ABSTRACT
Background: At the end of 2021, concomitantly with the beginning of Omicron variant circulation, pre-exposure prophylaxis with the dual monoclonal long-acting monoclonal antibodies tixagevimab/cilgavimab became available in France to protect patients non-responding or non-eligible to SARS-CoV-2 vaccination at risk of severe COVID-19. Method(s): This study included patients who received tixagevimab/cilgavimab for pre-exposure prophylaxis independently of vaccination status or previous SARS-CoV-2 infection. This prophylaxis strategy was implemented at the Bichat-Claude Bernard University Hospital, Paris since December 2021 Last date of follow-up was November 1st, 2022. Incident SARS-CoV-2 infections were detected based on positive RT-PCR result and/or anti-nucleocapsid antibodies seroconversion. Severe COVID-19 was defined as an infection leading to an hospitalization requiring oxygenotherapy and/or high dose corticotherapy. Result(s): Among the 275 patients who received a tixagevimab/cilgavimab preexposure prophylaxis, 55% (n=153) were solid organ transplant recipients (50% lung, 46% kidney, 4% heart transplants), 42% (n=116) had an autoimmune disease, and 3% (n=6) had other indications. 51% (n=141) of all patients received rituximab. No severe adverse event of tixagevimab/cilgavimab was observed. Incident SARS-CoV-2 infection was diagnosed in 67 patients (24%). Among them, 59% (n=40) were solid organ transplant recipients, 36% (n=24) had an autoimmune disease and overall 52% had received rituximab. For the 56 patients whose infection date was available, the median delay between the last infusion of tixagevimab/cilgavimab and SARS-CoV-2 infection was 62 days (IQR=[30-97]). During the study period, 57% of incident infections occurred between December 17th, 2021 and May 31st, 2022, when BA.1 and BA.2 were the major Omicron sublineages in France, and 43% between June 1st, 2022 and November 2022 1st, a period during which BA.4 and BA.5 were predominant in France. Severe COVID-19 occurred in 6 patients out of 67 (9%);5 were solid organ transplant recipients and 3 received rituximab. No death due to COVID-19 was reported. Conclusion(s): Overall, 76% of patients receiving pre-exposure prophylaxis with tixagevimab/cilgavimab had no incident SARS-CoV-2 infection during the study period. Severe COVID-19 was observed in 9% of infected patients. These results suggest a potential protective effect in-vivo of tixagevimab/cilgavimab during the study period despite the circulation of different Omicron sublineages.
ABSTRACT
Vaccination and therapeutic monoclonal antibodies (mAb) provide high protection against severe forms of SARS-CoV-2 infection (COVID-19) in the general population. In France, vaccination campaign started on December 2020 and the first mAb was approved on August 2021. This national cohort study aimed to evaluate the persistent risk of hospitalization and death in heart transplant (HT) recipients who develop COVID-19. All HT recipients entered into the national registry CRISTAL between January 2020 and December 2021 were included in this study. Incidence rates of COVID-19 during the years 2020 and 2021 were calculated. Outcomes were intensive care unit (ICU) admission and case fatality rate in COVID-19 patients. Association of clinical characteristics, laboratory data, immunosuppressive regimen and year of infection with outcomes was assessed using multivariable logistic model. Among 5 898 HT recipients, 647 (195 aged ≥65 years, 170 females, 176 with coronary artery disease as HT indication, 68 with BMI >30 Kg/m², 228 with time since HT >10 years, 332 with glomerular filtration rate (GFR) <60 mL/min/m², 426 with calcineurin inhibitor-based, 175 mTOR inhibitor-based and 7 belatacept-based immunosuppression) developed COVID-19. COVID-19 incidence rate was 4.98 [4.37;5.59] and 7.61 [6.86;8.37] per 100 person-years in 2020 and 2021, respectively. ICU admission and case fatality rates were 8.4% vs 10.2% and 13.0% vs 14.1%, in 2021 vs 2020 respectively. Age, coronary artery disease as HT indication, time since HT, GFR <60 mL/min/m² and belatacept-based or mTOR inhibitor-based immunosuppression were associated with case fatality rate while year of infection was not (Figure). While incidence rate of COVID-19 increased in 2021 compared to 2020 in HT recipients in France, the risk of ICU hospitalization and death did not decrease. Our findings highlight the reduced efficacy of mAb and vaccination in this population and the need for new prophylactic treatments. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Serology studies provide limited information on immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This cross-sectional study aimed to assess prevalence and determinants of anti-SARS-CoV-2 cellular immunity in a cohort of heart transplant (HT) recipients. All consecutive HT recipients followed-up at our outpatient clinic between February and June 2022 providing informed consent were included in this observational cross-sectional study. We quantified SARS-CoV-2 Spike (S)-reactive and Nucleocapsid (N)-reactive T cells using enzyme-linked immunospot assay. A positive response was defined as S or N reactivity >8 spots/2 × 105 lymphocytes. Clinical characteristics, laboratory data, immunosuppressive regimen and vaccination status were compared between patients with and without SARS-CoV-2 S-reactive T cells. Categorical variables were described as number (%) and continuous variables with median [IQR]. Among 201 patients (age 58 [45-65] years, 77% males, time since transplantation 51 months [24-81]), 97 (48%) exhibit S-specific T cells, of which 58 had in addition N-reactive T cells. CD4 and CD8 T lymphocyte count, glomerular filtration rate, immunosuppressive regimen were associated with T cell response (Table). Among patients with detectable SARS-Co-V-2 cellular immunity, numbers of S-reactive T cells were higher in patients who had detectable N-reactive T cells (277 vs 93 /106 T cells) (Figure). Our study provides new information on cellular immunity against SARS-CoV-2 in HT recipients. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Background: Recent studies reported poor to moderate humoral response after two vaccine doses in heart transplant recipients (HTR). Currently, French healthcare authorities recommend 2 and 3 vaccine injections for transplant recipients with and without prior SARS-CoV-2 infection, respectively. This study aimed to evaluate level and durability of humoral immunity with this vaccination strategy. Methods: This single-center cohort study included HTR followed at Paris Bichat hospital between January 2020 and September 2021. Analyses were performed using automated immunoassays (Abbot) to quantify anti-spike IgG (cut-off ≥ 7.1 BAU/mL) and anti-nucleocapsid IgG (cut-off index > 0.49), respectively. Categorical variables were described as number (%) and continuous variables with median (IQR). Results: A total of 181 HTR (75.7% males, age 58 y [47-66]) transplanted between June 1990 and June 2021, with cardiomyopathy (n=95), coronary artery disease (n=61), valvular cardiomyopathy (n=19) or other transplant indications were included. Median time from transplantation to first vaccine dose was 4.2 y [1.8-6.6]. 143 HTR (79%) had no SARS-CoV-2 infection history (HTRn) and 38 (21%) contracted the infection (HTRi) (56% before and 42% after vaccination initiation). After 2 vaccine injections, anti-S IgG seroconversion was observed for only 16% (n=12/76) of HTRn. Overall, anti-S IgG titers were lower in HTRn than in HTRi (0.5 [0.2-2.6] vs 578 [1.4-4449] BAU/mL, respectively, p=0.0001). The 3rd vaccine dose enabled to obtain 42% (n=33/72) of seroconversion among HTRn with median anti-S titers of 3.2 BAU/mL [0.4-35.0]. Only half seroconverters HTRn reached the 260 BAU/mL cut-off chosen by French authorities to define vaccination efficacy. Interestingly, these patients seem to have a sustained humoral response 4 months after the 3rd dose. Conclusion: This study gives new insights on the effect of the 3rd vaccine dose in HTR with low rate of seroconversion and low titers of anti-S IgG but sustained humoral response when seroconversion occurs. Studies on vaccine efficacy against SARS-CoV-2 variants and cell-mediated immune response in this cohort are ongoing.
