Early prediction of disease progression in COVID-19 pneumonia patients with chest CT and clinical characteristics

Zhichao Feng, Qizhi Yu, Shanhu Yao, Lei Luo, Wenming Zhou, Xiaowen Mao, Jennifer Li, Junhong Duan, Zhimin Yan, Min Yang, Hongpei Tan, Mengtian Ma, Ting Li, Dali Yi, Ze Mi, Huafei Zhao, Yi Jiang, Zhenhu He, Huiling Li, Wei Nie, Yin Liu, Jing Zhao, Muqing Luo, Xuanhui Liu, Pengfei Rong, Wei Wang, Zhichao Feng, Qizhi Yu, Shanhu Yao, Lei Luo, Wenming Zhou, Xiaowen Mao, Jennifer Li, Junhong Duan, Zhimin Yan, Min Yang, Hongpei Tan, Mengtian Ma, Ting Li, Dali Yi, Ze Mi, Huafei Zhao, Yi Jiang, Zhenhu He, Huiling Li, Wei Nie, Yin Liu, Jing Zhao, Muqing Luo, Xuanhui Liu, Pengfei Rong, Wei Wang

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. Study workflow.
Fig. 1. Study workflow.
The flow diagram shows the study population enrollment and observation period.
Fig. 2. Representative chest CT images of…
Fig. 2. Representative chest CT images of patients with COVID-19 pneumonia.
a Subpleural patchy areas of GGO with crazy-paving sign in the right middle lobe. b Multiple patchy areas of consolidation in the right middle lobe, left upper lobe, and bilateral lower lobes and air bronchogram in the right middle lobe. c Multiple patchy areas of organizing pneumonia in the right middle and lower lobes on the sagittal image with CT severity score of 9 for the right lung. d Bilateral and peripheral multiple patchy areas of GGO with reticular and intralobular septal thickening. e Multiple mixed distributed pure GGO, GGO with consolidation, and interlobular septal thickening in bilateral lungs. f Bilateral multiple patchy and thin areas of GGO in the posterior parts of the lungs.
Fig. 3. Development and performance of nomogram.
Fig. 3. Development and performance of nomogram.
a A nomogram for the prediction of developing severe COVID-19 pneumonia. Calibration curves of the nomogram in the derivation (b) and validation (c) cohorts, respectively, which depict the calibration of the nomogram in terms of the agreement between the predicted risk of severe COVID-19 pneumonia and observed outcomes. The 45° blue line represents a perfect prediction, and the dotted red lines represent the predictive performance of the nomogram. The closer the dotted red line fit is to the ideal line, the better the predictive accuracy of the nomogram is. Plots show the ROC curves of the nomogram in the derivation (d) and validation (e) cohorts, respectively.
Fig. 4. Correlation between CT characteristics and…
Fig. 4. Correlation between CT characteristics and inflammatory indexes.
Heatmaps depict the correlations between the baseline CT characteristics and inflammatory indexes (within the blue dotted box) on admission (a) and on day 3 after admission (b) showing the correlation coefficients r with P < 0.05 of all pairs.

