding Author: Daqing Ma, e-mail: cjr.madaqing@vip.163.com
Source of support: Departmental sources
Background: SARS is not only an acute disease, but also leads to long-term impaired lung diffusing capacity in some survi-
vors. However, there is a paucity of data regarding long-term CT findings in survivors after SARS. The aim of
this study was to assess the changes in lung function and lung thin-section computed tomography (CT) fea-
tures in patients recovering from severe acute respiratory syndrome (SARS), especially the dynamic changes in
ground-glass opacity (GGO).
Material/Methods: Clinical and radiological data from 11 patients with SARS were collected. The serial follow-up thin-section CTs
were evaluated at 3, 6, and 84 months after SARS presentation. The distribution and predominant thin-sec-
tion CT findings of lesions were evaluated.
Results: The extent of the lesions on the CT scans of the 11 patients decreased at 6 and 84 months compared to 3
months. The number of segments involved on 84-month follow-up CTs was less than those at 6 months (P<0.05).
The predominant thin-section CT manifestation at 84 months (intralobular and interlobular septal thickening)
was different than that at 6 months, at which GGO was predominant.
Conclusions: During convalescence after SARS, GGO and intralobular and interlobular septal thickening were the main thin-
section CT manifestation. Intralobular and interlobular septal thickening predominated over GGO at 84 months.
MeSH Keywords: Pneumonia, Viral • Severe Acute Respiratory Syndrome • Tomography Scanners, X-Ray Computed
Full-text PDF: http://www.medscimonit.com/abstract/index/idArt/896985
Authors’ Contribution:
Study Design A
Data Collection B
Statistical Analysis C
Data Interpretation D
Manuscript Preparation E
Literature Search F
Funds Collection G
1 Department of Radiology, Beijng Friendship Hospital, Capital Medical University,
Beijing, P.R. China
2 Department of Radiology, Beijng Xiaotangshan Hospital, Beijing, P.R. China
e-ISSN 1643-3750
© Med Sci Monit, 2016; 22: 2793-2799
DOI: 10.12659/MSM.896985
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Background
Severe acute respiratory syndrome (SARS) is an emergent
infectious disease that was epidemic in 2002 and 2003 [1].
Between November 2002 and July 2003, an outbreak of SARS
in southern China infected about 8000 people and led to 774
recorded deaths, mostly in Hong Kong [1]. Within weeks, SARS
spread from Hong Kong to 37 countries [2]. A novel corona-
virus (SARS-CoV) is responsible for SARS. The coronavirus re-
sponsible for Middle East Respiratory Syndrome (MERS-CoV)
is similar to SARS-CoV. A better understanding of the features
of SARS-CoV would help to guide control measures and treat-
ment for similar diseases, such as MERS-CoV [3,4].
Lung injury caused by SARS-CoV is one of the main clinical
manifestations and directly affects prognosis. Imaging plays
an important role in the diagnosis and evaluation of patients
with SARS. Thin-section computed tomography (CT) can show
pulmonary abnormalities in patients with normal findings on
plain X-ray and is useful in depicting the patterns and extent
of the abnormalities [5–8]. During the acute phase of SARS,
the more distinctive radiographic features include the pre-
dominant involvement of lung periphery and lower zone, and
the absence of cavitation, hilar lymphadenopathy, and pleu-
ral effusion [9,10]. Radiographic progression from unilateral
focal lesion to either multifocal or bilateral involvement dur-
ing the second phase of the disease, followed by radiographic
improvement with treatment, are commonly observed [9,10].
SARS is not only an acute disease, but also leads to long-
term impaired lung diffusing capacity in about 24% of sur-
vivors [11], resulting in significantly lower exercise tolerance
compared with the age-matched general population [11–13].
Another study suggested that the lung function impairment
might not be related to the disease itself, but rather to extra-
pulmonary muscle weakness [14]. Nevertheless, 75% of SARS
survivors still show lung abnormalities on thin-section CT 5
years after their illness onset [14].
However, there is a paucity of data regarding long-term CT find-
ings in survivors after SARS. Therefore, the aim of the pres-
ent study was to assess the changes in lung function and lung
thin-section CT features in patients recovering from SARS, es-
pecially the dynamic changes in ground-glass opacity (GGO).
Material and Methods
Patients
Eleven patients who had been discharged after treatment
for SARS as inpatients between February and June 2003 at
Beijing Friendship Hospital were followed up at 3, 6, and 84
months using thin-section CT and were included in the present
study. The diagnosis of SARS was based on the World Health
Organization criteria [15].
This study received Ethics Committee approval from Beijing
Friendship Hospital affiliated to Capital Medical University
(Approval ID: 2015-P2-076-01). The committees waived the
need for individual consent because of the retrospective na-
ture of the study.
CT scans
The CT examinations were performed with an 8-row multi
-
detector CT scanner (High Speed Ultra; GE Medical Systems,
Milwaukee, WI, USA), and a 64-row multidetector CT scanner
(LightSpeed Ultra; GE Medical Systems, Milwaukee, WI, USA)
using the following parameters: 120 kVp, 150 mA, 5-mm col-
limation, 1.35:1 pitch, and reconstruction matrix of 512×512.
The subjects were scanned in a supine position during breath-
holding at full inspiration. Thin-section CT images were re-
constructed with 0.625-mm or 1.25-mm collimation with a
high spatial frequency algorithm or standard algorithm and
then sent to the workstation (ADW 4.2; GE Medical Systems,
Milwaukee, WI, USA) for analyzing. Thin-section CT images
were evaluated using a lung window, with a window level of
–600 HU and window width of 1500 HU. The soft-tissue win-
dow was not evaluated.
Image interpretation
All thin-section CT images were reviewed by 2 radiologists. The
radiologists were aware of the diagnosis of SARS. For all scans,
the radiologists were blinded to the names of the patients and
the length of time since onset, but they were aware of which
images belonged to the same patient. A consensus had to be
reached between the 2 radiologists about the abnormalities.
