Cardiac inflammation and microvascular procoagulant changes are decreased in second wave compared to first wave deceased COVID-19 patients

Linghe Wu; Umit Baylan; Britt van der Leeden; Bernadette Schurink; Eva Roos; Casper G Schalkwijk; Marianna Bugiani; Paul van der Valk; Albert C van Rossum; Sacha S Zeerleder; Leo M A Heunks; Reinier A Boon; Onno J de Boer; Allard C van der Wal; Hans W M Niessen; Paul A J Krijnen

doi:10.1016/j.ijcard.2021.11.079

Cardiac inflammation and microvascular procoagulant changes are decreased in second wave compared to first wave deceased COVID-19 patients

Int J Cardiol. 2022 Feb 15:349:157-165. doi: 10.1016/j.ijcard.2021.11.079. Epub 2021 Dec 3.

Authors

Linghe Wu¹, Umit Baylan², Britt van der Leeden³, Bernadette Schurink⁴, Eva Roos⁴, Casper G Schalkwijk⁵, Marianna Bugiani⁶, Paul van der Valk⁴, Albert C van Rossum⁷, Sacha S Zeerleder⁸, Leo M A Heunks⁹, Reinier A Boon¹⁰, Onno J de Boer², Allard C van der Wal², Hans W M Niessen¹¹, Paul A J Krijnen¹²

Affiliations

¹ Dept. of Pathology and Amsterdam Cardiovascular Sciences (ACS), Amsterdam University Medical Centre (AUMC), location VUmc, De Boelelaan 1017, 1081HV Amsterdam, the Netherlands.
² Dept. of Pathology and ACS, AUMC, location VUmc, the Netherlands.
³ Dept. of Pathology and Amsterdam institute for Infection and Immunity, AUMC, the Netherlands.
⁴ Dept. of Pathology, AUMC, location VUmc, the Netherlands.
⁵ Dept. of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands.
⁶ Dept. of Pathology, AUMC, location VUmc and AMC, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
⁷ Dept. of Cardiology and ACS, AUMC, location VUmc, the Netherlands.
⁸ Dept. of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Freiburgstrasse 18, 3010 Bern, Switzerland; Dept. for BioMedical Research, University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
⁹ Dept. Intensive Care Medicine, AUMC, location VUmc, the Netherlands.
¹⁰ Department of Physiology, AUMC, location VUmc, Amsterdam, the Netherlands; Institute for Cardiovascular Regeneration, Centre for Molecular Medicine and German center for Cardiovascular Research (DZHK), Goethe University, Frankfurt am Main, Germany.
¹¹ Dept. of Pathology and ACS and Dept. of Cardiac Surgery, AUMC, location VUmc, the Netherlands.
¹² Dept. of Pathology and ACS, AUMC, location VUmc, the Netherlands. Electronic address: paj.krijnen@amsterdamumc.nl.

Abstract

Background: Compelling evidence has shown cardiac involvement in COVID-19 patients. However, the overall majority of these studies use data obtained during the first wave of the pandemic, while recently differences have been reported in disease course and mortality between first- and second wave COVID-19 patients. The aim of this study was to analyze and compare cardiac pathology between first- and second wave COVID-19 patients.

Methods: Autopsied hearts from first- (n = 15) and second wave (n = 10) COVID-19 patients and from 18 non-COVID-19 control patients were (immuno)histochemically analyzed. CD45+ leukocyte, CD68+ macrophage and CD3+ T lymphocyte infiltration, cardiomyocyte necrosis and microvascular thrombosis were quantified. In addition, the procoagulant factors Tissue Factor (TF), Factor VII (FVII), Factor XII (FXII), the anticoagulant protein Dipeptidyl Peptidase 4 (DPP4) and the advanced glycation end-product N(^ε)-Carboxymethyllysine (CML), as markers of microvascular thrombogenicity and dysfunction, were quantified.

Results: Cardiac inflammation was significantly decreased in second wave compared to first wave COVID-19 patients, predominantly related to a decrease in infiltrated lymphocytes and the occurrence of lymphocytic myocarditis. This was accompanied by significant decreases in cardiomyocyte injury and microvascular thrombosis. Moreover, microvascular deposits of FVII and CML were significantly lower in second wave compared to first wave COVID-19 patients.

Conclusions: These results show that in our cohort of fatal COVID-19 cases cardiac inflammation, cardiomyocyte injury and microvascular thrombogenicity were markedly decreased in second wave compared to first wave patients. This may reflect advances in COVID-19 treatment related to an increased use of steroids in the second COVID-19 wave.

Keywords: COVID-19; First and second wave; Heart; Inflammation; Thrombosis microvasculature.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19 Drug Treatment*
Humans
Inflammation
Pandemics
SARS-CoV-2