Remote Management of Patients with Cardiac Implantable Electronic Devices during the COVID-19 Pandemic.

Remote monitoring (RM) is the newest function of cardiac implantable electronic devices (CIEDs). In our observational retrospective analysis, we aimed to assess whether telecardiology could be a safe alternative to routine outpatient examinations during the COVID-19 pandemic. The in- and outpatient visits, the number of acute cardiac decompensation episodes, the RM data from CIEDs, and general condition were examined via questionnaires (KCCQ, EQ-5D-5L). Regarding the enrolled 85 patients, the number of personal patient appearances was significantly lower in the year following the pandemic outbreak compared to the previous year (1.4 ± 1.4 and 1.9 ± 1.2, p = 0.0077). The number of acute decompensation events was five before and seven during lockdown (p = 0.6). Based on the RM data, there was no significant difference in heart failure (HF) markers (all related p > 0.05); only patient activity increased after restrictions were lifted compared to that before the lockdown (p = 0.03). During restrictions, patients reported increased anxiety and depression compared to their previous state (p < 0.001). There was no subjective change in the perception of HF symptoms (p = 0.7). Based on the subjective perception and CIED data, the quality of life of patients with CIED did not deteriorate during the pandemic, but their anxiety and depression intensified. Telecardiology may be a safe alternative to routine inpatient examination.

Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions to PEG-containing Covid-19 vaccines: Evidence for immunogenicity of PEG.

A small fraction of recipients who receive polyethylene-glycol (PEG)-containing COVID-19 mRNA-LNP vaccines (Comirnaty and Spikevax) develop hypersensitivity reactions (HSRs) or anaphylaxis. A causal role of anti-PEG antibodies (Abs) has been proposed, but not yet been proven in humans.We used ELISA for serial measurements of SARS-CoV-2 neutralizing Ab (anti-S) and anti-PEG IgG/IgM Ab levels before and after the first and subsequent booster vaccinations with mRNA-LNP vaccines in a total of 291 blood donors. The HSRs in 15 subjects were graded and correlated with anti-PEG IgG/IgM, just as the anti-S and anti-PEG Ab levels with each other. The impacts of gender, allergy, mastocytosis and use of cosmetics were also analyzed. Serial testing of two or more plasma samples showed substantial individual variation of anti-S Ab levels after repeated vaccinations, just as the levels of anti-PEG IgG and IgM, which were over baseline in 98-99 % of unvaccinated individuals. About 3-4 % of subjects in the strongly left-skewed distribution had 15-45-fold higher values than the median, referred to as anti-PEG Ab supercarriers. Both vaccines caused significant rises of anti-PEG IgG/IgM with >10-fold rises in about âˆ¼10 % of Comirnaty, and all Spikevax recipients. The anti-PEG IgG and/or IgM levels in the 15 vaccine reactors (3 anaphylaxis) were significantly higher compared to nonreactors. Serial testing of plasma showed significant correlation between the booster injection-induced rises of anti-S and anti-PEG IgGs, suggesting coupled anti-S and anti-PEG immunogenicity.Conclusions: The small percentage of people who have extremelevels of anti-PEG Ab in their blood may be at increased risk for HSRs/anaphylaxis to PEGylated vaccines and other PEGylated injectables. This risk might be further increased by the anti-PEG immunogenicity of these vaccines. Screening for anti-PEG Ab "supercarriers" may help predicting reactors and thus preventing these adverse phenomena.

Factors influencing the SARS-CoV-2 infection and vaccination induced immune response in rheumatoid arthritis.

