Trying to Protect HT Patients Poor Vaccine Responders: Reducing MMF or Trust Tixagevimab/Cilgavimab? Insights from CONTRAST Study

Heart transplanted (HT) patients (pts) are poor responders to booster doses;there is an unmet need to find strategies to protect this fragile category of pts in the context of Omicron variants. It has been suggested that MMF could limit the immune response to vaccine. Tixagevimab/cilgavimab (T/C) has been approved for prophylaxis, but there are still few data on its safety and efficacy. We present our experience with T/C and with the reduction of MMF after the third (booster dose). All HT pts followed in our Center after November 2021 (when Omicron became the dominant in our Country) without significant anti-RBD antibodies (<100 ng/ml) after the booster dose were selected: before T/C availability, we reduced of 50% the dose of MMF one week before and after the forth dose if there was no recent rejection;after its availability, we interrupted this approach. The endpoint is the incidence of SARS-CoV-2 infection at two months in both strategies and the safety of T/C. 379 pts (23.1% vaccinated with 4 doses, 62% with 3 doses, 11.5% 2 doses, 3.4% not vaccinated) had 103 infections (4 reinfections), with an incidence of 20.0±2.2% at 6 months from the last dose of vaccine;17.4% were hospitalized, 3 pts (2.9%) died, one of whom was not vaccinated. 24.2% received antivirals, 13.5% sotrovimab without adverse effects and 100% survival.38% of 200 pts had low anti-RBD antibodies after the third dose. Among 84 undergoing to the forth dose, 41/57 for whom antibodies were known had low levels: 8 underwent to MMF reduction, in 23 the dose ws unchanged. The incidence of COVID-19 infection was 18.8±6.9% at two months and 26.5±8.1% at 6 months, with a borderline significant difference between the group were MMF was reduced compared to the one where it was unchanged (p=0.06).28 patients underwent to tixagevimab/cilgavimab (T/C) administration;the incidence of COVID-19 was 6.6±6.4% at two months. No adverse effects were noticed. While confirming the good outcomes of Omicron variants in a HT pts with high prevalence of vaccination and with the actuarial therapies, this small observational study suggests that in patients without detectable anti-RBD antibodies after the booster dose, MMF reduction may be somehow v beneficial, but T/C appears to give a better protection against the infection in the first two months. Larger studies are needed to confirm these results. [ABSTRACT 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 abstract 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 abstract. (Copyright applies to all Abstracts.)

Exposure to psychotropic medications and COVID-19 course after hospital admission: Results from a prospective cohort study.

OBJECTIVE: There is evidence of a bidirectional association between COVID-19 disease and psychiatric disorders. We aimed to assess whether exposure to psychotropic medications prior to hospitalization was associated with mortality or discharge within 30 days after hospital admission. METHODS: In this prospective study, we included all individuals with a laboratory-confirmed COVID-19 infection who were admitted to the Bologna University Hospital between 1st March 2020 and 31st January 2021. We collected data about pre-existing psychiatric disorders and the use of psychotropic medications at the admission. As univariate analyses, we estimated cumulative incidence functions for 30-day mortality and discharge stratifying by exposure to each of the psychotropic medication classes. Finally, we fitted Cox regression models to estimate cause-specific Hazard Ratios (HR) of 30-day mortality and discharge. Results were adjusted for sociodemographic (age, sex), clinically relevant variables (comorbidity, c-reactive protein levels, severity of disease at presentation, history of smoking, study period), and psychiatric variables (psychiatric disorder diagnosis, number of psychotropic medications). RESULTS: Out of a total of 1238 hospitalized patients, 316 were prescribed psychotropic medications at the time of admission. Among these, 45 (3.6%) were taking a first-generation antipsychotics (FGA) and 66 (5.3%) a second generation antipsychotic (SGA). Exposure to SGA was associated with increased rates of 30-day mortality (HR = 2.01, 95%CI = 1.02-3.97) and exposure to FGA was associated with decreased rates of 30-day discharge (HR = 0.55, 95%CI = 0.33-0.90). CONCLUSION: Patients with COVID-19 infection exposed to FGA and SGA may have worse COVID-19 infection outcomes.

