J Korean Med Sci.  2021 Oct;36(40):e286. 10.3346/jkms.2021.36.e286.

Myocarditis-induced Sudden Death after BNT162b2 mRNA COVID-19 Vaccination in Korea: Case Report Focusing on Histopathological Findings

• Choi S
• Lee S
• Seo JW
• Kim Mj
• Jeon YH
• Park JH
• Lee JK
• Yeo NS

• KMID: 2521432
• DOI: http://doi.org/10.3346/jkms.2021.36.e286

Abstract

We present autopsy findings of a 22-year-old man who developed chest pain 5 days after the first dose of the BNT162b2 mRNA vaccine and died 7 hours later. Histological examination of the heart revealed isolated atrial myocarditis, with neutrophil and histiocyte predominance. Immunohistochemical C4d staining revealed scattered single-cell necrosis of myocytes which was not accompanied by inflammatory infiltrates. Extensive contraction band necrosis was observed in the atria and ventricles. There was no evidence of microthrombosis or infection in the heart and other organs. The primary cause of death was determined to be myocarditis, causally-associated with the BNT162b2 vaccine.

Keyword

Sudden Cardiac Death; Myocarditis; Coronavirus Disease 19; Vaccination; mRNA Vaccines; Adverse Event Following Immunization

Figure

• 

  Fig. 1 Histopathology of the heart. (A) Hematoxylin and eosin stains of atrial septum shows massive inflammatory infiltration with neutrophil predominance. (B) The myocytes often show contraction band necrosis (yellow arrows), which were highlighted by Masson's trichrome staining. (C) The atrioventricular node area shows extension of atrial myocarditis to the superficial layer of the node. (D) The ventricular myocardium is free of inflammatory infiltrates, but there are multiple large foci of contraction band necrosis (yellow arrows) particularly in the left ventricular wall and the ventricular septum. Bars represent 100 µm. The blue arrows in insets show where the section was taken from the low magnification views. Hematoxylin and eosin stain was used for the specimen shown in (A) and Masson's trichrome stain was used for the specimen shown in (B-D).RA = right atrium, LA = left atrium, RV = right ventricle, LV = left ventricle.

• 

  Fig. 2 Immunohistochemistry of the heart. (A) Immunohistochemical staining for CD68 shows that most of the inflammatory cells are histiocytes. (B) Most of the inflammatory cells are negative for CD3 staining, indicating a paucity of lymphocytes. (C) Positive staining for C4d shows scattered single-cell necrosis of atrial myocytes. Bars represent 100 µm.

Reference

1. Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, et al. The advisory committee on immunization practices' interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020. MMWR Morb Mortal Wkly Rep. 2020; 69(50):1922–1924. PMID: 33332292.

2. Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, et al. The advisory committee on immunization practices' interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020. MMWR Morb Mortal Wkly Rep. 2021; 69(5152):1653–1656. PMID: 33382675.

3. Ammirati E, Cavalotti C, Milazzo A, Pedrotti P, Soriano F, Schroeder JW, et al. Temporal relation between second dose BNT162b2 mRNA Covid-19 vaccine and cardiac involvement in a patient with previous SARS-COV-2 infection. Int J Cardiol Heart Vasc. Forthcoming. 2021; DOI: 10.1016/j.ijcha.2021.100778.

4. Kim HW, Jenista ER, Wendell DC, Azevedo CF, Campbell MJ, Darty SN, et al. Patients with acute myocarditis following mRNA COVID-19 vaccination. JAMA Cardiol. Forthcoming. 2021; DOI: 10.1001/jamacardio.2021.2828.

5. Larson KF, Ammirati E, Adler ED, Cooper LT Jr, Hong KN, Saponara G, et al. Myocarditis after BNT162b2 and mRNA-1273 vaccination. Circulation. 2021; 144(6):506–508. PMID: 34133884.

6. Mansour J, Short RG, Bhalla S, Woodard PK, Verma A, Robinson X, et al. Acute myocarditis after a second dose of the mRNA COVID-19 vaccine: a report of two cases. Clin Imaging. 2021; 78:247–249. PMID: 34166884.

7. Marshall M, Ferguson ID, Lewis P, Jaggi P, Gagliardo C, Collins JS, et al. Symptomatic acute myocarditis in seven adolescents following Pfizer-BioNTech COVID-19 vaccination. Pediatrics. 2021; 148(3):e2021052478. PMID: 34088762.

8. Montgomery J, Ryan M, Engler R, Hoffman D, McClenathan B, Collins L, et al. Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military. JAMA Cardiol. Forthcoming. 2021; DOI: 10.1001/jamacardio.2021.2833.

9. Rosner CM, Genovese L, Tehrani BN, Atkins M, Bakhshi H, Chaudhri S, et al. Myocarditis temporally associated with COVID-19 vaccination. Circulation. 2021; 144(6):502–505. PMID: 34133885.

10. Verma AK, Lavine KJ, Lin CY. Myocarditis after Covid-19 mRNA vaccination. N Engl J Med. 2021; 385(14):1332–1334. PMID: 34407340.

11. Snapiri O, Rosenberg Danziger C, Shirman N, Weissbach A, Lowenthal A, Ayalon I, et al. Transient cardiac injury in adolescents receiving the BNT162b2 mRNA COVID-19 vaccine. Pediatr Infect Dis J. 2021; 40(10):e360–e363. PMID: 34077949.

12. Kim IC, Kim H, Lee HJ, Kim JY, Kim JY. Cardiac imaging of acute myocarditis following COVID-19 mRNA vaccination. J Korean Med Sci. 2021; 36(2):e229. PMID: 34402228.

13. Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ Jr, et al. Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol. 1987; 1(1):3–14. PMID: 3455232.

14. Leone O, Pieroni M, Rapezzi C, Olivotto I. The spectrum of myocarditis: from pathology to the clinics. Virchows Arch. 2019; 475(3):279–301. PMID: 31297595.

15. Tse R, Garland J, Kesha K, Triggs Y, Modahl L, Milne D, et al. A rare case of isolated atrial myocarditis causing death with no post mortem computed tomography scan correlation. Am J Forensic Med Pathol. 2018; 39(2):123–125. PMID: 29120873.

16. Duffy M, O'Connor K, Milne D, Ondruschka B, Tse R, Garland J. Isolated atrial neutrophilic myocarditis: a rare cause of death and potential “Blind Spot” for postmortem computed tomography and postmortem examination. Am J Forensic Med Pathol. Forthcoming. 2021; DOI: 10.1097/PAF.0000000000000684.

17. Halushka MK, Vander Heide RS. Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 postmortem examinations. Cardiovasc Pathol. 2021; 50:107300. PMID: 33132119.

18. Jum'ah H, Loeffler A, Tomashefski JF Jr. Histopathological findings in the hearts of COVID-19 autopsies: a letter to cardiovascular pathology journal editor in response to Halushka et al. 2020. Cardiovasc Pathol. 2021; 52:107333. PMID: 33741530.

19. Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020; 8(7):681–686. PMID: 32473124.

20. Baroldi G, Mittleman RE, Parolini M, Silver MD, Fineschi V. Myocardial contraction bands. Definition, quantification and significance in forensic pathology. Int J Legal Med. 2001; 115(3):142–151. PMID: 11775016.