ABSTRACT
Purpose The COVID-19 pandemic has deeply affected organ transplant activity across the world. During the first and second epidemic waves, the Agence de la biomedecine in agreement with the French scientific societies has pursued the heart transplant program where transplant's capacity was ensured. This study aimed to examine the impact of COVID-19 on new listings, waitlist outcomes and transplant activity in France. Methods All patients newly registered on the national waiting list for heart transplantation between January and September 2018-2020 were included in the study (n=1 311). The number of new listings and transplants per million population (pmp) in 2018-2019 period and in 2020 COVID era were compared. Cumulative incidence of transplantation and waitlist mortality estimated with the competing risk analysis with transplantation and death or delisting for medical condition as the competing events were compared between the study periods. Results In 2020 compared with the 2018-2019 period, the total number of patients newly registered on the waiting list declined 11%, from 6.8 to 5.9 pmp and the number of transplants performed decreased 22%, from 4.6 to 3.5 pmp. While 3-month cumulative incidence of transplantation (Figure 1) decreased from 51% [47-54] to 45% [40-50], a non-significant increase in cumulative incidence of death or delisting for medical condition (9% [7-11] versus 12% [9-15]) (Figure 2) was observed. Conclusion In 2020 COVID era, the waitlist and transplant access significantly declined in France without significant change in waitlist mortality.
ABSTRACT
Purpose Heart transplant recipients with SARS-CoV-2 infection are at high risk of poor outcomes. Given the high waitlist mortality in heart transplant candidates, the Agence de la biomedecine after discussion with the French scientific societies decided to pursue the transplant program where transplant's capacity was ensured. This study aimed to assess the impact of COVID-19 on heart recipient mortality in France. Methods All heart recipients with SARS-CoV-2 infection reported in the French national registry CRISTAL between February 1st and September 30th 2020 were included in the study (n=86). Patient characteristics were extracted from CRISTAL. Cumulative number of cases by month since February (Figure 1) and case fatality rate (CFR) were calculated. Mortality rates from February to September in the whole 2019 and 2020 recipient cohorts were compared. Survival curves were estimated using Kaplan-Meier method and compared using the log-rank test. Results Of the 86 patients included (median age (IQR) 59 years (46-67), 69% male gender, median time from transplantation 6.9 years (3.0-15.2)) 77% required hospitalization including 39% in ICU. Twenty patients died (CFR: 23%). No difference in 3-month survival was observed between 2020 and 2019 recipient cohorts (98.8% [98.5%-99.1%] versus 99.0% [98.7%-99.2%], respectively) (Figure 2). Conclusion While COVID-19 was associated with high fatality rate in heart transplant recipients, we could not identify an excess mortality in 2020 heart recipient cohort. These findings suggest that continuing heart transplant activity during the COVID-19 pandemic was a reasonable option.
ABSTRACT
Purpose Data on outcomes in lung transplant recipients with SARS-CoV-2 infection remains limited. Given the potential higher COVID-19 severity in lung recipients, the Agence de la biomedecine has limited the transplant program to patients with high-urgency status during the first epidemic wave. The program has been fully restored where possible during the second epidemic wave. This study aimed to assess the impact of COVID-19 on lung recipient mortality in France. Methods All lung recipients with COVID-19 reported in the French national registry CRISTAL between February 1st and September 30th 2020 were included in the study. Patient characteristics were extracted from CRISTAL. Cumulative number of cases by month since February (Figure 1) and case fatality rate (CFR) were calculated. Mortality rates from February to September in the whole 2019 and 2020 recipient cohorts were compared. Survival curves were estimated using Kaplan-Meier method and compared using the log-rank test. Results Of the 46 patients (median age (IQR) 51 years (39-60), 54% female, median time from transplantation 3.5 years (0.8-7.1)) 88% required hospitalization including 21% in ICU. Eight patients died (CFR: 17.4%). No difference in 3-month survival was observed between 2020 and 2019 recipient cohorts (98.6% 95%CI [98.0%-99.0%] vs 98.4% [97.8%-98.8%], respectively) (Figure 2). Conclusion COVID-19 was associated with lower fatality rate in lung recipients than in other organ transplant recipients and did not result in an excess mortality. These findings suggest that continuing lung transplant activity during the COVID-19 pandemic was a reasonable option.