International Journal of Coronaviruses

International Journal of Coronaviruses

Current Issue Volume No: 4 Issue No: 4

Case-report Article Open Access
  • Available online freely Peer Reviewed

  • Pyrexia And Liver Injury After A Second SARS-CoV-2 Vaccination: Macrophage Activation Manifested In Liver

    Ryu Tomiko 1     Onozato Yusuke 1     Umeda Ayano 1     Abe Keiko 2     Mimori Akio 3     Miura Hideaki 4     Komeno Yukiko 1    

    1 Department of Haematology, Japan Community Healthcare Organization (JCHO) Tokyo Yamate Medical Centre, Shinjuku-Ku, Tokyo, Japan 

    2 Department of Pathology, Japan Community Healthcare Organization (JCHO) Tokyo Yamate Medical Centre, Shinjuku-Ku, Tokyo, Japan 

    3 Department of Rheumatology and Clinical Immunology, Japan Community Healthcare Organization (JCHO) Tokyo Yamate Medical Centre, Shinjuku-Ku, Tokyo, Japan 

    4 Department of Hepatology, Japan Community Healthcare Organization (JCHO) Tokyo Yamate Medical Centre, Shinjuku-Ku, Tokyo, Japan 

    Abstract

    Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-Co V-2) has contributed to control of the coronavirus disease 2019 (COVID-19). On the other side, vaccination of SARS-CoV-2 could trigger autoimmune or inflammatory diseases. We present a 50-year-old female with well-controlled optic neuromyelitis with prednisolone (PSL) maintained at a dose of 2.5 mg/day. She ran a fever and liver injury was indicated 5 weeks after a second COVID-19 vaccination (BNT162b2 mRNA/Pfizer ). Liver biopsy showed accumulation of macrophages around the central veins, identified using anti-CD68 antibodies. As the treatment, cyclosporine A improved liver injury. COVID- 19 vaccination may have triggered liver inflammation due to cytokine storm via macrophage activation in the liver.
    Author Contributions
    Received Jul 18, 2023     Accepted Aug 01, 2023     Published Aug 08, 2023

    Copyright© 2023 Ryu Tomiko, et al.
    License
    Creative Commons License   This work is licensed under a Creative Commons Attribution 4.0 International License. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Competing interests

    The authors have declared that no competing interests exist.

    Funding Interests:

    Citation:

    Ryu Tomiko, Onozato Yusuke, Umeda Ayano, Abe Keiko, Mimori Akio et al. (2023) Pyrexia And Liver Injury After A Second SARS-CoV-2 Vaccination: Macrophage Activation Manifested In Liver International Journal of Coronaviruses. - 4(4):32-37
    DOI 10.14302/issn.2692-1537.ijcv-23-4679

    Introduction

    Introduction

    The world has faced the pandemic of COVID-19 since December 2019. As a countermeasure of SARS-CoV-2 infection, vaccines of different mechanisms have been approved. SARS-CoV-2 infection has been associated with the development of autoimmune process1, such as Guillain-Barre syndrome, systemic lupus erythematosus, autoimmune haemolytic anaemia, immune thrombocytopenic purpura, autoimmune thyroid disease and Kawasaki disease2. It is speculated that SARS-CoV-2 can disturb self-tolerance and trigger autoimmune response through cross-reactivity with host cells. There are also reports of immune diseases that develop after COVID-19 vaccination. COVID-19 vaccination could trigger auto-immunity, as same as other vaccines.

    Recently, several cases of immune thrombocytopenic purpura (ITP) developing after COVID-19 vaccination 3 have been reported to the Vaccine Adverse Event

    Reporting System. Autoimmune hepatitis (AIH) after COVID-19 vaccination is extremely rare. Until now, about 10 cases of AIH has been reported in the literature 45678. Although the exact mechanism of autoimmune develop is unknown, molecular mimicry and bystander activation is a potential mechanism. In vitro study, Vojdani A et al. showed a molecular mimicry mechanism between the nucleoprotein/spike protein of SARS-CoV-2 and self-antigens 9.

    Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of autoimmune disease, viral infection and malignancy. It is a subset of hemophagocytic lympohistiocyto-sis (HLH). The excessive activation and proliferation of macrophages and T lymphocytes leads to inflammation via cytokine storm.

