Glycolytic stress deteriorates 229E virulence to improve host defense response.

Viral infection treatment is a difficult task due to its complex structure and metabolism. Additionally, viruses can alter the metabolism of host cells, mutate, and readily adjust to harsh environments. Coronavirus stimulates glycolysis, weakens mitochondrial activity, and impairs infected cells. In this study, we investigated the efficacy of 2-DG in inhibiting coronavirus-induced metabolic processes and antiviral host defense systems, which have not been explored so far. 2-Deoxy-d-glucose (2-DG), a molecule restricting substrate availability, has recently gained attention as a potential antiviral drug. The results revealed that 229E human coronavirus promoted glycolysis, producing a significant increase in the concentration of fluorescent 2-NBDG, a glucose analog, particularly in the infected host cells. The addition of 2-DG decreased its viral replication and suppressed infection-induced cell death and cytopathic effects, thereby improving the antiviral host defense response. It was also observed that administration of low doses of 2-DG inhibited glucose uptake, indicating that 2-DG consumption in virus-infected host cells was mediated by high-affinity glucose transporters, whose levels were amplified upon coronavirus infection. Our findings indicated that 2-DG could be a potential drug to improve the host defense system in coronavirus-infected cells.

Prevalence of adverse drug reactions associated with emergency department visits and risk factors for hospitalization

Objective: Adverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. Method(s): Observational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Result(s): 10,799 patients visited the emergency department and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 +/- 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24, 95% CI: 1.47-7.13, p = 0.003, in Charlson comorbidity index 4-6;and aOR 20.07, 95% CI: 6.87-58.64, p = 0.000, in Charlson comorbidity index >= 10). Conclusion(s): The prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.Copyright © 2022 Sociedad Espanola de Farmacia Hospitalaria (S.E.F.H)

The Impact Of Years Since Transplant On The Clinical Course After SARS-CoV-2 Infection In Heart Transplant Recipients

Introduction: The risk of Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2) infection and mortality is higher in heart transplant (HT) recipients compared to immunocompetent individuals. The impact of years since transplant on clinical course risk is unknown. We evaluated the differences in clinical phenotypes and outcomes according to years since transplant in HT recipients with active SARS-CoV-2 infection. Method(s): Consecutive HT recipients from our National Transplant Centre with confirmed SARS-CoV-2 between April 2020 and March 2022 were enrolled in this retrospective observational study. Patients were stratified into 2 groups: <5 years after HT (Group A) and >/= 5 years after HT (Group B). Result(s): A total of 63 HT recipients were enrolled [median age 56 (41,66) years, 32% female] with 33% of patients (n=21) assigned to Group A, and 67% (n=42) to Group B. In Group B patients, the prevalence of diabetes mellitus and cardiac allograft vasculopathy was significantly higher compared to those in Group A. Meanwhile, Group A patients were more likely to have a history of neutropenia prior to SARS-CoV-2 infection and were more frequently taking maintenance steroids and antimetabolite immunosuppressants (Table 1). Those recipients less than 5 years since HT were also significantly more likely than those >5 years out to develop the infection despite a 3rd dose of COVID vaccine (60% vs 31%, p 0.03).During the active infection, Group A recipients more frequently developed neutropenia (73% vs 27%, p 0.01), and trended towards higher rates of hospitalizations (57% vs 32%, p 0.06). Notably, none of the patients in Group A required mechanical ventilation compared to just under 10 % (n=4) of those in Group B. Further, no Group A patients died during the active infection hospitalization compared to 14% (n=6) of those in Group B. Conclusion(s): In HT recipients, years since transplant is a simple, clinically useful parameter stratifying outcomes after SARS-CoV-2 infection. While patients with less than 5 years since transplant are more likely to develop infection despite booster vaccination and require hospitalization, greater number of years since transplant was associated with more severe consequences during hospitalization.Copyright © 2022

A Study of Long-Term Outcome of Mycophenolate Dose Modulation in Renal Allograft Recipients With SARS-CoV2 Infection During COVID-19 Pandemic