Discrepancies were solved by discussion.
The radiologists determined the extent of the following thin-
section CT abnormalities: ground-glass opacity, consolidation,
reticular pattern, patchy decreased attenuation, and subpleu-
ral line, in accordance with the standard morphologic descrip-
tors based on the Fleischner Society Nomenclature Committee
recommendations [16] and other studies [17,18]. The evalua-
tion of the extent of lung involvement was based on the seg-
ments of the lung anatomy: 10 segments in the right lung and
10 segments in the left lung (2 segments were considered in
the apicoposterius segment left upper lobe and 2 segments
were considered in the inferior front segment of the left low-
er lobe). The following rules were used to evaluate the lobe
involvement: if more than half of the segment on the biggest
scope of lesion level on axial thin-section CT was involved,
then the segment (1 point) was recorded as being involved;
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if no more than half of the segment was involved, then 0.5
point was recorded.
To evaluate the distribution of the lesion, it was also classi-
fied into 3 categories: 1) subpleural and/or peribronchovascu-
lar, 2) diffuse, or 3) irregular. In addition, each CT was divided
into 3 categories: 1) anterior, 2) posterior, or 3) anterior and
posterior. Finally, for every CT scan, the radiologists were re-
quired to generalize the main CT manifestation: 1) GGO pre-
dominant, or 2) fine reticulation predominant.
Pulmonary function test (PFT)
The PFT of the patients was classified into mild, moderate, or
serious. We evaluated lung volumes (total lung capacity [TLC],
vital capacity [VC], residual volume [RV], functional residual
capacity [FRC] using the nitrogen washout method), spirometry
(forced vital capacity [FVC], forced expiratory volume in 1 sec-
ond [FEV1], FEV1/FVC ratio), and surface area for gas exchange
(diffusion capacity adjusted for hemoglobin [DLCO]). The DLCO
was determined using the single-breath carbon monoxide tech-
nique and an infrared analyzer. FEV1/expected% of <30%, 30–
50%, 50–80%, and >80% were regarded as extremely serious,
serious, moderate, and mild, respectively. DLCO values <80%
of predicted were regarded as being impaired.
Statistical analysis
Descriptive statistics are presented. Continuous data are pre-
sented as means ± standard deviation (SD). Categorical data
are presented as frequencies. SPSS 16.0 (IBM, Armonk, NY,
USA) was used for statistical analysis.
Case
number Gender Age at
onset
3 months 6 months 84 months
Predominant
HRCT findings
Segments
involved
Predominant
HRCT findings
Segments
involved
Predominant
HRCT findings
Segments
involved PFT
1 F 30 GGO 15
Reticulation
and
interlobular
thickening
15
Reticulation
and interlobular
thickening
15 Mild
2 M 35 GGO 3 GGO 2 GGO 1 Mild
3 M 54
Consolidation
and GGO 8 GGO 6
Reticulation
and interlobular
thickening
4 N
4 F 38 Diffuse GGO 9 GGO 3
Reticulation
and interlobular
thickening
3 Mild
5 F 42
Consolidation
and GGO 13
Reticulation
and
interlobular
thickening
7
Reticulation
and interlobular
thickening
5 Mild
6 F 32 GGO 14
Reticulation
and interlobular
thickening
11.5 Mild
7 M 31 GGO 18
Reticulation
and interlobular
thickening
9.5 Mild
8 F 31
Reticulation
and
interlobular
thickening
5
Reticulation
and interlobular
thickening
3.5 Mild
9 F 40 GGO 9
Reticulation
and interlobular
thickening
6.5
Moderate
10 F 48 GGO 18 GGO 16 Mild
11 F 36 GGO 9 Normal 0 N
Table 1. Characteristics of the patients.
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Results
Characteristics of the patients
Eleven patients (8 females and 3 males; age range: 30–54 years,
mean age: 38.6 years) met the selection criteria. Table 1 pres-
ents the demographic data and changes in lung function and
lung radiographic features of the 11 patients during follow-
up. All of the 11 patients were healthy before developing SARS
and none were smokers. In acute phase, glucocorticoid was
used in all 11 patients (methylprednisolone; the biggest dose
was 840 mg/d, mean duration 9.5 days, and after improving
for 2 or 3 days, methylprednisolone dose was decreased). All
patients were still alive during the study period. Twenty-seven
CT scans were evaluated. At 84 months, 5 patients were still
experiencing persistent dyspnea, 4 had cough, 2 had sputum
production, and 2 experienced all 3 symptoms. The mean time
from discharge to the first follow-up was 3 months (range, 2
to 4 months).
Thin-section CT findings
Table 2 presents the thin-section CT findings. All 11 patients
underwent CT scans at 6- and 84-month follow-up. Multiple
lobes or segments were involved in all 11 cases. Among them,
48 segments (average of 10 segments per patient) were in-
volved at 3 months, 106 segments (average of 9.6 per case)
were involved at 6 months, and 75 segments (average of
6.8 per case) were involved at 84 months. At 3 months, as
the predominant thin-section CT feature, 2 patients (40.0%)
showed GGO (Figure 1) and 3 showed consolidation and GGO
(60.0%) (Figure 2). At 6 months, as the predominant thin-sec-
tion CT feature, 3 patients (27.3%) showed reticulation and
interlobular thickening (Figure 3) and 8 (72.7%) showed GGO.
At 84 months, as the predominant thin-section CT feature, 1
patient (9.1%) had no lung abnormality, 8 patients (72.7%)
showed reticulation and interlobular thickening, and 2 (18.2%)
showed GGO. Traction bronchiectasis was found in 3 patients
(Figure 3), while patchy decreased attenuation was found in 1
patient (Figure 1). Traction bronchiectasis was found at 6- and
84-month thin-section CT, and patchy decreased attenuation
was found at 3-, 6-, and 84-month thin-section CT.