Background: To investigate the factors that have significant impact on the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection and vaccination induced immune response in rheumatoid arthritis (RA). Methods: Serological response was measured by quantifying anti-SARS-CoV-2 specific antibodies, while the cell-mediated response was measured by a whole-blood test quantifying the interferon (IFN)-γ response to different SARS-CoV-2-specific domains. Results: We prospectively enrolled 109 RA patients and 43 healthy controls. The median time (IQR) between the confirmed infection or the last vaccination dose and the day when samples were taken ("sampling interval") was 3.67 (2.03, 5.50) months in the RA group. Anti-Spike (anti-S) specific antibodies were detected in 94% of RA patients. Among the investigated patient related variables, age (p<0.004), sampling interval (p<0.001), the brand of the vaccine (p<0.001) and targeted RA therapy (TNF-inhibitor, IL-6 inhibitor, anti-CD20 therapy) had significant effect on the anti-S levels. After covariate adjustment TNF-inhibitor therapy decreased the anti-S antibody concentrations by 80% (p<0.001). The same figures for IL-6 inhibitor and anti-CD20 therapy were 74% (p=0.049) and 97% (p=0.002), respectively. Compared to subjects who were infected but were not vaccinated, the RNA COVID-19 vaccines increased the anti-S antibody levels to 71.1 (mRNA-1273) and 36.0 (BNT162b2) fold (p<0.001). The corresponding figure for the ChAdOx1s vaccine is 18.1(p=0.037). Anti-CCP (anti-cyclic citrullinated peptides) positive patients had 6.28 times (p= 0.00165) higher anti-S levels, than the anti-CCP negative patients. Positive T-cell response was observed in 87% of the healthy volunteer group and in 52% of the RA patient group. Following vaccination or infection it declined significantly (p= 0.044) but more slowly than that of anti-S titer (6%/month versus 25%). Specific T-cell responses were decreased by 65% in patients treated with anti-CD20 therapy (p=0.055). Conclusion: Our study showed that the SARS-CoV-2-specific antibody levels were substantially reduced in RA patients treated with TNF-α-inhibitors (N=51) and IL-6-inhibitor (N=15). In addition, anti-CD20 therapy (N=4) inhibited both SARS-CoV-2-induced humoral and cellular immune responses. Furthermore, the magnitude of humoral and cellular immune response was dependent on the age and decreased over time. The RNA vaccines and ChAdOx1s vaccine effectively increased the level of anti-S antibodies.

Potassium reduction with sodium zirconium cyclosilicate in patients with heart failure.

AIMS: Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin-angiotensin-aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non-absorbed intestinal potassium binder proven to lower serum potassium concentrations. METHODS AND RESULTS: PRIORITIZE-HF was an international, multicentre, parallel-group, randomized, double-blind, placebo-controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID-19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. CONCLUSIONS: PRIORITIZE-HF was terminated prematurely due to COVID-19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium-reducing agent SZC compared with placebo.

Radiomorphological signs and clinical severity of SARS-CoV-2 lineage B.1.1.7.

Objective: We aimed to assess the differences in the severity and chest-CT radiomorphological signs of SARS-CoV-2 B.1.1.7 and non-B.1.1.7 variants. Methods: We collected clinical data of consecutive patients with laboratory-confirmed COVID-19 and chest-CT imaging who were admitted to the Emergency Department between September 1- November 13, 2020 (non-B.1.1.7 cases) and March 1-March 18, 2021 (B.1.1.7 cases). We also examined the differences in the severity and radiomorphological features associated with COVID-19 pneumonia. Total pneumonia burden (%), mean attenuation of ground-glass opacities and consolidation were quantified using deep-learning research software. Results: The final population comprised 500 B.1.1.7 and 500 non-B.1.1.7 cases. Patients with B.1.1.7 infection were younger (58.5 ± 15.6 vs 64.8 ± 17.3; p < .001) and had less comorbidities. Total pneumonia burden was higher in the B.1.1.7 patient group (16.1% [interquartile range (IQR):6.0-34.2%] vs 6.6% [IQR:1.2-18.3%]; p < .001). In the age-specific analysis, in patients <60 years B.1.1.7 pneumonia had increased consolidation burden (0.1% [IQR:0.0-0.7%] vs 0.1% [IQR:0.0-0.2%]; p < .001), and severe COVID-19 was more prevalent (11.5% vs 4.9%; p = .032). Mortality rate was similar in all age groups. Conclusion: Despite B.1.1.7 patients were younger and had fewer comorbidities, they experienced more severe disease than non-B.1.1.7 patients, however, the risk of death was the same between the two groups. Advances in knowledge: Our study provides data on deep-learning based quantitative lung lesion burden and clinical outcomes of patients infected by B.1.1.7 VOC. Our findings might serve as a model for later investigations, as new variants are emerging across the globe.

Short and mid-term characteristics of COVID-19 disease course in athletes: A high-volume, single-center study.