Introduction: A significant reduction of acute rejection rates was observed after using Mycophenolate mofetil (MMF) in renal transplant recipients (RTR). However, side-effects like hematological and gastrointestinal intolerance often occur when MMF is used in routine doses.MMF dose reduction is required during its side-effects or co-existing infection in RTR.The outcome of MMF dose modulation in RTR is not well established. COVID-19 pandemic has given an opportunity to study the effect of MMF dose modulation on graft function as large number of RTR who had Covid19 received MMF dose reduction or discontinuation. This study's objective was to determine whether MMF dose reduction or discontinuation was associated with the effect on allograft function after renal transplantation. We included all RTR who had an infection with SARS-CoV2 and received MMF dose reduction or discontinuation Methods: We prospectively collected data of Renal transplant recipients developing covid 19 infection during the first and second covid waves. Management including decision on admission, immunosuppression modulation, antibiotics were done based on clinician's discretion subject to logistics and the prevailing guidelines by the ISOT. All patients were followed up for minimum 15 months for graft dysfunction, biopsy rate, biopsy proven acute rejection ( BPAR). The effect of immunosuppression modulation - MMF cessation (Group A) Vs MMF reduction/no manipulation (Group B) and its bearing on the incidence of rejection and was compared. Additional factors such as follow - up sub therapeutic CNI levels, development of DSA ( when done ), steroid increment were studied regression model. Kaplan - meier survival curves for 24 months drawn. Result(s): Among 251 renal transplant patients with SARS-CoV2 infection, 38 patients died during Index admission. 45 patients has not completed for 15 months.168 patients completed 15 month follow - up. Among them, anti-metabolite were reduced in 115 ( 68.5%), stopped in 42 (25%), not manipulated in 5 ( 3%) and 6 patients were not on anti-metabolites and hence excluded from present analysis. Of the 162 patients, MMF had been stopped for 2 weeks or until presumed clinical recovery in 42 patients ( Group A) and the rest in 120 patients ( Group B). Mean age was 41.18 ( +/- 12.8) and 75.6 % had mild COVID. Median duration of follow-up was 18 months ( 14q1-22q3 months). Total Readmission rate was 66 ( 40.7%) (Group A 21( 50%) Vs Group B 45 ( 37.5 %). Graft Biopsy was done in 16% of patients. 9.3 % patients had acute rejection ( 11.9% Vs 8.3%, p 0.05). Among those who had rejection, ABMR was seen in 2, ACR in 3, CABMR in 5 and combined rejection in 1. Conclusion(s): MMF dose modulation to tackle an infectious episode may be associated with graft dysfunction and rejection on follow-up and close follow up is needed in any patient in whom MMF dose in manipulated No conflict of interestCopyright © 2023

Clinical Profile, Immunosuppressive Managment and Outcome in Adult Renal Allograft Recipients with Covid-19 Infection: A Case Series from Single Centre in Bangladesh

