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It was reported that mRNA-based Covid-19 vaccines rarely cause myocarditis. Although endomyocardial biopsy (EMB) is considered the gold standard for diagnosing myocarditis, no standardized study has been performed after Covid-19 vaccination in humans. Because routine EMB is frequently performed in heart transplant recipients (HTX), we aimed here to investigate effects of Covid-19 vaccination by analyzing myocardial inflammation with state-of-the-art quantitative immunohistochemistry. Consecutive patients after HTX who underwent routine EMB at a median of 167 days before and 136 days after the first Covid 19 vaccination with an mRNA vaccine were included and divided into groups with and without postvaccination inflammatory response, defined as increased CD3+ lymphocyte count >14/ mm2. Patients with evidence of rejection (ISHLT grade >1) or >14 CD3+ lymphocytes/mm2 at baseline were excluded. The final analysis included 46 patients with a mean age of 63 years and a time after HTX of 2.4 years. Thirty-six (78%) patients remained below the threshold of 14 CD3+ lymphocytes/mm2. However, in 10 (22%) recipients, we detected significant leukocyte infiltration by quantitative analysis of EMB after vaccination (4 vs. 33.7 leukocytes/ mm2, p=0.001). The groups did not differ with respect to age (63 vs. 57 years, p=0.21), body mass index (25 vs. 24 kg/m2, p=0.24), NYHA class (≥2 at 19 vs. 10%, p=0.4), NT-ProBNP levels (592 vs. 514 ng/l, p=0.55) or myocardial CD3+ cell count (4.9 vs. 2.6 cells/mm2, p=0.07) before vaccination. Patients with leukocyte infiltration remained clinically inapparent with stable NYHA class (≥2 in 10 vs. 20%, p=0.99) and did not have increased NT-ProBNP levels (514 vs. 478 ng/l, p=0.03). No hospitalizations for suspected myocarditis were reported. For the first time, we report subclinical myocardial leukocyte infiltration after Covid-19 mRNA vaccination in one in five patients without clinical sequelae during the short observation period. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infections after heart transplantation (HTx) can cause development of cardiac allograft vasculopathy (CAV). Consequently, frequent monitoring and prophylaxes for CMV-DNAemia within the first weeks after HTx is regularly performed. However, CMV-DNAemia after termination of the perioperative prophylaxes is commonly observed. All adult patients undergoing HTx between September of 2010 and 2021 surviving the first 90 days (n=196) were retrospectively reviewed in September 2022. Patients were divided regarding the prevalence of CMV-DNAemia during the first postoperative year after termination of the institutional 90-day CMV prophylaxis. A total of n=35 (20.1%) developed CMV-DNAemia (CMV group) and were compared to patients without CMV-DNAemia (Controls, n=139). The remaining patients (n=22) were excluded due to incomplete data. CMV prophylaxis consisted of val-/ganciclovir as well as intravenous CMV immunoglobulin for high-risk D+/R- CMV IgG match. D+/R- and D-/R+ serology was significantly increased and D-/R- decreased in the CMV group (p<.01). In addition, mean age was 57.7±8.7 years but only 53.6±10.0 years for Controls (p=.03). Furthermore, ICU (p=.02) and total hospital stay (p=.03) after HTx was about 50% longer compared to the controls. Interestingly, incidence of CMV-DNAemia during the regular prophylaxis was only numerically increased in the CMV group (5.7% respectively.7%, p=.10), the same effect was also overserved for postoperative infective complications. Multivariate analyses could confirm that increased recipient age and D+/R- and D-/R+ CMV IgG match of donors and recipients were independent risk factors for post-prophylaxis CMV-DNAemia within the first year after heart transplantation. Our data should raise awareness for CMV-DNAemia after termination of regular prophylaxis schemes, as this affects one of five HTx patients and can contribute to the development of CAV. Especially old recipients as well as D+/R- and D-/R+ serology share an elevated risk for late CMV-DNAemia. For these patients, prolongation or repetition of CMV prophylaxis including antiviral drugs and CMV immunoglobulins may be considered. [ABSTRACT FROM AUTHOR]

Immunosuppression after Heart transplantation (HTx) carries a life-long risk for infection and reactivation of herpesviridae. Especially changes in the immunosuppressive therapy regime can promote viral reactivation. Infections with SARS-CoV-2 can also alter the immune response. However, potential effects on herpesviridae reactivation still needs to be examined in this context. Since emerge of the COVID-19 pandemic in the early 2020, n=61 of our HTx or heart and kidney transplant (HKTx) patients had positive polymerase chain reaction (PCR) for SARS-CoV-2. Relevant patient data including results for potential concomitant herpes simplex virus (HSV-1, HSV-2), cytomegalovirus (CMV), Epstein-Barr-virus (EBV), varicella zoster virus (CZV) and human herpesvirus-8 (HHV-8) DNAemia were retrospectively reviewed in September 2022 to evaluate its clinical impact. Most patients have received at least one and up to six doses of COVID-19 vaccine before contracting SARS-CoV-2. In general, HTx and HKTx patients developed symptomatic but mild COVID-19, which was most likely caused by any kind of omicron subvariant. SARS-CoV-2 positive HTx and HKTx patients were pharmacologically treated for COVID-19. DNAemia of herpesviridae was examined in about one third of the patients (n=20). HSV-1 DNAemia was confirmed in 6.25% of tested patients with a maximum viral load of 1,130,000 HSV-1-DNA copies/µg-DNA. In not a single patient HSV-2, VZV and HHV-8 DNA was found. In contrast, CMV was observed in 20% of tested patients with a maximum of 195 CMV-DNA copies/µg-DNA and EBV in 23.5% (maximum 1230 EBV-DNA copies/µg-DNA). In one patient simultaneous CMV- and EBV-DNAemia and in another patient EBV- and HSV-1-DNAemia were found. Nevertheless, none of these patients developed clinically relevant infection or reactivation of herpesviridae and therefore no targeted treatment was initiated. Recently, SARS-CoV-2 infections are commonly observed in patients after HTx and HKTx. Fortunately, patients rarely suffer from severe COVID-19-related symptoms. Meanwhile, concomitant infections or reactivation of herpesviridae, especially CMV and EBV, are regularly observed. Although we did not overserved CMV or EBV disease, regularly testing for herpesviridae seems reasonable in these patients. [ABSTRACT FROM AUTHOR]