key: cord-0886371-kwj8boi3
authors: Hejazi, Mohammad Esmaeil; Malek Mahdavi, Aida; Navarbaf, Zahra; Tarzamni, Mohammad Kazem; Moradi, Rozhin; Sadeghi, Armin; Valizadeh, Hamed; Namvar, Leila
title: Relationship between chest CT scan findings with SOFA score, CRP, comorbidity, and mortality in ICU patients with COVID‐19
date: 2021-09-22
journal: Int J Clin Pract
DOI: 10.1111/ijcp.14869
sha: fbca1d9754a2b18c57573640d2457752cf46cb36
doc_id: 886371
cord_uid: kwj8boi3

OBJECTIVE: This study aimed to investigate the relationship between chest computed tomography (CT) scan findings with sequential organ failure assessment (SOFA) score, C‐reactive protein (CRP), comorbidity, and mortality in intensive care unit (ICU) patients with coronavirus disease 19 (COVID‐19). METHOD: Adult patients (≥18 years old) with COVID‐19 who were consecutively admitted to the Imam‐Reza Hospital, Tabriz, East‐Azerbaijan Province, North‐West of Iran between March 2020 and August 2020 were screened and total of 168 patients were included. Demographic, clinical, and mortality data were gathered. Severity of disease was evaluated using the SOFA score system. CRP levels were measured and chest CT scans were performed. RESULTS: Most of patients had multifocal and bilateral ground glass opacity (GGO) pattern in chest CT scan. There were significant correlations between SOFA score on admission with multifocal and bilateral GGO (P = .010 and P = .011, respectively). Significant relationships were observed between unilateral and bilateral GGO patterns with CRP (P = .049 and P = .046, respectively). There was significant relationship between GGO patterns with comorbidities including overweight/obesity, heart failure, cardiovascular diseases, and malignancy (P < .05). No significant relationships were observed between chest CT scan results with mortality (P > .05). CONCLUSION: Multifocal bilateral GGO was the most common pattern. Although chest CT scan characteristics were significantly related with SOFA score, CRP, and comorbidity in ICU patients with COVID‐19, a relationship with mortality was not significant.

mortality. [6] [7] [8] [9] [10] Furthermore, underlying diseases such as obesity, diabetes mellitus, chronic respiratory disease, cardiovascular disease, hypertension and cancer have an association with higher risk of mortality. 11, 12 Most patients with COVID-19 present pneumonia thus computed tomography (CT) scanning of the thorax can be a useful tool in screening and diagnosis. 13 Chest CT scan is able to present typical radiological findings of COVID-19 even before the appearance of clinical symptoms. [14] [15] [16] Moreover, chest CT scan is a sensitive method in comparison with reverse transcription polymerase chain reaction (RT-PCR) and assists physicians to identify COVID-19 patients who initially had negative RT-PCR results. 14, 17 The typical chest CT scan indicates numerous ground glass opacity (GGO) and/or consolidations in a peripheral distribution, which also presents the severity of pulmonary inflammation. [18] [19] [20] It has been reported that consolidation and GGO on chest CT scans are more common in non-survivors than survivors. 8, 21 In addition, majority of the patients with COVID-19 have bilateral infiltrates on chest CT scans. 11 Due to its availability, chest CT scan may help first-line triage of patients admitting to the hospital. 22 Chest CT scan is also helpful in assessing the severity and progression of disease, monitoring the clinical course as well as assessing the treatment. 23, 24 Elevation in consolidative opacities and GGO as well as interstitial septal thickening on chest CT scan is associated with exacerbating pneumonia. 15, 25 Chest CT features of COVID-19 pneumonia have been studied mostly in Chinese individuals; however, radiological manifestations should be clarified in other populations and areas around the world that have a quickly increasing number of confirmed cases.

SARS-CoV-2 infection is a multifaceted disease; therefore a reliable and appropriate biomarker is required to show changes in pattern of lung involvement and predict the severity of COVID-19 pneumonia. C-reactive protein (CRP) can be useful in the early diagnosis of pneumonia, 26 and patients with severe pneumonia had high CRP concentrations. Recently, studies have indicated that CRP has a positive association with severe dengue infection. 27, 28 Changes in CRP have been demonstrated in COVID-19 patients, but little is known about its correlation with disease severity. 29, 30 According to the research in COVID-19 patients, CRP concentration increased as the disease progressed and positive correlation was observed between CRP concentration with lung lesion and disease severity. 31 Furthermore, serum high-sensitivity CRP concentration and CT scores have a good consistency, and their combination can effectively evaluate disease progression and therapeutic effects. 32 Since Iran has the largest number of approved COVID-19 cases in Asia after China and to the best of our knowledge, there is no study investigating the relationship between chest CT scan characteristics with SOFA score, CRP, comorbidity, and mortality in Iranian COVID-19 patients, current study designed to assess the chest CT scan features in ICU patients with COVID-19 and to find whether there is a relationship between the chest CT scan features with SOFA score, CRP, comorbidity, and mortality. 