Introduction: The Novel Coronavirus disease 2019 (COVID-19), a respiratory infection has become a global concern. Given to the extent of the COVID-19 pandemic, it has been explored that Renal Allograft Recipients are considered high risk group for unfavourable outcome due to multiple comorbidities, long term immunosuppressive medications and residual CKD. This case series demonstrates clinical characteristics and outcome of COVID-19 infection in Renal Allograft Recipients. Method(s): Here we present 20 adult Renal Allograft Recipients admitted with moderate to severe symptom and RT PCR confirmed COVID-19 infection at united hospital limited from August 2020 to December 2021. We assessed demographic characteristics, comorbidities, clinical and laboratory parameters, radiological findings, immunosuppressive management and outcome. Result(s): Among all,15 patients were male with median age 55 years (range,34-75years). Mean time interval between renal transplantation were 90 months (24-132 months). Common comorbidities were hypertension (n=19), DM (n=18), lung diseases (n=13), IHD (n=9). Fever (100%) was most common symptom followed by cough(80%), sore throat(75%), and diarrhoea(60%). Nine (45%) patients who presented with dyspnoea during admission further progressed to poor outcome. During admission mean baseline creatinine was 1.51mg/dl(0.66-3.1 mg/dl), 15 patients had lymphopenia and 11 patients had higher inflammatory markers like high ferritin level, CRP, procalcitonin, LDH and D-dimer. Total 15 patients had abnormal HRCT findings and most common finding was unilateral or bilateral Ground glass opacity followed by consolidation, pleural effusion and interlobular septal thickening with mean TSS scoring being 8 (range 4-16). All patients were on triple immunosuppressive regimen (antimetabolites, CNI, low dose steroid).After admission antimetabolites were withdrawn in all patients, CNI were continued in 10 patients, 50% reduction in 2 patients, complete cessation of CNI in 8 patients and low dose steroids were switched to dexamethasone 6mg/ day. Other treatments included antiviral (Favipiravir, Remdisivir), antibiotics, LMWH followed by Rivaroxaban. Total 3 patients received Tocilizumab and Convalescent plasma was administered in 2 patients. Among all, 18 patients received different form of oxygen therapy, 9 patients were transferred to ICU, 7 patients required mechanical ventilation and 4 patients developed ARDS. 8 patients had other bacterial or fungal coinfection. six patients developed AKI and 2 of them needed Renal replacement therapy (RRT). Total 4 patients of AKI and 1 patient who required RRT finally expired. Total 6 patients died and after a median 18 days of admission. Conclusion(s): In this case series we describe 30% mortality rate. Older age, severe symptom specially dyspnoea during presentation, multiple comorbidities, high inflammatory markers, high baseline creatinine developing AKI, high TSS score at HRCT and requirement of mechanical ventilation were associated with high risk of death. No conflict of interestCopyright © 2023

Kidney Transplantation during the Three Years (2020-2022) of Covid-19 Pandemic: Single-Center Experience

Introduction: During the first year of coronavirus disease (COVID)-19 outbreak, kidney transplant programs were suspended in several countries in the World. Republic of Belarus did not suspend organ transplant program carefully weighed the risks and benefits of pursuing or postponing kidney transplantation. In cooperation with national-level efforts, our transplant program adopted universal donor and recipient screening using reverse transcriptase polymerase chain reaction for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) with or without chest CT scans before kidney transplantation. Thus, national kidney transplant activities in Republic of Belarus remained stable for both living and deceased donor transplantation compared with the same period during the previous year. The objective was to study the safety of kidney transplantation, the incidence of COVID-19 disease in kidney transplant patients and medical care providing for transplanted patients during this pandemic period. Method(s): A retrospective review of all patients who had received a kidney transplant at State Institution "Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology" in Minsk, Republic of Belarus was performed from January 2020 to November 2022. Result(s): Dynamics of kidney transplantations number, clinical data of recipients during 3 years Covid-19 pandemic compared with the previous year are presented in table 1. The rate of infection in early postoperative period was low: 1,1% (2020), 0,5% (2021) and 0% (November 2022). In case of SARS-CoV2 infection modifications of immunosuppression (IS) therapy were based on the clinical conditions. For asymptomatic patients "wait and see approach" was mostly used;a suspension of antimetabolites drugs was adopted in the majority of patients with symptomatic COVID-19 infections. For CNIs, withdrawal was the preferred choice in severely symptomatic patients. A discontinuation of all IS drugs was used only in severely symptomatic COVID-19 patients on invasive mechanical ventilation. Since 2022 we started to use remdesivir in recipients with symptomatic course of disease with positive results. [Formula presented] From the middle of 2021 we commenced specific vaccination among transplanted patients. Most widely available vaccines in Belarus were CoronaVac (Sinovac Life Sciences, Beijing, China) and Gam-COVID-Vac (Gamaleya Research Institute of Epidemiology and Microbiology, Russia). There were no revealed any adverse effects of vaccination among our group. Conclusion(s): In our experience, the current kidney transplant program seems viable and safe, even during periods of health emergencies. No conflict of interestCopyright © 2023