Pulmonary function test
The PFT results of the 11 patients at 84 months are present-
ed in Table 1. Two patients (18%) had a normal PFT. Nine pa-
tients (81.8%) had a low DLCO. Eight patients (72.7%) had
mild lung function damage, and 1 (9.1%) had moderate lung
function damage.
Trends in changes in predominant thin-section CT findings
over time
Table 2 shows that the predominant CT findings in SARS sur-
vivors shift from a predominance of the GGO feature at 3
(100.0%) and 6 (72.7%) months to the predominance of re-
ticulation and interlobular thickening at 84 months (72.7%).
Figuress 1–3 present typical thin-section CT imaging at 3, 6,
and 84 months, respectively.
CT findings 3 months (n=5) 6 months (n=11) 84 months (n=11)
GGO 5 (100.0%) 11 (100.0%) 10 (90.9%)
Consolidation 5 (100.0%) 0 0
Reticulation 5 (100.0%) 9 (81.7%) 10 (90.9%)
Subpleural line 1 (20.0%) 1 (9.1%) 1 (9.1%)
Traction brochiectasis 0 2 (18.2%) 2 (18.2%)
Air trapping 1 (20.0%) 1 (9.1%) 1 (9.1%)
Small nodule 2 (40.0%) 2 (18.2%) 2 (9.1%)
GGO predominance 5 (100.0%) 2 (18.2%)
Reticulation predominance 0 3 (27.3%) 8 (72.7%)
Distribution of peripheral 3 (60.0%) 9 (81.7%) 9 (81.7%)
Distribution on axial section (anterior and
posterior) 5 (100.0%) 11 (100.0%) 10 (90.9%)
Segments involved 48 (48/500) 106 (106/2200) 75 (75/2200)
Table 2. CT findings during follow-up.
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Discussion
During viral lung infections, the lungs histologically show dif-
fuse alveolar damage, including interstitial lymphocyte infil-
tration, air-space hemorrhage, edema, fibrosis, type 2 cell hy-
perplasia, and hyaline tissue formation [19]. Diffuse alveolar
damage is found in some kinds of viral pneumonia, but it is
usually self-limited and radiologic abnormalities usually di-
minish within 3 weeks in immunocompetent patients [20].
In SARS-CoV-infected patients, intralobular and interlobular
septal thickening, subpleural lines, and traction bronchiecta-
sis were observed as late as 84 months after SARS infection
in the present study. All these thin-section CT manifestations
were also found at 3 and 6 months during the recovery phase
A B C
Figure 1. Case 1, SARS survivor, female, 30 years old. (A) The CT scan at 3 months showed diffuse bilateral GGO (arrow). (B) Six
months later, GGO was reduced. (C) At 84 months, GGO was greatly reduced and fine reticulation (intralobular and
interlobular septal thickening) predominated (arrow). Patchy decreased attenuation was seen at 3-, 6-, and 84-month CT
(triangle).
A B C
Figure 2. Case 7, SARS survivor, male, 31 years old. (A) Chest radiography showed consolidation in the lower lobes of both lungs in
acute phase. (B) Six months later, GGO (triangle) and reticulation (arrow) were observed in both lungs. (C) Fine reticulation
(arrow) still persisted but GGO could not be found at 84-month CT.
A B C
Figure 3. Case 6, SARS survivor, female, 32 years old. (A) X-ray radiography showed a large consolidation in the lower lobes of both
lungs in acute phase. (B) Six months later, X-ray revealed GGO, septal thickening, and fine-mesh shadows (white arrow).
Traction bronchiectasis was found in the left lower lobe. (C) At 84 months, GGO was reduced and interlobular thickening
predominated. Traction bronchiectasis was still present.
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of SARS, which may indicate lung fibrosis, as observed in pre-
vious studies [21,22]. To the best of our knowledge, the pres-
ent study is the first to report abnormal imaging at up to 7
years after SARS-CoV pneumonia.
The characteristic thin-section CT finding in SARS survivors
changed from GGO predominance at 3–6 months to fine re-
ticulation (intralobular and interlobular septal thickening)
predominance at 7 years. GGO was found in 8 patients at 6
months and in 2 patients at 84 months. Some studies report-
ed the imaging features of the recovery phase in patients with
SARS [21,22]. Antonio et al. [21] analyzed the thin-section CT
findings at an average of 36.5 days in 24 patients and observed
that the main findings in the recovery phase were GGO, intra-
lobular and interlobular septal thickening, traction bronchi-
ectasis, and subpleural lines. They also reported that fibrosis
began early and tended to be found in elderly and more seri-
ously affected patients. However, in the present study, all 11
patients showed abnormalities that may indicate fibrosis at 6
months, and 10 patients still had signs of lung fibrosis after
7 years. All patients were 30–54 years old when they were in-
fected by SARS-CoV; therefore, lung fibrosis could be a long-
term sequela of SARS-CoV infection.
Importantly, the thin-section CT lung abnormalities observed in
the present study seemed to be different from those induced
by other pneumonia viruses [23,24]. It is known that many
SARS patients suffer from ARDS/DAD in the acute phase [25].
Nevertheless, the present study suggests that either the lung
fibrosis is very slow to disappear after infection or that the CT
abnormality is different from lung fibrosis induced by other
pneumonia viruses. However, the results of the present study
do not resolve this issue. With regard to the physical impair-
ment that may accompany the abnormalities on thin-section
CT, some previous studies suggest that the physical impair-
ment after SARS persists for at least 12 months [11,13], while
another study suggests only mild impairments at 5 years [14].
