Changes in Therapy and Outcome of Patients Requiring Veno-Venous Extracorporeal Membrane Oxygenation for COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome requiring veno-venous extracorporeal membrane oxygenation (vv-ECMO) is related with poor outcome, especially in Germany. We aimed to analyze whether changes in vv-ECMO therapy during the pandemic were observed and lead to changes in the outcome of vv-ECMO patients. METHODS: All patients undergoing vv-ECMO support for COVID-19 between 2020 and 2021 in a single center (n = 75) were retrospectively analyzed. Weaning from vv-ECMO and in-hospital mortality were defined as primary and peri-interventional adverse events as secondary endpoints of the study. RESULTS: During the study period, four infective waves were observed in Germany. Patients were assigned correspondingly to four study groups: ECMO implantation between March 2020 and September 2020: first wave (n = 11); October 2020 to February 2021: second wave (n = 23); March 2021 to July 2021: third wave (n = 25); and August 2021 to December 2021: fourth wave (n = 20). Preferred cannulation technique changed within the second wave from femoro-femoral to femoro-jugular access (p < 0.01) and awake ECMO was implemented. Mean ECMO run time increased by more than 300% from 10.9 ± 9.6 (first wave) to 44.9 ± 47.0 days (fourth wave). Weaning of patients was achieved in less than 20% in the first wave but increased to approximately 40% since the second one. Furthermore, we observed a continuous numerically decrease of in-hospital mortality from 81.8 to 57.9% (p = 0.61). CONCLUSION: Preference for femoro-jugular cannulation and awake ECMO combined with preexisting expertise and patient selection are considered to be associated with increased duration of ECMO support and numerically improved ECMO weaning and in-hospital mortality.

Transplantation of hearts from SARS-CoV-2 positive donors.

Incidence of SARS-CoV-2 remains high in the population. Consequently, an increasing percentage of reported organ donors are also SARS-CoV-2 positive. Although donors may not have experienced COVID-19-related symptoms, there is a chance of unnoticed cardiovascular effects associated with this disease. Therefore, SARS-CoV-2 donor grafts have been regularly rejected for heart transplantation (HTx) for a long time. We hereby present three consecutive patients receiving grafts from SARS-CoV-2 positive donors (defined by the PCR cycle threshold value < 30). All patients underwent HTx after a previous triple mRNA vaccination (mRNA-BNT162b2 vaccine, Comirnaty) without adverse events and with a regular post-operative course. Cardiovascular magnetic resonance and endomyocardial biopsies confirmed excellent graft function without signs of rejection or viral myocarditis. After a mean follow-up of 135 days after HTx, all patients were in good conditions without heart failure, viral myocarditis, or SARS-CoV-2 infection. Thus, we conclude that HTx with SARS-CoV-2 positive donors seems safe and feasible.

Heart transplantation in the era of corona virus disease 2019: Impact of the pandemic on donors, recipients and outcome.

INTRODUCTION: Since March 2020, the COVID-19 pandemic has tremendously impacted health care all around the globe. We analyzed the impact of the pandemic on donors, recipients, and outcome of heart transplantation (HTx). METHODS: Between 2010 and early 2022, a total of n = 235 patients underwent HTx in our department. Patients were assigned to the study groups regarding the date of the performed HTx. Group 1 (09/2010 to 02/2020): n = 160, Group 2 (03/2020 to 02/2022): n = 75. RESULTS: Since the pandemic, the etiology of heart failure in the recipients has shifted from dilated (Group 1: 53.8%, Group 2: 32.0%) to ischemic cardiomyopathy (Group 1: 39.4%, Group 2: 50.7%, p < .01). The percentage of high urgency status of the recipients dropped from 50.0% to 36.0% (p = .05), and the use of left ventricular assist (LVAD) support from 56.9% to just 37.3% (p < .01). Meanwhile, the waiting time for the recipients also decreased by about 40% (p = .05). Since the pandemic, donors were 2- times more likely to have been previously resuscitated (Group 1: 21.3%, Group 2: 45.3% (p < .01), and drug abuse increased by more than 3-times (p < .01), indicating acceptance of more marginal donors. Surprisingly, the incidence of postoperative severe primary graft dysfunction requiring extracorporeal life support decreased from 33.1% to 19.4% (p = .04) since the pandemic. CONCLUSION: The COVID-19 pandemic affected both donors and recipients of HTX but not the postoperative outcome. Donors nowadays are more likely to suffer from ischemic heart disease and are less likely to be on the high-urgency waitlist and on LVAD support. Simultaneously, an increasing number of marginal donors are accepted, leading to shorter waiting times.

Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection.

BACKGROUND: The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. Several studies have found an association between HLA variants and differential COVID-19 outcomes and have shown that HLA genotypes are associated with differential immune responses against SARS-CoV-2, particularly in severely ill patients. Information, whether HLA haplotypes are associated with the severity or length of the disease in moderately diseased individuals is absent. METHODS: Next-generation sequencing-based HLA typing was performed in 303 female and 231 male non-hospitalized North Rhine Westphalian patients infected with SARS-CoV2 during the first and second wave. For HLA-Class I, we obtained results from 528 patients, and for HLA-Class II from 531. In those patients, who became ill between March 2020 and January 2021, the 22 most common HLA-Class I (HLA-A, -B, -C) or HLA-Class II (HLA -DRB1/3/4, -DQA1, -DQB1) haplotypes were determined. The identified HLA haplotypes as well as the presence of a CCR5Δ32 mutation and number of O and A blood group alleles were associated to disease severity and duration of the disease. RESULTS: The influence of the HLA haplotypes on disease severity and duration was more pronounced than the influence of age, sex, or ABO blood group. These associations were sex dependent. The presence of mutated CCR5 resulted in a longer recovery period in males. CONCLUSION: The existence of certain HLA haplotypes is associated with more severe disease.

Auswirkungen der COVID-19-Pandemie auf die Herzchirurgie Impact of the COVID-19 pandemic on cardiac surgery

Seit Anfang des Jahres 2020 die COVID-19-Pandemie weltweit das Leben massiv beeinflusst und auch verändert hat, lassen sich naturgemäß gerade im Gesundheitssektor schwerwiegende Konsequenzen beobachten. Diese betreffen Patienten in gleichem Maß wie medizinisches Personal aller Berufsgruppen, sowohl im ambulanten als auch im stationären Bereich. Die Herzchirurgie als eine Disziplin, die wie keine zweite von der vorhandenen Kapazität auf Intensivstationen abhängig ist, war erwartungsgemäß von den Auswirkungen der Pandemie schwer betroffen. Dieser Beitrag gibt einen Überblick über die Konsequenzen für die klinische Versorgung, die Forschung und die Lehre sowie für die herzchirurgische Weiterbildung

COVID-19 nach Herztransplantation: Erfahrungen eines deutschen Transplantationszentrums COVID-19 after heart transplantation: experiences from a German transplantation center