Clinical Characteristics of Serologic Non-Responders to COVID-19 Booster Vaccination in a Cohort of Solid Organ Transplant Recipients

Purpose: The purpose of this study was to assess the clinical characteristics of serologic non-responders to COVID-19 booster vaccination in a cohort of solid organ transplant recipients. Method(s): All solid organ transplant recipients our center who received COVID-19 booster vaccination and had SARS-CoV-2 Spike IgG antibodies checked at least 4 weeks after the dose were included. We evaluated the patients who were found to have negative SARS-CoV-2 Spike IgG antibodies despite booster vaccination (i.e. serologic non-responders). Result(s): Among 657 solid organ transplant patients who had received a booster COVID-19 vaccination, 168 patients had Spike IgG antibodies checked during the study period. Forty-nine patients (29.2%) were found to be seronegative and were included in the analysis. 69% were male with a median age of 60 years. The majority of the cohort (47%) were kidney transplant recipients who had received primary vaccination series at a median of 206 days post-transplant. 65% had received basiliximab for induction immunosuppression. Most of the patients (65%) received primary vaccination with Pfizer COVID-19 vaccine and 67% received Pfizer COVID-19 booster vaccination at a median of 187 days after primary vaccination series. Spike IgG antibodies were checked at a median of 41 days from booster vaccination. No patients received rATG within 90 days of booster administration. Similarly, no patients received high dose (>250mg methylprednisolone equivalent) steroids within 30 days prior to booster vaccination. For immunosuppression, 27% were maintained on belatacept and 82% were on anti-metabolites at the time of the booster vacciantion. Ten patients (20%) experienced a COVID-19 infection postcompletion of their booster vaccination. Conclusion(s): In our solid organ transplant cohort, the majority of serologic nonresponders underwent basiliximab induction and were on an antimetabolite for maintenance immunosuppression. A limitation of our study was the use of different laboratory assays for determining IgG levels. Future work includes evaluating the clinical characteristics of COVID 19 booster serologic responders and comparing the two populations. (Table Presented).

Additional Dose of SARS-CoV-2 Vaccine Increases Neutralization Capacity in Solid Organ Transplant Recipients

Purpose: Solid organ transplant recipients (SOTR) develop weak antibody responses after SARS-CoV-2 vaccination. Published data on neutralizing activity of plasma, a better measure of protection, in SOTR following an additional dose of SARSCoV- 2 vaccine is limited. Method(s): Plasma was longitudinally collected from SOTR following initial COVID- 19 vaccination. Neutralizing activity against SARS-CoV-2 was assessed using the cPass Neutralization Antibody Detection Kit (GenScript, Biotech). ELISAs were performed against SARS-CoV-2 proteins (S1, N, RBD), CMV (glycoprotein B), Influenza A H1N1 (nucleoprotein), HSV-1, EBV glycoprotein (gp350), and tetanus toxoid for comparison. Result(s): Demographic and clinical characteristics are summarized in table 1. No participants had evidence of COVID-19 infection as IgG titers to SARS-CoV-2 N protein were low. Neutralizing activity against SARS-CoV-2 RBD was observed in 39.6% of individuals (N=21/53) ~93 days after initial vaccination. Participants with neutralizing activity were more likely to have received a liver transplant (47.6% vs 6.25%, p=0.001), and less likely to be on an anti-metabolite (52.4% vs. 87.5%, p=0.009) or triple immunosuppression (14.3% vs. 53.1%, p=0.008). After an additional vaccine dose, 78.1% (N=25/32) of participants developed neutralizing activity with significant increases in viral neutralization (figure 1, median 36.8% [95%CI 18.9-64.6] to 97.2% [95%CI 74.0-98.9], p<0.0001). Participants with low neutralizing activity demonstrated adequate antibody titers to other microbial antigens (figure 2). Conclusion(s): An additional dose of SARS-CoV-2 vaccine increased the number of SOTR with neutralizing activity and the magnitude of the seroresponse. SOTR with low neutralizing activity maintain humoral responses to other microbial antigens suggesting the diminished seroresponse might be related to inhibition of new B cell responses.