INTRODUCTION: At the pandemic's beginning, significant concern has risen about the prevalence of myocardial involvement after SARS-CoV-2 infection. We assessed the cardiovascular burden of SARS-CoV-2 in a large cohort of athletes and identified factors that might affect the disease course. We included 633 athletes in our study on whom we performed extensive cardiology examinations after recovering from SARS-CoV-2 infection. More than half of the athletes (n = 322) returned for a follow-up examination median of 107 days after the commencement of their infection. RESULTS: Troponin T positivity was as low as 1.4% of the athletes, where the subsequently performed examinations did not show definitive, ongoing myocardial injury. Altogether, 31% of the athletes' rapid training rebuild was hindered by persistent or reoccurring symptoms. Female athletes reported a higher prevalence of return to play (RTP) symptoms than their male counterparts (34% vs. 19%, p = 0.005). The development of long COVID symptoms was independently predicted by increasing age and acute symptoms' severity in a multiple regression model (AUC 0.75, CI 0.685-0.801). Athletes presenting with either or both cough and ferritin levels higher than >150 µg/L had a 4.1x (CI 1.78-9.6, p = 0.001) higher odds ratio of developing persistent symptoms. CONCLUSION: While SARS-CoV-2 rarely affects the myocardium in athletes, about one in three of them experience symptoms beyond the acute phase. Identifying those athletes with a predisposition to developing long-standing symptoms may aid clinicians and trainers in finding the optimal return-to-play timing and training load rebuild pace.

The diagnostic value of rapid anti IgM and IgG detecting tests in the identification of patients with SARS CoV-2 virus infection / [A specifikus IgM- és IgG-antitesteket detektáló gyorstesztek értéke a SARS CoV-2 vírusfertozés kimutatásában (A COVID-19-pandémia orvosszakmai kérdései)]

Introduction: At the end of March, 2020, rapid tests detecting the presence of antiviral IgM and IgG antibodies against SARS-CoV-2 virus were introduced in Hungary for the identification of SARS-CoV-2 infection (COVID-19 disease). Aim: We evaluated two rapid tests (Anhui and Clungene) in comparison with those of real-time PCR tests considered as the gold standard in the detection of infection. Method: Between 16, March and 14, April, 2020, we performed rapid IgM and IgG detecting tests without PCR; PCR without rapid tests; and PCR WITH rapid tests in 4140, 3210 and 1654 patients, respectively. (Out of these 1654 patients, Anhui and Clungene tests were used for testing in 625 and 1029 patients, respectively.) Patients were considered as positive in PCR and rapid tests when PCR positivity and IgM or IgG positivity occurred at any time, respectively. (Note: Clungene test is also marketed as 'Lungene'.) Results: The prevalence of PCR positivity in 4864 patients tested with PCR was 6.3%. The sensitivity and specificity of Anhui and Clungene tests were 33.3% and 72.85%, and 35.48% and 85.02%, respectively. At 6% PCR positivity, the positive and negative predictive values of Anhui and Clungene were 7.28%, 94.48%, 13.13%, and 95.38%, respectively. Conclusion: The low positive predictive values indicate that Anhui and Clungene rapid tests detecting the presence of anti-IgM and anti-IgG against SARS-CoV-2 virus infection are not suitable for screening SARS-CoV-2 vírus infection in the general population. These results strongly support that Anhui and Clungene rapid tests detecting IgM and IgG antibodies against SARS-CoV-2 virus should not be used in the differential diagnosis of infection. Orv Hetil. 2020; 161(20): 807-812.

Impact of a Targeted Project for Shortening of Imaging Diagnostic Waiting Time in Patients with Suspected Oncological Diseases in Hungary.

