Reply to: “Comment on “Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: Causality or casualty?””

To the Editor:

We read with interest the comment by Capecchi et al. ¹ regarding our Letter to the Editor describing a case of autoimmune hepatitis (AIH) developing after COVID-19 vaccination.² We thank the authors for their interest in our manuscript and for their thoughtful insight, which complemented our report.

As we carefully expressed in our original letter, and Capecchi et al. further reinforced, a causal relationship between the vaccine and the development of AIH cannot be proven. Other factors, such as the postpartum status, could have acted as confounding factors. Another possibility is that the vaccine unmasked a process that was already developing. Yet, while we recognized that the temporal association could have been coincidental, we felt compelled to report this case for several reasons.

There is already significant evidence supporting a strong link between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the development of autoimmunity.³ Among 45 consecutive patients admitted with SARS-CoV-2 pneumonia, 35.6% were found to have positive antinuclear antibodies.⁴ As the spike protein believed to be responsible for autoimmunity is the same used in vaccines, there is physiological feasibility for an association between COVID-19 vaccines and autoimmune conditions. In support of this, cases of immune thrombocytopenia,⁵ acquired hemophilia A⁶ and other autoimmune processes have been reported days after COVID-19 vaccination. Unfortunately, the proportion of vaccine-related adverse events reported to the Vaccine Adverse Event Reporting System (VAERS) is likely low. Therefore, there is an urgent need to share potential adverse events to increase awareness among patients and physicians, and to encourage them to report them to the appropriate authorities. Only a large and comprehensive pharmacovigilance effort will help us answer the question as to whether these vaccines can induce autoimmunity or not.

Since the publication of our letter, we have been approached by at least 4 patients throughout United States via email claiming that they have been diagnosed with autoimmune hepatitis after COVID-19 vaccination. Moreover, a quick glimpse at the 2021 VAERS database (available online at https://vaers.hhs.gov/data/datasets.html) describes several cases consistent with acute liver injury and even an AIH flare. While we do not have any further information and we understand that these cases are only anecdotal at this time, it further strengthens the importance of sharing information and experiences, in order to advance our understanding of SARS-CoV-2 infection and develop better strategies to contain the virus.

Finally, and most importantly, while we ratify that it is important to further explore the potential link between COVID-19 vaccines and autoimmunity, this should not discourage patients and physicians from prescribing and/or receiving these vaccines. Even if confirmed in the future, cases of vaccine-induced autoimmunity appear to be uncommon as evidenced by only a handful of reports despite massive vaccination worldwide. Furthermore, it is likely that SARS-CoV-2 infection can trigger the same autoimmune processes as its vaccines do, leaving unvaccinated people not only at risk of developing the autoimmune process, but also the other complications associated with COVID-19.

Financial support

The authors received no financial support to produce this manuscript.

Authors’ contributions

Both authors contributed equally.

Conflict of interest

The authors declare no conflicts of interest that pertain to this work.

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Supplementary data

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