A study has shown that the immune response after SARS per-
sists for at least 90 days [26], but no data is available to deter-
mine exactly how long it persists and whether it could involve
lungs as a long-term sequela. In our study, mild or moderate
pulmonary function damage was still present in 81.8% of the
patients at 7 years after SARS infection.
Some studies have shown that after the acute phase of ARDS,
CT findings are variable [26–28]. In ARDS, although complete
resolution of abnormalities may occur, the typical CT findings
at the later stage are that of a coarse reticular pattern and GGO
in the anterior part of the lungs [25,27,29]. In this setting, it
is likely that GGO represents areas of fine fibrosis, which are
observed on thin-section CT. Our study shows that the CT ab-
normalities of all patients had a diffuse distribution, which was
similar that reported in a recent study by Masclans et al. [30].
Indeed, Masclans et al. [30] found that 76% of patients had
abnormalities on high-resolution CT at 6 months after infec-
tion, and these abnormalities were typically areas of reticula-
tion and GGO. Therefore, the distribution of thin-section abnor-
malities in our study seem to be different from those reported
in some other studies [25,27,29] on late-stage ARDS. However,
drawing conclusions is impossible because of the lack of ac-
companying histopathological examination in most patients
with SARS and ARDS.
Another finding of the present study is the presence of trac-
tion bronchiectasis, which represents airway abnormalities, as
well as patchy decreased attenuation, which probably repre-
sents airway abnormalities. Traction bronchiectasis was found
in 3 patients, while patchy decreased attenuation was found in
1 patient. Similar results in SARS patients were also reported
in some other studies [24,31]. Masclans et al. [30] found that
airway disease was more common in ARDS survivors, again
suggesting the possibility of the presence of underlying lung
fibrosis in these survivors of SARS.
The present study is not without limitations. This was a retro-
spective review of patients evaluated at 2 centers, with all of
the issues of selection and observational biases that this de-
sign entails. Secondly, the sample size was smaller than that
of prior studies and may not represent most patients. Thirdly,
the pulmonary function test results at 3 and 6 months were
unavailable in most patients.
Conclusions
This study of 11 SARS patients found that lung abnormalities
on thin-section CT still existed in SARS survivors 7 years af-
ter infection, though the extent became less. During convales-
cence after SARS, GGO and intralobular and interlobular sep-
tal thickening were the main thin-section CT manifestations.
From 6 months to 7 years after SARS, the predominant thin-
section CT findings changed from GGO predominance to fine
reticulation predominance, which probably represents the in-
terstitial fibrotic proliferation recovery phase of diffuse alveo-
lar damage. These abnormalities were consistent with the PFT.
Conflict of interest
The authors declare that they have no actual or potential con-
flicts of interest.
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... This can affect the respiratory, cardiovascular, neuromuscular, gastrointestinal, and psychological systems of the body, as well as functional abilities and participation in daily life (International Classification of Functioning, Disability and Health (ICF)) [8][9][10][11]. The most commonly reported impairment is a respiratory compromise with reduced lung function [12][13][14][15][16][17][18][19][20]. Long-term fatigue is also a prevalent symptom in post COVID-19 condition reported to last for about 6 months from the onset of the acute disease [2,21]. ...
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Background The implementation of standardized assessments in physiotherapeutic practice strongly supports diagnostic and treatment plans. Previous studies reported insufficient usage of standardized assessments due to lack of time, lack of knowledge, lack of resources and other barriers. Physiotherapy in outpatient settings became essential for the rehabilitation of patients with post COVID-19 condition but it remains unknown to what extent assessments are implemented into the evaluation of these patients. In this study, we explored the current use and barriers regarding the implementation of physiotherapeutic assessments to evaluate patients with post COVID-19 condition. Methods A cross-sectional online survey was carried out among 180 physiotherapists working in outpatient settings in Austria and South Tyrol. Results The majority of physiotherapists (88%) indicated that standardized assessments are useful, though less than a fifth of participants actually implement assessments in practice. Among implementation barriers, “insufficient experience” (41.8%) and “lack of knowledge” (36.6%) were mentioned most often. Concerning specific post COVID-19 assessments, the evaluation of “physical and respiratory function”, “quality of life” and “activities of daily living” were stated to be of particular relevance. Conclusions Our study revealed a low implementation rate and identified the main barriers regarding the non-usage of standardized assessments for post COVID-19 patients. Trial registration The Private University for Health Sciences and Health Technology (UMIT TIROL), and the Research Committee for Scientific Ethical Questions granted approval for the survey (RCSEQ, Hall in Tirol, Austria, Number 2834).
... In the last decades several investigations aimed to detect the long-term fibrotic burden after severe acute respiratory syndrome coronavirus (SARS-CoV) [9,10]. Since the early phase of the pandemic, the similarities between COVID-19 and SARS have brought to hypothesize a similar risk of progression to lung fibrosis. ...
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While lung ultrasonography (LUS) proved to be a useful diagnostic and prognostic tool in acute phase of COVID 19 pneumonia, its role in detecting long-term pulmonary sequelae has yet to be explored. In our prospective observational study we assessed the potential of LUS in detecting the presence of computed tomography (CT) fibrotic-like changes after 6 months from COVID-19 pneumonia. Patients who were discharged with a diagnosis of severe COVID-19 pneumonia were enrolled. After 6 months from hospital discharge they underwent LUS, chest CT scan and pulmonary function tests. A logistic regression analysis was performed to assess the association between presence of symptoms, LUS score and diffusing capacity for carbon monoxide (DLCO) at 6-month after hospital discharge and CT scan fibrotic-like changes. A second logistic model was performed to assess the value of some predefined baseline factors (age, sex, worst PaO2/FiO2, ventilator support, worst CRP value, worst D-dimer value and worst LUS score during hospitalization) to predict fibrotic-like changes on 6-month CT scan. Seventy-four patients were enrolled in the study. Twenty-four (32%) showed lung abnormalities suitable for fibrotic-like changes. At multivariate logistic regression analysis LUS score after 6 months from acute disease was significantly associated with fibrotic-like pattern on CT scan. The second logistic model showed that D-dimer value was the only baseline predictive variable of fibrotic-like changes at multivariate analysis. LUS performed after 6 months from severe COVID-19 pneumonia may be a promising tool for detection and follow-up of pulmonary fibrotic sequelae.