Demographic and clinical characteristics were gathered using a data collection form. The demographic data including age, sex, and smoking; comorbidities including hypertension, diabetes, chronic respiratory disease, coronary artery disease, heart failure, cardiovascular disease, chronic renal failure, malignancy, rheumatologic disease, and chronic liver disease; clinical symptoms including cough, fever, dyspnea, myalgia, fatigue, hemoptysis, chill, headache, sore throat,

Chest CT scan can be a useful tool in screening and diagnosis and is able to present typical radiological findings of COVID-19 even before the appearance of clinical symptoms. Chest CT scan is also helpful in assessing the severity and progression of disease, monitoring the clinical course as well as assessing the treatment.

Multifocal bilateral GGO was the most common pattern in chest CT scan. There were significant correlations between SOFA score on admission with multifocal and bilateral GGO. Significant relationships were observed between unilateral and bilateral GGO patterns with CRP.

There was significant relationship between GGO patterns with comorbidities including overweight/obesity, heart failure, cardiovascular diseases, and malignancy. No significant relationships were observed between chest CT scan results with mortality.

anorexia, nausea/vomiting, anosmia, taste loss, and diarrhea; vital signs including blood pressure, respiratory rate, heart rate, blood O 2 saturation, and body temperature as well as mortality (survived or died) were gathered. The SOFA score system was used to determine severity of disease with higher scores reflecting more severe illness. 34 Blood samples were also collected on admission and CRP levels were measured by immunoturbidimetry method. Due to wide variation in CRP level, we classified it into three categories: 1+:

<10 mg/dL, 2+: 10-50 mg/dL, and 3+: >50 mg/dL. 35 The date of disease onset was ascertained as the day when the first symptom was appeared.

Chest CT scans were conducted by a multi-detector CT scanner 16 slice (Siemens, Munich, Germany) with detailed parameters as below: tube voltage, 120 kV; tube current, standard (60-120 mAs); slice thickness, 1-1.5 mm; reconstruction interval, 1-1.5 mm. The 

Statistical analysis was carried out by SPSS 16.0 software (SPSS, Chicago, IL). The normal distribution of variables was assessed using the Kolmogorov-Smirnov test. Categorical variables were presented as number with percentage. Continuous variables were expressed as mean ±SD or median (interquartile range), as appropriate. Comparisons between groups were made by Chi-square test, Independent sample t-test, or Mann-Whitney U test, as appropriate.

Correlations between variables were determined by Spearman correlation analysis. P <.05 was defined statistically significant.

Total of 168 ICU patients with COVID-19 were studied. Baseline characteristics of patients are presented in Table 1 .

As presented in Table 2 , most of patients who had multifocal and bilateral GGO pattern on chest CT scans had SOFA scores <5 on admission (day 1). Significant relationships were only observed between the SOFA score classification on admission (day 1) with multifocal and bilateral GGO (P = .016 and P = .044, respectively). (14) Chronic respiratory disease 20 (12) Chronic renal failure 17 (11) Heart failure 15 ( Table 3 presents correlations between chest CT scan with SOFA scores on admission (day 1) and on day 5 in study patients.

According to Table 3 , there were only significant correlations between SOFA score on admission (day 1) with multifocal and bilateral GGO (P = .010 and P = .011, respectively). In addition, there were significant correlations between SOFA scores on admission (day 1) and on day 5 with multifocal bilateral GGO (P = .035 and P = .044, respectively). Table 4 shows relationship between chest CT scan and mortality with CRP in study patients. According to Table 4 , most patients with GGO patterns on chest CT scans had CRP 1+. Significant relationships were observed between unilateral and bilateral GGO patterns on chest CT scans with CRP (P = .049 and P = .046, respectively).