APN-Driven COVID-19 Monitoring Model for Kidney Transplant Patients

Purpose: COVID-19 infection in kidney transplant (KT) recipients is characterized by an unpredictable course and can be life-threatening. Prompt adjustment of immunosuppression and hospitalization when decompensated are potential strategies to increase survival. Our objective is to determine if advanced practice nurse (APN)-driven COVID-19 monitoring would result in better health outcomes for KT recipients. Method(s): We performed a retrospective study on KT patients diagnosed with COVID-19 between 4/1/2020 and 11/30/2021. The patients were stratified into two groups: (1) a control group who initially presented to the emergency department (ED) with COVID-19 symptoms, (2) an intervention group where patients were diagnosed with COVID-19 outside of the ED and followed by the APN team. The APNs monitored this group daily via telephone and/or video call for symptom assessment, immunosuppression adjustment, health counseling, and emotional support. If the patients were distressed, the APNs arranged admission to the nearest hospital or transplant center. Data were analyzed using Pearson Chi-squared for comparisons and linear or logistic regression modeling with adjustment for age, ethnicity, diabetes, and obesity Results: In our cohort, there were 102 KT patients that were infected with the SARS-CoV-2 virus. The majority were Hispanic ethnicity and male gender who presented with fever and flu like symptoms. Fourty-four patients required oxygen therapy. Immunosuppression was adjusted earlier in the intervention group . When the APNs recommended hospitalization, those patients experienced less acute kidney injury (AKI), shorter duration of illness, lower readmission rates, and greater survival than the control group. Conclusion(s): In this single transplant center study, KT recipients diagnosed with COVID-19 had better clinical outcomes when intervention occurred in a timely manner by the APN team. Possible explanations include earlier withdrawal of antimetabolites, prompt triage for hospitalization, and enforcing of nursing practices (dietary educations, blood pressure/glucose management, emotional support). Interpretation and generalization of these findings should be cautious due to a small sample size. As more treatment options for COVID-19 emerge, earlier interventions and close monitoring as demonstrated in our APN-driven model has the potential to achieve better health outcomes.

Clinical Features and Outcomes of Hospitalized Solid Organ Transplant and Hematopoietic Stem Cell Recipients with Sars- CoV-2 Infection in the Midwestern United States: A Multi-Center Retrospective Cohort Study

Purpose: Immunocompromised hosts are at risk for severe complications or death from SARS-CoV-2 infection. Few studies describe the clinical features, outcomes and treatment strategies in this population across multiple sites. Method(s): A multi-center retrospective analysis from academic medical centers in the Midwestern US was conducted for hospitalized patients with SARS-CoV-2 infection. Data was collected electronically using standardized intake and 28-day follow up case report forms. The centers included Northwestern University, University of Nebraska, Cleveland Clinic, University of Chicago, Indiana University and University of Kansas. Result(s): The cohort included 272 patients hospitalized from March 2020 to November 2021. Demographics are in Table 1. Mean admission was 6.84 +/- 6.42 days after symptom onset. The most commonly reported symptoms were cough (71.4%), dyspnea (59.6%), fatigue (55.3%), fever (54.9%), and diarrhea (43.9%). Admission CXR had pneumonia in 31.6%;63% with multifocal or patchy opacities. 87 patients had a chest CT;72 (82.7%) showed pneumonia. 97 patients (36.1%) required ICU admission. Treatments included remdesivir (58.5%), dexamethasone (54.4%), convalescent plasma (3.0%), IL-6 inhibitor (4.5%). Immunosuppression management included holding (44.2%) or decreasing (26.6%) the dose of antimetabolite. 76 patients (28.3%) had documented bacterial co-infection, in blood (34.1%), lung (30.6%) and urine (30.6%). 6 (2.2%) patients experienced rejection within 30 days and 8 patients (3.0%) developed CMV viremia. 26 patients (9.7%) died by day 28. Conclusion(s): This cohort had high rates of ICU admission (36.1%), bacterial coinfection (28.3%), rehospitalization (31.5%) and mortality (9.7%).

