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Zusammenfassung Hintergrund Die SARS-CoV-2-Pandemie hat zu einer globalen Gesundheitskrise mit hohen Mortalitätsraten insbesondere bei Betroffenen in Hochrisikogruppen geführt. Eine stetig wachsende Zahl klinischer Fallberichte zeigt die Folgen von COVID-19 bei Patienten nach solider Organtransplantation (SOT) und deutet auf schwerwiegende klinische Auswirkungen und eine insgesamt hohe Sterblichkeit in dieser Patientengruppe hin. Systematische Daten zu SARS-CoV-2-Infektionen bei SOT-Empfängern in Deutschland fehlten zunächst jedoch weitgehend. Patienten und Methoden Wir führten deshalb eine Umfrage zum SARS-CoV-2-Infektionsstatus unter insgesamt 387 Patienten nach SOT durch, die in den letzten 5 Jahren an unserem Zentrum transplantiert wurden. Die Umfrage wurde 2 Monate nach dem ersten SARS-CoV-2-Ausbruch in unserer relativ stark betroffenen Region und den damit verbundenen staatlich verordneten Einschränkungen durchgeführt. Ergebnisse In unserer SOT-Kohorte wurde eine Rate von 0,4% SARS-CoV-2-positiven Patienten ermittelt, was gut mit den lokalen Infektionsraten in der Allgemeinbevölkerung zum damaligen Zeitpunkt übereinstimmt. Allerdings führte die einzige uns in diesem Kollektiv bekannt gewordene SARS-CoV-2-Infektion zu schwerer Morbidität mit verlängerter mechanischer Beatmung, einem Krankenhausaufenthalt > 60 Tage und resultierte letztlich im irreversiblen Verlust der Transplantatfunktion. Schlussfolgerung Unsere Daten zeigen, dass SOT-Empfänger im Vergleich zur Allgemeinbevölkerung zwar ein vergleichbares Risiko für eine SARS-CoV-2-Infektion haben, diese jedoch mit der Gefahr von schwerwiegenderen Verläufen assoziiert zu sein scheint.

The rapid emergence of the omicron variant and its large number of mutations led to its classification as a variant of concern (VOC) by the WHO. Subsequently, omicron evolved into distinct sublineages (e.g. BA1 and BA2), which currently represent the majority of global infections. Initial studies of the neutralizing response towards BA1 in convalescent and vaccinated individuals showed a substantial reduction.We assessed antibody (IgG) binding, ACE2 (Angiotensin-Converting Enzyme 2) binding inhibition, and IgG binding dynamics for the omicron BA1 and BA2 variants compared to a panel of VOC/VOIs, in a large cohort (n = 352) of convalescent, vaccinated, and infected and subsequently vaccinated individuals.While omicron was capable efficiently binding to ACE2, antibodies elicited by infection or immunization showed reduced binding capacities and ACE2 binding inhibition compared to WT. Whereas BA1 exhibited less IgG binding compared to BA2, BA2 showed reduced inhibition of ACE2 binding. Among vaccinated samples, antibody binding to omicron only improved after administration of a third dose.omicron BA1 and BA2 can still efficiently bind to ACE2, while vaccine/infection-derived antibodies can bind omicron. The extent of the mutations within both variants prevent a strong inhibitory binding response. As a result, both omicron variants are able to evade control by pre-existing antibodies.

The rapid emergence of the Omicron variant and its large number of mutations has led to its classification as a variant of concern (VOC) by the WHO(1). Initial studies on the neutralizing response towards this variant within convalescent and vaccinated individuals have identified substantial reductions(2-8). However many of these sample sets used in these studies were either small, uniform in nature, or were compared only to wild-type (WT) or, at most, a few other VOC. Here, we assessed IgG binding, (Angiotensin-Converting Enzyme 2) ACE2 binding inhibition, and antibody binding dynamics for the omicron variant compared to all other VOC and variants of interest (VOI)(9), in a large cohort of infected, vaccinated, and infected and then vaccinated individuals. While omicron was capable of binding to ACE2 efficiently, antibodies elicited by infection or immunization showed reduced IgG binding and ACE2 binding inhibition compared to WT and all VOC. Among vaccinated samples, antibody binding responses towards omicron were only improved following administration of a third dose. Overall, our results identify that omicron can still bind ACE2 while pre-existing antibodies can bind omicron. The extent of the mutations appear to inhibit the development of a neutralizing response, and as a result, omicron remains capable of evading immune control.

