Acute effects of COVID-19 vaccination on inflammatory, macrovasular and microvascular biomarkers

Purpose: To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Methods: Thirty-two participants (mean age 37±8 years, 20 men) that received the BNT162b2 mRNA COVID-19 vaccine were studied in 3 sessions in a sequence-randomized, sham-controlled, assessor-blinded, cross-over design. Primary outcome was endothelial function assessed by brachial artery flow-mediated dilatation (FMD), and secondary outcomes were aortic stiffness, evaluated with carotid-femoral pulse wave velocity (PWV), microvascular function that was estimated with hyperemic mean blood flow velocity (HMBFV) of the brachial artery, and inflammation measured by high-sensitivity C-reactive protein (hsCRP) and interleukins (hsIL-6 and hsIL-1b) in blood samples. The outcomes were assessed prior to, and at 8h, 24h post the 1st dose of vaccination, and 8h, 24h and 48h post the 2nd. Results: There was an increase in hsCRP that was apparent at 24h after both the 1st dose (−0.60 [95% Confidence intervals [CI]: −1.60 to −0.20], p=0.013) and the 2nd dose (max median difference at 48h −6.60 [95% CI: −9.80 to −3.40], p<0.001) compared to sham. Similarly, interleukins also increased. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p=0.037) at 24h post the 2nd dose (Figure). FMD values returned towards baseline at 48h. HMBFV remained unchanged during the 1st dose but at 48h post the 2nd dose was numerically lower than the sham procedure but the difference between the 2 sessions was not statistically significant (max mean difference at 48h 8.6 [95% CI: −0.6 to 17.8], p=0.067). Conclusions: Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose and a transient deterioration of endothelial function at 24h that returns towards baseline at 48h. These results confirm the short-term cardiovascular safety of the vaccine. Funding Acknowledgement: Type of funding sources: None.Figure 1

THE EFFECT OF COVID-19 VACCINE ON ARTERIAL FUNCTION

Objective: To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Design and method: Thirty-two participants (mean age 37 ± 8 years, 20 men) that received the BNT162b2 mRNA COVID-19 vaccine were studied in 3 sessions in a sequence-randomized, sham-controlled, assessor-blinded, cross-over design. The primary outcome was endothelial function assessed by brachial artery flow-mediated dilatation (FMD), and secondary outcomes were aortic stiffness, evaluated with carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx@75), and inflammation measured by high-sensitivity C-reactive protein (hsCRP) in blood samples. The outcomes were assessed prior to, and at 8 h, 24 h post the 1st dose of vaccination, and 8 h, 24 h, and 48 h post the 2nd. Results: There was an increase in hsCRP that was apparent at 24 h after both the 1st dose (-0.60 [95% Confidence intervals [CI]: -1.60 to -0.20], p = 0.013) and the 2nd dose (max median difference at 48 h -6.60 [95% CI: -9.80 to -3.40], p < 0.001) compared to sham. The vaccine did not change PWV or AIx@75. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p = 0.037) at 24 h post the 2nd dose. FMD values returned towards baseline at 48 h. Conclusions: Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose, and a transient deterioration of endothelial function at 24 h that returns towards baseline at 48 h. These results confirm the short-term cardiovascular safety of the vaccine.

Deformation analysis in post-hospitalised patients with moderate SARS-CoV-2 infection

Background: SARS-CoV-2 infection is associated with multiple cardiac manifestations (1,2). Global longitudinal strain (GLS) by speckle tracking echocardiography (STE) is a novel transthoracic echocardiography (TTE) measure of myocardial deformation, which could early recognize subclinical cardiac injury in COVID-19 patients (3,4). Purpose: We aimed to explore GLS profiles in post-hospitalized COVID-19 patients to identify features of eventual subclinical cardiac injury and to investigate the possible correlation with the severity of infection. Methods: We enrolled 33 patients (mean age 59.2 ± 13, 64% men) with positive SARS-CoV-2 RT-PCR, hospitalized for moderate COVID-19 disease, with no admission to intensive care unit. Patients were submitted to TTE 1-2 months after discharge. Images were anonymised and analysed offline by two accredited cardiologists. Clinical parameters and laboratory findings from hospitalization were also collected. Acute myocardial infarction and pulmonary embolism were exclusion criteria. Results: Mean duration of hospitalization was 12.9 ± 8.0 days. Study population had normal systolic function with a mean LV ejection fraction 58.6% (±3.6) while the majority of patients had relative low values of LV global longitudinal strain, mean 15.2% (±2.3). Arterial hypertension was present in 51.5% of patients and a history of previous myocardial infarction was referred in 6.1% of the population. Only 24.2% of patients had elevated troponin levels during the previous in-hospital period (mean maximal value of hs-troponin was 18.1 ±16.6 pg/mL) whereas 81.8% had abnormal D-Dimers values (mean 2424 μg /L, range ±2825) and 93.1% had high hs-CRP values (138.2 ±92.0 mg/L) . Duration of hospitalization had strong significant correlation with D-Dimers (rho: 0.708, p: <0.001) and hs CRP (rho:0383, p:0.028) and marginal association with troponin ( rho: 0.335, p:0.056). Moreover, global longitudinal strain showed significant association with duration of hospitalization (rho:-0.545, p: 0.007). Traditional systolic indices as LVEF and the various diastolic parameters showed no significant association with severity of disease reflected by the duration of hospitalization and the other clinical and laboratory biomarkers. Conclusion: Cardiac manifestations of SARS-CoV-2 infections could be present in mild to moderate disease and seems to associate with the severity of infection. The novel echocardiographic parameters such as GLS could add valuable information and identify possible subclinical cardiac injury often unrecognized by traditional TTE examination.