As demonstrated in Table 5 , significant relationships were observed between unifocal, unilateral, and bilateral GGO patterns on chest CT scans with overweight/obesity (P = .006, P = .045, and P = .034, respectively). Furthermore, significant relationships were observed between multifocal and bilateral GGO patterns on chest CT scans with heart failure (P = .001 and P = .001, respectively). In addition, there were significant relationships between unifocal, multifocal, unilateral, and bilateral GGO patterns on chest CT scans with cardiovascular diseases (P = .041, P = .005, P = .027 and P = .003, respectively). Significant relationships were also observed between unifocal and unilateral GGO patterns on chest CT scans with malignancy (P = .012 and P = .006, respectively). Significant relationship was also observed between multifocal bilateral GGO pattern with cardiovascular diseases (P = .041).

According to Table 6 , no significant relationships were observed between chest CT scan results with mortality (P >.05).

To the best of our knowledge, this is the first study to assess the relationship between chest CT scan findings with SOFA score, CRP, comorbidity, and mortality in ICU patients with COVID-19 in East-Azerbaijan Province, which is one of the high-risk regions in the North-West of Iran. Consistent with previous studies, 18-20,36-44 our research indicated that multifocal and bilateral GGO were the most common patterns on chest CT scans. Furthermore, multifocal and bilateral consolidation were more prevalent than unifocal and unilateral consolidation patterns. A GGO pattern has been suggested to be a very common feature in COVID-19 pneumonia as 100% of individuals whose diagnosis was affirmed by RT-PCR had this feature. 38 Also, there was no significant difference in the CT scan features between subjects with confirmed COVID-19 who needed admission and subjects who were discharged. 38 Since a GGO pattern can be present in different phases of the disease, 45 warranted to completely understand the prognostic power of this finding in patients with COVID-19.

Our study preliminarily demonstrated a significant correlation between chest CT scan features including multifocal and bilateral GGO patterns with SOFA score on admission (day 1). In addition, significant correlations were noticed between multifocal bilateral GGO with SOFA scores on admission (day 1) and on day 5. These findings indicate that in more severe disease, more abnormalities can be observed on chest CT scan. The SOFA score is an important index to reflect the state and degree of multiple organ dysfunctions 11 and can predict the severity and outcome of the disease. 53, 54 In a study by Francone et al, 55 CT score was significantly higher in critical and severe patients than in mild stage subjects which was consistent with our research. In addition, Shen et al 56 found that CT imaging was helpful in classifying disease severity as a larger proportion of scans from critically ill patients presented bilateral lung involvement compared with mild cases. In another study on COVID-19 patients, higher CT scores had a significant relationship with more severe disease. 57 Wu et al 40 also suggested that chest CT scan could be used to assess the severity of the disease and had a considerable function in clinical practice. Therefore, it seems that CT is the main procedure to determine the severity of the disease and can be used to identify disease progression. The main benefit of the CT scan is that the test is available immediately and results are accessible directly after scanning. This benefit depends on the accessibility of a CT scan, personnel and a well-designed approach to perform these scans.

Increased inflammatory parameters, such as CRP were reported in COVID-19. 31 Note: Data were expressed as frequency (percentage).

Abbreviations: CT, Computed tomography; GGO, ground glass opacity. P < .05 was considered significant.

*P values indicate comparison between groups (Chi-square).

CT scan and C-reactive protein in study patients (n = 168)

Chest CT scan This study had some limitations including a single-center study and having small sample size. Thus, additional large-scale multicenter studies would be helpful. Furthermore, we did not follow-up these patients who survived and correlated their chest CT or clinical findings with outcomes. Lastly, no autopsy was conducted in the deceased patients.

In conclusion, multifocal bilateral GGO was the most common pattern on chest CT scans. Furthermore, multifocal bilateral consolidation was more prevalent than unifocal unilateral consolidation pattern. Although chest CT scan characteristics were significantly related with SOFA score, CRP, and comorbidity in ICU patients with COVID-19, a relationship with mortality was not significant.

The authors declared that they have no conflicts of interests.

Data available on request from the authors. The data that support the findings of this study are available from the corresponding author upon reasonable request. Note: Data were expressed as frequency (percentage).

Abbreviations: CT, Computed tomography; GGO, ground glass opacity. P < .05 was considered significant.

*P values indicate comparison between groups (Chi-square).

