Pathological Findings Associated With SARS-CoV-2 on Postmortem Core Biopsies: Correlation With Clinical Presentation and Disease Course

Abstract

BackgroundAutopsies can shed light on the pathogenesis of new and emerging diseases.AimTo describe needle core necropsy findings of the lung, heart, and liver in decedents with COVID-19.MaterialCross-sectional study of needle core necropsies in patients who died with virologically confirmed COVID-19. Histopathological analyses were performed, and clinical data and patient course evaluated.ResultsChest core necropsies were performed in 71 decedents with a median age of 81 years (range 52–97); 47 (65.3%) were men. The median interval from symptoms onset to death was 17.5 days (range 1–84). Samples of lung (n = 62, 87.3%), heart (n = 48, 67.6%) and liver (n = 39, 54.9%) were obtained. Fifty-one lung samples (82.3%) were abnormal: 19 (30.6%) showed proliferative diffuse alveolar damage (DAD), 12 (19.4%) presented exudative DAD, and 10 (16.1%) exhibited proliferative plus exudative DAD. Of the 46 lung samples tested for SARS-CoV-19 by RT-PCR, 39 (84.8%) were positive. DAD was associated with premortem values of lactate dehydrogenase of 400 U/L or higher [adjusted odds ratio (AOR) 21.73; 95% confidence interval (CI) 3.22–146] and treatment with tocilizumab (AOR 6.91; 95% CI 1.14–41.7). Proliferative DAD was associated with an onset-to-death interval of over 15 days (AOR 7.85, 95% CI 1.29–47.80). Twenty-three of the 48 (47.9%) heart samples were abnormal: all showed fiber hypertrophy, while 9 (18.8%) presented fibrosis. Of the liver samples, 29/39 (74.4%) were abnormal, due to steatosis (n = 12, 30.8%), cholestasis (n = 6, 15.4%) and lobular central necrosis (n = 5, 12.8%).ConclusionProliferative DAD was the main finding on lung core needle necropsy in people who died from COVID-19; this finding was related to a longer disease course. Changes in the liver and heart were common.

Cellular and molecular features of COVID-19 associated ARDS: therapeutic relevance

“…Additional studies on patients who died following COVID-19 infection also showed that lung tissue was characterized by an increased infiltration of alveolar macrophages [ 105 ]. Conversely other analysis have found an increased infiltration of CD8 + T-lymphocytes [ 106 ].…”

“…Analysis of postmortem lung tissue taken from patients who died from COVID-19 showed that SARS-CoV-2 infection caused diffuse alveolar damage (DAD) characterized by formation of hyaline membranes in lung parenchyma and perivascular lung vessels inflammation inducing intravasal fibrin thrombi/microthrombi [ 122 – 124 ]. Moreover, DAD extension was positively correlated with male sex and premortem serum LDH levels [ 106 ], while large vessels thrombosis and microthrombi of lung vessels were found in deceased COVID-19 patients who had a longer average disease duration compared to COVID-19 patients who died after a short disease duration [ 125 ].…”

SARS-CoV-2 viral replication persists in the human lung for several weeks after symptom onset

“…40.5% (17/42) had a secondary bacterial infection and 11% (4/38) had bacterial bronchopneumonia (microbiologically and histopathological confirmed). The median time from onset of symptoms to death, ICU admission to death and high flow oxygen admission to death was 17 (IQR; 9-22), 5 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and 11 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15) days, respectively.…”

“…SARS-CoV-2 detection (ascertained through PCR positivity or antigen detection) can persist for several weeks from symptom onset 11 . Indeed, postmortem studies have shown persistence of SARS-CoV-2 in tissues detected by PCR and immunohistochemistry for up to several weeks after symptom onset 12,13 .…”

Molecular Pathogenesis of Fibrosis, Thrombosis and Surfactant Dysfunction in the Lungs of Severe COVID-19 Patients

“…In COVID-19-related lung disease, there are also two distinct phenotypes induced by inflammation and other processes connected with fibrosis. The first phenotype is COVID-19-related acute respiratory distress syndrome (ARDS), which exhibits a classical histopathological pattern of fibrotic diffuse alveolar damage (DAD) in exudative and organizing phases, with or without pulmonary artery thrombosis in different stages of development, as was confirmed in postmortem analyses [ 9 ]. The second phenotype is post-COVID pulmonary fibrosis (PCPF) [ 10 ].…”