tetano
Editor, Senior Moderator
Med
. 2023 Apr 21;S2666-6340(23)00104-6.
doi: 10.1016/j.medj.2023.04.001. Online ahead of print. RNase2 is a possible trigger of acute-on-chronic inflammation leading to mRNA vaccine-associated cardiac complication
Eugenia Z Ong[SUP] 1 [/SUP], Clara W T Koh[SUP] 2 [/SUP], Danny J H Tng[SUP] 3 [/SUP], Justin S G Ooi[SUP] 2 [/SUP], Jia Xin Yee[SUP] 1 [/SUP], Valerie S Y Chew[SUP] 1 [/SUP], Yan Shan Leong[SUP] 1 [/SUP], Kurugulasigamoney Gunasegaran[SUP] 4 [/SUP], Chin Pin Yeo[SUP] 5 [/SUP], Lynette L E Oon[SUP] 5 [/SUP], Jean X Y Sim[SUP] 6 [/SUP], Kuan Rong Chan[SUP] 7 [/SUP], Jenny G Low[SUP] 8 [/SUP], Eng Eong Ooi[SUP] 9 [/SUP]
Affiliations
Background: Post-mRNA vaccination-associated cardiac complication is a rare but life-threatening adverse event. Its risk has been well balanced by the benefit of vaccination-induced protection against severe COVID-19. As the rate of severe COVID-19 has consequently declined, future booster vaccination to sustain immunity, especially against infection with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, may encounter benefit-risk ratios that are less favorable than at the start of the COVID-19 vaccination campaign. Understanding the pathogenesis of rare but severe vaccine-associated adverse events to minimize its risk is thus urgent.
Methods: Here, we report a serendipitous finding of a case of cardiac complication following a third shot of COVID-19 mRNA vaccine. As this case was enrolled in a cohort study, pre-vaccination and pre-symptomatic blood samples were available for genomic and multiplex cytokine analyses.
Findings: These analyses revealed the presence of subclinical chronic inflammation, with an elevated expression of RNASE2 at pre-booster baseline as a possible trigger of an acute-on-chronic inflammation that resulted in the cardiac complication. RNASE2 encodes for the ribonuclease RNase2, which cleaves RNA at the 3' side of uridine, which may thus remove the only Toll-like receptor (TLR)-avoidance safety feature of current mRNA vaccines.
Conclusions: These pre-booster and pre-symptomatic gene and cytokine expression data provide unique insights into the possible pathogenesis of vaccine-associated cardiac complication and suggest the incorporation of additional nucleoside modification for an added safety margin.
Funding: This work was funded by the NMRC Open Fund-Large Collaborative Grant on Integrated Innovations on Infectious Diseases (OFLCG19May-0034).
Keywords: COVID-19; RNASE2; Translation to patients; cardiac complication; mRNA vaccination; severe adverse event.
. 2023 Apr 21;S2666-6340(23)00104-6.
doi: 10.1016/j.medj.2023.04.001. Online ahead of print. RNase2 is a possible trigger of acute-on-chronic inflammation leading to mRNA vaccine-associated cardiac complication
Eugenia Z Ong[SUP] 1 [/SUP], Clara W T Koh[SUP] 2 [/SUP], Danny J H Tng[SUP] 3 [/SUP], Justin S G Ooi[SUP] 2 [/SUP], Jia Xin Yee[SUP] 1 [/SUP], Valerie S Y Chew[SUP] 1 [/SUP], Yan Shan Leong[SUP] 1 [/SUP], Kurugulasigamoney Gunasegaran[SUP] 4 [/SUP], Chin Pin Yeo[SUP] 5 [/SUP], Lynette L E Oon[SUP] 5 [/SUP], Jean X Y Sim[SUP] 6 [/SUP], Kuan Rong Chan[SUP] 7 [/SUP], Jenny G Low[SUP] 8 [/SUP], Eng Eong Ooi[SUP] 9 [/SUP]
Affiliations
- PMID: 37105176
- DOI: 10.1016/j.medj.2023.04.001
Background: Post-mRNA vaccination-associated cardiac complication is a rare but life-threatening adverse event. Its risk has been well balanced by the benefit of vaccination-induced protection against severe COVID-19. As the rate of severe COVID-19 has consequently declined, future booster vaccination to sustain immunity, especially against infection with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, may encounter benefit-risk ratios that are less favorable than at the start of the COVID-19 vaccination campaign. Understanding the pathogenesis of rare but severe vaccine-associated adverse events to minimize its risk is thus urgent.
Methods: Here, we report a serendipitous finding of a case of cardiac complication following a third shot of COVID-19 mRNA vaccine. As this case was enrolled in a cohort study, pre-vaccination and pre-symptomatic blood samples were available for genomic and multiplex cytokine analyses.
Findings: These analyses revealed the presence of subclinical chronic inflammation, with an elevated expression of RNASE2 at pre-booster baseline as a possible trigger of an acute-on-chronic inflammation that resulted in the cardiac complication. RNASE2 encodes for the ribonuclease RNase2, which cleaves RNA at the 3' side of uridine, which may thus remove the only Toll-like receptor (TLR)-avoidance safety feature of current mRNA vaccines.
Conclusions: These pre-booster and pre-symptomatic gene and cytokine expression data provide unique insights into the possible pathogenesis of vaccine-associated cardiac complication and suggest the incorporation of additional nucleoside modification for an added safety margin.
Funding: This work was funded by the NMRC Open Fund-Large Collaborative Grant on Integrated Innovations on Infectious Diseases (OFLCG19May-0034).
Keywords: COVID-19; RNASE2; Translation to patients; cardiac complication; mRNA vaccination; severe adverse event.