key: cord-1031376-4ezt6o0o
authors: Fox, Sharon E.; Lameira, Fernanda S.; Rinker, Elizabeth B.; Vander Heide, Richard S.
title: Cardiac Endotheliitis and Multisystem Inflammatory Syndrome After COVID-19
date: 2020-07-29
journal: Ann Intern Med
DOI: 10.7326/l20-0882
sha: f976ab05359aaf3d15bcc46b885bdf1a7f359d7b
doc_id: 1031376
cord_uid: 4ezt6o0o

nan

Background: Endotheliitis and microangiopathy have been identified as key features of the pathophysiology of severe coronavirus disease 2019 (COVID-19) (1, 2) . In addition, a multisystem inflammatory syndrome (MIS) similar to Kawasaki disease has been increasingly reported in association with COVID-19 in children and young adults (3) (4) (5) . Although vascular damage seems to be a component of both of these presentations, the pathologic features of MIS remain elusive.

Objective: To provide what we believe to be the first report on the pathologic findings of vasculitis of the small vessels of the heart, which likely represents MIS, leading to death in a young adult after presumed resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Case Report: The patient was a 31-year-old African American woman with a body mass index of 36.1 kg/m 2 , hypertension controlled with lisinopril, and diabetes with poor adherence to metformin and glipizide (hemoglobin A 1c level, 13.9%). She was admitted for fever, dry cough, and abdominal discomfort of 5 days. She was positive for SARS-CoV-2 by reverse transcriptase polymerase chain reaction testing of a nasopharyngeal swab specimen and was treated with a course of azithromycin and 2 days of hydroxychloroquine. At discharge, she was afebrile and her oxygen saturation was 95% on room air.

The patient returned 12 days later with sudden fever; throbbing, left-sided neck pain; nausea; and vomiting. She had a fever of 39.8°C, with sinus tachycardia of approximately This article was published at Annals.org on 29 July 2020. 

LETTERS 120 beats/min on electrocardiography. Her physical examination was remarkable for parotitis. A computed tomography scan of her neck showed bilaterally enlarged parotid glands and swelling in the posterior nasopharynx to oropharynx, and a computed tomography scan of her chest showed interval improvement of bibasilar ground-glass opacities, with cervical and anterior mediastinal lymphadenopathy. Reverse transcriptase polymerase chain reaction of a new nasopharyngeal swab was negative for SARS-CoV-2. Laboratory results at the time showed an elevated leukocyte count of 17.7 x10 9 cells/L, a D-dimer level of 2.48 nmol/L, and C-reactive protein levels trending upward (Table) . While she was being evaluated for hospital admission, she developed hemodynamic instability and ventricular fibrillation and could not be resuscitated. Permission for autopsy was granted by the next of kin, and this study was determined to be exempt by the institutional review board at Louisiana State University Health Sciences Center. Gross abnormalities noted at autopsy (4 hours after death) were conjunctival injection, enlarged cervical and mediastinal lymph nodes, and vascular thrombi with focal surrounding hemorrhage in the left lower lung, which probably contributed to illness but were not likely the primary cause of death. Pulmonary microscopic examination showed focal acute hemorrhage and numerous megakaryocytes, consistent with our previously reported findings (2) . Most of the lung showed predominantly reparative changes. Flow cytometry of an enlarged cervical lymph node revealed reactive changes, with a ratio of CD4 to CD8 T cells of 3:1.

The heart had a grossly normal appearance, without evidence of coronary artery aneurysm, atherosclerosis, or steno- immunostain showing reduced numbers of CD8 + compared with CD4 + lymphocytes. G. A similar neutrophilic vasculitis was seen in occasional portal triads of the liver, involving small arteries and veins with surrounding congestion and no direct inflammation of hepatocytes. Levels of aspartate aminotransferase and alanine aminotransferase became elevated just before death (Table). sis. Microscopically, however, endotheliitis and vasculitis were present, diffusely involving the small cardiac vessels and extending into the surrounding epicardial fat and interstitial spaces ( Figure, A and B) . There was no lymphocytic infiltrate of the myocardium (2, 3) . The vasculitis was composed of numerous neutrophils (Figure, C) , as well as CD4 + >CD8 + lymphocytes ( Figure, E and F) . Inflammation was not present in the coronary arteries or larger blood vessels (Figure, D) . Similar inflammation was noted in occasional portal triad vessels within the liver (Figure, G) . Discussion: Multisystem inflammatory syndrome is currently defined as fever, systemic inflammation, end-organ dysfunction, or symptoms similar to Kawasaki disease or toxic shock syndrome (4, 5) . The clinical picture in this adult patient of sudden lymphadenopathy and parotitis combined with small-vessel cardiac vasculitis after COVID-19 is strongly suggestive of a similar systemic inflammatory process. Of note, the coronary arteries were spared, and neutrophils were identified along with CD4 + >CD8 + lymphocytes. The appearance was not that of a lymphocytic or eosinophilic myocarditis, and cardiac myocytes did not seem to be the target of the inflammatory process.

The autopsy was also significant for the presence of new pulmonary thrombi in a background of otherwise reparative changes in the lungs. These thrombi indicate a potential for hypercoagulability affecting the pulmonary vasculature beyond the initial course of COVID-19, as well as the need for continued monitoring of laboratory markers and possible anticoagulation.

Our report highlights the potential for serious complications due to endothelial damage and describes potential pathologic characteristics of MIS after COVID-19, a possible mimicker of true myocarditis. Careful monitoring of laboratory markers of inflammation, as well as therapeutic intervention to target this inflammatory process, may improve patient outcomes. 

Endothelial cell infection and endotheliitis in COVID-19

Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans

Unexpected features of cardiac pathology in COVID-19 infection

Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City

Kawasaki-like disease: emerging complication during the COVID-19 pandemic