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
The combination of cilgavimab-tixagevimab (Evusheld, Astra Zeneca) became the mainstay for protecting transplant recipients with poor response to vaccination against the omicron variant. Serum neutralizing capacity against SARS-CoV-2 is positively associated with protection against severe forms of Covid-19. Both anti-RBD IgG titers and neutralizing antibody titers against the omicron BA.1 variant were measured in serum samples collected from 63 adult kidney transplant recipients who received prophylactic injections of Evusheld. Patients who received prophylactic Ronapreve (casirivimab-imdevimab, n = 39) and those who were infected with SARS-CoV-2 during the fifth wave of the pandemic (n = 14) served as negative and positive controls, respectively. After a median interval from injection of 29 days (interquartile range 29-33 days), only 9.5% of patients who received Evusheld were able to neutralize the omicron variant compared to 71% of patients who were infected with SARS-CoV-2 and 2.6% of those who received Ronapreve. Interestingly, convalescent patients displayed higher levels of neutralizing antibodies than those who received Evusheld (median: 2.3 log IC50, IQR: 1.5-2.7 versus 0.00 log IC50, IQR: 0- 0.05; p<0.001). A high interindividual variability in anti-RBD IgG titers was observed after Evusheld (range: 262-7032 BAU/mL). This variability was largely explained by the patients' body mass index, which showed an inverse correlation with anti-RBD IgG titers. These findings suggest that Evusheld given at a dose of 300 mg is not sufficient to elicit an anti-RDB titer that confers in vivo neutralizing activity and support recent FDA recommendations, derived from in vitro models, regarding the need to increase the dose of Evusheld.
Subject(s)
COVID-19ABSTRACT
While the combination of casirivimab-imdevimab (Ronapreve Roche Regeneron) has been shown to confer satisfactory protection against the delta variant kidney transplant recipients (KTRs) with COVID-19, it has limited neutralizing activity against the current variants of concern (Omicron BA.1, BA.1.1 and BA.2). In contrast, cilgavimab-tixagevimab combination (Evusheld, Astra Zeneca) retains a partial neutralizing activity against omicron in vitro. We examined whether preexposure prophylaxis with Evusheld can effectively protect kidney transplant recipients (KTRs) against the Omicron variant. Of the 416 KTRs who received intramuscular prophylactic injections of Evusheld (150 mg tixagevimab and 150 mg cilgavimab), 39 (9.4%) developed COVID-19. With the exception of one patient, all KTRs were symptomatic. Hospitalization and admission to an intensive care unit were required for 14 (35.9%) and three patients, respectively. Two KTRs died of COVID-19-related acute respiratory distress syndrome. SARS-CoV-2 sequencing was carried out in 15 cases (BA.1, n = 5; BA.1.1, n = 9; BA.2, n=1). Viral neutralizing activity of the serum against BA.1 variant was negative in the 12 tested patients, suggesting that this prophylaxis strategy provides insufficient protection against this variant of concern. Preexposure prophylaxis with Evusheld does not adequately protect KTRs against Omicron. Further clarification of the optimal dosing can assist in our understanding of how best to harness its protective potential.
Subject(s)
Respiratory Distress Syndrome , COVID-19ABSTRACT
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.