Background and Objectives: Medical imaging is a key element in the clinical workup of patients with suspected oncological disease. In Hungary, due to the high number of patients, waiting lists for Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) were created some years ago. The Municipality of Budapest and Semmelweis University signed a cooperation agreement with an extra budget in 2020 (HBP: Healthy Budapest Program) to reduce the waiting lists for these patients. The aim of our study was to analyze the impact of the first experiences with the HBP. Material and Methods: The study database included all the CT/MRI examinations conducted at Semmelweis University with a referral diagnosis of suspected oncological disease within the first 13 months of the HBP (6804 cases). In our retrospective, two-armed, comparative clinical study, different components of the waiting times in the oncology diagnostics pathway were analyzed. Using propensity score matching, we compared the data of the HBP-funded patients (n = 450) to those of the patients with regular care provided by the National Health Insurance Fund (NHIF) (n = 450). Results: In the HBP-funded vs. the NHIF-funded patients, the time interval from the first suspicion of oncological disease to the request for imaging examinations was on average 15.2 days shorter (16.1 vs. 31.3 days), and the mean waiting time for the CT/MRI examination was reduced by 13.0 days (4.2 vs. 17.2 days, respectively). In addition, the imaging medical records were prepared on average 1.7 days faster for the HBP-funded patients than for the NHIF-funded patients (3.4 vs. 5.1 days, respectively). No further shortening of the different time intervals during the subsequent oncology diagnostic pathway (histological investigation and multidisciplinary team decision) or in the starting of specific oncological therapy (surgery, irradiation, and chemotherapy) was observed in the HBP-funded vs. the NHIF-funded patients. We identified a moderately strong negative correlation (r = -0.5736, p = 0.0350) between the CT/MR scans requested and the active COVID-19 case rates during the pandemic waves. Conclusion: The waiting lists for diagnostic CT/MR imaging can be effectively shortened with a targeted project, but a more comprehensive intervention is needed to shorten the time from the radiological diagnosis, through the decisions of the oncoteam, to the start of the oncological treatment.

Coronary CTA Amidst the COVID-19 Pandemic: A Quicker Examination Protocol with Preserved Image Quality Using a Dedicated Cardiac Scanner.

There has been an ongoing debate on the means to minimize the time patients spend at health care providers during the COVID-19 pandemic. We propose a strategy relying solely on intravenous (i.v.) beta-blocker administration for heart-rate (HR) control prior to coronary CT angiography (CCTA). We aimed to assess a potential difference in CCTA image quality (IQ) after implementation of a modified strategy compared to our standard protocol of oral premedication during the first wave of COVID-19. We analyzed CCTA examinations conducted one year before (n = 1511) and after (n = 1064) implementation of this new regime. Examinations were performed both on our 256-slice multidetector CT (MDCT) and dedicated cardiac CT (DCCT) scanners. We used a four-point Likert scale (excellent/good/moderate/non-diagnostic) for IQ assessment of the coronaries. We detected a significant increase in mean HR during examinations on both CT scanners (MDCT: 62.4 ± 10.0 vs. 65.3 ± 9.7, p < 0.001; DCCT: 61.7 ± 15.2 vs. 65.0 ± 10.7, p < 0.001). The rate of moderate/non-diagnostic IQ significantly increased on the MDCT (192/1005, 19.1% vs. 144/466, 30.9%, p < 0.001), while this ratio did not change significantly on the DCCT (62/506, 12.3% vs. 84/598, 14.0%, p = 0.38). The improved temporal resolution of DCCT allows the stand-alone use of i.v. premedication with preserved IQ; hence, the duration of visits can be shortened.

Zymosan Particle-Induced Hemodynamic, Cytokine and Blood Cell Changes in Pigs: An Innate Immune Stimulation Model with Relevance to Cytokine Storm Syndrome and Severe COVID-19.

Hemodynamic disturbance, a rise in neutrophil-to-lymphocyte ratio (NLR) and release of inflammatory cytokines into blood, is a bad prognostic indicator in severe COVID-19 and other diseases involving cytokine storm syndrome (CSS). The purpose of this study was to explore if zymosan, a known stimulator of the innate immune system, could reproduce these changes in pigs. Pigs were instrumented for hemodynamic analysis and, after i.v. administration of zymosan, serial blood samples were taken to measure blood cell changes, cytokine gene transcription in PBMC and blood levels of inflammatory cytokines, using qPCR and ELISA. Zymosan bolus (0.1 mg/kg) elicited transient hemodynamic disturbance within minutes without detectable cytokine or blood cell changes. In contrast, infusion of 1 mg/kg zymosan triggered maximal pulmonary hypertension with tachycardia, lasting for 30 min. This was followed by a transient granulopenia and then, up to 6 h, major granulocytosis, resulting in a 3-4-fold increase in NLR. These changes were paralleled by massive transcription and/or rise in IL-6, TNF-alpha, CCL-2, CXCL-10, and IL-1RA in blood. There was significant correlation between lymphopenia and IL-6 gene expression. We conclude that the presented model may enable mechanistic studies on late-stage COVID-19 and CSS, as well as streamlined drug testing against these conditions.