References

    1. Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5.
    1. Wu, Z. & McGoogan, J. M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA, 10.1001/jama.2020.2648 (2020).
    1. Wang Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395:1569–1578. doi: 10.1016/S0140-6736(20)31022-9.
    1. Grein J, et al. Compassionate use of remdesivir for patients with severe covid-19. N. Engl. J. Med. 2020;382:2327–2336. doi: 10.1056/NEJMoa2007016.
    1. Chen N, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513. doi: 10.1016/S0140-6736(20)30211-7.
    1. Yang, Y. et al. Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China. medRxiv. Preprint at 10.1101/2020.02.10.20021675 (2020).
    1. Wang D, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069. doi: 10.1001/jama.2020.1585.
    1. Guan WJ, et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020;382:1708–1720. doi: 10.1056/NEJMoa2002032.
    1. Das KM, et al. CT correlation with outcomes in 15 patients with acute Middle East respiratory syndrome coronavirus. Am. J. Roentgenol. 2015;204:736–742. doi: 10.2214/AJR.14.13671.
    1. Ai T, et al. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. 2020;296:E32–E40. doi: 10.1148/radiol.2020200642.
    1. Pan F, et al. Time course of lung changes at chest CT during recovery from coronavirus disease 2019 (COVID-19) Radiology. 2020;295:715–721. doi: 10.1148/radiol.2020200370.
    1. Shi H, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect. Dis. 2020;20:425–434. doi: 10.1016/S1473-3099(20)30086-4.
    1. Chen T, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091. doi: 10.1136/bmj.m1091.
    1. Liu J, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J. Transl. Med. 2020;18:206. doi: 10.1186/s12967-020-02374-0.
    1. Zhou F, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. doi: 10.1016/S0140-6736(20)30566-3.
    1. Wu C, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern. Med. 2020;180:1–11. doi: 10.1001/jamainternmed.2019.4346.
    1. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin. Immunopathol. 2017;39:529–539. doi: 10.1007/s00281-017-0629-x.
    1. Qin C, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin. Infect. Dis. 2020;71:762–768. doi: 10.1093/cid/ciaa248.
    1. Vabret N, et al. Immunology of COVID-19: current state of the science. Immunity. 2020;52:910–941. doi: 10.1016/j.immuni.2020.05.002.
    1. Liu Y, et al. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J. Infect. 2020;81:e6–e12.
    1. Curbelo J, et al. Neutrophil count percentage and neutrophil-lymphocyte ratio as prognostic markers in patients hospitalized for community-acquired pneumonia. Arch. Bronconeumol. 2019;55:472–477. doi: 10.1016/j.arbres.2019.02.005.
    1. Curbelo J, et al. Inflammation biomarkers in blood as mortality predictors in community-acquired pneumonia admitted patients: importance of comparison with neutrophil count percentage or neutrophil-lymphocyte ratio. PLoS ONE. 2017;12:e0173947. doi: 10.1371/journal.pone.0173947.
    1. Liu Y, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci. China Life Sci. 2020;63:364–374. doi: 10.1007/s11427-020-1643-8.
    1. Chang YC, et al. Pulmonary sequelae in convalescent patients after severe acute respiratory syndrome: evaluation with thin-section CT. Radiology. 2005;236:1067–1075. doi: 10.1148/radiol.2363040958.
    1. Chiarenza A, et al. Chest imaging using signs, symbols, and naturalistic images: a practical guide for radiologists and non-radiologists. Insights Imaging. 2019;10:114. doi: 10.1186/s13244-019-0789-4.
    1. Zhou P, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–273. doi: 10.1038/s41586-020-2012-7.
    1. de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat. Rev. Microbiol. 2016;14:523–534. doi: 10.1038/nrmicro.2016.81.
    1. Hoffmann M, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–280 e278. doi: 10.1016/j.cell.2020.02.052.
    1. Ooi GC, et al. Severe acute respiratory syndrome: temporal lung changes at thin-section CT in 30 patients. Radiology. 2004;230:836–844. doi: 10.1148/radiol.2303030853.
    1. Koo HJ, Lim S, Choe J, Choi S-H, Sung H, Do K-H. Radiographic and CT features of viral pneumonia. Radiographics. 2018;38:719–739. doi: 10.1148/rg.2018170048.
    1. Wu J, et al. Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19) J. Intern. Med. 2020;288:128–138. doi: 10.1111/joim.13063.
    1. Guo L, et al. Clinical features predicting mortality risk in patients with viral pneumonia: the MuLBSTA score. Front. Microbiol. 2019;10:2752. doi: 10.3389/fmicb.2019.02752.
    1. Liang W, et al. Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. JAMA Intern. Med. 2020;180:1–9. doi: 10.1001/jamainternmed.2020.2033.
    1. Mehta P, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034. doi: 10.1016/S0140-6736(20)30628-0.
    1. Liu Y, et al. Association between ages and clinical characteristics and outcomes of coronavirus disease 2019. Eur. Respir. J. 2020;55:2001112. doi: 10.1183/13993003.01112-2020.
    1. Song F, et al. Emerging 2019 novel coronavirus (2019-nCoV) pneumonia. Radiology. 2020;295:210–217. doi: 10.1148/radiol.2020200274.
    1. ACR. Recommendations for the use of chest radiography and computed tomography (CT) for suspected COVID-19 infection. https://wwwacrorg/Advocacy-and-Economics/ACR-Position-Statements/Recommendations-for-Chest-Radiography-and-CT-for-Suspected-COVID19-Infection (2020).
    1. Chung M, et al. CT imaging features of 2019 novel coronavirus (2019-nCoV) Radiology. 2020;295:202–207. doi: 10.1148/radiol.2020200230.

Source: PubMed

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