key: cord-0703826-6qbpmmnu
authors: Beydoğan, Engin; Yürük Atasoy, Pınar
title: The relationship between CRP at admission and thorax CT findings in patients diagnosed with COVID‐19
date: 2021-11-05
journal: Int J Clin Pract
DOI: 10.1111/ijcp.14962
sha: ea7520b3ce632c26b4fa64135ad3cac30f08d03f
doc_id: 703826
cord_uid: 6qbpmmnu

INTRODUCTION: The current study aims to evaluate the relationship between C‐reactive protein (CRP) levels, thorax CT findings and CT‐SS in patients presenting to the emergency department with COVID‐19. METHODS: Patients diagnosed with COVID‐19 by nasopharyngeal rt‐PCR (+) in the emergency department were included in the study. In addition to the CRP, ferritin and D‐dimer examinations of patients at admission, thorax CT involvement findings and CT‐SS results were recorded. The relationship of CRP value with CT‐SS and clinical outcome was evaluated. RESULTS: A total of 974 COVID‐19 patients, 572 males (58.7%) and 402 females (41.3%), with a mean age of 59.64 ± 17.34 years, were included in the study. The CRP values of the patients who needed intensive care and needed respiratory support were also significantly higher at admission (95.1 mg/dL vs 31.05 mg/dL) (P < .001). The CRP values of the patients who developed any complications during the treatment of COVID‐19 were higher (79.9 mg/dL vs 41.85 mg/dL) (P < .001). In the case of CRP >124.5, a thorax CT density score 7.35 times higher was determined to be severe. In addition, it was determined that there was a 9.09‐fold increase in the incidence of negative imaging findings in terms of COVID‐19 in cases where the CRP value was <12.5 mg/dL. CONCLUSION: The CRP levels of COVID‐19 patients measured upon admission to the emergency room are correlated with the severity of lung involvement and are an important predictor of clinical outcomes.

COVID-19 is mainly diagnosed by reverse transcriptionpolymerase chain reaction (RT-PCR) to detect SARS CoV-2 nucleic acid in a nasopharyngeal swab (NS) sample. However, because of inappropriate clinical sampling, low patient viral load, and differences in detection rates of different RT-PCR kits, the sensitivity of RT-PCR for COVID-19 infection is approximately 71%. 6 In addition, direct chest radiographs (x-ray) are less sensitive than thoracic CT, especially in the early stage of COVID-19. 7 According to current reports, CT can detect the disease before the development of clinical symptoms. 8, 9 Therefore, thorax CT is vital in preclinical screening and is highly recommended as a first-line strategy for investigating possible cases of COVID-19. 10 In addition, the combination of routine laboratory biomarkers (CRP, LDH, and ferritin ±D-dimer) can be used for the diagnosis of COVID-19 with an accepted sensitivity and specificity before making a definitive diagnosis by RT-PCR. 11 However, different results have been reported between CRP levels and the severity of thorax CT involvement, clinical outcomes and disease prognosis in patients diagnosed with COVID-19. [12] [13] [14] This study demonstrates that the increase in CRP levels in correlation with CT-SS in patients with COVID-19 presenting to the emergency department successfully predicted adverse clinical outcomes.

Patients who met the inclusion criteria from among those who came to the emergency room with the suspicion of COVID-19 from April 01, 2020 and December 31, 2020 were included in the study. The medical records of the patients included in the study were analysed through the hospital data processing database. Patients aged 18 years and older who applied to the emergency department of our hospital, for whom the COVID-19 diagnosis code (U07.3) was entered according to the ICD-10 classification, were included in the study. Patients younger than 18 years of age, for whom the COVID-19 diagnosis code was not entered, and patients with the COVID-19 diagnosis code but did not have RT-PCR and Thorax CT examination were excluded from the study. Cases with SARS-CoV-2 detected by molecular methods, among the cases suitable for a possible COVID-19 case definition, were included in the study. Patients over 18 years of age and with a hospital stay of 48 hours or more were included in the study. On the contrary, patients who were found to have another infection focus within the first 48 hours were excluded from the study.

rRT-PCR analysis was performed on materials obtained by NS from patients admitted to the emergency department. 