Evaluation of breakthrough infections in solid organ transplant recipients: the prospective CONTRAST cohort

Background. Solid organ transplant (SOT) recipients are at higher risk than general population for complicated COVID-19 course. Moreover COVID-19 vaccination in this setting is associated with a suboptimal immune response. However, the impact of this finding on the risk of breakthrough infection (BI) in SOT recipients has to be yet determined. Methods. Single-center prospective longitudinal cohort of adult SOT recipients who received three doses of mRNA COVID-19 vaccine between February and December 2021 and were followed up to March 30 2022. Patients were tested for antibody response at several timepoints (1 st dose, 2 nd dose, 3+/-1 month after 1 st dose, and 1 month after 3 rd dose). Main endpoints were: i) BI defined as laboratory confirmed SARS-CoV2 infection diagnosed >=14 day after 2 nd dose;ii) positive antibody response (AbR) defined as anti-rapid binding domain titer >=5 U/ml determined by Elecsys Anti-SARS-CoV-2 ECLIA assay (Roche Diagnostics, CH), the last available determination before BI was considered. Results. Study cohort consists of 642 SOT (277 kidney, 191 liver, 144 heart, 37 lung) recipients: 63.9% males, median age 54 +/- 14.5 years. Of them, 111 (17.8%) developed BI, BI rates were 19.9%, 18.1%, 15.2% and 10.8% among liver, heart, kidney and lung transplant recipients, respectively. Positive-AbR was observed in 60% of all patients, but rates varied from 8.7% to 91.3% among patients with BI and without BI, respectively. Predictors of BI infection at multivariable analysis were liver (vs. other grafts) transplant (OR 2.98, 95%CI 1.47-6.03), mycophenolate (1.63, 0.92-2.88) and steroids (1.8, 1.05- 3.33), while positive-AbR (0.61, 0.35-1.04) and age (0.97, 0.95-0.99) were protective. On the other hand, liver transplant (1.94, 1.02-3.69), time from transplant (1.09, 1.05-1.21), and Moderna vaccine (2.32, 1.46-3.70) were associated with positive-AbR, while age (0.97, 0.95-0.98), heart transplant (0.56, 0.33-0.96), mycophenolate (0.65, 0.39-1.06) and steroids (0.39, 0.23-0.65) with lower probability of positive-AbR. Conclusion. Although associated with positive-AbR, liver transplant and younger age were also BI predictors, suggesting the importance of social factors and the controversial role of immune monitoring.

Enoxaparin in COVID-19 moderate to severe hospitalized patients (INHIXACOV19)

Background : COVID-19 (Coronavirus Disease 2019) is associated with High rates of thrombosis in hospitalized patients leading to varying pharmacologic thromboprophylaxis use based on rapidly changing societal guidance, institutional protocols from local expertise, and geographic patterns of practice. Aims : To assess the efficacy and safety of enoxaparin in hospitalized patients with moderate to severe COVID-19 infection. Methods : Phase II single-arm interventional prospective study including all patients treated with the study drug and an observational prospective cohort study including all patients screened for receiving the study drug but not included in the phase II study. Each patient was followed-up for a minimum of 90 days after COVID19 diagnosis. Patients included in the interventional study received subcutaneous enoxaparin in a single daily dose of:60 mg once daily in case of body weight of 45 to 60 kg 80 mg per day in case of weight from 61 to 100 kg or 100 mg once daily in case of bodyweight >100 kg for 14 days, with dose adjustments on the basis of anti-factor Xa activity monitoring. Patients included in the observational cohort received standard thrombo-prophylaxis with subcutaneous enoxaparin 40 mg/die. Primary outcomes were all-cause in-hospital 30-day and 90 mortality rates. Secondary outcomes were the proportion of patients in the severe or critical stage of disease at the end of treatment, proportion of patients who developed major and non-major bleeding events and thromboembolic complications, time to first negative RT-PCR on nasofaringeal swab, reduction of viral load in blood. Results : Recruitment of 100 patients enrolled phase II single-arm interventional prospective study has been completed, while the recruitment of 200 patients in the observational prospective cohort study is ongoing. Conclusions : Full results will be available by June 2021.