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Are reports of "hepatitis" really worth worrying about?
In recent days, "hepatitis" has become a hot word on the Internet, initially originating from the continuous emergence of children's unexplained hepatitis reports in many countries in Europe and the United States, and a recent study in Germany on "mRNA vaccine may cause autoimmune hepatitis" has been widely forwarded in major media and public accounts, and even some media have linked these two unrelated events to report. This has also made the people who are still in the midst of the continuous attack of the new crown pneumonia epidemic more panicked and uneasy. Whether the report of "hepatitis" is really worth worrying about, and whether the safety of mRNA vaccines should be questioned, we still need to look at it scientifically rationally.
In response to unexplained hepatitis in children in many countries in Europe and the United States, there have been claims on social media that the disease is related to the vaccination of the new crown. This claim has also been identified as nonsense by subsequent studies. According to the Health Safety Agency's "Investigation into Acute Hepatitis of Unknown Cause in Children in England" published on 25 April, none of the unexplained cases of hepatitis in children of unknown cause in the UK have been vaccinated against COVID-19 [1]. The Scottish Ministry of Health also announced on 19 April that hepatitis cases were not related to the COVID-19 vaccine, as it was also because sick children had not been vaccinated against COVID-19. And according to the data of the British Ministry of Health, 77% of the cases of adenovirus test positive, and acute hepatitis is not a common feature of children infected with new crown, which can be inferred that unexplained hepatitis in children is not related to new crown infection or new crown vaccine, and more likely to be liver damage caused by adenovirus.
On April 21, an article titled SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatites was published in the Journal of Hepatology, an international journal in the field of liver disease. Its research suggests that a joint Pfizer/BioNTech COVID-19 mRNA vaccine (BNT162b2) may trigger a rare type of T-cell-mediated autoimmune hepatitis.
However, a closer look at the article reveals that this is only a case report, and the authors found that the disease characteristics of the case are similar to those associated with natural COVID-19 infection, and it is not possible to determine whether it is a coincidence or causal relationship with vaccination [2]. With regard to autoimmune liver disease, there have been a small number of cases of vaccines widely used worldwide, such as mRNA vaccines, adenovirus vaccines, and inactivated vaccines [3-4]. However, in the cases reported so far, a causal relationship between immune liver disease and the COVID-19 vaccine has not been confirmed, and no severe cases of liver failure have been reported, with a good prognosis [2].
Autoimmune hepatitis (AIH), a very rare chronic progressive inflammatory disease of the liver mediated by an autoimmune response, is a type of autoimmune disease. The pathogenesis of autoimmune diseases is very complex, and a variety of factors, including viral infections, may be related to inducing autoimmune diseases. COVID-19 infection can trigger autoimmune diseases by triggering an organ-specific autoimmune response [5], and there have been cases of AUTOIM triggered by COVID-19 infection [6]. Experimental studies in vitro have shown that anti-S protein-specific antibodies can also bind to certain human tissue proteins, which may be responsible for autoimmune diseases triggered by covid-19 infection [7]. A recent large-scale study based on 1.1 million vaccinated people in Hong Kong shows that autoimmune diseases requiring hospitalization following mRNA and inactivated COVID-19 vaccines are very rare and have a similar incidence to those of unvaccinated populations [8].
Meanwhile, the European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) reviewed literature data, AIH cases reported to the EudraVigilance database, and further data provided by marketing authorization holders to conclude that there is currently no evidence to support a causal relationship between the mRNA COVID-19 vaccine and autoimmune hepatitis (AIH) and that product information for the vaccine does not need to be updated at this time [9].
The two mRNA vaccines currently on the market have been widely used worldwide, with billions of doses. From the large sample data released by various countries, mRNA vaccines have a good safety profile, and most of them are mild to moderate adverse reactions [10-11]. On March 7, 2022, the U.S. Centers for Disease Control and Prevention published data from a six-month U.S. safety study on mRNA vaccines at The Lancet-Infectious Diseases [10]. The study assessed adverse events for 298 million doses of the U.S. mRNA vaccine (BNT162b2 and mRNA-1273) administered in the United States during this period using data reported by both VAERS and v-safe surveillance systems between December 14, 2020 and June 14, 2021. The researchers concluded from the analysis that most adverse event reports were mild and short-lived. The results of the two surveillance systems in the 6 months prior to mRNA vaccination in the United States were consistent with premarket clinical trials and early postmarket reports. This reaffirms the good safety of mRNA vaccines.