CT imaging was performed in the supine position with the arms raised and at the end of inspiration (Toshiba Alexion/Advance, Toshiba Medical Systems Corporation Nashua). Patients were instructed to hold their breath if clinically possible. Two radiologists experienced in thoracic CT radiology, respectively, reviewed the thin-section CT images and a decision was reached by consensus.

Readers identified predominant appearances in CT images such as ground-glass density, crazy-paving pattern, consolidation and other findings. Both radiologists were unaware of the PCR test results as these were only available after 12-24 hours.

Two experienced radiologists with 11 and 15 years of clinical experience in thoracic CT radiology, respectively, reviewed the thin-slice CT images and reached a consensus. They classified the dominant patterns on CT scans as ground-glass opacification (GGO, hazy areas of increasing attenuation that do not block underlying vessels), cobblestone appearance (GGO with interlobular

Chest CT is vital in preclinical screening and is highly recommended as a first-line strategy for investigating possible cases of COVID-19.

CRP levels and CT-SS increase, the risk in relation to the patient's need for intensive care increases. and intralobular septal thickening) and consolidation (homogeneous opacification of the parenchyma). Some other minor findings such as air bronchogram, cavitation, bronchiectasis, pleural effusion, pericardial effusion, pneumothorax and mediastinal lymphadenopathy (>1 cm in short axis diameter) were also recorded in the scans. A pulmonary nodule was defined as a well-or ill-defined round opacity less than 3.0 cm in diameter. 15 Pleural effusions were recorded. In the current study, a semi-quantitative CT severity scoring suggested by the RSNA, 16 taking into account the severity of radiological involvement, was calculated separately for 6 lung zones as follows: 1, <0%-25% involvement; 2, 25-50% involvement; 3, 50%-75% involvement; 4, 75%-100% involvement.

The overall CT score was calculated as the sum of the individual zonal scores, and the maximum score was 24. Odds ratio values were calculated with 95% confidence intervals according to these cut-off values. While quantitative variables were expressed as mean (standard deviation) and median (minimum/maximum) and median (percentile 25/percentile 75) in the tables, categorical variables were shown as n (%). Variables were analysed at a 95% confidence level and a P < .05 was considered significant. 

The most common complaints of patients presenting to the emergency department were found to be shortness of breath (29.1%), cough (21.7%), fatigue (11.5%) and fever (11.4%). However, 111 (5.3%) patients were found to be asymptomatic (contact). Other application complaints are summarised in Table 2 .

Laboratory tests performed during the patients' admission to the emergency department are summarised in Table 1 

Thorax CT findings obtained during the patients' admission to the emergency department are summarised in Table 1 Table 1 ).

Antiviral treatment (favipiravir) was initiated in all patients because of rt-PCR positivity. In addition, 595 (33.4%) of the patients were given additional antibiotic therapy, while 85 (4.8%) were also given convalescent immune plasma therapy (Table 4 ).

The median hospital stay of the patients was 8 (1-95) days, while the mean thorax CT-SS was 7.59 ± 4. were determined in order of frequency, they were at lower rates (Tables 3 and 4 ).

CRP values measured at admission were higher in males than fe- and needed respiratory support, were also found to be significantly higher at admission (95.1 mg/dL vs 31.05 mg/dL) (P < .001) ( Table 2) . Table 2 ).

In the analysis performed to predict the severity of clinical findings and the need for respiratory support, it was determined that a CRP value >32.6 mg/dL increased the need for additional respiratory support by 5.05 times. In addition, when the cut-off value of CRP > 65.95 was taken, it was determined that there was a 3.81-fold increase in the risk of death. If the CRP value was >125 mg/dL, mortality increased significantly (Table 5 ).

