tetano
Editor, Senior Moderator
Am J Respir Crit Care Med
. 2022 Jun 7.
doi: 10.1164/rccm.202109-2150OC. Online ahead of print.
Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and ARDS
Julian A Villalba[SUP] 1 2 [/SUP], Caroline F Hilburn[SUP] 1 2 [/SUP], Michelle A Garlin[SUP] 3 4 [/SUP], Grant A Elliott[SUP] 5 [/SUP], Yijia Li[SUP] 6 [/SUP], Keiko Kunitoki[SUP] 7 8 [/SUP], Sergio Poli[SUP] 9 [/SUP], George A Alba[SUP] 10 [/SUP], Emilio Madrigal[SUP] 1 2 [/SUP], Manuel Taso[SUP] 11 12 [/SUP], Melissa C Price[SUP] 13 [/SUP], Alexis J Aviles[SUP] 1 [/SUP], Milagros Araujo-Medina[SUP] 1 14 [/SUP], Liana Bonanno[SUP] 1 2 [/SUP], Baris Boyraz[SUP] 1 15 [/SUP], Samantha N Champion[SUP] 1 2 16 17 [/SUP], Cynthia K Harris[SUP] 1 2 [/SUP], Timothy L Helland[SUP] 1 2 [/SUP], Bailey Hutchison[SUP] 1 2 [/SUP], Soma Jobbagy[SUP] 1 2 [/SUP], Michael S Marshall[SUP] 1 2 [/SUP], Daniel J Shepherd[SUP] 1 2 [/SUP], Jaimie L Barth[SUP] 1 [/SUP], Yin P Hung[SUP] 1 2 [/SUP], Amy Ly[SUP] 1 2 [/SUP], Lida P Hariri[SUP] 1 2 [/SUP], Sarah E Turbett[SUP] 1 2 18 [/SUP], Virginia M Pierce[SUP] 1 2 19 [/SUP], John A Branda[SUP] 1 2 [/SUP], Eric S Rosenberg[SUP] 1 2 18 [/SUP], Javier Mendez-Pena[SUP] 1 [/SUP], Ivan Chebib[SUP] 1 2 [/SUP], Ivy A Rosales[SUP] 1 2 14 [/SUP], Rex N Smith[SUP] 1 2 14 [/SUP], Miles A Miller[SUP] 3 [/SUP], Ivan O Rosas[SUP] 20 [/SUP], Charles C Hardin[SUP] 10 21 [/SUP], Lindsey R Baden[SUP] 22 21 [/SUP], Benjamin D Medoff[SUP] 10 21 [/SUP], Robert B Colvin[SUP] 1 2 23 [/SUP], Brent P Little[SUP] 13 24 [/SUP], James R Stone[SUP] 1 2 [/SUP], Mari Mino-Kenudson[SUP] 1 25 [/SUP], Angela R Shih[SUP] 1 2 [/SUP]
Affiliations
Abstract
Rationale The leading cause of death in coronavirus disease 2019(COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome(ARDS) and diffuse alveolar damage(DAD). Whether DAD in fatal COVID-19 is distinct from other causes of DAD remains unknown. Objective To compare lung parenchymal and vascular alterations between patients with fatal COVID-19 pneumonia and other DAD-causing etiologies using a multidimensional approach. Methods This autopsy cohort consisted of consecutive patients with COVID-19 pneumonia(n=20) and with respiratory failure and histologic DAD(n=21; non-COVID-19 viral and non-viral etiologies). Premortem chest computed tomography(CT) scans were evaluated for vascular changes. Postmortem lung tissues were compared using histopathological and computational analyses. Machine-learning-derived morphometric analysis of the microvasculature was performed, with a random forest classifier quantifying vascular congestion(CVasc) in different microscopic compartments. Respiratory-mechanics and gas-exchange parameters were evaluated longitudinally in patients with ARDS. Measurements and Main Results On premortem CT, COVID-19 patients showed more dilated vasculature when evaluating all lung segments (p=0.001) compared to DAD-controls. Histopathology revealed vasculopathic changes including hemangiomatosis-like-changes(p=0.043), thromboemboli(p=0.0038), pulmonary infarcts(p=0.047), and perivascular inflammation(p<0.001). Generalized estimating equations revealed significant regional differences in the lung microarchitecture among all DAD-causing entities. COVID-19 showed a larger overall CVasc-range(p=0.002). Alveolar-septal-congestion was associated with a significantly shorter time-to-death from symptom onset(p=0.03), length-of-hospital-stay(p=0.02), and increased ventilatory ratio[an estimate for pulmonary dead space fraction(Vd); p=0.043] in all cases of ARDS. Conclusions Severe COVID-19 pneumonia is characterized by significant vasculopathy and aberrant alveolar-septal-congestion. Our findings also highlight the role that vascular alterations may play in Vd and clinical outcomes in ARDS in general.
Keywords: ARDS; COVID-19; Vascular Congestion; Vasculopathy; Ventilatory ratio.