Cardiopulmonary examinations of athletes returning to high-intensity sport activity following SARS-CoV-2 infection.

After SARS-CoV-2 infection, strict recommendations for return-to-sport were published. However, data are insufficient about the long-term effects on athletic performance. After suffering SARS-CoV-2 infection, and returning to maximal-intensity trainings, control examinations were performed with vita-maxima cardiopulmonary exercise testing (CPET). From various sports, 165 asymptomatic elite athletes (male: 122, age: 20y (IQR: 17-24y), training:16 h/w (IQR: 12-20 h/w), follow-up:93.5 days (IQR: 66.8-130.0 days) were examined. During CPET examinations, athletes achieved 94.7 ± 4.3% of maximal heart rate, 50.9 ± 6.0 mL/kg/min maximal oxygen uptake (V̇O2max), and 143.7 ± 30.4L/min maximal ventilation. Exercise induced arrhythmias (n = 7), significant horizontal/descending ST-depression (n = 3), ischemic heart disease (n = 1), hypertension (n = 7), slightly elevated pulmonary pressure (n = 2), and training-related hs-Troponin-T increase (n = 1) were revealed. Self-controlled CPET comparisons were performed in 62 athletes: due to intensive re-building training, exercise time, V̇O2max and ventilation increased compared to pre-COVID-19 results. However, exercise capacity decreased in 6 athletes. Further 18 athletes with ongoing minor long post-COVID symptoms, pathological ECG (ischemic ST-T changes, and arrhythmias) or laboratory findings (hsTroponin-T elevation) were controlled. Previous SARS-CoV-2-related myocarditis (n = 1), ischaemic heart disease (n = 1), anomalous coronary artery origin (n = 1), significant ventricular (n = 2) or atrial (n = 1) arrhythmias were diagnosed. Three months after SARS-CoV-2 infection, most of the athletes had satisfactory fitness levels. Some cases with SARS-CoV-2 related or not related pathologies requiring further examinations, treatment, or follow-up were revealed.

Swimming competitions in the era of COVID-19: Lessons from successfully hosting the International Swimming League.

Background: Organization of mass sport events in the COVID-19 era is utterly complicated. Containments measures, required to avoid a virus outbreak, force athletes to compete under circumstances they never experienced before, most likely having a deleterious effect on their performance. Purpose: We aimed to design a so-called athlete-friendly bubble system for the International Swimming League 2020 event, which is strict enough to avoid a COVID-19 outbreak, but still provides a supportive environment for the athletes. Methods: To avoid the feeling of imprisonment, athletes were permitted to spend a certain amount of time in the parks surrounding the hotels. Such alleviations were possible to apply with strict adherence to the hygienic and social distancing protocols and regular COVID-19 testing. Evaluation of every COVID-19 positive case was key, and if prolonged PCR positivity or false positive PCR result was identified, the unnecessary quarantine was planned to be lifted. Return to play protocol (RTP) was planned, in case of a COVID-19 infection of an athlete inside the bubble. To test, if the athlete-friendly system provided a supportive environment, we evaluated athlete performance. Results: 11,480 PCR tests were performed for 1,421 individuals. 63 COVID-19 positive cases were detected, of which 5 turned out to be clinically insignificant, either because of prolonged PCR positivity or because of a false positive result. 93.1% of the positive cases were detected in the local crew, while no athlete got infected inside the bubble, as the two infected athletes were tested positive upon arrival. RTP was provided for two athletes. 85% of the athletes showed improvement during the bubble and 8 world records were broken. Conclusion: The applied protocol proved to be effective, as no athlete got infected inside the bubble, moreover, the athlete-friendly system supported the athletes to improve their performance.