It was determined that the increase in the severity of involvement in thorax CT was positively correlated with CRP (P < .001 In some studies, it has been shown that there are more frequent changes in some laboratory parameters in COVID-19 patients (such as lymphocyte count, CRP, LDH, D-dimer and fibrinogen). 26, 27 Lymphopenia, CRP, LDH, D-dimer and fibrinogen elevation can be used as an auxiliary diagnostic tool in suspected patients with high clinical and thorax CT scanning features, despite a double negative RT-PCR test. 28 In addition, systemic inflammation as measured by CRP is strongly associated with VTE, AKI, critical illness and mortality in COVID-19. Evaluating the associations between CRP concentrations and respiratory failure requiring mechanical ventilation, patients with a recent CRP > 5 mg/dL had an approximately fivefold greater reported risk for acute respiratory distress syndrome (ARDS). 29, 30 In light of the studies mentioned above, it is clear that high CRP, ESR, IL-6, procalcitonin and serum ferritin levels are associated with worse outcomes and increased mortality in COVID-19

patients. CRP-based approaches to risk stratification and treatment should be tested. 31 In the current study, CRP levels were high in severe and fatal A CRP level of >4 mg/dL has been shown to be beneficial in the triage of PCR (+) cases presenting with respiratory symptoms/ fever [odds ratio (OR) 4.75; 95% CI 3.28-6.88]. 33 In most of these studies, CRP with a dual-threshold value was used. Recommended values for estimating in-patient mortality ranged from >10 to >76mg/dL. In addition to a dual threshold, CRP was also studied in a trichotomised model with two thresholds at >40 and >100 mg/ dL. 34 In the current study, in the analysis performed to predict the need for respiratory support according to the severity of clinical findings, it was determined that a CRP value of >32.6 mg/ dL increased the need for additional respiratory support by 5.05

times. In addition, it was determined that when the CRP value was >65.95, there was a 3.81-fold increase in the risk of death, and if the CRP value was >125 mg/dl, the mortality rate increased significantly.

Recently, with the increase in clinical data, the relationship between liver injury and clinical outcomes of COVID-19 has been further investigated. Ponziani et al 35 Therefore, in this study, the time between symptom onset and hospital admission and CT imaging after PCR positivity was detected was very short. This seems to have resulted in negative results with regard to thoracic CT and an increase in the frequency of thorax CT applications even in asymptomatic cases.

In the current study, we aimed to determine the benefit of CRP levels and thorax CT-SS results in determining the clinical outcome and prognosis based on this information. It was determined that patients with typical COVID-19 thorax CT findings had higher CRP levels compared with those of other patients, and thorax CT-SS was positively correlated with CRP (P < .001). In addition, it was determined that a cut-off value of CRP > 124.5 mg/dL increased the risk of severe involvement of thorax CT-SS 7.35 times, and negative imaging findings in terms of COVID-19 were detected more frequently in cases where the CRP value was <12.5 mg/dL, and the CRP cutoff value should be >12.35 mg/dL to detect COVID-19-related lung involvement in any severe condition. This study demonstrates that the thorax CT severity score constitutes a useful tool for the initial assessment of COVID-19 patients, as it positively correlates with markers of disease severity and offers promising efficacy in predicting critical illness and intensive care unit admissions.

There are some inevitable limitations in relation to our study, which was conducted using a retrospective file-scanning-based method.

Some of these deficiencies are the contact status of the patients, information about the incubation period, and the inability to access medical treatment and examination histories before presentation at the emergency department. In addition, some clinical features were not recorded regularly in some patients in this study, except fever and length of hospital stay. Therefore, only the basic clinical features at presentation, the dynamic change of clinical features, and the relationship between clinical features and CT findings could be analysed. However, in the current study, the evaluation of a high number of PCR (+) patients with laboratory tests, CT images and clinical outcome characteristics is a strength.

As a result, as CRP levels and CT-SS increase, the risk in relation to the patient's need for intensive care increases. This information will help guide the management of patients and determine the appropriate treatment. CRP levels measured at emergency room admission of COVID-19 patients are correlated with the severity of lung involvement and are an important predictor of clinical outcomes.

The authors have declared no conflicts of interest. 

This study was reviewed and approved by the Health Science

Committee (approval number: 2020/09). Written and verbal consent forms were obtained from all participants in the study.

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How to cite this article: Beydoğan E, Yürük Atasoy P. The relationship between CRP at admission and thorax CT findings in patients diagnosed with COVID-19