INTRODUCTION

Coronavirus disease-2019 (COVID-19) infection, a highly contagious disease caused by the severe acute respiratory syndrome coronavirus-2 virus, was first reported in Wuhan, China, and the World Health Organization declared this increasingly spreading disease as a global public health emergency (pandemic) on January 30, 2020 (1). Chest computed tomography (CT) plays an important role in the diagnosis and treatment of COVID-19. The common chest CT findings of COVID-19 are multiple ground-glass opacity, consolidation, and interlobular septal thickening in both lungs, which are mostly distributed under the pleura. A significant correlation between the severity of the pulmonary inflammation, basic clinical symptoms, and laboratory test results was reported (2,3). In addition, data on the efficacy of chest CT findings alone in predicting the clinical disease prognosis is limited (4). Thus, this study aimed to investigate the validity of the first CT findings in treatment guidance, beyond specific diagnosis, by the physicians involved in the diagnosis and treatment of patients with COVID-19.

METHODS

The study was approved by the Scientific Research Platform of Directorate General for Health Services, the Ministry of Health of the Republic of Turkey, and the Ethics Committee of University of Health Seciences Turkey, Prof. Dr. Cemil Tascioglu City Hospital, (no: 48670771-514.10, 12.05.2020/158). A total of 50 out of 320 patients, admitted to the intensive care unit (ICU) due to COVID-19 [severe COVID-19-related acute respiratory distress syndrome (ARDS)] between March 20, 2020, and June 1, 2020, were included in the study through random selection.

The first chest CT scans of patients, taken before the admission to the ICU, were blindly evaluated by 50 physicians, without receiving information, including the names and recent clinical conditions of patients. Afterward, three questions were asked to all participants and the answers were noted. The actual data of 50 patients were compared to the given answers.

The three questions:

1. “Where should this patient be followed up and treated according to the examined thoracic tomography data?”

a. Quarantine at home

b. Treatment in the hospital clinic

c. In intensive cared. No necessary treatment

2. “Are there signs of severe ARDS in the examined thoracic tomography?”

a. Yes, partial pressure of oxygen/fraction of inspired oxygen (PaO₂/FiO₂) of <100 mmHg, indication severe ARDS

b. Yes, PaO₂/FiO₂ of 100-200 mmHg, indication moderate ARDS

c. Yes, PaO₂/FiO₂ of 200-300 mmHg, indication mild ARDS

d. No, PaO₂/FiO₂ of >300

3. “What kind of treatment plan is suitable if the patient is followed up in the ICU according to the examined thoracic tomography data?”

a. Medical treatment + supportive treatment + invasive mechanical ventilation

b. Medical treatment + supportive treatment + non-invasive mechanical ventilation (HFNC)

Statistical Analysis

Data were expressed as mean or median, and answers were calculated in percentage (%).

Inclusion and Exclusion Criteria

Over 18 years old, with COVID-19- related severe ARDS diagnosis in the ICU (PaO₂/FiO₂ of <100 mmHg)

RESULTS

All 50 physicians answered 7,500 questions in 2,500 surveys. Three CT scanners (Scanner-Toshiba-Alexion 16 slice, Scanner Philips-Brilliance 40 -slice, ans Scanner Philips-Ingenuity Core 128-slice) were used for examinations. The simultaneous laboratory analysis found a C-reactive protein (CRP) of >40 mg/L in 72% [minimum-maximum (min-max) (median) 3.24-513.78 (86.99)]; D-dimer was >1000 ng/mL [min-max (median) 78-27.000 (1100)] and ferritin was >500 ng/mL [min-max (median) 24.5-8378 (614.6)] in 57%; and lymphocyte count of <800 µL [min-max (median) 0.2-16.15 (0.92)] in 50% of patients (Table 1, Figure 1a, b, c, d).

To the question “Where should this patient be followed up and treated according to the examined thoracic tomography data?”, 53% of participants responded as “in the ICU”, 28.2% as “in the inpatient care”, 17.4% as “in quarantine at home”, and 1.4% stated that no treatment was required (Figure 2).

To the question “Are there signs of severe ARDS in the examined thoracic tomography?”, 60.2% of participants responded as moderate-severe ARDS, 19.6% as mild ARDS, and 20.2% stated that the clinical presentation was not ARDS (Figure 3). All patients included were in the ICU due to severe ARDS.

To the question “What kind of treatment plan is suitable if the patient is followed up in the ICU according to the examined thoracic tomography data?”, 58.2% of participants responded as medical treatment + supportive treatment + HFNC and 41.8% as medical treatment + supportive treatment + invasive mechanical ventilation (Figure 4).

DISCUSSION

This study analyzed the chest CT findings of 50 patients treated for severe COVID-19-related ARDS in the ICU examined by 50 physicians without the real-time laboratory test results, as well as the clinical data and the validity of first CT findings alone in treatment guidance, beyond specific diagnosis.

The meta-analyses of the high-risk group of patients with symptomatic COVID-19 primarily observed the ground-glass opacities (83.31%) and consolidation involving the bilateral lungs in a peripheral distribution (76.95%) in the chest CT. Compared to ordinary patients, characteristics specific to COVID-19 in the thoracic CT play an important role in guiding the treatment and evaluating the disease severity (5,6).