... [24,25] Similarly, former studies of SARS, H1N1, and Ebola revealed that fatigue, myalgia, and breathlessness were persistent for long time after discharge in more than half of patients even after 1 year. [36][37][38] A Canadian study reported that 40% of SARS survivors still had a chronic fatigue problem for a mean period of 41.3 months of follow-up. [39] Various studies had inconsistent results about the determinants of persistent symptoms such as age and sex. ...
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Background: The Isfahan COVID Cohort (ICC) study was designed to investigate the short- and long-term consequences of patients with COVID-19 in Iran. This report presents the rationale, methodology, and initial results of ICC. Materials and Methods: ICC is a 5-year multicentric prospective cohort study that is ongoing on two groups including 5000 patients hospitalized with moderate or severe and 800 nonhospitalized patients with mild or asymptomatic COVID-19 in Isfahan. The ICC endpoints are morbidity, mortality, incident cases, or worsening of underlying noncommunicable diseases (NCDs) and their risk factors. In the current analysis, we examined the persistent symptoms and incident NCDs or risk factors in 819 previously hospitalized patients who completed 1-year follow-up. Results: The two most common symptoms were joint pain/myalgia (19.7%) and dry cough/dyspnea (18.7%). Around 60% of patients had at least one symptom which was more common among women than men and in middle aged than younger or older patients. Female (odds ratio [OR] =1.88, 95% confidence interval [CI]: 1.39–2.55) and highly-educated patients (OR = 2.18, 95% CI: 1.56–3.04) had higher risk of having any symptom in 1-year follow-up. New cases of hypertension followed by diabetes then coronary heart disease (CHD) were the most common incident NCDs. Conclusion: During 1-year follow-up after hospital discharge, about 60% of patients experienced persistent symptoms. Incident hypertension, diabetes, and CHD were the most common events seen. Close monitoring and extensive health services with integrative approaches are needed to improve the health status of these patients.
... Kewan et al, 202090 Tocilizumab Similar rates of hospital-acquired infections occurred in both cohorts (18% in treatment and 22% in control)Pettit et al, 2020 48 Tocilizumab Overall infection rate was similar (16.2% treatment vs 17.5% control), but late onset infections occurred in more treated patients (23% vs 8%; p=0.013). In treated, 26% experienced an increase to >5 times upper limit normal of LFTs Rodríguez-Baño et al, 2020 56 Tocilizumab Secondary bacterial infection similar in both groups (treated 12.5% vs 10.3% control; p=0.57) ...
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Interstitial lung diseases (ILD) encompass a heterogeneous group of immuno-inflammatory and fibrotic diseases of the lung parenchyma. The most common and severe ILD is idiopathic pulmonary fibrosis (IPF), a chronic progressive fibrotic lung disease of unknown aetiology associated with poor prognosis. A substantial proportion of individuals with ILDs other than IPF also develop progressive fibrosis with clinical, radiological, and genetic similarities, suggesting a shared final common pathway across progressive fibrotic ILDs irrespective of aetiology. Study of shared mechanisms of progression has the potential to aid prognostication, enable a precise approach to therapeutic strategies and allow stratification into clinical trials. Biomarkers are objectively measured and reproducible characteristics that enable stratification of disease phenotypes. The aim of this thesis was to examine and characterise the role of clinical biomarkers in fibrotic lung diseases to enable early identification of progressive fibrotic phenotypes. An evidence synthesis of blood biomarkers as prognosticators in IPF highlighted several biomarkers with prognostic potential and identified priorities for future blood biomarker research. The first individual participant data (IPD) meta-analysis in IPF of matrix metalloproteinase-7 demonstrated baseline measurements were independently associated with disease outcomes. To evaluate the role of physiological variables as prognostic biomarkers and as surrogate trial endpoints, the largest analysis of interventional trial placebo arms in IPF was performed using robust IPD methodology. Baseline and three-month change in physiological variables, particularly FVC were independently associated with disease outcomes, supporting their role as prognostic biomarkers. The association between short-term change in FVC and disease outcomes were replicated in individuals receiving anti-fibrotics using pooled analysis of pirfenidone and nintedanib treatment arms. Moreover, a difference in FVC change over three-months between treatment and placebo arms was observed, supporting three-month FVC as a surrogate endpoint in future IPF trials. An ongoing prospective multi-centre observational cohort study (INJUSTIS) to assess longitudinal disease behaviour and the role of biomarkers in other fibrotic lung diseases was established. Interim analysis suggested a significant proportion of individuals with non-IPF fibrotic ILD had progressive phenotypes that were comparable with disease behaviour in IPF. Lung function, particularly FVC change over three-months was independently associated with poorer outcomes. The role of home spirometry in fibrotic ILD was assessed, and though measurements were accurate and reliable when compared with hospital spirometry, daily FVC measurements were unable to predict mortality at earlier timepoints. An exploratory blood biomarker analysis performed in individuals with extremes of IPF offered further support for the role of CA-125 as a prognostic biomarker and identified several biomarkers and biological pathways for more focussed assessment in the complete INJUSTIS cohort. Taken collectively, the data presented in this thesis strongly support an important role for biomarkers in fibrotic ILD to identify progressive fibrotic phenotypes and enable personalised approaches to patient management. Whilst the COVID-19 pandemic was severely disruptive, the work presented forms the basis for further study of biomarkers in progressive pulmonary fibrosis.
