Research clinicians at the DZL sites in Hannover and Munich have discovered that lung-transplanted patients infected with SARS-CoV-2 (Delta variant), when treated with monoclonal antibodies, which target the spike protein of the virus, have a noticably milder disease progression and are less likely to die compared to untreated patients. The study has been published in the renowned European Respiratory Journal (DOI: 10.1183/13993003.00124-2022).
Lung transplant patients are, among other things, due to immunosuppression, particularly prone to infections, especially respiratory and pulmonary infections. Already in the early stages of the Corona pandemic, it was recognised that they have a substantially increased risk of becoming seriously ill with COVID-19 and approximately 30% of those infected will die as a result of the infection - an observation that was clearly confirmed in the DZL study. Lung transplants can sustain particularly extensive tissue damage from invasive Corona viruses. The natural defence processes, including the formation of the body’s own antibodies after vaccination, are affected in these patients by the immunosuppression, so that the virus can multiply particularly well. Furthermore, inflammation promotes acute and chronic rejection processes which complicate and exacerbate the disease processes. The treatment of SARS-CoV-2-infected lung transplant patients thus presented the clinicians with an enormous challenge.
In the transplant centres in Hannover and Munich, the effectiveness of early therapy with antibody preparations (Casirivimab-Imdevimab) in SARS-CoV-2-infected lung transplant patients was thus examined during the pandemic with dominant Delta variants, directed against the spike protein of SARS-CoV-2. As the spike protein plays a central role in the entry of viruses into the cell, these antibodies prevent the infection of somatic cells and thus the spread of the virus. This treatment resembles a passive immunization, as used, for example, in the protection against suspected tetanus or rabies in non-immunized patients. Treatment with Casirivimab-Imdevimab is particularly advisable for immunosuppressed lung transplant patients suffering from COVID-19, since their ability to produce their own antibodies after immunization or infection is severely limited.
In the two centres during the examination period, a total of 1.631 lung transplant patients were observed, of whom 133 were infected with the Delta variant of SARS-CoV-2. Of those infected, 44 received within three days of onset of the symptoms an injection of the antibodies directed against the spike protein of SARS-CoV-2. In the thus treated patient group, fortunately no serious illness or death occurred, whereas in the non-treated group, over 50% of the patients became seriously ill and 30% of them died. Even though this was a retrospective study, it clearly demonstrates that early treatment with Casirivimab-Imdevimab represents a significantly longer survival for lung transplant patients with COVID-19. These findings are only applicable to the Delta variant of the SARS-CoV-2 virus, which is now no longer dominant. With the current variants, the antibody compound can no longer be used. However, the operating principles and research approaches of this study can form the basis for future studies and in this way accelerate the finding process for new methods of treatment.
The lead author of the publication of this study is Prof. Dr. Jens Gottlieb, DZL scientist at the BREATH site, who has been Head of the Lung Transplantation Department at Hannover Medical School for many years.
Text: DZL/ BREATH
Foto: MHH/ Tom Figiel
Lead author of the publication of this study and Head of the Lung Transplantation Department at Hannover Medical School Prof. Dr. Jens Gottlieb