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Covid-19: Vaccine candidate may be more than 90% effective, interim results indicate

BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4347 (Published 09 November 2020) Cite this as: BMJ 2020;371:m4347

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Could COVID-19 mRNA vaccines cause autoimmune diseases?

Dear Editor,

Mass vaccination offers the best exit strategy from the COVID-19 pandemic. Pfizer/BioNTech's recent announcement, therefore, is encouraging.[1] Their vaccine candidate was more than 90% effective in preventing COVID-19 infection in participants without prior infection. Being an mRNA vaccine, mass production is cheaper and more straightforward than with other vaccine formulations.

mRNA vaccines effect coded protein production in the recipient’s body. In the case of COVID-19, inert spike (S) antigen proteins are produced. Normally, these enable SARS-CoV-2 coronavirus particles to enter host cells, but therapeutically, inoculation triggers humoral (antibody-mediated) acquired immunity.

Severe/fatal cases of COVID-19 are associated with immune hyperactivation and excessive cytokine release, leading to multiorgan failure. A broad range of mechanisms (with a final common pathway) appear to be involved. However, it has been suggested that molecular mimicry may contribute to this problem, with antibodies to SARS-CoV-2 spike glycoproteins cross-reacting with structurally similar host heptapeptide protein sequences (for example, in interleukin 7 and alveolar surfactant proteins), and raising an acute (auto)immune response against them.[2] Autoinflammatory dysregulation in genetically susceptible individuals, and other autoimmune mechanisms such as epitope spreading and bystander activation, might also contribute to acute but also chronic autoimmunity during and after COVID-19. [3]

In the understandable socioeconomic rush towards mass vaccination without longer-term safety testing, it would seem that an essential stage in any vaccine licensing process should involve careful analysis of the human proteome against vaccine peptide sequences. This should minimize the risks both of acute autoimmune reactions to inoculation and future chronic autoimmune pathology.

References
1. Mahane E. Covid-19: Vaccine candidate may be more than 90% effective, interim results indicate. BMJ 2020;371:m4347.
2. Ehrenfeld M, Tincani A, Andreoli L, et al. Covid-19 and autoimmunity. Autoimmun Rev 2020;19:102597.
3. Caso F, Costa L, Ruscitti P. Could Sars-coronavirus-2 trigger autoimmune and / or autoinflammatory mechanisms in genetically predisposed subjects? Autoimmun Rev 2020;19:102524.

Competing interests: No competing interests

16 November 2020
Stuart M White
Consultant Anaesthetist
Brighton and Sussex University Hospitals NHS Trust
Eastern Road, Brighton, East Sussex, BN2 5BE.