tetano
Editor, Senior Moderator
Circulation
. 2020 Nov 16.
doi: 10.1161/CIRCULATIONAHA.120.050754. Online ahead of print.
COVID-19-associated Non-Occlusive Fibrin Microthrombi in the Heart
Melanie C Bois[SUP] 1 [/SUP], Nicholas A Boire[SUP] 1 [/SUP], Andrew J Layman[SUP] 1 [/SUP], Marie-Christine Aubry[SUP] 1 [/SUP], Mariam P Alexander[SUP] 1 [/SUP], Anja C Roden[SUP] 1 [/SUP], Catherine E Hagen[SUP] 1 [/SUP], Reade A Quinton[SUP] 1 [/SUP], Christopher Larsen[SUP] 2 [/SUP], Young Erben[SUP] 3 [/SUP], Ramanath Majumdar[SUP] 1 [/SUP], Sarah M Jenkins[SUP] 4 [/SUP], Benjamin R Kipp[SUP] 1 [/SUP], Peter T Lin[SUP] 1 [/SUP], Joseph J Maleszewski[SUP] 5 [/SUP]
Affiliations
Abstract
Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, COVID-19, is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of COVID-19 individuals undergoing postmortem evaluation is provided, with four aims: 1) describe the pathologic spectrum of the myocardium; 2) compare to an alternate viral illness; 3) investigate angiotensin converting enzyme 2 (ACE2) expression; and 4) provide the first description of the cardiac findings in patients with cleared infection. Methods: Study cases were identified from institutional files and included COVID-19 (n=15; 12 active, 3 cleared), influenza A/B (n=6), and non-virally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An ACE2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction (ddPCR). Results: Male sex was more common in the COVID-19 group (p=0.05). Non-occlusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls), and were more common in the active COVID-19 cohort (p=0.006). Four active COVID-19 cases showed focal myocarditis, while one case of cleared COVID-19 showed extensive disease. Arteriolar ACE2 endothelial expression was lower in COVID-19 cases versus controls (p=0.004). ACE2 myocardial expression did not differ by disease category, sex, age or number of patient comorbidities (p=0.69, p=1.00, p=0.46, p=0.65, respectively). SARS-CoV-2 immunohistochemistry showed non-specific staining, while ultrastructural examination and ddPCR were negative for viral presence. Four (26.7%) COVID-19 patients had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations. Conclusions: This detailed histopathologic, immunohistochemical, ultrastructural and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of active and cleared COVID-19 patients, but is usually limited in extent. Histologic features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.
Keywords: COVID-19; SARS-CoV-2; autopsy.
. 2020 Nov 16.
doi: 10.1161/CIRCULATIONAHA.120.050754. Online ahead of print.
COVID-19-associated Non-Occlusive Fibrin Microthrombi in the Heart
Melanie C Bois[SUP] 1 [/SUP], Nicholas A Boire[SUP] 1 [/SUP], Andrew J Layman[SUP] 1 [/SUP], Marie-Christine Aubry[SUP] 1 [/SUP], Mariam P Alexander[SUP] 1 [/SUP], Anja C Roden[SUP] 1 [/SUP], Catherine E Hagen[SUP] 1 [/SUP], Reade A Quinton[SUP] 1 [/SUP], Christopher Larsen[SUP] 2 [/SUP], Young Erben[SUP] 3 [/SUP], Ramanath Majumdar[SUP] 1 [/SUP], Sarah M Jenkins[SUP] 4 [/SUP], Benjamin R Kipp[SUP] 1 [/SUP], Peter T Lin[SUP] 1 [/SUP], Joseph J Maleszewski[SUP] 5 [/SUP]
Affiliations
- PMID: 33197204
- DOI: 10.1161/CIRCULATIONAHA.120.050754
Abstract
Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, COVID-19, is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of COVID-19 individuals undergoing postmortem evaluation is provided, with four aims: 1) describe the pathologic spectrum of the myocardium; 2) compare to an alternate viral illness; 3) investigate angiotensin converting enzyme 2 (ACE2) expression; and 4) provide the first description of the cardiac findings in patients with cleared infection. Methods: Study cases were identified from institutional files and included COVID-19 (n=15; 12 active, 3 cleared), influenza A/B (n=6), and non-virally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An ACE2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction (ddPCR). Results: Male sex was more common in the COVID-19 group (p=0.05). Non-occlusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls), and were more common in the active COVID-19 cohort (p=0.006). Four active COVID-19 cases showed focal myocarditis, while one case of cleared COVID-19 showed extensive disease. Arteriolar ACE2 endothelial expression was lower in COVID-19 cases versus controls (p=0.004). ACE2 myocardial expression did not differ by disease category, sex, age or number of patient comorbidities (p=0.69, p=1.00, p=0.46, p=0.65, respectively). SARS-CoV-2 immunohistochemistry showed non-specific staining, while ultrastructural examination and ddPCR were negative for viral presence. Four (26.7%) COVID-19 patients had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations. Conclusions: This detailed histopathologic, immunohistochemical, ultrastructural and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of active and cleared COVID-19 patients, but is usually limited in extent. Histologic features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.
Keywords: COVID-19; SARS-CoV-2; autopsy.