COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review

doi:10.1016/j.cmi.2022.03.021

Review

. 2022 Aug;28(8):1066-1075.

doi: 10.1016/j.cmi.2022.03.021. Epub 2022 Mar 23.

COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review

Raghed Almamlouk¹, Tarek Kashour², Sawsan Obeidat¹, Melanie C Bois³, Joseph J Maleszewski⁴, Osama A Omrani⁵, Rana Tleyjeh¹, Elie Berbari⁶, Zaher Chakhachiro⁷, Bassel Zein-Sabatto⁷, Dana Gerberi⁸, Imad M Tleyjeh⁹; Cardiac Autopsy in COVID-19 Study Group; Alberto E Paniz Mondolfi¹⁰, Aloke V Finn¹¹, Amaro Nunes Duarte-Neto¹², Amy V Rapkiewicz¹³, Andrea Frustaci¹⁴, Arthur-Atilla Keresztesi¹⁵, Brian Hanley¹⁶, Bruno Märkl¹⁷, Christelle Lardi¹⁸, Clare Bryce¹⁹, Diana Lindner²⁰, Diego Aguiar¹⁸, Dirk Westermann²⁰, Edana Stroberg²¹, Eric J Duval²¹, Esther Youd²², Gaetano Pietro Bulfamante²³, Isabelle Salmon²⁴, Johann Auer²⁵, Joseph J Maleszewski⁴, Klaus Hirschbühl²⁶, Lara Absil²⁷, Lisa M Barton²¹, Luiz Fernando Ferraz da Silva²⁸, Luiza Moore²⁹, Marisa Dolhnikoff¹², Martin Lammens³⁰, Melanie C Bois³, Michael Osborn³¹, Myriam Remmelink²⁷, Paulo Hilario Nascimento Saldiva¹², Philippe G Jorens³², Randall Craver³³, Renata Aparecida de Almeida Monteiro¹², Roberto Scendoni³⁴, Sanjay Mukhopadhyay³⁵, Tadaki Suzuki³⁶, Thais Mauad¹², Tony Fracasso¹⁸, Zachary Grimes¹⁹

Affiliations

¹ College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
² Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia.
³ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
⁴ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
⁵ The Royal London Hospital, Barts Health NHS Trust, London, UK; Barts and the London School of Medicine and Dentistry, Queen Mary University, London, UK.
⁶ Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
⁷ Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon.
⁸ Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA.
⁹ College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Infectious Diseases Section, Department of Medical Specialties King Fahad Medical City, Riyadh, Saudi Arabia; Division of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. Electronic address: Tleyjeh.Imad@mayo.edu.
¹⁰ Department of Pathology, Molecular and Cell-Based Medicine, New York, NY, USA.
¹¹ CVPath Institute, Inc., Gaithersburg, and University of Maryland, Baltimore, MD, USA.
¹² Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
¹³ NYU Winthrop Hospital, Department of Pathology, Long Island School of Medicine, Long Island, NY, USA.
¹⁴ Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, La Sapienza University, Rome, Italy; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy.
¹⁵ Fogolyan Kristof Emergency County Hospital, Covasna County Institution of Forensic Medicine, Covasna, Romania.
¹⁶ Department of Cellular Pathology, Northwest London Pathology, Imperial College London NHS Trust, London, UK; Centre for Inflammatory Disease, Imperial College London, London, UK.
¹⁷ Institute of Pathology and Molecular Diagnostics, University Medical Center Augsburg, Augsburg, Germany.
¹⁸ University Center of Legal Medicine, Geneva University Hospital, Geneva, Switzerland.
¹⁹ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²⁰ Department of Cardiology, University Heart and Vascular Centre, Hamburg, Germany; DZHK-German Center for Cardiovascular Research, Partner site, Hamburg/Kiel/Lübeck, Germany.
²¹ Office of the Chief Medical Examiner, Oklahoma City, OK, USA.
²² Forensic Medicine and Science, University of Glasgow, Glasgow, UK.
²³ Unità di Anatomia Patologica, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy; Struttura Complessa di Anatomia Patologica e Genetica Medica, ASST Santi Paolo e Carlo, Milan, Italy.
²⁴ Department of Pathology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium; Centre Universitaire inter Régional d'expertise en Anatomie Pathologique Hospitalière, Jumet, Belgium; DIAPath, Center for Microscopy and Molecular Imaging, ULB, Gosselies, Belgium.
²⁵ Department of Cardiology and Intensive Care, St. Josef Hospital Braunau, Austria; Department of Cardiology and Intensive Care, Kepler University of Medicine Linz, Austria.
²⁶ Department of Hematology and Clinical Oncology, University Medical Center Augsburg, Augsburg, Germany.
²⁷ Department of Pathology, Erasme Hospital, ULB, Brussels, Belgium.
²⁸ Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Serviço de Verificação de Óbitos da Capital, Universidade de São Paulo, São Paulo, Brazil.
²⁹ Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Ageing and Somatic Mutation, Wellcome Sanger Institute, Cambridge, UK.
³⁰ Department of Pathology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium.
³¹ Department of Cellular Pathology, Northwest London Pathology, Imperial College London NHS Trust, London, UK; Death Investigation Committee, Royal College of Pathologists, London, UK; Nightingale NHS Hospital, London, UK.
³² Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium; Department of Medicine and Health Sciences, Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium; Department of Intensive Care Medicine, Antwerp University Hospital, University of Antwerp, Edegem, Belgium.
³³ Children's Hospital of New Orleans and Louisiana State University Health Sciences Center, New Orleans, LA, USA.
³⁴ Institute of Legal Medicine, Department of Law, University of Macerata, Macerata, Italy.
³⁵ Department of Pathology, Cleveland Clinic, Cleveland, OH, USA.
³⁶ National Institute of Infectious Diseases, Tokyo, Japan.