. 2022 Jun 7.
doi: 10.1164/rccm.202109-2150OC. Online ahead of print.
Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and ARDS
Julian A Villalba[SUP] 1 2 [/SUP], Caroline F Hilburn[SUP] 1 2 [/SUP], Michelle A Garlin[SUP] 3 4 [/SUP], Grant A Elliott[SUP] 5 [/SUP], Yijia Li[SUP] 6 [/SUP], Keiko Kunitoki[SUP] 7 8 [/SUP], Sergio Poli[SUP] 9 [/SUP], George A Alba[SUP] 10 [/SUP], Emilio Madrigal[SUP] 1 2 [/SUP], Manuel Taso[SUP] 11 12 [/SUP], Melissa C Price[SUP] 13 [/SUP], Alexis J Aviles[SUP] 1 [/SUP], Milagros Araujo-Medina[SUP] 1 14 [/SUP], Liana Bonanno[SUP] 1 2 [/SUP], Baris Boyraz[SUP] 1 15 [/SUP], Samantha N Champion[SUP] 1 2 16 17 [/SUP], Cynthia K Harris[SUP] 1 2 [/SUP], Timothy L Helland[SUP] 1 2 [/SUP], Bailey Hutchison[SUP] 1 2 [/SUP], Soma Jobbagy[SUP] 1 2 [/SUP], Michael S Marshall[SUP] 1 2 [/SUP], Daniel J Shepherd[SUP] 1 2 [/SUP], Jaimie L Barth[SUP] 1 [/SUP], Yin P Hung[SUP] 1 2 [/SUP], Amy Ly[SUP] 1 2 [/SUP], Lida P Hariri[SUP] 1 2 [/SUP], Sarah E Turbett[SUP] 1 2 18 [/SUP], Virginia M Pierce[SUP] 1 2 19 [/SUP], John A Branda[SUP] 1 2 [/SUP], Eric S Rosenberg[SUP] 1 2 18 [/SUP], Javier Mendez-Pena[SUP] 1 [/SUP], Ivan Chebib[SUP] 1 2 [/SUP], Ivy A Rosales[SUP] 1 2 14 [/SUP], Rex N Smith[SUP] 1 2 14 [/SUP], Miles A Miller[SUP] 3 [/SUP], Ivan O Rosas[SUP] 20 [/SUP], Charles C Hardin[SUP] 10 21 [/SUP], Lindsey R Baden[SUP] 22 21 [/SUP], Benjamin D Medoff[SUP] 10 21 [/SUP], Robert B Colvin[SUP] 1 2 23 [/SUP], Brent P Little[SUP] 13 24 [/SUP], James R Stone[SUP] 1 2 [/SUP], Mari Mino-Kenudson[SUP] 1 25 [/SUP], Angela R Shih[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35671465
- DOI: 10.1164/rccm.202109-2150OC
Abstract
Rationale The leading cause of death in coronavirus disease 2019(COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome(ARDS) and diffuse alveolar damage(DAD). Whether DAD in fatal COVID-19 is distinct from other causes of DAD remains unknown. Objective To compare lung parenchymal and vascular alterations between patients with fatal COVID-19 pneumonia and other DAD-causing etiologies using a multidimensional approach. Methods This autopsy cohort consisted of consecutive patients with COVID-19 pneumonia(n=20) and with respiratory failure and histologic DAD(n=21; non-COVID-19 viral and non-viral etiologies). Premortem chest computed tomography(CT) scans were evaluated for vascular changes. Postmortem lung tissues were compared using histopathological and computational analyses. Machine-learning-derived morphometric analysis of the microvasculature was performed, with a random forest classifier quantifying vascular congestion(CVasc) in different microscopic compartments. Respiratory-mechanics and gas-exchange parameters were evaluated longitudinally in patients with ARDS. Measurements and Main Results On premortem CT, COVID-19 patients showed more dilated vasculature when evaluating all lung segments (p=0.001) compared to DAD-controls. Histopathology revealed vasculopathic changes including hemangiomatosis-like-changes(p=0.043), thromboemboli(p=0.0038), pulmonary infarcts(p=0.047), and perivascular inflammation(p<0.001). Generalized estimating equations revealed significant regional differences in the lung microarchitecture among all DAD-causing entities. COVID-19 showed a larger overall CVasc-range(p=0.002). Alveolar-septal-congestion was associated with a significantly shorter time-to-death from symptom onset(p=0.03), length-of-hospital-stay(p=0.02), and increased ventilatory ratio[an estimate for pulmonary dead space fraction(Vd); p=0.043] in all cases of ARDS. Conclusions Severe COVID-19 pneumonia is characterized by significant vasculopathy and aberrant alveolar-septal-congestion. Our findings also highlight the role that vascular alterations may play in Vd and clinical outcomes in ARDS in general.
Keywords: ARDS; COVID-19; Vascular Congestion; Vasculopathy; Ventilatory ratio.