At present, the domestic Omicron epidemic is at its peak, and the mainland Hong Kong region has just survived the impact of the fifth wave of the epidemic. The high mortality rate from the fifth wave in Hong Kong illustrates the need to improve population-wide immunization protection, particularly COVID-19 vaccination coverage for people at high risk for severe illness [12,13]. Summarizing the lessons learned from the fifth round of COVID-19 in Hong Kong, Professor Jin Dongyan of the University of Hong Kong's Li Ka Shing School of Medicine believes that people who have not completed full vaccination, especially the elderly, need to be vaccinated with more efficient COVID-19 vaccines [14]. Based on a large number of data on heterologous booster vaccination worldwide, such as 11.17 million people in Chile, the mRNA vaccine (BNT162b2) or adenovirus vaccine (AZD1222) after two doses of inactivated vaccine (CoronaVac) increased the effectiveness of infection prevention by approximately 20 to 30 percent compared with three doses of inactivated vaccine [15]. Hong Kong's latest immunization policy recommends that people over 60 years of age and people with weakened immune systems may choose the mRNA vaccine as a cross-functional booster for a fourth dose [16].
Vaccine safety has always been of great concern to national health departments and research institutions, and since the launch of the new crown vaccine, governments have been closely monitoring safety signals in vaccination. At present, the Omicron variant is spreading globally, vaccination is one of the effective ways to prevent the new crown virus infection, and a large number of studies have also proved that the third dose of the new crown vaccine still has a good protective effect on the Omicron variant. The third dose of COVID-19 vaccination in China is relatively lagging behind, and the vaccination rate of the elderly is still low, and the vaccination rate of intensive injections is even lower. The epidemic situation in Shenzhen and Shanghai also reflects the problem of "vaccination hesitation" in the elderly population, and the fear of adverse reactions after vaccination is one of the main reasons for the "vaccination hesitation" of the elderly. Therefore, it is particularly crucial to further promote vaccination work, especially the vaccination of key populations, and should not be exaggerated by case studies to affect the overall promotion of current COVID-19 vaccination.
bibliography:
1.Increase in hepatitis(liver inflammation)cases in children under investigation,https://www.gov.uk/government/news/increase-in-hepatitis-liver-inflammation-cases-in-children-under-investigation
3.Cao Z,et al. Letter to the editor:Exacerbation of autoimmune hepatitis after COVID-19 vaccination. Hepatology.2022;75(3):757-759.doi:10.1002/hep.32269
4.Rela M,et al. Auto-immune hepatitis following COVID vaccination. J Autoimmun.2021 Sep;123:102688.doi:10.1016/j.jaut.2021.102688.Epub 2021 Jul 3.
5.Ehrenfeld M,et al. Covid-19 and autoimmunity. Autoimmun Rev.2020;19(8):102597.doi:10.1016/j.autrev.2020.102597
6.Kaba am G,Wahlin S,Efe C.Autoimmune hepatitis triggered by COVID-19:A report of two cases. Liver Int.2021;41(10):2527-2528.doi:10.1111/liv.15044
7.Vojdani A,Kharrazian D.Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases. Clin Immunol 2020;217:108480
8.Li X,et al. Autoimmune conditions following mRNA(BNT162b2)and inactivated(CoronaVac)COVID-19 vaccination:A descriptive cohort study among 1.1 million vaccinated people in Hong Kong.J Autoimmun.2022;130:102830.doi:10.1016/j.jaut.2022.102830
9.Meeting highlights from the Pharmacovigilance Risk Assessment Committee(PRAC)4-7 April 2022，https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-4-7-april-2022
10.Rosenblum HG,et al. Safety of mRNA vaccines administered during the initial 6 months of the US COVID-19 vaccination programme:an observational study of reports to the Vaccine Adverse Event Reporting System and v-safe. Lancet Infect Dis.2022 Mar 7:S1473-3099(22)00054-8.doi:10.1016/S1473-3099(22)00054-8.Epub ahead of print
11.Klein N P.Surveillance for adverse events after COVID-19 mRNA vaccination[J]. JAMA,2021,326(14):1390-1399.
12.Smith DJ,Hakim AJ,Leung GM,et al. COVID-19 Mortality and Vaccine Coverage-Hong Kong Special Administrative Region,China,January 6,2022-March 21,2022.China CDC Wkly.2022;4(14):288-292.doi:10.46234/ccdcw2022.071
13.Cheung P-HH,Chan C-P,Jin D-Y. Lessons learned from the fifth wave of COVID-19 in Hong Kong in early 2022.Emerg Microbes Infect.2022;11(1):1072-1078.doi:10.1080/22221751.2022.2060137
14.n vaccinated people in Hong Kong.J Autoimmun.2022;130:102830.doi:10.1016/j.jaut.2022.102830
15.Jara A,Undurraga EA,et.al.Effectiveness of homologous and heterologous booster doses for an inactivated SARS-CoV-2 vaccine:a large-scale prospective cohort study. Lancet Glob Health.2022 Apr 22:S2214-109X(22)00112-7.doi:10.1016/S2214-109X(22)00112-7.
16. The Scientific Committee of the Centre for Health Protection (CHP) updates the Provisional Consensus Recommendation on COVID-19 Vaccination in Hong Kong, https://www.info.gov.hk/gia/general/202204/07/P2022040700248.htm
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