... [24,33] These observations are reminiscent of the previous SARS that cause residual GGO, intralobular and interlobular septal thickening after 84 months post recovery. [78] However, the recovery and stability of pulmonary lesions were observed among recovered patients on an annual follow-up that had lasted for 15 years after SARS infection. [79] Therefore, the respiratory consequences of COVID-19 may need a longer time to be revealed. ...
Article
Objectives: The objective of this review was to describe the COVID-19 complications after recovery. Methods: The researchers systematically reviewed studies that reported post-COVID-19 complications from three databases: PubMed, Google Scholar and the World Health Organization (WHO) COVID-19 database. The search was conducted between 21 November 2020 and 14 January 2021. Inclusion criteria were articles written in English, with primary data, reporting complications of COVID-19 after full recovery. The review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Key findings: This review included 69 studies with 146 725 patients from 22 countries related to post-COVID-19 complications. Thirty-six studies reported post-cure respiratory complications, ranging from dyspnoea to residual pulmonary fibrosis. Cardiac symptoms were reported in nine studies, including palpitation, chest pain and diastolic dysfunction. Neurological complications included post-traumatic stress syndrome, anxiety, depression, memory issues, insomnia and sleeping disturbance, cognitive impairments and stigma. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and acute liver injury. The physical decline was the most common symptom reported in the musculoskeletal complications. Conclusion: COVID-19 may cause several types of complications after recovery (testing negative PCR). The identified complications include respiratory, neurological/mental, cardiovascular, gastrointestinal tract, urinary tract, musculoskeletal and miscellaneous complications. However, the key impairments were pulmonary consequences, psychological problems and exercise intolerance. Thus, COVID-19 patients may need long-term follow-up.
... There are serious doubts whether the observed fibrotic abnormalities resolve fully, and indeed, there is evidence that a non-negligible percentage will develop irreversible pulmonary fibrosis [5]. In a 15-year follow-up study of 71 survivors from SARS-CoV-1 infection, the coronavirus that emerged in Southeast Asia in 2003, pulmonary diffusion abnormalities were observed in approximately one-third of patients [6], and a 6-month follow-up study of computed tomography images for 40 SARS-CoV-1 patients revealed long-term sequelae, such as air trapping, ground-glass opacities, reticulations, and bronchial distortion, in more than half of the participants [7]. One-year follow-up studies in COVID-19 patients showed that although the proportion of radiological abnormalities in the lung is very significant at 3 months after hospital discharge, similar to those observed in SARS-CoV-1, radiological changes only persisted one year later in about 5-20% of them [8][9][10]. ...
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Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease associated with high morbidity and mortality. Although many patients recover, long-term sequelae after infection have become increasingly recognized and concerning. Among other sequelae, the available data indicate that many patients who recover from COVID-19 could develop fibrotic abnormalities over time. To understand the basic pathophysiology underlying the development of long-term pulmonary fibrosis in COVID-19, as well as the higher mortality rates in patients with pre-existing lung diseases, we compared the transcriptomic fingerprints among patients with COVID-19, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD) using interactomic analysis. Patients who died of COVID-19 shared some of the molecular biological processes triggered in patients with IPF, such as those related to immune response, airway remodeling, and wound healing, which could explain the radiological images seen in some patients after discharge. However, other aspects of this transcriptomic profile did not resemble the profile associated with irreversible fibrotic processes in IPF. Our mathematical approach instead showed that the molecular processes that were altered in COVID-19 patients more closely resembled those observed in COPD. These data indicate that patients with COPD, who have overcome COVID-19, might experience a faster decline in lung function that will undoubtedly affect global health.
... During the severe acute respiratory syndrome (SARS) outbreak in 2003, residual pulmonary fibrosis was found in 67% of patients 1 month after the infection, and some of those abnormalities were still observed 7 years later. 22,23 In contrast, the time-course of pulmonary sequelae in the current COVID-19 pandemic remains unclear. ...
Article
Coronavirus disease 2019 (COVID‐19) often causes radiological and functional pulmonary sequelae. However, evidence on 1‐year follow‐up of pulmonary sequelae is limited. We aimed to investigate the characteristics and time‐course of pulmonary sequelae after recovery from COVID‐19 through 1‐year follow‐up. We searched PubMed and EMBASE databases on 25 February 2022, and included studies with computed tomography (CT) findings at the 1‐year follow‐up. The extracted data on CT findings were analysed using a one‐group meta‐analysis. We further analysed the data in relation to COVID‐19 severity, improvement rate and lung function. Fifteen eligible studies (N = 3134) were included. One year after COVID‐19, 32.6% (95% CI 24.0–42.6, I2 = 92.9%) presented with residual CT abnormalities. Ground‐glass opacity and fibrotic‐like changes were frequently observed in 21.2% (95% CI 15.4–28.4, I2 = 86.7%) and 20.6% (95% CI 11.0–35.2, I2 = 91.9%), respectively. While the gradual recovery was seen on CT (52.9% [mid‐term] vs. 32.6% [1 year]), the frequency of CT abnormalities was higher in the severe/critical cases than in the mild/moderate cases (37.7% vs. 20.7%). In particular, fibrotic changes showed little improvement between 4–7 months and 1 year after COVID‐19. Pulmonary function tests at 1 year also showed the decline in diffusing capacity of the lung for carbon monoxide, especially in severe/critical cases. Our meta‐analysis indicated that residual CT abnormalities were common in hospitalized COVID‐19 patients 1 year after recovery, especially fibrotic changes in severe/critical cases. As these sequelae may last long, vigilant observations and longer follow‐up periods are warranted. One‐year follow‐up CT findings in COVID‐19 patients‐ A systematic review and meta‐analysis
... However, it has recently been argued that those fibrotic-like changes, in the setting of recovery from an acute lung injury, may have a completely different significance than in the setting of chronic lung diseases [22,26]. Bands probably represent limited organizing pneumonia, GGO that reduces in extension or attenuation may reflect inflammation and immature fibrosis remodeling, and bronchial distortion and traction bronchiectasis may not be irreversible (as previously described in SARS pneumonia follow-up CT scans) [20][21][22]27]. These hypotheses are in keeping with the progressive reduction of lung residual changes over time, even from 6 to 12 month follow-up CT scans, as shown in this study and by the other recent literature [13,[15][16][17][18][19]28]. ...
