Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases

Abstract

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown.

Objective: To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection.

Design, setting, and participants: This cohort study used data from consecutive autopsy cases from Germany between April 8 and April 18, 2020. All patients had tested positive for SARS-CoV-2 in pharyngeal swab tests.

Exposures: Patients who died of coronavirus disease 2019.

Main outcomes and measures: Incidence of SARS-CoV-2 positivity in cardiac tissue as well as CD3+, CD45+, and CD68+ cells in the myocardium and gene expression of tumor necrosis growth factor α, interferon γ, chemokine ligand 5, as well as interleukin-6, -8, and -18.

Results: Cardiac tissue from 39 consecutive autopsy cases were included. The median (interquartile range) age of patients was 85 (78-89) years, and 23 (59.0%) were women. SARS-CoV-2 could be documented in 24 of 39 patients (61.5%). Viral load above 1000 copies per μg RNA could be documented in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. Comparison of 15 patients without cardiac infection with 16 patients with more than 1000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field.

Conclusions and relevance: In this analysis of autopsy cases, viral presence within the myocardium could be documented. While a response to this infection could be reported in cases with higher virus load vs no virus infection, this was not associated with an influx of inflammatory cells. Future investigations should focus on evaluating the long-term consequences of this cardiac involvement.

Figure 1.. Virus Infection and Inflammatory Response in Cardiac Tissue From Coronavirus Disease 2019 Deaths

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected by reverse transcriptase–polymerase chain reaction in 24 of 39 patients (61.5%). Patients were grouped according to SARS-CoV-2 copy numbers. Virus replication was determined in the 5 patients with the highest virus load. Gene expression data of a cytokine response panel revealed increased proinflammatory response in cardiac tissue with copy numbers more than 1000 compared with noninfected cardiac tissue, whereas immunohistochemistry staining revealed no difference in leukocyte infiltrates. F indicates female; IL, interleukin; IQR, interquartile range; interferon γ, IFNγ; M, male; max, maximum; min, minimum; tumor necrosis growth factor α, TNFα.

Figure 2.. In-situ Hybridization to Detect Virus RNA in SARS-CoV-2–Infected Cardiac Tissue

Paraffin-embedded cardiac tissue section of a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection revealed interstitial cells carrying virus RNA detected.

Figure 3.. Histological Analyses of Cardiac Tissue

Paraffin-embedded cardiac tissue sections either virus-negative (light blue) or with more than 1000 copies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (dark blue) were analyzed and depicted as Tukey-style box plots with median and interquartile range. The comparison of the 15 patients without cardiac infection to the 16 patients with more than 1000 copies revealed no infiltrates or differences in leukocyte numbers per high power field. Representative images for patient 39 with no cardiac infection and patient 8 revealing the highest copy number in the cardiac tissue are displayed. H&E indicates hematoxylin-eosin.