The SARS-CoV-2 pandemic has caused an unprecedented global health crisis, with exceptionally high mortality rates in high-risk groups of affected patients. It is alarming that a steadily increasing number of clinical reports on outcomes of COVID-19 in solid organ transplant (SOT) recipients suggests a detrimental impact linked to high overall mortality. However, systematic data on SARS-CoV-2 infections in SOT recipients in Germany are still scarce.We conducted a survey on SARS-CoV-2 infection status among 387 SOT recipients treated at our centre during the past 5 years - located in a severely affected region in Germany. The survey was sent out two months after the first SARS CoV-2 outbreak in our region had resulted in government-imposed lockdown measures.An incidence rate of 0.4% SARS-CoV-2-positive SOT recipients was determined in our cohort, in line with reported local infection rates in the general population at this time. However, the only SARS CoV-2 infection known to us within this group of patients led to severe morbidity - resulting in prolonged mechanical ventilation, hospitalisation 60 days and finally in irreversible loss of graft function.Our data demonstrate that SOT recipients are at equal risk for SARS-CoV-2 infections when compared to the general population, while SARS-CoV-2 infections in SOT recipients seem to be associated with deleterious clinical consequences.Die SARS-CoV-2-Pandemie hat zu einer globalen Gesundheitskrise mit hohen Mortalitätsraten insbesondere bei Betroffenen in Hochrisikogruppen geführt. Eine stetig wachsende Zahl klinischer Fallberichte zeigt die Folgen von COVID-19 bei Patienten nach solider Organtransplantation (SOT) und deutet auf schwerwiegende klinische Auswirkungen und eine insgesamt hohe Sterblichkeit in dieser Patientengruppe hin. Systematische Daten zu SARS-CoV-2-Infektionen bei SOT-Empfängern in Deutschland fehlten zunächst jedoch weitgehend.Wir führten deshalb eine Umfrage zum SARS-CoV-2-Infektionsstatus unter insgesamt 387 Patienten nach SOT durch, die in den letzten 5 Jahren an unserem Zentrum transplantiert wurden. Die Umfrage wurde 2 Monate nach dem ersten SARS-CoV-2-Ausbruch in unserer relativ stark betroffenen Region und den damit verbundenen staatlich verordneten Einschränkungen durchgeführt.In unserer SOT-Kohorte wurde eine Rate von 0,4% SARS-CoV-2-positiven Patienten ermittelt, was gut mit den lokalen Infektionsraten in der Allgemeinbevölkerung zum damaligen Zeitpunkt übereinstimmt. Allerdings führte die einzige uns in diesem Kollektiv bekannt gewordene SARS-CoV-2-Infektion zu schwerer Morbidität mit verlängerter mechanischer Beatmung, einem Krankenhausaufenthalt 60 Tage und resultierte letztlich im irreversiblen Verlust der Transplantatfunktion.Unsere Daten zeigen, dass SOT-Empfänger im Vergleich zur Allgemeinbevölkerung zwar ein vergleichbares Risiko für eine SARS-CoV-2-Infektion haben, diese jedoch mit der Gefahr von schwerwiegenderen Verläufen assoziiert zu sein scheint.

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging health systems all over the world. Particularly high-risk groups show considerable mortality rates after infection. In 2020, a huge number of case reports, case series, and consecutively various systematic reviews have been published reporting on morbidity and mortality risk connected with SARS-CoV-2 in solid organ transplant (SOT) recipients. However, this vast array of publications resulted in an increasing complexity of the field, overwhelming even for the expert reader. Methods We performed a structured literature review comprising electronic databases, transplant journals, and literature from previous systematic reviews covering the entire year 2020. From 164 included articles, we identified 3451 cases of SARS-CoV-2–infected SOT recipients. Results Infections resulted in a hospitalization rate of 84% and 24% intensive care unit admissions in the included patients. Whereas 53.6% of patients were reported to have recovered, cross-sectional overall mortality reported after coronavirus disease 2019 (COVID-19) was at 21.1%. Synoptic data concerning immunosuppressive medication attested to the reduction or withdrawal of antimetabolites (81.9%) and calcineurin inhibitors (48.9%) as a frequent adjustment. In contrast, steroids were reported to be increased in 46.8% of SOT recipients. Conclusions COVID-19 in SOT recipients is associated with high morbidity and mortality worldwide. Conforming with current guidelines, modifications of immunosuppressive therapies mostly comprised a reduction or withdrawal of antimetabolites and calcineurin inhibitors, while frequently maintaining or even increasing steroids. Here, we provide an accessible overview to the topic and synoptic estimates of expectable outcomes regarding in-hospital mortality of SOT recipients with COVID-19.