Impact of Immunosuppressive Medications on SARS-CoV-2 Vaccination Response in Kidney Transplant Patients

Purpose: The COVID-19 pandemic portends significant morbidity and mortality in immunocompromised individuals. Vaccination against COVID-19 among immunocompromised population is an essential step to minimize deadly complications. Numerous studies have shown an association between immune status, disease severity, and suboptimal responsiveness to vaccination. Additionally, data suggests that elevated IgG levels correlated with host viral neutralization. We herein present data indicating that induction and maintenance immunosuppression therapy affects responsiveness to vaccination among kidney transplant recipients. Method(s): The study data was retrospectively analyzed for 48 kidney transplant patients who received mRNA type COVID-19 vaccine at our institution. Majority of patients received vaccination between January and March 2021;two doses in total. The 30 days post-vaccination SARS-CoV-2 spike antigen-specific IgG levels were measured to assess immunological response to vaccine. Result(s): The included patients underwent kidney transplantation between 1983 and 2020. Among these patients, 35% showed detectable peak COVID IgG serum levels 30 days after the 2nd vaccine dose. A total of 31 patients (65%) did not show any response;majority of these non-responders (62%) were heavily immunocompromised, either on high dose Mycophenolate (at least 720 mg twice daily) in addition to standard Calcineurin inhibitor/Sirolimus+/-Prednisone), or had received high dose Thymoglobulin (6 mg/kg or more) within a year of vaccination. Among immunocompetent patients, over 95% immunological responsiveness or viral neutralization after the second vaccination dose has been reported. Conclusion(s): Anti-thymocyte globulin as induction immunosuppression and antimetabolites like Mycophenolate as maintenance immunosuppression serve as the cornerstone of transplantation management. However, their utilization impacts B cell proliferation, thereby reducing antibody production and the effectiveness of the SARS-CoV-2 vaccine in transplant patients. The ability of these immunosuppressive medications to suppress responsiveness to the SARS CoV-2 vaccine supports the need for 1) regular immunological surveillance post-vaccination among transplant patients, and 2) the need for a third or possibly fourth booster dose to achieve a sustained and effective response.

Management and Outcomes of Coronavirus Disease 2019 in Solid Organ Transplant Recipients

Purpose: The purpose of this study was to assess treatment of coronavirus disease 2019 (COVID-19) and immunosuppression modification in solid organ transplant (SOT) recipients, and identify risk factors that contribute to mortality among SOT recipients with COVID-19. Method(s): The primary endpoint was 90-day mortality. Secondary endpoints include COVID-19 treatment regimen, laboratory abnormalities, maintenance immunosuppression modification, concomitant infections, complications such as renal replacement therapy (RRT) and more. This retrospective chart review included all SOT recipients who presented to our institution with a positive COVID-19 test over an 18-month period. Dual organ transplant recipients were excluded. Result(s): A total of 112 patients met inclusion criteria. The average age was 56 +/- 13 years and 58% of patients were male. The majority of patients identified as Latino (39%), followed by African-American (29%) and Caucasian (28%). Forty-nine percent required treatment in the intensive care unit. Inflammatory markers were elevated in the majority of patients. Most immunosuppression modification strategies held antimetabolites and prednisone if receiving treatment with glucocorticoids. The primary endpoint of 90-day mortality was observed in 24% (27/112) of patients. Mortality rates by organ type can be found in Table 1. Common comorbidities in these patients are depicted in Figure 1. There was no significant difference in mortality between patients receiving remdesivir 12/27 vs. 20/85 (p=0.05). A 50% (4/8) mortality rate was observed among patients who received rabbit antithymocyte globulin within 6 months of COVID-19 infection (p=0.09). Concomitant respiratory infections showed a statistically significant difference in mortality 12/27 vs. 9/85 (p<0.05). All 6 patients that required extracorporeal membrane oxygenation expired. Fifty-two percent (14/27) of patients in the mortality group required RRT vs. 7% (6/85) of those that survived (p<0.05). While most cases were prior to the advent of COVID-19 vaccines, all 9 patients that received at least one dose of any COVID-19 vaccine prior to infection survived at 90 days. Conclusion(s): Concomitant respiratory infections and RRT were significant predictors of mortality among SOT recipients with COVID-19. Administration of rabbit antithymocyte globulin within 6 months of COVID-19 infection and treatment with remdesivir should be investigated in future studies as they may demonstrate significant associations in a larger sample size.