Hintergrund Die durch SARS-CoV‑2 (Severe acute respiratory syndrome coronavirus type 2) verursachte Erkrankung gilt bei immunsupprimierten Patienten als besonders gefährlich. Patienten nach einer Herztransplantation zählen zu den Gruppen mit langjähriger, meist 3‑facher Immunsuppression. In der Literatur werden schwerwiegende klinische Verläufe beschrieben. Ziel der Arbeit (Fragestellung) In dieser Arbeit wird über unsere Erfahrungen mit COVID-19 (coronavirus disease 2019) bei herztransplantierten Patienten an einem deutschen Transplantationszentrum longitudinal über die bisherigen Pandemiewellen berichtet und es erfolgt eine Einordnung dieser in publizierte Erfahrungen anderer Zentren. Material und Methoden Alle adulten herztransplantierten Patienten unseres Zentrums, bei denen nach der Herztransplantation eine SARS-CoV-2-Infektion nachgewiesen wurde (n = 12), wurden eingeschlossen und retrospektiv analysiert. Ergebnisse Das Durchschnittsalter betrug 61,5 (49 bis 63) Jahre;die Mehrheit der Patienten war männlich (83 %). Die häufigsten Komorbiditäten waren Diabetes (42 %), arterielle Hypertonie (43 %) sowie chronische Niereninsuffizienz (67 %). Bei 50 % erfolgte bei Krankenhausaufnahme eine passive Immunisierung (Rekonvaleszenzplasma/monoklonale Antikörper). Eine Sauerstoffgabe war bei 33 % der Patienten notwendig;nur ein Patient erhielt eine nichtinvasive Ventilation (8 %). Kein Patient benötigte eine invasive Beatmung oder eine mechanische Herz-Kreislauf-Unterstützung (ECMO). Es fanden sich keine neuen kardiovaskulären oder thrombembolischen Ereignisse. Zusammenfassung In dieser Kohorte konnten wir longitudinal keine schweren Verläufe oder eine erhöhte Mortalität von COVID-19 in herztransplantierten Patienten detektieren. Prospektive Studien sind notwendig, um in Zukunft bessere Prognoseabschätzungen bei COVID-19 in (herz-)transplantierten Patienten treffen zu können.

Venovenöse extrakorporale Membranoxygenierung bei COVID-19 : Erkenntnisse eines Zentrums aus 96 konsekutiven Fällen Venovenous extracorporeal membrane oxygenation for COVID-19Findings of a centre from 96 consecutive cases

Hintergrund Seit Beginn der COVID-19-Pandemie werden die globalen Gesundheitssysteme vor eine Vielzahl neuartiger Probleme gestellt. Die venovenöse extrakorporale Membranoxygenierung (vv-ECMO) stellt bei Krankheitsverläufen mit therapierefraktärem ARDS häufig eine Ultima Ratio der Therapie dar. Für eine verbesserte medizinische Versorgung ist es notwendig, potenzielle Einflussfaktoren auf den Therapieerfolg zu identifizieren. Fragestellung In dieser Arbeit sollen die Erkenntnisse eines ECMO Zentrums vorgestellt werden. Insbesondere interessierte die Frage, durch welche Faktoren das Therapieergebnis einer vv-ECMO-Therapie von COVID-19-Patienten beeinflusst wird. Material und Methoden In der Zeit zwischen März 2020 und Dezember 2021 wurden insgesamt n = 96 Patienten in unserem Zentrum mit einer vv-ECMO aufgrund eines ARDS bei COVID-19 behandelt. Es erfolgte eine retrospektive Auswertung der demografischen und gesundheitsspezifischen Faktoren. Hierbei wurden Patienten mit letalem Therapieausgang (L-Gruppe, n = 62) sowie die Überlebenden (Ü-Gruppe, n = 34) miteinander verglichen. Ergebnisse Insgesamt überlebten n = 34 (35 %) der Patienten den Krankenhausaufenthalt. Die verstorbenen Patienten hatten ein mittleres Alter von 56,7 ± 9,5 Jahren, verglichen mit 47,9 ± 12,9 Jahren bei den Überlebenden. Unter den behandelten Patienten befanden sich n = 72 (75 %) männliche und n = 24 (25 %) weibliche Patienten. In der Gruppe der verstorbenen Patienten waren n = 51 (82,3 %) Männer sowie n = 11 (17,7 %) Frauen (p = 0,047). Die Prävalenz von Vorerkrankungen wie COPD, Diabetes mellitus, Herz-Kreislauf-Erkrankungen sowie chronischer Niereninsuffizienz zeigte keinerlei Unterschiede zwischen den beiden Gruppen. Auch in Bezug auf das Vorliegen von arterieller Hypertonie und Adipositas konnte kein signifikanter Trend für einen negativen Therapieeinfluss nachgewiesen werden. Es zeigte sich für Patienten mit einem Nikotinabusus in der Anamnese jedoch eine negative Tendenz. Die häufigsten Gründe für ein Versterben waren respiratorische Insuffizienz, neurologische Insulte, Multiorganversagen und Sepsis. Diskussion Der Einsatz einer vv-ECMO bei therapierefraktärem ARDS im Rahmen einer COVID-19-Erkrankung geht weiterhin mit einer hohen Sterblichkeit einher und ist somit nur als Ultima Ratio in Betracht zu ziehen. In unserem Patientenkollektiv konnten wir erwartungsgemäß bessere Ergebnisse bei jüngeren Patienten beobachten, jedoch auch bei Frauen. Für die meisten Begleiterkrankungen konnten wir bis dato keinen negativen Einfluss auf das Therapieergebnis nachweisen. Diese Erkenntnisse könnten helfen, zukünftige Risikopatienten zu identifizieren.