    We present a case of pyrexia and liver injury after a second COVID-19 vaccination (BNT162b2 mRNA/Pfizer). Pathological findings of liver biopsy showed accumulation of macrophages around the central veins. As our case did not fill HLH-2004 diagnostic criteria, MAS was denied. Organ damage due to macrophage activation was only manifested in the liver. COVID-19 vaccination may cause a single organ inflammation as an abnormal immune response. Administration of cyclosporine A for immunosuppression was effective, and liver damage improved. As far as we could confirm, this is the first reported case.

    Discussion

    Discussion

    We presented a rare case of pyrexia and liver injury following a second COVID-19 vaccination. Although reports of liver injury from COVID-19 vaccination are rare, AIH and HLH have been reported.

    The first case of AIH after COVID-19 vaccination in the literature was presented by Bril F et al. in 2021 4. They reported a case of autoimmune hepatitis in which the patient developed itchiness, jaundice, and hepatic damage one week after COVID-19 vaccination. The liver biopsy findings included pan-lobular hepatitis and lobular inflammation, severe portal and periportal lymphocyte infiltration with plasma cells, periseptal interface hepatitis, spotty necrosis, and limiting plate disorder.

    Afterward, the number of cases shared in the literature has increased up to about 11 cases. Avci E et al. reported a female case of AIH after COVID-19 vaccine 7. She had Hashimoto s thyroiditis. Lessard EV et al. reported a case of a 76-year-old woman with Hashimoto thyroiditis and prior COVID-19 infection who developed severe autoimmune hepatitis following COVID-19 vaccination (mRNA-1273, Moderna). Caution may be warranted when vaccinating individuals with known autoimmune diseases. Cumali E et al. evaluated clinical features, treatment response and outcomes of liver injury following COVID-19 vaccination in a large case series, including 87 patients from 18 countries 10. Liver injury was diagnosed a medium 15 days after vaccination. 51 cases (59%) were attributed to the BNT162b2 mRNA/Pfizer vaccine, 20 cases (23%) to the Oxford-Astra Zeneca (ChAdOX1 nCoV-19) vaccine and 16 cases (18%) to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given more often for patients with than without immune-mediated hepatitis. All patients showed resolution of liver injury except for one man who developed liver failure.

    Our case had optic neuromyelitis maintained with PSL at a dose of 2.5 mg/day. AIH was denied accord-ing to blood examination and pathological findings of liver biopsy. Muench F et al. reported a first case of adult-onset Still s disease (AOSD) who developed macrophage activation syndrome (MAS) after SARS-CoV-2 vaccination with BNT162b2 mRNA/Pfizer 11. MAS is a complication of AOSD with high mortality rate. However, the occurrence of MAS after vaccination is extremely rare and has been described in a few cases after measles or influenza vaccinations and more recently after COVID-19 vaccination.

    Hieber ML et al. reported a 24-year-old female who developed HLH after immunization with COVID-19 vaccine, BNT162b2 mRNA/Pfizer 12. Diagnosis was made according to HLH-2004 criteria. In 16 cases of post-vaccine HLH in a literature search, the meantime from vaccination to symptom onset was 7.4 days. In our case, the time from a second COVID-19 vaccination to symptom onset was 5 weeks. The reasons for the longer time to symptom onset were thought to be the immunosuppressive effect of PSL, which the patient was taking for optic neuromyelitis.

    A detailed etiology of hepatopathy caused by MAS following COVID-19 vaccination has not been elucidated. SARS-CoV-2 spike proteins were possibly produced following the vaccination, which induced humoral and cellular immunity. These spike proteins and other analogs within the body might have further induced abnormal or excessive immune reactions, thereby activating macrophages and causing hepatopathy. COVID-19 vaccine also might have induced Th1 cell activation, which in turn prompted the secretion of cytokines, such as IFN-γ and IL-2. Consequently, the activated macrophages and the ensuing inflammatory reactions triggered hepatopathy 13.

    Given the risks of autoimmune and inflammatory diseases caused by vaccination, careful consideration of administering vaccination is essential, for patients with autoimmune diseases. An early diagnosis and prompt initial treatment are very important for favorable outcome.

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