Since the first outbreak in December 2019, the COVID-19 pandemic has lasted for two years and five months. As the key to curbing the new crown epidemic, the new crown vaccine has also been available for 1 year and 8 months. To date, 4.64 billion people worldwide have been vaccinated against COVID-19.
Vaccines (Source: Figureworm Creative)
After vaccination, the vast majority of people do not have obvious discomfort, and a small number of people have redness and tenderness at the vaccination site (such as arms), or mild self-limiting symptoms such as fever, headache, and fatigue. Severe adverse reactions such as allergic reactions due to vaccination, thrombotic thrombocytopenia syndrome, myocarditis and pericarditis, and Guillain-Barre syndrome are extremely rare [2].
Recently, however, doctors in Germany have discovered that the COVID-19 mRNA vaccine (BNT162b2) developed by Pfizer can cause a rare type of T-cell-mediated autoimmune hepatitis. This is reported in the journal Journal of Hepatology, a top journal in hepatology.
Screenshot of the first page of the paper
The 52-year-old middle-aged man who developed hepatitis after receiving the Pfizer mRNA vaccine was a 52-year-old man. He has no previous history of hepatitis, but has a long history of medication with levothyroxine due to hypothyroidism. He received two doses of the Pfizer mRNA vaccine, both of which had episodes of acute hepatitis.
From the 10th day of the first injection, patients begin to feel progressive nausea, fatigue, loss of appetite and itchy skin, with jaundice, liver function tests showing acute mixed hepatocyte/cholestatic hepatitis. On the 41st day after the first dose, the patient completed the second dose. However, on the 20th day after the second injection, the patient developed fatigue, nausea and other symptoms again, and was diagnosed with a recurrence of acute mixed hepatitis.
What causes hepatitis in this patient? The researchers performed virological examinations on the patients to rule out hepatophage infections such as hepatitis A, B, C, and E, cytomegalovirus, and Epstein-Barr virus. Serum immunology shows elevated globulin levels and positive autoantibodies such as antinuclear antibodies, antimitochondrial antibodies, and anti-smooth muscle antibodies. Subsequently, liver tissue biopsy found that the patient's liver lobules were necrotic, and a apoptosis foci appeared, accompanied by lymphocyte and plasma cell infiltration. Clinical symptoms and examination results were consistent with autoimmune hepatitis, and the patient was diagnosed with autoimmune hepatitis and recovered after eight weeks of glucocorticoid immunosuppressive therapy.
Autoimmune hepatitis is an inflammation of the liver caused by the body's immune system attacking its own liver cells[4], characterized by elevated serum transaminases, positive autoantibodies, hyperimmunoglobulinemia, and interfacial hepatitis with lymphocyte and plasma cell infiltration in liver histology, and is generally treated with immunosuppressants, which can often lead to cirrhosis and liver failure if left untreated.
A major feature of autoimmune hepatitis is infiltration of B cells and plasma cells in the liver. However, this patient differed in that the proportion of B cells and plasma cells in his liver tissue was relatively low, while CD8+ T cells were extremely abundant. After vaccination, CD8+ T cells are significantly more activated than healthy people, even before hepatitis has occurred. After the onset of hepatitis, vaccine-provoked Scanthorn protein-specific CD8+ T cells of the new coronavirus were significantly enriched in the liver. Moreover, the degree of activation of CD8+ T cells and S spinin-specific CD8+ T cells varies with immunosuppressant therapy.
Given that in this patient, CD8+ T cells are closely related to the onset and treatment of hepatitis, the researchers believe that Pfizer's covid-19 mRNA vaccine can induce autoimmune hepatitis by inducing cellular immunity, which is mediated by CD8+ T cells and is a special type of autoimmune hepatitis.
Thesis research process
Coincidentally, the case announced in Germany this time is not an isolated case. Since the first outbreak of cases of autoimmune hepatitis with Pfizer mRNA vaccine on April 20, 2021 [5], in just one year, more than 10 cases have been reported in Europe and the United States alone. Although the underlying conditions of these patients are different, they have no previous history of autoimmune hepatitis, and they have been diagnosed with autoimmune hepatitis without exception after receiving the mRNA vaccine from Pfizer or Modena.
Although these case reports have not explored the immune-related factors of post-vaccination hepatitis as in this case, the relationship between the new crown mRNA vaccine and autoimmune hepatitis, between coincidence and cause and effect, is believed to be that the mRNA vaccine induces autoimmune hepatitis, and it is speculated that some proteins in the liver cells are similar to the new crown virus S echinoin antigen, resulting in antibodies and cytotoxic T cells induced by the new crown mRNA vaccine attacking the liver cells[6], it is also possible that " Bystander activation effect"[7].