Radiomorphological signs and clinical severity of SARS-CoV-2 lineage B.1.1.7

Objective: We aimed to assess the differences in the severity and chest-CT radiomorphological signs of SARS-CoV-2 B.1.1.7 and non-B.1.1.7 variants. Methods: We collected clinical data of consecutive patients with laboratory-confirmed COVID-19 and chest-CT imaging who were admitted to the Emergency Department between September 1– November 13, 2020 (non-B.1.1.7 cases) and March 1–March 18, 2021 (B.1.1.7 cases). We also examined the differences in the severity and radiomorphological features associated with COVID-19 pneumonia. Total pneumonia burden (%), mean attenuation of ground-glass opacities and consolidation were quantified using deep-learning research software. Results: The final population comprised 500 B.1.1.7 and 500 non-B.1.1.7 cases. Patients with B.1.1.7 infection were younger (58.5 ± 15.6 vs 64.8 ± 17.3;p < .001) and had less comorbidities. Total pneumonia burden was higher in the B.1.1.7 patient group (16.1% [interquartile range (IQR):6.0–34.2%] vs 6.6% [IQR:1.2–18.3%];p < .001). In the age-specific analysis, in patients <60 years B.1.1.7 pneumonia had increased consolidation burden (0.1% [IQR:0.0–0.7%] vs 0.1% [IQR:0.0–0.2%];p < .001), and severe COVID-19 was more prevalent (11.5% vs  4.9%;p = .032). Mortality rate was similar in all age groups. Conclusion: Despite B.1.1.7 patients were younger and had fewer comorbidities, they experienced more severe disease than non-B.1.1.7 patients, however, the risk of death was the same between the two groups. Advances in knowledge: Our study provides data on deep-learning based quantitative lung lesion burden and clinical outcomes of patients infected by B.1.1.7 VOC. Our findings might serve as a model for later investigations, as new variants are emerging across the globe.

The Added Value of Atrial Strain Assessment in Clinical Practice.

Speckle tracking echocardiography has emerged as a sensitive tool to analyze myocardial function with improved diagnostic accuracy and prognostic value. Left atrial strain assessment has become a novel imaging method in cardiology with superior prognostic value compared to conventional left atrial volume indices. Left atrial function is divided into three phases, reservoir function being the most important. This review summarizes the added value of speckle tracking echocardiography derived left atrial strain assessment in clinical practice. Recently published data suggest the prognostic value of left atrial reservoir function in heart failure, atrial fibrillation, stroke and valvular heart disease. Furthermore, left atrial reservoir strain proved to be a predictor of cardiovascular morbidity and mortality in the general population. Thus, routine assessment of left atrial function can be an optimal strategy to improve cardiovascular risk prediction and supplement the current risk prediction models.

Factors influencing the SARS-CoV-2 infection and vaccination induced immune response in rheumatoid arthritis

Background To investigate the factors that have significant impact on the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection and vaccination induced immune response in rheumatoid arthritis (RA). Methods Serological response was measured by quantifying anti-SARS-CoV-2 specific antibodies, while the cell-mediated response was measured by a whole-blood test quantifying the interferon (IFN)-γ response to different SARS-CoV-2-specific domains. Results We prospectively enrolled 109 RA patients and 43 healthy controls. The median time (IQR) between the confirmed infection or the last vaccination dose and the day when samples were taken (“sampling interval”) was 3.67 (2.03, 5.50) months in the RA group. Anti-Spike (anti-S) specific antibodies were detected in 94% of RA patients. Among the investigated patient related variables, age (p<0.004), sampling interval (p<0.001), the brand of the vaccine (p<0.001) and targeted RA therapy (TNF-inhibitor, IL-6 inhibitor, anti-CD20 therapy) had significant effect on the anti-S levels. After covariate adjustment TNF-inhibitor therapy decreased the anti-S antibody concentrations by 80% (p<0.001). The same figures for IL-6 inhibitor and anti-CD20 therapy were 74% (p=0.049) and 97% (p=0.002), respectively. Compared to subjects who were infected but were not vaccinated, the RNA COVID-19 vaccines increased the anti-S antibody levels to 71.1 (mRNA-1273) and 36.0 (BNT162b2) fold (p<0.001). The corresponding figure for the ChAdOx1s vaccine is 18.1(p=0.037). Anti-CCP (anti-cyclic citrullinated peptides) positive patients had 6.28 times (p= 0.00165) higher anti-S levels, than the anti-CCP negative patients. Positive T-cell response was observed in 87% of the healthy volunteer group and in 52% of the RA patient group. Following vaccination or infection it declined significantly (p= 0.044) but more slowly than that of anti-S titer (6%/month versus 25%). Specific T-cell responses were decreased by 65% in patients treated with anti-CD20 therapy (p=0.055). Conclusion Our study showed that the SARS-CoV-2-specific antibody levels were substantially reduced in RA patients treated with TNF-α-inhibitors (N=51) and IL-6-inhibitor (N=15). In addition, anti-CD20 therapy (N=4) inhibited both SARS-CoV-2-induced humoral and cellular immune responses. Furthermore, the magnitude of humoral and cellular immune response was dependent on the age and decreased over time. The RNA vaccines and ChAdOx1s vaccine effectively increased the level of anti-S antibodies.