Article
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Prior studies variably reported residual chest CT abnormalities after COVID-19. This study evaluates the CT patterns of residual abnormalities in severe COVID-19 pneumonia survivors. All consecutive COVID-19 survivors who received a CT scan 5–7 months after severe pneumonia in two Italian hospitals (Reggio Emilia and Parma) were enrolled. Individual CT findings were retrospectively collected and follow-up CT scans were categorized as: resolution, residual non-fibrotic abnormalities, or residual fibrotic abnormalities according to CT patterns classified following standard definitions and international guidelines. In 225/405 (55.6%) patients, follow-up CT scans were normal or barely normal, whereas in 152/405 (37.5%) and 18/405 (4.4%) patients, non-fibrotic and fibrotic abnormalities were respectively found, and 10/405 (2.5%) had post-ventilatory changes (cicatricial emphysema and bronchiectasis in the anterior regions of upper lobes). Among non-fibrotic changes, either barely visible (n = 110/152) or overt (n = 20/152) ground-glass opacities (GGO), resembling non-fibrotic nonspecific interstitial pneumonia (NSIP) with or without organizing pneumonia features, represented the most common findings. The most frequent fibrotic abnormalities were subpleural reticulation (15/18), traction bronchiectasis (16/18) and GGO (14/18), resembling a fibrotic NSIP pattern. When multiple timepoints were available until 12 months (n = 65), residual abnormalities extension decreased over time. NSIP, more frequently without fibrotic features, represents the most common CT appearance of post-severe COVID-19 pneumonia.
Article
Background: A number of patients with COVID-19 pneumonia were discharged from hospitals in central India.This study highlights the relevant affecting factors, and to describe the chest CT ndings and sequelae during follow up. Aims And Objectives: our aim was to determine the cumulative percentage of complete radiological resolution at the time of active disease and at follow up after discharge ,highlight the predominant ndings in follow-up post covid CT and to correlate CTSS and the type of lung parenchymal opacity with chances of radiological resolution. Methods: Patients with COVID-19 pneumonia conrmed by RT-PCR who were discharged consecutively from the hospital between September 2020 and November 2020 and who underwent serial chest CT scans on their visit to post COVID OPD were enrolled in a retrospective observational study. The radiological characteristics of all patients were collected, analyzed and the total CT score was calculated. Imaging features and distributions were analyzed across different time points. Results: A total of 385 patients were evaluated; there were 286 (74.2%) men and 99 (28.7%) women, with a median age of 43 years old (IQR 36–56). Complete radiological resolution was seen in 74(19%) patients on follow up CT, while 49(12.7%) patients showed normal chest CT during active disease. Patients ≤40 years old showed a slightly higher cumulative percentage of complete radiological resolution than patients > 40 years old at the follow-up CT. The predominant patterns of abnormalities observed during the active disease were ground-glass opacity (GGO) (321 [83.3%]), consolidation (283 [73.5%]), and subpleural atelectatic brotic bands (235 [61%]). While on follow up scan, the positive count of GGO and consolidations gradually decreased, few brotic bands remained in almost all 235 patients who showed brotic changes earlier. Conclusion: Most of the lung lesions in COVID-19 pneumonia patients can be absorbed completely during short-term followup with sequelae of subcentimetric pleural atelectatic brotic bands only. The optimal time point for early radiological estimation might be three to four weeks after discharge.
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Background The COVID-19 pandemic follows SARS and MERS coronavirus epidemics. Some survivors of COVID-19 infection experience persistent respiratory symptoms, yet their cause and natural history remains unclear. Follow-up after SARS and MERS may provide a model for predicting the long-term pulmonary consequences of COVID-19. Methods This systematic review and meta-analysis aims to describe and compare the longitudinal pulmonary function test (PFT) and computed tomography (CT) features of patients recovering from SARS, MERS and COVID-19. Meta-analysis of PFT parameters (DerSimonian and Laird random effects model) and proportion of CT features (Freeman-Tukey transformation random effects model) were performed. Findings Persistent reduction in the diffusing capacity for carbon monoxide (DLco) following SARS, and COVID-19 infection is seen at 6 months follow-up and 12 months after MERS. Other PFT parameters recover in this time. 6 months after SARS and COVID-19, ground-glass opacity (GGO), linear opacities and reticulation persist in over 30% of patients; honeycombing and traction dilatation reported less. Severe/ critical COVID-19 infection leads to greater CT and PFT abnormality compared to mild/ moderate infection. Interpretation Persistent diffusion defects suggestive of parenchymal lung injury occur after SARS, MERS and COVID-19 infection, but improve over time. After COVID-19 infection, CT features are suggestive of persistent parenchymal lung injury, in keeping with a post-COVID-19 interstitial lung syndrome (PCOILS) – it is yet to be determined if this is a regressive or progressive disease.
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Objective: Severe acute respiratory syndrome (SARS) was a highly virulent atypical pneumonia caused by a novel coronavirus that resulted in a pandemic in 2003. Singapore was one of the most severely affected countries, and SARS took a heavy toll on our health care system. The lessons learned during the pandemic have shaped our national contagion response plan and have proved valuable in subsequent epidemics. We describe the lessons learned for the radiology department. Conclusion: Our experience with SARS has shaped and changed our daily practice of radiology.
