Time-related aortic inflammatory response, as assessed with 18F-FDG PET/CT, in patients hospitalized with severely or critical COVID-19

Aim: Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19. Method(s): Between November 2020 and May 2021, in this pilot, casecontrol study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59+/-12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring 18F-FDG uptake in PET/CT performed 20-120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR. Result(s): There was no significant difference in aortic 18F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40-1.57] vs. 1.43 [1.32-1.70], respectively, p=0.422 and IAS-TBR: 1.60 [1.50-1.67] vs. 1.50 [1.42-1.61], respectively, p=0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to 18F-FDG PET-CT scan (Spearman's rho=-0.528, p=0.017 and Spearman's rho=-0.480, p=0.032, respectively), Figure 1. Patients who were scanned less than or equal to 60 days from admission (n=11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42-1.60] vs. 1.40 [1.33-1.45], respectively, p=0.016 and IAS-TBR: 1.64 [1.51-1.74] vs. 1.52 [1.46-1.60], respectively, p=0.038). There was a significant difference in IAS-TBR between patients scanned <=60 days and controls (1.64 [1.51-1.74] vs. 1.50 [1.41-1.61], p=0.036), Figure 2. Conclusion(s): This is the first study suggesting that aortic inflammation, as assessed by 18F-FDG PET/CT imaging, is increased in the early post-COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.

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

CLINICAL PROFILE OF COVID-19 INFECTION AND IMMUNE RESPONSE AFTER 3AND6 MONTH VACCINATION AGAINST SARS-COV-2 IN ADULT PATIENTS WITH TRANSFUSION-DEPENDENT THALASSAEMIATHE EXPERIENCE OF A GREEK CENTER

Background: Patients with transfusion-dependent-thalassaemia (TDT) are considered as increased risk population for severe and/or morbid COVID-19 infection. Timely vaccination is the main preventive method for severe COVID-19. Aims: To provide an overview of the clinical profile and outcome of COVID-19 infection in patients with TDT as well as to study the immune response after 3 and 6 months after vaccination against COVID-19 in adult patients with transfusion-dependent thalassaemia. Methods: This analysis focused on the evaluation in TDT patients on the long-term immune response post vaccination and on the course of COVID-19 infection and its correlation with immunization status. Serum was collected at 4 pre-defined time points, namely, just before 1st dose (TP1), 7 weeks after the 1st dose (TP2), 3 months (TP3) and 6 months (TP4) after 2nd dose. Neutralizing antibodies (NAbs) against SARS-CoV-2 were measured using FDA-approved methods. According to manufacturer, the scale of NAbs titer is 0-100%, with ≥30% considered as positive and ≥50% as clinically relevant viral inhibition. Age-matched healthy volunteers (median age: 46 years, range: 24-64 years, 24 males / 53 females) who received mRNA vaccines served as the control group for NAbs evaluation. Results: 340 (170female/170male) TDT patients older than 18 years (mean 43.6±11.5 years) followed in a single unit were included in the analysis. 270 patients (79%) were vaccinated with 2 or 3 doses. Immune response to vaccination was evaluated in 90 patients (median age: 46 years, range: 19-63 years, 40 males / 50 females). NAbs were at the level of non-immunity in all the patients at baseline (TP1) (mean 16.57% ±11.85) and showed a significant increase after the second dose (TP2) mean 86.96%±12.95 (p<0.0001). At TP3 and TP4 Nabs showed a significant decrease but remained in protective levels for the majority of the patients (mean 88.75% ±9.7 and 74.64% ±17.2 respectively(p<0.0001). The kinetics of NAbs were similar to controls except for levels at TP4 (p=0.02) (Figure 1). Up to 10/FEB/2022, 43 TDT patients (median age 43.52 range 18.6-57.9 years) were diagnosed with COVID-19, with 1 of them being infected twice. Of them, 17 were unvaccinated, 18 had received 2 doses of vaccine, while 8 had received 3 doses of the vaccine. The incidence rate was 9.6% and 24.3% for vaccinated and unvaccinated patients, respectively. The severity of the COVID-19 for vaccinated and unvaccinated patients were as follows, respectively, ;Grade 1 (asymptomatic): 0 and 1, Grade 2 (mild symptoms, symptomatic therapy, no COVID19 specific therapy): 23 and 9, Grade 3 (mild symptoms, symptomatic therapy, with COVID19 specific therapy): 1 and 3, Grade 4 (moderate: pneumonia, thrombophlebitis, Hospitalization): 2 and 3, Grade 5 (Hospitalization requiring ICU, death): 0 and 1. Thrombotic event was documented in 1 patient. All patients except one from unvaccinated group are alive. Summary/Conclusion: Immune response to vaccination may wean faster in TDT patients. in Unvaccinated TDT patients were more likely to be infected and to develop more serious COVID-19 infection compared to vaccinated patients. (Figure Presented).