COVID-19 pandemic deteriorates aftercare attendance in heart transplant recipients independently of perceived impact on social life.

BACKGROUND: Heart transplant (HTx) recipients are at an increased risk of developing infections or malignancies due to immunosuppressive medication. Thus, regular aftercare in those patients is of utmost importance. The extent of collateral damage due to the COVID-19 pandemic (delayed or canceled clinical visits and diagnostics) on high-risk patients is yet unknown. We believe that, especially for HTx-patients, data acquisition on potential pandemic-related nonattendance is crucial to improve clinical care in the future. Therefore, we aim to decipher possible COVID-19-related alterations in attendance to clinical care after HTx using a survey-based approach. METHODS: HTx recipients, 2 years beyond transplantation were selected (n = 75). We filed a paper-based questionnaire or an online survey containing nine items about COVID-19-related exceptional circumstances. Fifty-two patients (69%) returned fully answered questionnaires. RESULTS: A perceived impact on daily life was evident with 79% of all patients, reporting a moderate-to-severe negative influence of the COVID-19 pandemic on daily routine. We detected increased nonattendance of clinical care during the COVID-19 pandemic compared to prepandemic time (38 vs. 6%, p < .0001). The various diagnostic modalities of aftercare were heterogeneously affected, ranging from 2% nonattendance for influence vaccination and 18% for colonoscopy. Off note, nonattendance to clinical care within the pandemic was independent of perceived impact of the pandemia on daily life (p > .68). CONCLUSIONS: For the first time, we objectively demonstrate a significant decrease in attendance to clinical care in HTx recipients during the COVID-19 pandemic. Efforts are needed to increase attendance in this highly vulnerable patient cohort.

Adequate immune response after SARS-CoV-2 infection and single dose vaccination despite rapid heart transplantation.

Adequate immune response to vaccination remains a challenge in patients after solid organ transplantation. We report a case of a 61-year-old male patient who received a left ventricular assist device as a bridge to transplant therapy. Three months before transplantation, he suffered mild SARS-CoV-2 infection and was successfully discharged thereafter. Eight days before his successful heart transplantation, he received mRNA BNT 162b2 vaccination. Immediately after transplantation, we detected sufficient rise of nucleocapsid and spike antibodies despite immune suppression therapy. We suspect potential booster effects of the previous SARS-CoV-2 infection giving rise to adequate immune response following single vaccination.

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19.