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the lombardy region

Clinical outcomes of COVID-19 in Wuhan, China: a large cohort study

A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab

Critically Ill patients with coronavirus disease 2019 in a designated ICU: clinical features and predictors for mortality

Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a singlecentered, retrospective, observational study

Coronavirus Disease 2019 (COVID-19): role of chest CT in diagnosis and management

Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases

Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): a study of 63 patients in Wuhan, China

The first case of 2019 novel coronavirus pneumonia imported into Korea from Wuhan, China: implication for infection prevention and control measures

Use of chest CT in combination with negative RT-PCR assay for the 2019 novel coronavirus but high clinical suspicion

Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERSCoV, and 2019-nCoV

CT imaging features of 2019 novel coronavirus (2019-nCoV)

Emerging coronavirus 2019-nCoV pneumonia

Chest CT findings related to mortality of patients with COVID-19: a retrospective case series study

How imaging should properly be used in COVID-19 outbreak: an Italian experience

Chest CT findings in coronavirus disease-19 (COVID-19): relationship to duration of infection

Temporal changes of CT findings in 90 patients with COVID-19 pneumonia: a longitudinal study

Coronavirus disease 2019 (COVID-19): a systematic review of imaging findings in 919 patients

Early diagnosis of pneumonia in severe stroke: clinical features and the diagnostic role of C-reactive protein

Utility of C-reactive protein levels for early prediction of dengue severity in adults

The differences between interleukin-6 and c-reactive protein levels among adult patients of dengue infection with and without plasma leakage

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city

C-reactive protein levels in the early stage of COVID-19. Médecine Et Maladies Infectieuses

Factors related to the initial stroke severity of posterior circulation ischemic stroke

Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance

On behalf of the Working Group on sepsis-related problems of the European Society of Intensive Care Medicine. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure

StatPearls [Internet

Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review

Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan

Chest CT features of COVID-19 in

Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2

Chest CT findings in patients with corona virus disease 2019 and its relationship with clinical features

Imaging features of coronavirus disease 2019 (COVID-19): evaluation on thin-section CT

Early clinical and CT manifestations of coronavirus disease 2019 (COVID-19) pneumonia

Relation between chest CT findings and clinical conditions of coronavirus disease (COVID-19) pneumonia: a multicenter study

Clinical characteristics and chest CT imaging features of critically ill COVID-19 patients

Analysis of coronavirus disease-19 (COVID-19) based on SARS autopsy

Lymphatic changes in respiratory diseases: more than just remodeling of the lung?

Detection of 2019-nCoV in the pathological paraffin embedded tissue

CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan

Radiographic and CT features of viral pneumonia

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

Pneumonia associated with 2019 novel coronavirus: can computed tomographic findings help predict the prognosis of the disease?

Asymptomatic novel coronavirus pneumonia patient outside Wuhan: the value of CT images in the course of the disease

SOFA and mortality end-points in randomized controlled trials: a systematic review and metaregression analysis

Prognostic accuracy of the SOFAscore, SIRS criteria, and qSOFA score for in-hospital mortality among adults with suspected infection admitted to the intensive care unit

Chest CT score in COVID-19 patients: correlation with disease severity and short-term prognosis

Epidemiology and clinical course of COVID-19 in Shanghai

The clinical and chest CT features associated with severe and critical COVID-19 pneumonia

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

Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19

C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early

C-reactive protein: a critical update

Coronavirus-positive nasopharyngeal aspirate as predictor for severe acute respiratory syndrome mortality

Role of procalcitonin and Creactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia

Correlations of CT scan with highsensitivity C-reactive protein and D-dimer in patients with coronavirus disease 2019

Clinical and high-resolution CT features of the COVID-19 infection: comparison of the initial and follow-up changes

Plasma CRP level is positively associated with the severity of COVID-19

Comorbid chronic diseases are strongly correlated with disease severity among COVID-19 patients: a systematic review and meta-analysis

Clinical manifestations and radiological features by chest computed tomographic findings of a novel coronavirus disease-19 pneumonia among 92 patients in Japan

Is diabetes a risk factor for a severe clinical presentation of dengue?-review and meta-analysis

Apoptosis, vascular leakage and increased risk of severe dengue in a type 2 diabetes mellitus patient

Vascular endothelial function and hypertension: insights and directions

Association of "initial CT" findings with mortality in older patients with coronavirus disease 2019 (COVID-19)

Predictors of fatality including radiographic findings in adults with COVID-19

Correlation between chest computed tomography scan findings and mortality of COVID-19 cases; a cross sectional Study