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.

Dobutamine stress echocardiography during covid-19 pandemic: impact on volume and positivity rates in a tertiary hospital

Introduction: The emergence of coronavirus 2019 infection (covid-19) was accompanied by severe social and economic restrictions and applied significant pressure to the healthcare systems. The first pandemic wave started in March to May 2020 and was characterized by the peak of confinement measures and lockdown application. The second wave started in September and peaked in November to December 2020 and was characterized by improved healthcare organization but significant burden for the hospitals and intensive care units. Dobutamine stress echocardiography (DSE) is used for evaluation of ischemia in patients with known or suspected coronary artery disease. Purpose: To compare DSE volume and positivity rates between 2019 and 2020 time periods in a department of a public tertiary hospital. Methods: We retrospectively analysed DSE studies performed in our department in 2020 including the peak of covid-19 restrictions and compared the data to the 2019. Results: Volume of DSE studies decreased from 1516 in 2019 to 996 in 2020 (-34.3%). The study volume reduction was greater in April (-93.7%) and May (-54.5%) when the covid-19 restrictions were at the peak. Great decreases were also recorded in November (-46.8%) and December (-53.5%) when the second wave of covid-19 disease emerged. Conversely, small increases were recorded in September (7.1%) and October (10.6%) (figure 1). Regarding positivity rates, a statistically non-significant increase was recorded (33.6% vs 34.2% in 2019 and 2020 respectively, p = 0.73). Interestingly a statistically significant increase in positivity levels was recorded during the period March to May 2020 compared to the same period of 2019 (44.7% vs 36.9%, p = 0.029). On the contrary, positivity rates were decreased at the period September to December (27.1% vs 34.2%, p = 0.019) (figure 2). Conclusions: Volume of DSE studies was significantly reduced in 2020 when compared to 2019 during respective peaks of the pandemic and the accompanying restriction measures. Positivity rates were higher during the first pandemic wave, possibly due to decreased hospital attendance of mildly symptomatic patients in combination with stricter admission criteria at the emergency department. Lower positivity rates during the second pandemic wave possibly reflect an adjustment of both healthcare systems and patients to the new conditions imposed by the covid-19 pandemic.

Alterations in lymphocyte subsets and monocytes in patients diagnosed with SARS-CoV-2 pneumonia: a mini review of the literature.

OBJECTIVE: Complete blood count parameters are frequently altered in COVID-19 patients. Leucopenia and lymphopenia are the most common findings. This is not specific to COVID-19 as similar alterations are found in various other viral infections. This work is intended to summarize the evidence regarding white blood cell and lymphocyte subset alterations in COVID-19 and their clinical implications. MATERIALS AND METHODS: A PubMed search was conducted to identify relevant original studies. Articles not available in English or referring exclusively to pediatric patients were excluded. The study was designed as a narrative review from its inception. RESULTS: Complete white blood cell number and lymphocytes may be reduced in COVID-19 patients. Circulating CD4+ cells (helper T lymphocytes), CD8+ cells (cytotoxic T lymphocytes), regulatory T cells and natural killer (NK) cells may be reduced, with a greater reduction observed in critically ill patients. CD4+ and regulatory cell deficiencies may contribute to the cytokine storm and subsequent tissue damage observed in severe COVID-19 infection. NK and CD8+ cell deficiency might delay infection clearance. These aberrations of cellular immunity may contribute significantly to the pathogenesis of the disease. Alterations observed in monocyte function can also be implicated as they are effector cells responsible for tissue damage and remodeling. B cell dysfunction and maturation abnormalities have also been reported, suggesting that the virus also impairs humoral immunity. CONCLUSIONS: Lymphocyte subset abnormalities may be useful prognostic biomarkers for COVID-19, with circulating CD8+ cell count being the most promising as a predictor of severe disease requiring mechanical ventilation and mortality.

Prevalence and significance of mediastinal lymphadenopathy in patients with Severe Acute Respiratory Syndrome Corona Virus-2 infection.

Severe Acute Respiratory Syndrome Corona Virus-2 is the causative factor of Coronavirus Disease 2019. Early in the pandemic, mediastinal lymphadenopathy was not considered to be a significant radiologic finding of the SARS-COV-2 disease. Nevertheless, most recent studies associate mediastinal lymphadenopathy with more severe COVID-19 disease and poorer patient outcomes.