A Case Series of SARS-CoV-2 Reinfection in Elite Athletes.

OBJECTIVES: The actual frequency and the risk factors of SARS-CoV-2 reinfection is still a matter of intense scientific discussion. In this case series, we report three elite athletes who underwent COVID-19 reinfection with a short time frame. CASE PRESENTATIONS: As a part of contact tracing, three speed skaters (22-, 24-, and 29-year-old males) were found to be SARS-CoV-2 positive by polymerase chain reaction (PCR) tests. Later on, only one of the athletes experienced mild symptoms, such as fatigue, loss of smell and taste and subfebrility, while the other two athletes were asymptomatic. Following the quarantine period, detailed return-to-play examinations, including laboratory testing, ECG, 24-h Holter monitoring, transthoracic echocardiography and cardiac magnetic resonance imaging, revealed no apparent abnormality; therefore, the athletes restarted training. After a median of 74 days, all three athletes presented with typical symptoms of COVID-19, such as fever, marked fatigue and headache. SARS-CoV-2 PCR tests were performed again, showing recurrent positivity. Repeated return-to-play assessments were initiated, finding no relevant abnormality. Athletes were also tested for SARS-CoV-2 anti-nucleoprotein antibody titers, showing only modest increases following the second infection. CONCLUSIONS: We report a small cluster of elite athletes who underwent a PCR-proven SARS-CoV-2 reinfection. According to these findings, athletes may be considered as a high-risk group in terms of recurrent COVID-19.

Dutogliptin in Combination with Filgrastim in Early Recovery Post-Myocardial Infarction-The REC-DUT-002 Trial.

Patients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models. The REC-DUT-002 trial was a phase 2, multicenter, double-blind placebo-controlled trial which explored the safety, tolerability, and efficacy of dutogliptin and filgrastim in patients with ST-elevation Myocardial Infarction (STEMI). Patients (n = 47, 56.1 ± 10.7 years, 29% female) with STEMI, reduced left ventricular ejection fraction (EF ≤ 45%) and successful revascularization following primary PCI were randomized to receive either study treatment or matching placebo. Cardiac magnetic resonance imaging (cMRI) was performed within 72 h post-PCI and repeated after 3 months. The study was closed out early due to the SARS-CoV-2 pandemic. There was no statistically significant difference between the groups with respect to serious adverse events (SAE). Predefined mean changes within cMRI-derived functional and structural parameters from baseline to 90 days did not differ between placebo and treatment (left ventricular end-diastolic volume: +13.7 mL vs. +15.7 mL; LV-EF: +5.7% vs. +5.9%). Improvement in cardiac tissue health over time was noted in both groups: full-width at half-maximum late gadolinium enhancement (FWHM LGE) mass (placebo: -12.7 g, treatment: -19.9 g; p = 0.23). Concomitant treatment was well tolerated, and no safety issues were detected. Based on the results, the FDA and EMA have already approved an adequately powered large outcome trial.

The effect of COVID-19 pandemic on myocardial infarction care and on its prognosis - Experience at a high volume Hungarian cardiovascular center.

