The Pathologist's Approach to Acute Lung Injury

Beasley, Mary Beth

doi:10.5858/134.5.719

Cited by 116 publications

(47 citation statements)

References 45 publications

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“…Nearly all cases with microscopic pulmonary thrombi also had DAD. Formation of thrombi has been associated with localized alterations in coagulation 39 as well as SARS-CoV-2-associated endothelial injury, 19 though investigation of deep leg veins for gross thrombi remains an important component of a complete autopsy procedure.…”

Section: Discussionmentioning

confidence: 99%

A Postmortem Portrait of the Coronavirus Disease 2019 (COVID-19) Pandemic: A Large Multi-institutional Autopsy Survey Study

Hooper

Padera

Dolhnikoff

et al. 2021

Archives of Pathology &Amp; Laboratory Medicine

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Context: This study represents the largest compilation to date of clinical and postmortem data from decedents with coronavirus disease 2019 (COVID-19). It will augment previously published small series of autopsy case reports, refine clinicopathologic considerations, and improve the accuracy of future vital statistical reporting. Objective: To accurately reflect the pre-existing diseases and pathologic conditions of decedents with Sars-CoV-2 infection through autopsy. Design: Comprehensive data from 135 autopsy evaluations of COVID-19-positive decedents is presented, including histologic assessment. Postmortem examinations were performed by 36 pathologists at 19 medical centers or forensic institutions in the United States and Brazil. Data from each autopsy were collected through the online submission of multiple choice and openended survey responses. Results: Patients dying of or with COVID-19 had an average of 8.89 pathologic conditions documented at autopsy, spanning a combination of prior chronic disease and acute conditions acquired during hospitalization. Virtually all decedents were cited as having more than one preexisting condition, encompassing an average of 2.88 such diseases each. Clinical conditions during terminal hospitalization were cited 395 times for the 135 autopsied decedents and predominantly encompassed acute failure of multiple organ systems and/or impaired coagulation. Myocarditis was rarely cited. Conclusions: Cause-of-death statements in both autopsy reports and death certificates may not encompass the severity or spectrum of co-morbid conditions in those dying of or with COVID-19. If supported by additional research, this finding may have implications for public health decisions and reporting moving forward through the pandemic.

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Section: Discussionmentioning

confidence: 99%

A Postmortem Portrait of the Coronavirus Disease 2019 (COVID-19) Pandemic: A Large Multi-institutional Autopsy Survey Study

Hooper

Padera

Dolhnikoff

et al. 2021

Archives of Pathology &Amp; Laboratory Medicine

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“…1,2,5 Histopathologically, ALI is associated with a variety of manifestations that include diffuse alveolar damage (DAD), acute fibrinous and organizing pneumonia (AFOP), and organizing pneumonia (OP). 6 DAD lies on the severe end of the ALI spectrum and is the histopathologic pattern typically associated with clinical ARDS. DAD is caused by "endothelial and alveolar lining cell injury which leads to fluid and cellular exudation," culminating in physical disruption of the blood-air barrier.…”

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confidence: 99%

“…7 DAD is divided into three histopathological phases that generally correlate with the time from pulmonary injury: acute (exudative) phase, subacute (organizing) phase, and chronic (fibrotic) phase. [6][7][8] The acute phase of DAD (Fig 1A) occurs within 1 week of the initial injury and is characterized by intra-alveolar hyaline membranes, edema, and alveolar wall thickening without significant inflammation, unless it arises in conjunction with acute pneumonia. 6,7,9 Vascular thrombosis and microthrombosis are frequently observed in DAD, even in the absence of a systemic hypercoagulable state, and they are thought to result from local inflammation.…”

mentioning

confidence: 99%

“…[6][7][8] The acute phase of DAD (Fig 1A) occurs within 1 week of the initial injury and is characterized by intra-alveolar hyaline membranes, edema, and alveolar wall thickening without significant inflammation, unless it arises in conjunction with acute pneumonia. 6,7,9 Vascular thrombosis and microthrombosis are frequently observed in DAD, even in the absence of a systemic hypercoagulable state, and they are thought to result from local inflammation. 6,7,9,10 Angiographic studies also have confirmed that thrombosis occurs early in ARDS of diverse origins.…”

mentioning

confidence: 99%

“…6,7,9 Vascular thrombosis and microthrombosis are frequently observed in DAD, even in the absence of a systemic hypercoagulable state, and they are thought to result from local inflammation. 6,7,9,10 Angiographic studies also have confirmed that thrombosis occurs early in ARDS of diverse origins. 11 The subacute phase (Fig 1B) of DAD occurs approximately 1 week after the initial pulmonary injury and is characterized by microscopic organization of the fibrin followed by fibroblast migration and secretion of young "loose" collagen.…”

mentioning

confidence: 99%

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Lung Histopathology in Coronavirus Disease 2019 as Compared With Severe Acute Respiratory Sydrome and H1N1 Influenza