BACKGROUND: COVID-19, the pandemic disease caused by infection with SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients' adaptive immune responses without progression to severe disease with patients' Human Leukocyte Antigen (HLA) genetics, AB0 blood group antigens, and the presence or absence of near-loss-of-function delta 32 deletion mutant of the C-C chemokine receptor type 5 (CCR5). PATIENT AND METHODS: An exploratory observational study including 157 adult COVID-19 convalescent patients was performed with a median follow-up of 250 days. The impact of different HLA genotypes, AB0 blood group antigens, and the CCR5 mutant CD195 were investigated for their role in the clinical course of COVID-19. In addition, this study addressed levels of severity and morbidity of COVID-19. The association of the immunogenetic background parameters were further related to patients' humoral antiviral immune response patterns by longitudinal observation. RESULTS: Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01). They were associated with reduced durations of disease instead decreased (rather than increased) total anti-S IgG levels. They had a higher virus neutralizing capacity compared to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:02 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A suggestive association of a heterozygous CCR5 delta 32 mutation status with prolonged disease duration was implied by univariate analyses but could not be confirmed by hierarchical multivariate testing. CONCLUSION: The current study shows that the presence of HLA class II DRB1*01:01 and HLA class I B*35:01 is of even stronger association with reduced disease duration in mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations also including novel SARS-CoV-2 variants will be required to assess the impact of HLA genetics on the capacity of mounting protective vaccination responses in the future.

Correction to: The role of passive immunization in the age of SARS-CoV-2: an update.

An amendment to this paper has been published and can be accessed via the original article.

Informed consent and informed intervention: SARS-CoV-2 vaccinations not just call for disclosure of newly emerging safety data but also for hypothesis generation and testing.

BACKGROUND: COVID-19 infection is a major threat to patients and health care providers around the world. One solution is the vaccination against SARS-CoV-2. METHODS: We performed a comprehensive query of the latest publications on the prevention of viral infections including the recent vaccination program and its side effects. RESULTS: The situation is evolving rapidly and there is no reasonable alternative to population-scale vaccination programs as currently enrolled. CONCLUSION: Therefore, regulatory authorities should consider supplementing their conventional mandate of post-approval pharmacovigilance, which is based on the collection, assessment, and regulatory response to emerging safety findings.

Face masks: benefits and risks during the COVID-19 crisis.

BACKGROUND: The German government has made it mandatory to wear respiratory masks covering mouth and nose (MNC) as an effective strategy to fight SARS-CoV-2 infections. In many countries, this directive has been extended on shopping malls or public transportation. The aim of this paper is to critically analyze the statutory regulation to wear protective masks during the COVID-19 crisis from a medical standpoint. METHODS: We performed an extensive query of the most recent publications addressing the prevention of viral infections including the use of face masks in the community as a method to prevent the spread of the infection. We addressed the issues of practicability, professional use, and acceptability based on the community and the environment where the user resided. RESULTS: Upon our critical review of the available literature, we found only weak evidence for wearing a face mask as an efficient hygienic tool to prevent the spread of a viral infection. However, the use of MNC seems to be linked to relevant protection during close contact scenarios by limiting pathogen-containing aerosol and liquid droplet dissemination. Importantly, we found evidence for significant respiratory compromise in patients with severe obstructive pulmonary disease, secondary to the development of hypercapnia. This could also happen in patients with lung infections, with or without SARS-CoV-2. CONCLUSION: Epidemiologists currently emphasize that wearing MNC will effectively interrupt airborne infections in the community. The government and the politicians have followed these recommendations and used them to both advise and, in some cases, mandate the general population to wear MNC in public locations. Overall, the results seem to suggest that there are some clinically relevant scenarios where the use of MNC necessitates more defined recommendations. Our critical evaluation of the literature both highlights the protective effects of certain types of face masks in defined risk groups, and emphasizes their potential risks.

The history and value of face masks.

In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.

The role of passive immunization in the age of SARS-CoV-2: an update.

The rapid spread of the corona virus pandemic is an existential problem for many people in numerous countries. So far, there is no effective vaccine protection or proven therapy available against the SARS-CoV-2 virus. In this review, we describe the role of passive immunization in times of the corona virus. Passive immunization could be a bridging technology to improve the immune defense of critically ill patients until better approaches with effective medications are available.