ABSTRACT
Objective This single-center retrospective study evaluated the use of tixagevimab-cilgavimab as an early treatment for COVID-19 in kidney transplant recipients (KTRs) during the omicron wave. Methods KTRs were deemed at high risk for moderate-to-severe COVID-19 in presence of at least one comorbidity (age >60 years, diabetes, obesity, or cardiovascular disease) associated with a weak humoral response (<264 BAU/mL). All other KTRs were considered at low risk. The two groups were stratified according to the administration of tixagevimab-cilgavimab and compared in terms of COVID-19-related hospitalization, oxygen need, ICU admission, and mortality. Results Of the 61 KTRs at high risk, 26 received tixagevimab-cilgavimab. COVID-19-related hospitalizations (3.8% versus 34%, p=0.006) and oxygen need (3.8% versus 23%, p=0.04) were significantly less frequent in patients who received tixagevimab-cilgavimab. In addition, non-significant trends towards a lower number of ICU admissions (3.8% versus 14.3% p=0.17) and deaths (0 versus 3, p=0.13) were observed after administration of tixagevimab-cilgavimab. Ten of the 73 low-risk KTRs received tixagevimab-cilgavimab, and no significant clinical benefit was observed in this subgroup. Conclusion Early administration of tixagevimab-cilgavimab may be clinically useful in high-risk KTRs with COVID-19; however, no major benefit was observed for low-risk patients.
Subject(s)
COVID-19 , Obesity , Cardiovascular DiseasesABSTRACT
Transplant recipients, which receive therapeutic immunosuppression to prevent graft rejection, are characterized by high COVID-19-related mortality and defective response to vaccines. Having observed that previous infection by SARS-CoV-2 but not the standard “2 doses” scheme of vaccination, provided complete protection against COVID-19 to transplant recipients, we undertook this translational study to compare the cellular and humoral immune responses of these 2 groups of patients. Neutralizing anti-Receptor Binding Domain (RBD) IgG were identified as the critical immune effectors associated with protection. Generation of anti-RBD IgG was dependent upon spike-specific T follicular helper (Tfh) CD4+ T cells, which acted as limiting checkpoint. Tfh generation was impeded by high dose mycophenolate mofetil in non-responders to vaccine but not in infected patients, suggesting that increasing immunogenicity of vaccine could improve response rate to mRNA vaccine. This theory was validated in two independent prospective cohorts, in which administration of a 3 rd dose of vaccine resulted in the generation of anti-RBD IgG in half of non-responders to 2 doses. One sentence summary The generation of neutralizing IgG, which protects kidney transplant recipients from COVID-19, requires T follicular helper cells.
Subject(s)
COVID-19ABSTRACT
Data concerning the anti-SARS-CoV-2 antibody response after mRNA COVID-19 vaccine in kidney transplant recipients (KTRs) are currently lacking. Here, we sought to examine this issue by analyzing the serological response observed in 241 KTRs after a first vaccine injection. Our results indicate that KTRs have a weak anti-SARS-CoV-2 antibody response, ultimately resulting in a low seroconversion rate (26/241, 10.8%). This phenomenon likely stems from a high immunosuppression burden in this clinical population.
Subject(s)
COVID-19ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via RT-PCR and SARS-CoV-2 serology via ELISA and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study we examined hospitalized kidney transplant recipients with non-severe (n = 21) and severe (n =19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (p=0.0087) and mortality (p=0.024). All patients harbored antibodies the second week after symptom onset that persisted for two months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.