Hariri

North

Shih

et al. 2021

Chest

173

134

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Background Patients with severe Coronavirus Disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with acute respiratory distress syndrome (ARDS). It has been suggested that respiratory failure in COVID-19 represents a novel pathologic entity. Research Question How does the lung histopathology described in COVID-19 compare to the lung histopathology described in SARS and H1N1 influenza? Study Design and Methods: We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020 using search terms for COVID-19, H1N1 influenza and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-IPD guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients. Results In COVID-19, acute phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared to 24% of H1N1 influenza patients. Interpretation DAD, the histologic correlate of ARDS, is the predominant histopathologic pattern identified in lung pathology from patients with COVID-19, H1N1 influenza and SARS. Microthrombi were reported more frequently in both patients with COVID-19 and SARS as compared to H1N1 influenza. Future work is needed to validate this histopathologic finding and, if confirmed, elucidate the mechanistic underpinnings and characterize any associations with clinically important outcomes.

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Machine learning‐based analysis of alveolar and vascular injury in SARS‐CoV‐2 acute respiratory failure

Calabrese

Pezzuto

Fortarezza

et al. 2021

The Journal of Pathology

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Severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) pneumopathy is characterized by a complex clinical picture and heterogeneous pathological lesions, both involving alveolar and vascular components. The severity and distribution of morphological lesions associated with SARS‐CoV‐2 and how they relate to clinical, laboratory, and radiological data have not yet been studied systematically. The main goals of the present study were to objectively identify pathological phenotypes and factors that, in addition to SARS‐CoV‐2, may influence their occurrence. Lungs from 26 patients who died from SARS‐CoV‐2 acute respiratory failure were comprehensively analysed. Robust machine learning techniques were implemented to obtain a global pathological score to distinguish phenotypes with prevalent vascular or alveolar injury. The score was then analysed to assess its possible correlation with clinical, laboratory, radiological, and tissue viral data. Furthermore, an exploratory random forest algorithm was developed to identify the most discriminative clinical characteristics at hospital admission that might predict pathological phenotypes of SARS‐CoV‐2. Vascular injury phenotype was observed in most cases being consistently present as pure form or in combination with alveolar injury. Phenotypes with more severe alveolar injury showed significantly more frequent tracheal intubation; longer invasive mechanical ventilation, illness duration, intensive care unit or hospital ward stay; and lower tissue viral quantity ( p < 0.001). Furthermore, in this phenotype, superimposed infections, tumours, and aspiration pneumonia were also more frequent ( p < 0.001). Random forest algorithm identified some clinical features at admission (body mass index, white blood cells, D‐dimer, lymphocyte and platelet counts, fever, respiratory rate, and PaCO 2 ) to stratify patients into different clinical clusters and potential pathological phenotypes (a web‐app for score assessment has also been developed; https://r-ubesp.dctv.unipd.it/shiny/AVI-Score/ ). In SARS‐CoV‐2 positive patients, alveolar injury is often associated with other factors in addition to viral infection. Identifying phenotypical patterns at admission may enable a better stratification of patients, ultimately favouring the most appropriate management. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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The Pathologist's Approach to Acute Lung Injury

Cited by 116 publications

References 45 publications

A Postmortem Portrait of the Coronavirus Disease 2019 (COVID-19) Pandemic: A Large Multi-institutional Autopsy Survey Study

A Postmortem Portrait of the Coronavirus Disease 2019 (COVID-19) Pandemic: A Large Multi-institutional Autopsy Survey Study

Lung Histopathology in Coronavirus Disease 2019 as Compared With Severe Acute Respiratory Sydrome and H1N1 Influenza

Machine learning‐based analysis of alveolar and vascular injury in SARS‐CoV‐2 acute respiratory failure

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