While one of every five physicians who participated in the study diagnosed COVID-19 based on the chest CT, they incorrectly predicted the clinical course and prognosis of the disease based on the first CT findings alone, without clinical findings and laboratory test results. Contrarily, 17.4% of them suggested quarantine at home.

Advanced age, comorbidities, dyspnea, chest pain, cough, phlegm, decreased lymphocytes, and elevated inflammation indicators are risk factors for COVID-19 pneumonia (6). Significant differences were found between the ordinary patients and patients with severe/critical conditions in terms of clinical symptoms, laboratory examinations, and CT findings. Many factors related to the disease severity may help physicians identify the disease severity and evaluate the prognosis (4). Studies indicated a significant correlation between the severity of the pulmonary inflammation in the CT findings and main clinical symptoms (cough and high fever in 73% and 76% of patients, respectively) and laboratory test results in patients confirmed with coronavirus (7). No abnormality was observed in the thoracic CT scans of the early-stage (0-4 days). CT is a useful tool for evaluating the changes in the pulmonary abnormalities of patients in the acute and recovery period (7-9). Therefore, physicians need to evaluate the chest CT of patients in combination with the clinical course and laboratory findings.

Real-time polymerase chain reaction (RT-PCR) is accepted as a reference standard test in COVID-19 diagnosis. Chest CT findings may exist in the early stages before the onset of symptoms, and chest CT sensitivity is quite high, not only in the diagnosis but also in the follow-up of patients with COVID-19 having false-negative RT-PCR results (10). Our study observed a correlation between the initial CT findings, real-time laboratory test results, and clinical course. While 28.2% of physicians diagnosed severe ARDS based on the first chest CT scan, only 53% of them suggested a follow-up in the ICU and 28.2% suggested a follow-up in the inpatient care. Therefore, 20.2% of the participants declared that ARDS will not be developed. In reality, 50 patients were treated in the ICU due to respiratory distress with IMV. The arterial blood gas analysis identified a PaO₂/FiO₂ of <100 mmHg, indicating severe ARDS.

Hyperinflammation is observed in patients with critical COVID-19, and related biomarkers may be beneficial in risk classification. COVID-19 severity and poor prognosis were found related to 96% serum CRP, 85% procalcitonin, 77% D-dimer, and 76% serum ferritin in the performed meta-analyses. The severity and the disease prognosis may be evaluated in a patient with positive PCR without CT findings by evaluating the acute-phase reactants in the first stage (11). Chest CT is guiding the clinical diagnosis and is effective in predicting the treatment and the prognosis. All 50 patients included in the study were PCR-positive. The examined acute-phase reactants were found proportionate to the CT findings and the severity of hypoxemia. CRP was especially the most elevated acute-phase reactant, with the disease severity, followed by ferritin and D-dimer.

While acute-phase reactants were concurrently found to be as lymphocyte count of 680 µL, CRP of 90.81 mg/L, ferritin of 637 ng/mL, and D-dimer of 3.720 ng/mL (Figure 5) in a patient presenting with moderate to severe viral infection symptoms in the chest CT, another acute-phase reactant count was concurrently found to be normal in a patient with severe viral infection symptoms in the chest CT (lymphocyte count of 156 µL, CRP of 27.6 mg/L, ferritin of 121 ng/mL, and D-dimer 705 ng/mL) (Figure 6). Further studies on the correlation between the acute-phase reactants and chest CT findings are required. Treatment in the ICU has become increasingly difficult; therefore, early recognition of severe cases is necessary for a timely triaging of patients. Clinical conditions and concurrent comorbidities determine the necessity of treatment in the ICUs, whereas several laboratory parameters may help evaluate the disease severity. Physicians should also take the low lymphocyte count into account, as well as the CRP, D-dimers, ferritin, cardiac troponin, and interleukin-6 serum levels, to determine severe and fatal COVID-19 in inpatient care. The disease course is likely to be negative when one or more of these parameters are altered (12).

CONCLUSION

In conclusion, a correlation was found between the clinical symptoms, laboratory analyses, and CT findings of patients with severe to critical COVID-19. First chest CT alone may help physicians to determine the severity of the disease; however, additional laboratory data and clinical follow-up are needed to evaluate the prognosis and plan the treatment, as many factors are related to the severity of the disease.

Ethics

Ethics Committee Approval: The study was approved by the Scientific Research Platform of Directorate General for Health Services, the Ministry of Health of the Republic of Turkey, and the Ethics Committee of University of Health Seciences Turkey, Prof. Dr. Cemil Tascioglu City Hospital, (no: 48670771-514.10, 12.05.2020/158).

Informed Consent: Survey study.

Peer-review: Internally peer-reviewed.

Authorship Contributions

Concept: E.A.T., A.M., H.K., S.D.Ö., N.T., Design: E.A.T., N.T., Data Collection or Processing: E.A.T., A.M., H.K., Analysis or Interpretation: E.A.T., N.T., Literature Search: E.A.T., N.T., Writing: F.Ş., S.D.Ö., S.A., N.T.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.