The Influence of Covid‐19‐Based mRNA Vaccines on Measures of Conduit Artery and Microvascular Endothelial Function

Abstract

With the emergence of severe acute respiratory syndrome 2 (SARS‐CoV‐2), leading to coronavirus disease 19 (COVID‐19), a new class of messenger RNA (mRNA) vaccines have been broadly used. These vaccines have been associated with inflammatory sides effects such as myo‐ and peri‐carditis. Despite the well‐known link between inflammation and endothelial dysfunction, it is unknown whether these vaccines may transiently impair endothelial function, and therefore increase cardiovascular risk. Aim: To evaluate the influence of COVID‐19‐based mRNA vaccines on macro‐ and micro‐vascular endothelial function in healthy adults. We hypothesized that macro‐ and micro‐vascular endothelial function would be reduced following vaccination.MethodsPrior to, and ~48 hrs following the second dose of COVID‐19‐based mRNA vaccines, brachial artery flow‐mediated dilation (FMD, macrovascular function), reactive hyperemia (microvascular function), and cutaneous intradermal microdialysis coupled with laser Doppler flowmetry (microvascular function) were measured in healthy young adults. For microdialysis, a standard local heating protocol (42⁰C) was utilized, followed by infusion of the Nitric Oxide Synthase inhibitor Nω‐Nitro‐L‐arginine methyl ester hydrochloride (L‐NAME, 15mM), and induction of maximum vasodilation (43⁰C+28mM Sodium Nitroprusside). Sites included: control (lactated Ringer’s), ascorbic acid (10 mM), l‐arginine (10 mM), and tetrahydrobiopterin (BH4,10 mM). C‐reactive protein (CRP), a marker of systemic inflammation, was measured from fasting serum samples at both time points.ResultsVaccination (mRNA‐1273, n=3 and BNT162b2, n=6, 5men/4women, 34±2yrs) induced an increase in CRP (pre: 0.2±0.1mg/dL vs. post: 2.1±0.5mg/dL, p=0.008, r‐statistic=‐0.89), but had no effect on FMD (pre: 3.6±0.9% vs. post: 4.6±1.1%, p=0.43, Cohen’s d=0.28) or reactive hyperemia (pre: 20178±3236 AU vs. post: 28426±4573 AU, p=0.14, Cohen’s d=0.55). There was no association between the change in FMD (r=‐0.07, p=0.87) or reactive hyperemia (r=‐0.48, p=0.19) and the change in CRP. Vaccination also had no effect on microvascular nitric oxide (NO)‐dependent dilation (pre: 77.0±2.5% vs post: 77.3±2.4%, p=0.91, ηp2=0.002), nor was there an effect of microdialysis treatment on NO‐dependent dilation (p=0.74, ηp2=0.05). Following vaccination, the difference in NO‐dependent dilation relative to control was unaffected by treatment (p=0.25, η2=0.11) with no difference in the effects of BH4 (6.3±4.9%), l‐arginine (8.3±5.2%), or ascorbic acid (‐2.6±4.2%, all p>0.05). The change in NO‐dependent dilation at the control site was not related to the change in CRP (r=0.32, p=0.40).ConclusionsThere was a significant inflammatory response to COVID‐19‐based mRNA vaccines ~48 hrs following the second vaccine dose. Despite this, macro‐ and micro‐vascular endothelial function and NO‐dependent dilation were preserved in healthy adults.