Clinical implications of microvascular CT scan signs in COVID-19 patients requiring invasive mechanical ventilation

Giorgia Dalpiaz, Lorenzo Gamberini, Aldo Carnevale, Savino Spadaro, Carlo Alberto Mazzoli, Sara Piciucchi, Davide Allegri, Chiara Capozzi, Ersenad Neziri, Maurizio Bartolucci, Francesco Muratore, Francesca Coppola, Antonio Poerio, Emanuela Giampalma, Luca Baldini, Tommaso Tonetti, Iacopo Cappellini, Davide Colombo, Gianluca Zani, Lorenzo Mellini, Vanni Agnoletti, Federica Damiani, Giovanni Gordini, Cristiana Laici, Giuliano Gola, Antonella Potalivo, Jonathan Montomoli, Vito Marco Ranieri, Emanuele Russo, Stefania Taddei, Carlo Alberto Volta, Gaetano Scaramuzzo, Giorgia Dalpiaz, Lorenzo Gamberini, Aldo Carnevale, Savino Spadaro, Carlo Alberto Mazzoli, Sara Piciucchi, Davide Allegri, Chiara Capozzi, Ersenad Neziri, Maurizio Bartolucci, Francesco Muratore, Francesca Coppola, Antonio Poerio, Emanuela Giampalma, Luca Baldini, Tommaso Tonetti, Iacopo Cappellini, Davide Colombo, Gianluca Zani, Lorenzo Mellini, Vanni Agnoletti, Federica Damiani, Giovanni Gordini, Cristiana Laici, Giuliano Gola, Antonella Potalivo, Jonathan Montomoli, Vito Marco Ranieri, Emanuele Russo, Stefania Taddei, Carlo Alberto Volta, Gaetano Scaramuzzo

Abstract

Purpose: COVID-19-related acute respiratory distress syndrome (ARDS) is characterized by the presence of signs of microvascular involvement at the CT scan, such as the vascular tree in bud (TIB) and the vascular enlargement pattern (VEP). Recent evidence suggests that TIB could be associated with an increased duration of invasive mechanical ventilation (IMV) and intensive care unit (ICU) stay. The primary objective of this study was to evaluate whether microvascular involvement signs could have a prognostic significance concerning liberation from IMV.

Material and methods: All the COVID-19 patients requiring IMV admitted to 16 Italian ICUs and having a lung CT scan recorded within 3 days from intubation were enrolled in this secondary analysis. Radiologic, clinical and biochemical data were collected.

Results: A total of 139 patients affected by COVID-19 related ARDS were enrolled. After grouping based on TIB or VEP detection, we found no differences in terms of duration of IMV and mortality. Extension of VEP and TIB was significantly correlated with ground-glass opacities (GGOs) and crazy paving pattern extension. A parenchymal extent over 50% of GGO and crazy paving pattern was more frequently observed among non-survivors, while a VEP and TIB extent involving 3 or more lobes was significantly more frequent in non-responders to prone positioning.

Conclusions: The presence of early CT scan signs of microvascular involvement in COVID-19 patients does not appear to be associated with differences in duration of IMV and mortality. However, patients with a high extension of VEP and TIB may have a reduced oxygenation response to prone positioning.

Trial registration: NCT04411459.

Keywords: Acute respiratory distress syndrome; Mechanical ventilation; Novel coronavirus disease 2019; Pulmonary perfusion; Thoracic imaging.

Conflict of interest statement

The authors have nothing to disclose.

© 2022. Italian Society of Medical Radiology.

Figures

Fig. 1
Fig. 1
CT scans showing vascular enlargement pattern (VEP) and vascular tree-in-bud (TIB) in two patients with COVID-19 pneumonia. Notes: A—Bilateral peripheral areas of ground-glass opacification and crazy paving in the upper lobes. Dilated segmental and subsegmental vessels (VEP—arrowheads) are visible inside these areas. B—Targeted image shows striking dilatation of peripheral subpleural vessel in upper left lobe with a branching aspect resembling a budding tree (arrow). Please note that vascular TIB is visible only within the area of ground-glass-opacity in this picture
Fig. 2
Fig. 2
Spearman heatmap regarding the extension of the radiologic signs explored. Abbreviations: VEP—vascular enlargement pattern; TIB—tree in bud sign; GGO—ground glass opacities. Notes—the values reported in the cells refer to the rho coefficient for the bivariate correlation of the two variables; p < 0.05; *p < 0.01
Fig. 3
Fig. 3
Cumulative incidence functions of liberation from mechanical ventilation. Abbreviations: TIB—tree in bud; VEP—vascular enlargement pattern; MV—mechanical ventilation
Fig. 4
Fig. 4
Prevalence of extended radiologic signs in different contexts. Abbreviations: VEP—vascular enlargement pattern; TIB—tree in bud; PN—peripheral nodules; GGO—ground glass opacities; CP—crazy paving; Cons—consolidations. Notes: Graphs show the prevalence of VEP, TIB and PN involving 3 or more lobes and GGO, CP and Cons extended for over the 50% of pulmonary parenchyma. *p < 0.05 at Chi-square test

