Forty Postmortem Examinations in COVID-19 Patients

Abstract

Objectives: Although diffuse alveolar damage, a subtype of acute lung injury (ALI), is the most common microscopic pattern in coronavirus disease 2019 (COVID-19), other pathologic patterns have been described. The aim of the study was to review autopsies from COVID-19 decedents to evaluate the spectrum of pathology and correlate the results with clinical, laboratory, and radiologic findings.

Methods: A comprehensive and quantitative review from 40 postmortem examinations was performed. The microscopic patterns were categorized as follows: "major" when present in more than 50% of cases and "novel" if rarely or not previously described and unexpected clinically.

Results: Three major pulmonary patterns were identified: ALI in 29 (73%) of 40, intravascular fibrin or platelet-rich aggregates (IFPAs) in 36 (90%) of 40, and vascular congestion and hemangiomatosis-like change (VCHL) in 20 (50%) of 40. The absence of ALI (non-ALI) was novel and seen in 11 (27%) of 40. Compared with ALI decedents, those with non-ALI had a shorter hospitalization course (P = .02), chest radiographs with no or minimal consolidation (P = .01), and no pathologically confirmed cause of death (9/11). All non-ALI had VCHL and IFPAs, and clinically most had cardiac arrest.

Conclusions: Two distinct pulmonary phenotypic patterns-ALI and non-ALI-were noted. Non-ALI represents a rarely described phenotype. The cause of death in non-ALI is most likely COVID-19 related but requires additional corroboration.

Keywords: COVID-19 autopsy series; COVID-19 lung phenotypes; COVID-19 pulmonary pathology; Coronavirus; Pulmonary pathology.

Figure 1

The spectrum of lung pathology in coronavirus disease 2019 was categorized as “major” (A) and “minor” (B) pathologic patterns. ALI, acute lung injury; IFPA, intravascular fibrin or platelet aggregate; VCHL, vascular congestion and hemangiomatosis-like change. ^aCandida species, herpes simplex virus, and Aspergillus species. ^bCongestion, fibrosis, or chronic inflammation.

Image 1

Lung with and without acute lung injury (ALI). A, B, Lung with ALI phenotype. A, Eosinophilic hyaline membranes, the hallmark of diffuse alveolar damage, line alveolar septa (arrows) (H&E, ×8.3). B, A pulmonary artery has an organizing thrombus (H&E, ×1.2). C, D, A non-ALI phenotype. C, An intravascular fibrin-platelet aggregate (arrow) in a small-caliber vessel in a background of otherwise unremarkable lung parenchyma (H&E, ×40). D, CD61 immunohistochemical stain highlights the platelets within small vessels and capillaries of alveolar septa (×20).

Image 2

A, B, Lung from a region of vascular congestion and hemangiomatosis-like change (VCHL). The alveolar walls have patchy thickening of alveolar septa with a complex mesh-like framework (H&E, ×15). B, Thickened alveolar septa of VCHL and interspersed unremarkable septa (reticulin, ×40). C, Control case has vascular congestion but lacks the mesh-like framework and corresponding thickening of alveolar walls (H&E, ×15).

Figure 2

Associations between clinical, laboratory, radiologic, and microscopic findings. A, Correlation matrix of clinical, laboratory, major microscopic, and radiologic data. Circle size and color intensity are proportional to correlation coefficient, with red representing positive correlations and blue representing negative correlations. *Statistical significance (Holm-adjusted P < .05). B, Violin plot and dot plots for nonbinary and binary data, respectively, of clinical, laboratory, microscopic, and radiographic data distributions by ALI status. For any given clinical feature, the violin and dot color are proportional to the –log₁₀ (Holm-adjusted P value) of a Wilcoxon rank-sum or Fisher exact test for nonbinary and binary data, respectively, comparing the distribution of that feature in ALI vs non-ALI. Each circle corresponds to a single case. For binary data, 1 = presence, 0 = absence. ALI, acute lung injury; CPR, cardiopulmonary resuscitation; CXR, chest x-ray; IFPA, intravascular fibrin or platelet-rich aggregate; INR, international normalized ratio; pro-BNP, N-terminal prohormone of brain natriuretic peptide; Tmax, maximum temperature; VCHL, vascular congestion and hemangiomatosis-like change.

Figure 2

Associations between clinical, laboratory, radiologic, and microscopic findings. A, Correlation matrix of clinical, laboratory, major microscopic, and radiologic data. Circle size and color intensity are proportional to correlation coefficient, with red representing positive correlations and blue representing negative correlations. *Statistical significance (Holm-adjusted P < .05). B, Violin plot and dot plots for nonbinary and binary data, respectively, of clinical, laboratory, microscopic, and radiographic data distributions by ALI status. For any given clinical feature, the violin and dot color are proportional to the –log₁₀ (Holm-adjusted P value) of a Wilcoxon rank-sum or Fisher exact test for nonbinary and binary data, respectively, comparing the distribution of that feature in ALI vs non-ALI. Each circle corresponds to a single case. For binary data, 1 = presence, 0 = absence. ALI, acute lung injury; CPR, cardiopulmonary resuscitation; CXR, chest x-ray; IFPA, intravascular fibrin or platelet-rich aggregate; INR, international normalized ratio; pro-BNP, N-terminal prohormone of brain natriuretic peptide; Tmax, maximum temperature; VCHL, vascular congestion and hemangiomatosis-like change.

Figure 3

Potential mechanisms of decompensation in non–acute lung injury phenotype that include a vascular or cardiac pathway.