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Comment
. 2022 Oct;28(10):800-802.
doi: 10.1016/j.molmed.2022.07.008. Epub 2022 Sep 12.

COVID-19 mRNA vaccine-induced adverse effects: unwinding the unknowns

Ioannis P Trougakos  1 , Evangelos Terpos  2 , Harry Alexopoulos  3 , Marianna Politou  4 , Dimitrios Paraskevis  5 , Andreas Scorilas  6 , Efstathios Kastritis  2 , Evangelos Andreakos  7 , Meletios A Dimopoulos  2
Affiliations
Comment

COVID-19 mRNA vaccine-induced adverse effects: unwinding the unknowns

Ioannis P Trougakos et al. Trends Mol Med. 2022 Oct.
No abstract available

Keywords: COVID-19; SARS-CoV-2; adverse effect; immunity; mRNA vaccine.

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Figure 1
Figure 1
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection- and mRNA vaccine-induced immunity and the likely distribution of the related antigens. (A) The risk for severe coronavirus disease 2019 (COVID-19) increases significantly with age and pre-existing comorbidities, whereas healthy adults are largely spared from severe COVID-19. SARS-CoV-2 is a respiratory virus, and during asymptomatic infection or mild COVID-19 innate and adaptive immunity will efficiently contain SARS-CoV-2 in the respiratory system (RS), resulting in no systemic spread of replicating virus and/or related antigens. Viral antigen leakage in the circulation and/or viremia may occur during severe COVID-19, possibly correlating with ‘long COVID-19’. (B) Vaccination at the deltoid muscle triggers robust and durable anti-SARS-CoV-2 spike (S) protein systemic immune responses in the absence of disease; however, intramuscular vaccine administration may not optimally activate local mucosal responses, thus providing limited protection (compared with what would be desirable) at the main site of infection (i.e., the respiratory mucosa). Given that the mRNA-containing nanoparticles also localize in the liver (among other tissues), it is likely that the antigen(s) eventually enters the circulation (e.g., via the hepatic vein) and is distributed systemically. Both COVID-19- and mRNA vaccine-triggered immune responses are weaker in the elderly and in the presence of certain pre-existing comorbidities and/or medication (A and B, lower parts). Abbreviation: ACE2, angiotensin-converting enzyme 2.
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