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COVID-19-Associated Nonocclusive Fibrin Microthrombi in the Heart.
Bois, Melanie C; Boire, Nicholas A; Layman, Andrew J; Aubry, Marie-Christine; Alexander, Mariam P; Roden, Anja C; Hagen, Catherine E; Quinton, Reade A; Larsen, Christopher; Erben, Young; Majumdar, Ramanath; Jenkins, Sarah M; Kipp, Benjamin R; Lin, Peter T; Maleszewski, Joseph J.
  • Bois MC; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Boire NA; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Layman AJ; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Aubry MC; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Alexander MP; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Roden AC; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Hagen CE; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Quinton RA; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Larsen C; Arkana Laboratories, Little Rock (C.L.).
  • Erben Y; Division of Vascular Surgery, Mayo Clinic, Jacksonville, FL (Y.E.).
  • Majumdar R; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Jenkins SM; Division of Biomedical Statistics and Informatics (S.M.J.), Mayo Clinic, Rochester, MN.
  • Kipp BR; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Lin PT; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
  • Maleszewski JJ; Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN.
Circulation ; 143(3): 230-243, 2021 01 19.
Article in English | MEDLINE | ID: covidwho-1039948
Semantic information from SemMedBD (by NLM)
1. Heart LOCATION_OF Microthrombus
Subject
Heart
Predicate
LOCATION_OF
Object
Microthrombus
2. Evaluation TREATS COVID-19
Subject
Evaluation
Predicate
TREATS
Object
COVID-19
3. Evaluation USES Autopsy
Subject
Evaluation
Predicate
USES
Object
Autopsy
4. COVID-19 PROCESS_OF Persons
Subject
COVID-19
Predicate
PROCESS_OF
Object
Persons
5. Evaluation TREATS Persons
Subject
Evaluation
Predicate
TREATS
Object
Persons
6. Cardiac finding PROCESS_OF Patients
Subject
Cardiac finding
Predicate
PROCESS_OF
Object
Patients
7. COVID-19 PROCESS_OF Cohort
Subject
COVID-19
Predicate
PROCESS_OF
Object
Cohort
8. Microthrombus PROCESS_OF Cohort
Subject
Microthrombus
Predicate
PROCESS_OF
Object
Cohort
9. Comorbidity PROCESS_OF Patients
Subject
Comorbidity
Predicate
PROCESS_OF
Object
Patients
10. Digital Polymerase Chain Reaction NEG_DIAGNOSES Virus present
Subject
Digital Polymerase Chain Reaction
Predicate
NEG_DIAGNOSES
Object
Virus present
11. Heart LOCATION_OF Amyloidosis
Subject
Heart
Predicate
LOCATION_OF
Object
Amyloidosis
12. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
13. Amyloidosis PROCESS_OF Patients
Subject
Amyloidosis
Predicate
PROCESS_OF
Object
Patients
14. Myocardium LOCATION_OF Direct Contact Transmission Infection
Subject
Myocardium
Predicate
LOCATION_OF
Object
Direct Contact Transmission Infection
15. Amyloidosis PREDISPOSES Severe disease
Subject
Amyloidosis
Predicate
PREDISPOSES
Object
Severe disease
16. Heart LOCATION_OF Microthrombus
Subject
Heart
Predicate
LOCATION_OF
Object
Microthrombus
17. Evaluation TREATS COVID-19
Subject
Evaluation
Predicate
TREATS
Object
COVID-19
18. Evaluation USES Autopsy
Subject
Evaluation
Predicate
USES
Object
Autopsy
19. COVID-19 PROCESS_OF Persons
Subject
COVID-19
Predicate
PROCESS_OF
Object
Persons
20. Evaluation TREATS Persons
Subject
Evaluation
Predicate
TREATS
Object
Persons
21. Cardiac finding PROCESS_OF Patients
Subject
Cardiac finding
Predicate
PROCESS_OF
Object
Patients
22. COVID-19 PROCESS_OF Cohort
Subject
COVID-19
Predicate
PROCESS_OF
Object
Cohort
23. Microthrombus PROCESS_OF Cohort
Subject
Microthrombus
Predicate
PROCESS_OF
Object
Cohort
24. Comorbidity PROCESS_OF Patients
Subject
Comorbidity
Predicate
PROCESS_OF
Object
Patients
25. Digital Polymerase Chain Reaction NEG_DIAGNOSES Virus present
Subject
Digital Polymerase Chain Reaction
Predicate
NEG_DIAGNOSES
Object
Virus present
26. Heart LOCATION_OF Amyloidosis
Subject
Heart
Predicate
LOCATION_OF
Object
Amyloidosis
27. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
28. Amyloidosis PROCESS_OF Patients
Subject
Amyloidosis
Predicate
PROCESS_OF
Object
Patients
29. Myocardium LOCATION_OF Direct Contact Transmission Infection
Subject
Myocardium
Predicate
LOCATION_OF
Object
Direct Contact Transmission Infection
30. Amyloidosis PREDISPOSES Severe disease
Subject
Amyloidosis
Predicate
PREDISPOSES
Object
Severe disease
ABSTRACT

BACKGROUND:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (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 individuals with COVID-19 undergoing postmortem evaluation is provided, with 4

aims:

(1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 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 nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction.

RESULTS:

Male sex was more common in the COVID-19 group (P=0.05). Nonocclusive 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, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (P=0.004). Angiotensin-converting enzyme 2 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 nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 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 patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronary Thrombosis / Fibrin / SARS-CoV-2 / COVID-19 / Myocardium Type of study: Observational study / Prognostic study / Risk factors Limits: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged Language: English Journal: Circulation Year: 2021 Document Type: Article Affiliation country: CIRCULATIONAHA.120.050754

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronary Thrombosis / Fibrin / SARS-CoV-2 / COVID-19 / Myocardium Type of study: Observational study / Prognostic study / Risk factors Limits: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged Language: English Journal: Circulation Year: 2021 Document Type: Article Affiliation country: CIRCULATIONAHA.120.050754