Antibody Response to 3-Dose SARS-CoV-2 mRNA Vaccination in Pediatric Solid Organ Transplant Recipients

Purpose: We report the immunogenicity and safety of a third BNT162b2 vaccine in pediatric solid organ transplant recipients (pSOTRs). Method(s): Samples from pSOTRs (12-18 years) enrolled in our multicenter, observational study (COVID-19 Antibody Testing of Recipients of Solid Organ Transplants and Patients with Chronic Diseases) who received a third vaccine (V3) were analyzed for antibodies to SARS-CoV-2 spike protein receptor-binding domain, with a positive cutoff of >=0.8 and maximum titer of >2500 U/mL. Pre-V3 samples were 1-3 months after vaccine 2, and post-V3 were 1 month after vaccine 3. Result(s): Thirty-seven pSOTRs (46% heart, 24% liver, 27% kidney, 3% multi) received V3. Median (interquartile range [IQR]) age was 15 (14-16) years;42% were male and 78% white. pSOTRs were median (IQR) 9 (6-13) years from transplant. Four (11%) patients had prior SARS-CoV-2 infection. Antibody titers were positive in 26/37 (70%) patients pre-V3 and 32/37 (86%) post-V3 (Figure). Median (IQR) antibody titers were higher post-V3 (2500 [1581-2500] U/mL) than pre-V3 (211 [0.8-2500] U/mL) in paired analysis (p<0.001). 6/11 (55%) pSOTRs with negative pre-V3 titers seroconverted, with a post-V3 median (IQR) titer of 418 (132-1581) U/ mL. Transplant within 3 years was associated with negative post-V3 titer (p=0.037). Main side effects after V3 were pain (71%) and fatigue (50%). No patients reported allergic reaction, myocarditis, or rejection. One patient tested positive for SARSCoV- 2 between vaccines 2 and 3, with negative pre- and post-V3 titers. At time of first vaccine, this patient was transplanted a year ago, treated for rejection recently, and taking 3 immunosuppression agents including an antimetabolite. Conclusion(s): In this limited cohort, 86% of pSOTRs had a positive antibody response after three SARS-CoV-2 vaccines with no adverse events. Importantly, 55% of pSOTRs with prior negative response seroconverted post-V3, and 100% of pSOTRs with positive response increased their antibody titer or remained at maximum titer. Our preliminary results suggest the benefit of a third vaccine for adolescent pSOTRs based on antibody response;larger studies are needed to assess vaccine effectiveness.

Use of Monoclonal Antibodies for Treatment of Solid Organ Transplant Recipients with COVID-19: A Single Center Experience