Previous cases of autoimmune hepatitis caused by PFIZER and other companies with covid-19 mRNA vaccines have been reported
Since S spinoid protein is the key to the infection of human cells by the new crown virus, the new crown vaccines developed use S spinoid protein as a target for vaccine antigens. At present, globally, the new crown vaccines vaccinated are mainly divided into five categories: inactivated vaccines (represented by Kexing and Sinopharm), recombinant protein vaccines (represented by Zhifeilong Koma), adenoviral vector vaccines (represented by Johnson & Johnson and AstraZeneca), mRNA vaccines (represented by Pfizer and Modena) and DNA vaccines (represented by Kidas).
Compared with vaccines developed by traditional technologies such as inactivated vaccines, emerging mRNA vaccines have been rapidly put into clinical application during the COVID-19 epidemic due to their short development cycle and high protection rate. Among them, the new crown mRNA vaccine (BNT162b2) developed by Pfizer was first authorized by the FDA for emergency use in December 2020, and was officially approved for marketing in August 2021, and the number of vaccinated people has reached hundreds of millions, making it one of the most vaccinated vaccines in the world.
In previous clinical trials of tens of thousands of people, autoimmune hepatitis did not occur in people vaccinated with the new crown mRNA vaccine, so Pfizer and the FDA did not list autoimmune hepatitis as an adverse effect of the mRNA vaccine. However, with the mass vaccination of hundreds of millions of vaccines, the original potential adverse reactions are gradually becoming prominent.
Literature monitoring is an important complement to clinical trials and an important part of pharmacovigilance activities. Many adverse drug reactions, which were not found before marketing, were not first discovered by clinicians until they were widely used in the clinic after marketing. These suspected adverse reactions, reported in the form of academic papers, are comprehensively analyzed by regulatory agencies and pharmaceutical companies to confirm the causal relationship with drugs.
On 8 April, the European Medicines Agency's Pharmacovigilance Risk Assessment Committee published the results of its discussions on the above-mentioned German case, arguing that the available evidence is not sufficient to support a causal relationship between the COVID-19 mRNA vaccine and autoimmune hepatitis, that there is no need to update the vaccine's product information at this time, and that any new situation reports will continue to be closely monitored and appropriate measures taken if necessary.
The European Medicines Agency's Pharmacovigilance Risk Assessment Committee does not consider that the COVID-19 mRNA vaccine causes autoimmune hepatitis
Although regulators have not made prudent conclusions out of rigor, given that the new crown mRNA vaccine is the first marketed vaccine made by humans using mRNA, we must still be cautious and not take it lightly while boldly using it.
In addition, even if autoimmune hepatitis is an adverse reaction to the new crown mRNA vaccine, according to the reported cases, it is still very rare to speculate on its incidence, not to mention that the condition is not serious, although we need to treat it with caution, but we should not worry too much.
Since the epidemic continues to this day, there is no doubt about the effectiveness of the new crown vaccine, and the need for the new crown vaccine is also unquestionable. There are three types of domestic covid-19 vaccines available: inactivated vaccines, recombinant protein vaccines and adenovirus vector vaccines, and there is no mRNA vaccine. There are still 11.7% of the continent's population that has not yet been vaccinated[8], and refusing universal benefits due to rare risks is a form of folly for choking on food.
Therefore, the emergence of autoimmune hepatitis after the new crown mRNA vaccination is not necessarily a coincidence, but we do not have to worry too much about it to reject the vaccine.
The author | Chen Nencao
Source| Health Community - Clinical Frontline
Resources
[1]https://ourworldindata.org/covid-vaccinations?country=OWID_WRL
[2]https://cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/Pfizer-BioNTech.html
[3] Boettler T, Csernalabics B, Salié H, et al. SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis [published online ahead of print, 2022 Apr 21]. J Hepatol. 2022; S0168-8278(22)00234-3. doi:10.1016/j.jhep.2022.03.040
[4] Chinese Medical Association Hepatology Branch, Chinese Medical Association Gastroenterology Branch, Chinese Medical Association Infectious Diseases Branch. Consensus on the Diagnosis and Treatment of Autoimmune Hepatitis (2015) [J] . Chinese Journal of Infectious Diseases,2016,34 : 193-208. DOI:10.3760/cma.j.issn.1000-6680.2016.04.001
[5] Bril F, Al Diffalha S, Dean M, Fettig DM. Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: Causality or casualty?. J Hepatol. 2021;75(1):222-224. doi:10.1016/j.jhep.2021.04.003
[6] Tan CK, Wong YJ, Wang LM, Ang TL, Kumar R. Autoimmune hepatitis following COVID-19 vaccination: True causality or mere association?. J Hepatol. 2021;75(5):1250-1252. doi:10.1016/j.jhep.2021.06.009
[7] Camacho-Domínguez L, Rodríguez Y, Polo F, et al. COVID-19 vaccine and autoimmunity. A new case of autoimmune hepatitis and review of the literature. J Transl Autoimmun.2022;5:100140. doi:10.1016/j.jtauto.2022.100140[8]https://ourworldindata.org/covid-vaccinations?country=CHN