References

    1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the chinese center for disease control and prevention. JAMA J Am Med Assoc. 2020;323:1239–1242. doi: 10.1001/jama.2020.2648.
    1. Lodigiani C, Iapichino G, Carenzo L, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020;191:9–14. doi: 10.1016/j.thromres.2020.04.024.
    1. Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46:1089–1098. doi: 10.1007/s00134-020-06062-x.
    1. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383:120–128. doi: 10.1056/nejmoa2015432.
    1. Loo J, Spittle DA, Newnham M. COVID-19, immunothrombosis and venous thromboembolism: biological mechanisms. Thorax. 2021;76:412–420. doi: 10.1136/thoraxjnl-2020-216243.
    1. Grasselli G, Tonetti T, Protti A, et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med. 2020;8:1201–1208. doi: 10.1016/S2213-2600(20)30370-2.
    1. Patel BV, Arachchillage DJ, Ridge CA, et al. Pulmonary angiopathy in severe COVID-19: physiologic, imaging, and hematologic observations. Am J Respir Crit Care Med. 2020;202:690–699. doi: 10.1164/rccm.202004-1412OC.
    1. Li Q, Huang XT, Li CH, et al. CT features of coronavirus disease 2019 (COVID-19) with an emphasis on the vascular enlargement pattern. Eur J Radiol. 2021 doi: 10.1016/j.ejrad.2020.109442.
    1. Lv H, Chen T, Pan Y, et al. Pulmonary vascular enlargement on thoracic CT for diagnosis and differential diagnosis of COVID-19: a systematic review and meta-analysis. Ann Transl Med. 2020;8:878–878. doi: 10.21037/atm-20-4955.
    1. Bai HX, Hsieh B, Xiong Z, et al. Performance of radiologists in differentiating COVID-19 from non-COVID-19 viral pneumonia at chest CT. Radiology. 2020;296:E46–E54. doi: 10.1148/radiol.2020200823.
    1. Caruso D, Zerunian M, Polici M, et al. Chest CT features of COVID-19 in Rome, Italy. Radiology. 2020;296:E79–E85. doi: 10.1148/radiol.2020201237.
    1. Zhou S, Wang Y, Zhu T, Xia L. CT features of coronavirus disease 2019 (COVID-19) pneumonia in 62 patients in Wuhan, China. Am J Roentgenol. 2020;214:1287–1294. doi: 10.2214/AJR.20.22975.
    1. Liu J, Zheng X, Tong Q, et al. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J Med Virol. 2020;92:491–494. doi: 10.1002/jmv.25709.
    1. Eddy RL, Sin DD. Computed tomography vascular tree-in-bud: a novel prognostic imaging biomarker in COVID-19? Am J Respir Crit Care Med. 2020;202:642–644. doi: 10.1164/rccm.202007-2833ED.
    1. Scaramuzzo G, Gamberini L, Tonetti T, et al. Sustained oxygenation improvement after first prone positioning is associated with liberation from mechanical ventilation and mortality in critically ill COVID-19 patients: a cohort study. Ann Intensive Care. 2021;11:1–10. doi: 10.1186/s13613-021-00853-1.
    1. Gamberini L, Tonetti T, Spadaro S, et al (2020) Factors influencing liberation from mechanical ventilation in coronavirus disease 2019: multicenter observational study in fifteen Italian ICUs. 4:1–12
    1. Tack D, Nollevaux MC, Gevenois PA. Tree-in-bud pattern in neoplastic pulmonary emboli. Am J Roentgenol. 2001;176:1421–1422. doi: 10.2214/ajr.176.6.1761421.
    1. Lang M, Som A, Carey D, et al. Pulmonary vascular manifestations of COVID-19 pneumonia. Radiol Cardiothorac Imaging. 2020;2:e200277. doi: 10.1148/ryct.2020200277.
    1. Hansell DM, Bankier AA, Mcloud TC, et al. Fleischner society: glossary of terms for thoracic imaging. Radiology. 2008;246:697. doi: 10.1148/radiol.2462070712.