Introduction: The COVID-19 pandemic has impacted many aspects of acute myocardial infarction. Based on literature data, the prognosis of COVID+, STEMI patients is significantly worse than that of COVID- STEMI patients. On the other hand, physicians report fewer acute coronary syndrome (ACS) patients presenting to hospitals in countries severely affected by the pandemic. It is concerning that patients with life-threatening illness can suffer more complications or die due to their myocardial infarction. We aimed to investigate the changes in myocardial infarction care in the country's biggest PCI-center and to compare total 30-day mortality in COVID+ and COVID-patients with acute myocardial infarction treated at the Semmelweis University Heart and Vascular Center, and to investigate risk factors and complications in these two groups. Methods: Between 8 October 2020 and 30 April 2021, 43 COVID+, in 2018-2019, 397 COVID-patients with acute myocardial infarction were admitted. Total admission rates pre- and during the pandemic were compared. Results: Within 30 days, 8 of 43 patients in the COVID+ group (18.60%), and 40 of the 397 patients in the control group (10.07%) died (P = 0.01). Regarding the comorbidities, more than half of COVID+ patients had a significantly reduced ejection fraction (EF≤ 40%), and the prevalence of heart failure was significantly higher in this group (51.16% vs. 27.84%, P = 0.0329). There was no significant difference between the two patient groups in the incidence of STEMI and NSTEMI. Although there was no significant difference, VF (11.63% vs. 6.82%), resuscitation (23.26% vs. 10.08%), and ECMO implantation (2.38% vs. 1.26%) were more common in the COVID+ group. The mean age was 68.8 years in the COVID+ group and 67.6 years in the control group. The max. Troponin also did not differ significantly between the two groups (1,620 vs. 1,470 ng/L). There was a significant decline in admission rates in the first as well as in the second wave of the pandemic. Conclusions: The 30-day total mortality of COVID+ patients was significantly higher, and a more severe proceeding of acute myocardial infarction and a higher incidence of complications can be observed. As the secondary negative effect of the pandemic serious decline in admission rates can be detected.

Immunological response and temporal associations in myocarditis after COVID-19 vaccination using cardiac magnetic resonance imaging: An amplified T-cell response at the heart of it?

Introduction Although myocarditis after anti-SARS-CoV-2 vaccination is increasingly recognized, we have little data regarding the course of the disease and, consequently, the imaging findings, including the tissue-specific features. The purpose of this study is to describe the clinical, immunological, and cardiac magnetic resonance (CMR) features of myocarditis after COVID-19 immunization in the acute phase and during follow-up. We aimed to compare the trajectory of the disease to myocarditis cases unrelated to COVID-19. Methods We assembled a CMR-based registry of potentially COVID-19 vaccination-related myocarditis cases. All patients who experienced new-onset chest pain and troponin elevation after COVID-19 vaccination and imaging confirming the clinical suspicion of acute myocarditis were enrolled in our study. Participants underwent routine laboratory testing and testing of their humoral and cellular immune response to COVID-19 vaccination. Clinical and CMR follow-up was performed after 3–6 months. We included two separate, sex- and age-matched control groups: (1) individuals with myocarditis unrelated to COVID-19 infection or vaccination confirmed by CMR and (2) volunteers with similar immunological exposure to SARS-CoV-2 compared to our group of interest (no difference in the number of doses, types and the time since anti-SARS-CoV-2 vaccination and no difference in anti-nucleocapsid levels). Results We report 16 CMR-confirmed cases of myocarditis presenting (mean ± SD) 4 ± 2 days after administration of the anti-SARS-CoV-2 vaccine (male patients, 22 ± 7 years), frequently with predisposing factors such as immune-mediated disease and previous myocarditis. We found that 75% received mRNA vaccines, and 25% received vector vaccines. During follow-up, CMR metrics depicting myocardial injury, including oedema and necrosis, decreased or completely disappeared. There was no difference regarding the CMR metrics between myocarditis after immunization and myocarditis unrelated to COVID-19. We found an increased T-cell response among myocarditis patients compared to matched controls (p < 0.01), while there was no difference in the humoral immune response. Conclusion In our cohort, myocarditis occurred after both mRNA and vector anti-SARS-CoV-2 vaccination, frequently in individuals with predisposing factors. Upon follow-up, the myocardial injury had healed. Notably, an amplified cellular immune response was found in acute myocarditis cases occurring 4 days after COVID-19 vaccination.