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Acute lung injury usually causes hypoxaemic respiratory failure and acute respiratory distress syndrome CARDS). Although diffuse alveolar damage is the hallmark of ARDS, other histopathological patterns of injury, such as acute and fibrinoid organising pneumonia, can be associated with acute respiratory failure. Acute eosinophilic pneumonia can also cause acute hypoxaemic respiratory failure and mimic ARDS. This pictorial essay reviews the high-resolution CT findings of acute lung injury and the correlative histopathological findings.
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With increased globalisation comes the likelihood that infectious disease appearing in one country will spread rapidly to another, severe acute respiratory syndrome (SARS) being a recent example. However, although SARS infected some 10,000 individuals, killing around 1000, it did not lead to the devastating health impact that many feared, but a rather disproportionate economic impact. The disproportionate scale and nature of this impact has caused concern that outbreaks of more serious disease could cause catastrophic impacts on the global economy. Understanding factors that led to the impact of SARS might help to deal with the possible impact and management of such other infectious disease outbreaks. In this respect, the role of risk-its perception, communication and management-is critical. This paper looks at the role that risk, and especially the perception of risk, its communication and management, played in driving the economic impact of SARS. It considers the public and public health response to SARS, the role of the media and official organisations, and proposes policy and research priorities for establishing a system to better deal with the next global infectious disease outbreak. It is concluded that the potential for the rapid spread of infectious disease is not necessarily a greater threat than it has always been, but the effect that an outbreak can have on the economy is, which requires further research and policy development.
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This review compares the clinical features, laboratory aspects and treatment options of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS). Bats are the natural reservoirs of SARS-like coronaviruses (CoVs) and are likely the reservoir of MERS coronavirus (MERS-CoV). Although a small number of camels have been found to have positive nasal swabs by real-time polymerase chain reaction and to carry antibody against MERS-CoV, the transmission route and the intermediary animal source remain uncertain amongst the sporadic primary cases. Both SARS-CoV and MERS-CoV may cause severe respiratory failure and extrapulmonary features such as diarrhoea, whereas mild or asymptomatic cases also occur in both conditions. In comparison with SARS, patients with MERS are older with male predominance, more comorbid illness and relatively lower human-to-human transmission potential. Although the viral kinetics of MERS-CoV remain unknown, nosocomial infections of MERS occur early within the first week of illness of the index case, whereas those of SARS occurred mainly in the second week of illness when the patient's upper airway viral load peaks on day 10 of illness. In-vitro data suggest that interferon (IFN) with or without ribavirin and mycophenolic acid may inhibit MERS-CoV, whereas protease inhibitors and IFN have inhibitory activity against SARS-CoV. Although there are some similarities in the clinical features, MERS progresses to respiratory failure much more rapidly than SARS. The higher case fatality rate of MERS is likely related to older age and comorbid illness. More studies are needed to understand MERS-CoV in order to guide public health infection control measures and treatment.
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Objective Few studies have systematically evaluated high-resolution CT (HRCT) imaging of the thorax 5 years after severe ARDS to determine the association between radiologic findings and functional disability. The primary aim of this study was to determine chest radiologic abnormalities at 5 years in survivors of severe ARDS from the University of Toronto ARDS cohort. The secondary aim was to determine the relationship between the observed radiologic abnormalities on HRCT scan and pulmonary symptoms, pulmonary function test abnormalities, and health-related quality of life at 5-year follow-up. Methods HRCT scans were obtained in 24 of 64 eligible patients. Three anatomically comparable levels were selected for scoring, and each level was divided into four quadrants. The extent and distribution of individual CT image patterns (ground glass opacification, intense parenchymal opacification, reticular pattern, and decreased attenuation) were also reported. Results Eighteen patients (75%) had abnormal findings on HRCT imaging. These findings were minor and in the nondependent lung zones. No correlation was found between radiologic findings and patient symptoms, pulmonary function tests, 6-min walk distances, or heath-related quality of life measures. Conclusions Exercise and functional limitations experienced by survivors of severe ARDS are unlikely to be related to structural lung disease and may be more consistent with extrapulmonary muscle weakness.
Article
Chest radiography and computed tomography (CT) have a crucial role to play in the diagnosis and management of acute respiratory distress syndrome (ARDS). The identification of pulmonary opacification is a requirement for the definition of ARDS on the chest radiograph, while CT has a role to play, not only in the diagnosis of ARDS, but also in the identification of complications. This paper reviews the radiological appearances of ARDS that have been documented for some time, and also more recent research that has identified a role for CT in directing ventilation and in prognostication.
Article
ARDS can produce a loss of lung function with persistent sequelae. This study aimed to evaluate health-related quality of life (HRQL) in survivors of ARDS compared with a healthy reference population and to determine the middle/long-term radiographic abnormalities and functional status, as well as their relation to observed HRQL, in these patients. This was a prospective study carried out in three ICUs. HRQL in patients was determined with the Nottingham Health Profile immediately after ARDS diagnosis and 6 months after diagnosis. Patients underwent complete respiratory function testing, chest CT scan study, and the 6-min walk test. Follow-up was conducted in 38 patients with ARDS. Survivors of ARDS presented a poorer overall HRQL vs the general population, mainly because of lower scores in the dimensions related to mobility, energy, and social isolation. Limitations in daily life activities were documented in 40%. Respiratory function was altered in 67%, with a restrictive respiratory pattern in 58%. Radiologic study disclosed alterations in 76% (mainly reticular pattern). Patients were able to cover only 366 m (318-411 m) in the 6-min walk test and had a minimum pulse oximetry of 93% (90%-94%). A significant correlation was documented between the overall quality of life at first and at 6 months (r = 0.68, P < .01). Survivors of ARDS after 6 months had a poorer HRQL than the healthy population and showed mild radiographic and functional involvement. Early HRQL study in these patients enabled early detection of those who would present more long-term HRQL morbidity.