    1. Yehya N, Harhay MO, Curley MAQ, et al. Reappraisal of ventilator-free days in critical care research. Am J Respir Crit Care Med. 2019;200:828–836. doi: 10.1164/rccm.201810-2050CP.
    1. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin definition. JAMA J Am Med Assoc. 2012;307:2526–2533. doi: 10.1001/jama.2012.5669.
    1. Huang H, Cai S, Li Y, et al. Prognostic factors for COVID-19 pneumonia progression to severe symptoms based on earlier clinical features: a retrospective analysis. Front Med. 2020;7:1–7. doi: 10.3389/fmed.2020.557453.
    1. Şanli DET, Yildirim D. A new imaging sign in COVID-19 pneumonia: vascular changes and their correlation with clinical severity of the disease. Diagn Interv Radiol. 2021;27:172–180. doi: 10.5152/dir.2020.20346.
    1. Herold T, Jurinovic V, Arnreich C, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020;146:128–136.e4. doi: 10.1016/j.jaci.2020.05.008.
    1. Esposito A, Palmisano A, Toselli M, et al. Chest CT-derived pulmonary artery enlargement at the admission predicts overall survival in COVID-19 patients: insight from 1461 consecutive patients in Italy. Eur Radiol. 2021;31:4031–4041. doi: 10.1007/s00330-020-07622-x.
    1. Zhu QQ, Gong T, Huang GQ, et al. Pulmonary artery trunk enlargement on admission as a predictor of mortality in in-hospital patients with COVID-19. Jpn J Radiol. 2021;39:589–597. doi: 10.1007/s11604-021-01094-9.
    1. Malpani Dhoot N, Goenka U, Ghosh S, et al. Assigning computed tomography involvement score in COVID-19 patients: prognosis prediction and impact on management. BJR Open. 2020;2:20200024. doi: 10.1259/bjro.20200024.
    1. Carvalho ARS, Guimarães A, Werberich GM, et al. COVID-19 chest computed tomography to stratify severity and disease extension by artificial neural network computer-aided diagnosis. Front Med. 2020;7:1–11. doi: 10.3389/fmed.2020.577609.
    1. Ruch Y, Kaeuffer C, Ohana M, et al. CT lung lesions as predictors of early death or ICU admission in COVID-19 patients. Clin Microbiol Infect. 2020;26:1417.e5–1417.e8. doi: 10.1016/j.cmi.2020.07.030.
    1. Levi M, Coppens M. Vascular mechanisms and manifestations of COVID-19. Lancet Respir Med. 2021;9:551–553. doi: 10.1016/s2213-2600(21)00221-6.
    1. Mokhtari T, Hassani F, Ghaffari N, et al. COVID-19 and multiorgan failure: a narrative review on potential mechanisms. J Mol Histol. 2020;51:613–628. doi: 10.1007/s10735-020-09915-3.
    1. Stephens JR, Stümpfle R, Patel P, et al. Analysis of critical care severity of illness scoring systems in patients with coronavirus disease 2019: a retrospective analysis of three UK ICUs. Crit Care Med. 2020;49:E105–E107. doi: 10.1097/CCM.0000000000004674.
    1. Bardi T, Pintado V, Gomez-Rojo M, et al. Nosocomial infections associated to COVID-19 in the intensive care unit: clinical characteristics and outcome. Eur J Clin Microbiol Infect Dis. 2021;40:495–502. doi: 10.1007/s10096-020-04142-w.
    1. Ippolito M, Misseri G, Catalisano G, et al. Ventilator-associated pneumonia in patients with covid-19: a systematic review and meta-analysis. Antibiotics. 2021;10:1–19. doi: 10.3390/antibiotics10050545.
    1. Potere N, Valeriani E, Candeloro M, et al. Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis. Crit Care. 2020;24:1–12. doi: 10.1186/s13054-020-03022-1.

Source: PubMed

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