PMID: 35339672
PMCID: PMC8941843
DOI: 10.1016/j.cmi.2022.03.021

Review

COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review

Raghed Almamlouk et al. Clin Microbiol Infect. 2022 Aug.

. 2022 Aug;28(8):1066-1075.

doi: 10.1016/j.cmi.2022.03.021. Epub 2022 Mar 23.

Authors

Affiliations

¹ College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
² Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia.
³ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
⁴ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
⁵ The Royal London Hospital, Barts Health NHS Trust, London, UK; Barts and the London School of Medicine and Dentistry, Queen Mary University, London, UK.
⁶ Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
⁷ Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon.
⁸ Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA.
⁹ College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Infectious Diseases Section, Department of Medical Specialties King Fahad Medical City, Riyadh, Saudi Arabia; Division of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. Electronic address: Tleyjeh.Imad@mayo.edu.
¹⁰ Department of Pathology, Molecular and Cell-Based Medicine, New York, NY, USA.
¹¹ CVPath Institute, Inc., Gaithersburg, and University of Maryland, Baltimore, MD, USA.
¹² Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
¹³ NYU Winthrop Hospital, Department of Pathology, Long Island School of Medicine, Long Island, NY, USA.
¹⁴ Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, La Sapienza University, Rome, Italy; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy.
¹⁵ Fogolyan Kristof Emergency County Hospital, Covasna County Institution of Forensic Medicine, Covasna, Romania.
¹⁶ Department of Cellular Pathology, Northwest London Pathology, Imperial College London NHS Trust, London, UK; Centre for Inflammatory Disease, Imperial College London, London, UK.
¹⁷ Institute of Pathology and Molecular Diagnostics, University Medical Center Augsburg, Augsburg, Germany.
¹⁸ University Center of Legal Medicine, Geneva University Hospital, Geneva, Switzerland.
¹⁹ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²⁰ Department of Cardiology, University Heart and Vascular Centre, Hamburg, Germany; DZHK-German Center for Cardiovascular Research, Partner site, Hamburg/Kiel/Lübeck, Germany.
²¹ Office of the Chief Medical Examiner, Oklahoma City, OK, USA.
²² Forensic Medicine and Science, University of Glasgow, Glasgow, UK.
²³ Unità di Anatomia Patologica, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy; Struttura Complessa di Anatomia Patologica e Genetica Medica, ASST Santi Paolo e Carlo, Milan, Italy.
²⁴ Department of Pathology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium; Centre Universitaire inter Régional d'expertise en Anatomie Pathologique Hospitalière, Jumet, Belgium; DIAPath, Center for Microscopy and Molecular Imaging, ULB, Gosselies, Belgium.
²⁵ Department of Cardiology and Intensive Care, St. Josef Hospital Braunau, Austria; Department of Cardiology and Intensive Care, Kepler University of Medicine Linz, Austria.
²⁶ Department of Hematology and Clinical Oncology, University Medical Center Augsburg, Augsburg, Germany.
²⁷ Department of Pathology, Erasme Hospital, ULB, Brussels, Belgium.
²⁸ Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Serviço de Verificação de Óbitos da Capital, Universidade de São Paulo, São Paulo, Brazil.
²⁹ Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Ageing and Somatic Mutation, Wellcome Sanger Institute, Cambridge, UK.
³⁰ Department of Pathology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium.
³¹ Department of Cellular Pathology, Northwest London Pathology, Imperial College London NHS Trust, London, UK; Death Investigation Committee, Royal College of Pathologists, London, UK; Nightingale NHS Hospital, London, UK.
³² Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium; Department of Medicine and Health Sciences, Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium; Department of Intensive Care Medicine, Antwerp University Hospital, University of Antwerp, Edegem, Belgium.
³³ Children's Hospital of New Orleans and Louisiana State University Health Sciences Center, New Orleans, LA, USA.
³⁴ Institute of Legal Medicine, Department of Law, University of Macerata, Macerata, Italy.
³⁵ Department of Pathology, Cleveland Clinic, Cleveland, OH, USA.
³⁶ National Institute of Infectious Diseases, Tokyo, Japan.