The catheter-based Impella 5.0 left ventricular assist device is a powerful and less invasive alternative for patients in cardiogenic shock. The use as second-line therapy in patients with precedent extracorporeal life support (ECLS) has not been described before now. We analyzed our experience of consecutive patients treated with this alternative strategy. From April 2014 to December 2014, eight patients had been implanted as a second-line option after ECLS support. The reason for the change from ECLS to Impella 5.0 was absence of cardiac recovery for primary weaning and complications of ECLS therapy. The mean time of ECLS support prior to Impella implantation was 12 ± 7 days. The implantation of the Impella 5.0/CP was technically successful in all patients, and the ECLS could be explanted in all eight patients who received Impella implantation as a second-line treatment. The second-line Impella 5.0 therapy resulted in two patients who turned into left ventricular assist device (LVAD) candidates, two primary weaning candidates, and four patients who died in the setting of sepsis or absent cardiac recovery and contraindications for durable LVAD therapy. Thereby, the overall hospital discharge survival as well as the 180-day survival was 50% for Impella 5.0 implantations as second-line procedure after ECLS. The latest follow-up survival of this second-line strategy after ECLS was three out of eight, as one patient died after 299 days of LVAD support due to sepsis. The use of Impella 5.0 constitutes a possible second-line therapeutic option for those patients who do not show cardiac recovery during prolonged ECLS support or suffer from complications of ECLS therapy. This treatment allows additional time for decisions regarding cardiac recovery or indication for durable LVAD therapy.

The catheter-based Impella 5.0 left ventricular assist device (LVAD) is a powerful and less invasive alternative for patients in cardiogenic shock. The use of this device as a primary mechanical circulatory support strategy in INTERMACS II patients should be evaluated. From April 2014 to August 2014, eight Impella 5.0 devices were implanted in seven patients via the axillary artery access (six right and two left). We analyzed the outcome of the four patients in whom the Impella 5.0 device was implanted for the purpose of primary stabilization of cardiogenic shock (INTERMACS II). The remaining three patients had a contraindication for a permanent LVAD and received the device for prolonged weaning from extracorporeal life support (ECLS) system. The implantation of the Impella 5.0 was technically successful in all patients and resulted in the stabilization of the clinical situation. All four patients could be bridged to a long-term device (n = 3) or to cardiac recovery (n = 1). In one patient, 2 days of ECLS support was necessary because of pump thrombosis after 31 days of Impella 5.0 support. One patient with bronchopneumonia had the Impella 5.0 exchanged from the right to the left axillary artery after 22 days of support because of the progressive loss of purge flow and the need for longer bridging to a permanent LVAD. The last patient was supported for giant-cell myocarditis for 22 days and bridged to cardiac recovery. All patients were transferred to the intensive care unit with the Impella device in place. In INTERMACS II situations, the implantation of the Impella 5.0 via the right or left axillary access allowed additional time for decision making. Early patient mobilization, including walking with the Impella device in place, optimized the conditions for either weaning or the implantation of a permanent LVAD. This novel technique of left axillary approach leads to more flexibility in the case of anatomical- or device-related contraindications to right-side access, or when the device needs to be exchanged while continuous support is necessary.

Background The rapid emergence of the Omicron variant and its large number of mutations led to its classification as a variant of concern (VOC) by the World Health Organization. Subsequently, Omicron evolved into distinct sublineages (eg, BA.1 and BA.2), which currently represent the majority of global infections. Initial studies of the neutralizing response toward BA.1 in convalescent and vaccinated individuals showed a substantial reduction. Methods We assessed antibody (immunoglobulin G [IgG]) binding, ACE2 (angiotensin-converting enzyme 2) binding inhibition, and IgG binding dynamics for the Omicron BA.1 and BA.2 variants compared to a panel of VOCs/variants of interest, in a large cohort (N = 352) of convalescent, vaccinated, and infected and subsequently vaccinated individuals. Results While Omicron was capable of efficiently binding to ACE2, antibodies elicited by infection or immunization showed reduced binding capacities and ACE2 binding inhibition compared to wild type. Whereas BA.1 exhibited less IgG binding compared to BA.2, BA.2 showed reduced inhibition of ACE2 binding. Among vaccinated samples, antibody binding to Omicron only improved after administration of a third dose. Conclusions Omicron BA.1 and BA.2 can still efficiently bind to ACE2, while vaccine/infection-derived antibodies can bind to Omicron. The extent of the mutations within both variants prevents a strong inhibitory binding response. As a result, both Omicron variants are able to evade control by preexisting antibodies.