ABSTRACT
Background: The SARS-CoV-2 pandemic is leading to hospitalizations and increased mortality worldwide. With potentially high prevalence and severity of COVID-19 in cardiac transplantation, there is a great need to generate data in this at-risk cohort. We report here our experience on outcome and treatment of heart transplant recipients infected with SARS-CoV-2 at a German transplant center longitudinally over the previous pandemic waves. Method(s): All adult patients who had received a heart transplant at our center and had confirmed COVID-19 infection between December 2020 and July 2022 (n = 48) were included and retrospectively characterized. Result(s): The median age was 60.5 (46.3-63.8) years, and the majority were male (83%). The hospitalization rate was 83%. Comorbidities included diabetes (31%), arterial hypertension (73%), and chronic renal failure (90%). The percentage of SARS-CoV-2 positive patients since the beginning of our vaccination campaign (03/2021) was 90%, while from those 43 patients, 88% were fully vaccinated at the time of infection (vaccine breakthrough). The median time from vaccination to infection within those patients was 138 (85-225) days. Antiviral therapy was given in 83% of all cases, and passive immunization (convalescent plasma/monoclonal antibodies) was performed in 98% of all cases. Oxygen administration was required in 10% of patients;only one patient required noninvasive ventilation (2%), and no patient required invasive ventilation or mechanical cardiovascular support (ECMO). No new cardiovascular or thromboembolic events were found, and we observed no COVID-19-associated mortality. Conclusion(s): Under increasing numbers of vaccinated patients and treatment options, we could not detect severe courses or increased mortality of COVID-19 in heart transplanted patients. Prospective studies are needed to make better prognostic estimates of COVID-19 in (heart) transplanted patients in the future.
ABSTRACT
Numerous emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have shown significant immune evasion capacity and caused a large number of infections, as well as vaccine-breakthrough infections, especially in elderly populations. Recently emerged Omicron XBB was derived from the BA.2 lineage, but bears a distinct mutant profile in its spike (S) protein. In this study, we found that Omicron XBB S protein drove more efficient membrane-fusion kinetics on human lung-derived cells (Calu-3). Considering the high susceptibility of the elderly to the current Omicron pandemic, we performed a comprehensive neutralization assessment of elderly convalescent or vaccine sera against XBB infection. We found that the sera from elderly convalescent patients who experienced with BA.2 infection or breakthrough infection potently inhibited BA.2 infection, but showed significantly reduced efficacy against XBB. Moreover, recently emerged XBB.1.5 subvariant also showed more significant resistance to the convalescent sera of BA.2- or BA.5-infected elderly. On the other hand, we found that the pan-CoV fusion inhibitors EK1 and EK1C4 can potently block either XBB-S- or XBB.1.5-S-mediated fusion process and viral entry. Moreover, EK1 fusion inhibitor showed potent synergism when combined with convalescent sera of BA.2- or BA.5-infected patients against XBB and XBB.1.5 infection, further indicating that EK1-based pan-CoV fusion inhibitors are promising candidates for development as clinical antiviral agents to combat the Omicron XBB subvariants.