PMID: 35339672
PMCID: PMC8941843
DOI: 10.1016/j.cmi.2022.03.021

Abstract

Background: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size.

Objectives: The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies.

Data sources: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory.

Study eligibility criteria: Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection.

Participants: Confirmed COVID-19 patients with post-mortem cardiovascular findings.

Interventions: None.

Methods: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs).

Results: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%).

Conclusions: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19.

Keywords: COVID-19; Cardiac pathology; Myocarditis; Postmortem; SARS-CoV-2; Systematic review.

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Figures

**Fig. 1**
Preferred Reporting Items for Systematic Reviews and Meta-analyses 2009 flow diagram.

**Fig. 2**
Bar chart showing reported comorbidities of deceased patients included in this cohort. CAD, coronary artery disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction. Data labels show the prevalence of reported comorbidities (can overlap in a single patient).

**Fig. 3**
Box-and-whisker plot of cardiac autopsy findings of studies with ≥5 patients as median percentage prevalence and associated interquartile ranges. CAD, coronary artery disease.

See this image and copyright information in PMC

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References

1. Mehta N., Kalra A., Nowacki A.S., Anjewierden S., Han Z., Bhat P., et al. Association of use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with testing positive for coronavirus disease 2019 (COVID-19) JAMA Cardiol. 2020;5:1020–1026. - PMC - PubMed
1. Reynolds H.R., Adhikari S., Pulgarin C., Troxel A.B., Iturrate E., Johnson S.B., et al. Renin-angiotensin-aldosterone system inhibitors and risk of COVID-19. N Engl J Med. 2020;382:2441–2448. - PMC - PubMed
1. Mancia G., Rea F., Ludergnani M., Apolone G., Corrao G. Renin-angiotensin-aldosterone system blockers and the risk of COVID-19. N Engl J Med. 2020;382:2431–2440. - PMC - PubMed
1. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)—China, 2020. China CDC Weekly. 2020;2:113–122. - PMC - PubMed
1. Xie Y., Xu E., Bowe B., Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28:583–590. - PMC - PubMed

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[1] Mehta N., Kalra A., Nowacki A.S., Anjewierden S., Han Z., Bhat P., et al. Association of use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with testing positive for coronavirus disease 2019 (COVID-19) JAMA Cardiol. 2020;5:1020–1026. - PMC - PubMed

[2] Mehta N., Kalra A., Nowacki A.S., Anjewierden S., Han Z., Bhat P., et al. Association of use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with testing positive for coronavirus disease 2019 (COVID-19) JAMA Cardiol. 2020;5:1020–1026. - PMC - PubMed

[3] Reynolds H.R., Adhikari S., Pulgarin C., Troxel A.B., Iturrate E., Johnson S.B., et al. Renin-angiotensin-aldosterone system inhibitors and risk of COVID-19. N Engl J Med. 2020;382:2441–2448. - PMC - PubMed

[4] Reynolds H.R., Adhikari S., Pulgarin C., Troxel A.B., Iturrate E., Johnson S.B., et al. Renin-angiotensin-aldosterone system inhibitors and risk of COVID-19. N Engl J Med. 2020;382:2441–2448. - PMC - PubMed

[5] Mancia G., Rea F., Ludergnani M., Apolone G., Corrao G. Renin-angiotensin-aldosterone system blockers and the risk of COVID-19. N Engl J Med. 2020;382:2431–2440. - PMC - PubMed

[6] Mancia G., Rea F., Ludergnani M., Apolone G., Corrao G. Renin-angiotensin-aldosterone system blockers and the risk of COVID-19. N Engl J Med. 2020;382:2431–2440. - PMC - PubMed

[7] The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)—China, 2020. China CDC Weekly. 2020;2:113–122. - PMC - PubMed

[8] The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)—China, 2020. China CDC Weekly. 2020;2:113–122. - PMC - PubMed

[9] Xie Y., Xu E., Bowe B., Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28:583–590. - PMC - PubMed

[10] Xie Y., Xu E., Bowe B., Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28:583–590. - PMC - PubMed

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COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review

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COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review

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