Purpose: The risk of severe COVID-19 requiring hospitalization and death is higher in solid organ transplant recipients (SOTr). There remains limited data on the use of monoclonal antibodies and long-term outcomes in SOTr. Method(s): This is a retrospective study conducted at Jackson Health System-Miami Transplant Institute in SOTr with mild-moderate COVID-19, from November 2020 to October 2021. Bamlanivimab was used initially for outpatients with mild to moderate COVID-19 but switched to casirivimab/imdevimab on March 1, 2021, due to rising prevalence of SARS-CoV-2 variants in the Miami-Dade area. Outcomes assessed included emergency department visits, hospitalizations, allograft rejection, and death. Result(s): Ninety-two patients were treated, most commonly with casirivimab/imdevimab (74%). The median age was 51 (range, 18-81) years, with 61% male and 60% Hispanic ethnicity. Transplanted organs included 68 kidney (74%), 10 liver (10.8%), 10 heart (10.8%), and 7 lung (7.6 %). Forty-two (45.6%) had a vaccine breakthrough infection, of which 34 (80.9%) were during the delta variant predominance. The median time from positive SARS-CoV-2 test to administration of monoclonal antibody was 1 (range, 0 - 10) day. Anti-metabolite agents were decreased or held in 54.3% of cases. Median follow-up was 116 (range, 19 - 358) days. Five (5.8%) patients had an emergency department visit, 26 (28.2%) were hospitalized;of which 11 (42%) were due to worsening COVID-19 symptoms within 28-days of infusion. 63.6% (7/11) required supplemental oxygen, none required mechanical ventilation. The median hospital length of stay was 6 (range, 2-32) days and all patients were discharged alive. During follow-up, 6 (4 kidney, 2 heart;6.5%) developed biopsy proven rejection. No graft loss or death occurred in this cohort. Conclusion(s): Early use of monoclonal antibodies in SOTr is associated with favorable outcomes. Multi-center studies assessing use of monoclonal antibodies in breakthrough infections and association with allograft rejection are needed.

Three Month Antibody Durability and Kinetics in SARS-CoV-2 Mrna Vaccinated Heart and Lung Transplant Recipients: Differences Above the Diaphragm

Purpose: Heart and lung transplant (HT/LT) recipients have impaired humoral responses to SARS-CoV-2 vaccination compared to other solid organ transplant recipients (SOTRs). The purpose of this study is to describe antibody titer kinetics and durability among HT and LT recipients. Method(s): HT or LT recipients (> 18 years) with no known COVID-19 infection were included. Demographics and clinical characteristics were collected via survey. Serologic testing was performed on the Roche Elecsys anti-SARS-CoV-2 enzyme immuno-assay (EIA) or the EUROIMMUN EIA pre- and post-dose 2 (D2). Result(s): Among 93 HT recipients, 59 (63%) were seropositive 1 month and 66 (71%) 3 months post-D2 (Table 1). Seropositive HT recipients had a higher median length of time from transplant to vaccination. 7/66 (11%) had delayed seroconversion (were negative for antibodies 1-month post-D2). Median(IQR) anti-RBD was 81 (8, 250) 1-month post-D2 (n=38) and 231 (48, 438) U/mL 3-months post-D2 (n=43) (Figure 1). Among 68 LT recipients, 29/68 (43%) were seropositive 1-month and 30 (44%) 3-months post-D2. Seronegative LT recipients were more likely to younger (18-39 years old, 15% vs 3%), or older (> 60 years, 74% vs. 50%, p=0.01). Seronegative LT recipients were more likely to be on anti-metabolite therapy (79% vs. 53%, p=0.04) and had a lower median length of time from transplant to vaccination. Among seropositive LT recipients at 3-months, 3 (10%) had delayed seroconversion. Median (IQR) anti-RBD was 61 (4, 233) U/mL 1-month post-D2 (n=26) and 45(11, 299) U/mL 3-months post-D2. Conclusion(s): HT and LT recipients develop a delayed and variable antibody response to mRNA SARS-CoV-2 vaccination. HT recipients more frequently seroconverted, and had higher anti-RBD levels, than LT recipients. Persistent negative and low antibody titers may place LT recipients at the highest risk of breakthrough SARSCoV- 2 infection among SOTRs.

Decreased Mortality from Sars-CoV-2 Infection in Kidney Transplant Recipients Over the Course of the Pandemic

Purpose: We aimed to investigate the mortality from SARS-CoV-2 in kidney transplant recipients in the Bronx, New York since the beginning of the pandemic Methods: Between March 16, 2020 and November 5, 2021, 453 patients were diagnosed with SARS-CoV-2 infection. 316 were diagnosed by RT-PCR while the remaining 137 tested positive for anti-SARS-CoV-2 nucleocapsid IgG and did not have significant symptoms and had not been previously tested by RT-PCR Results: Of the 316 patients diagnosed by RT-PCR, 214 patients were hospitalized while 102 patients were managed at home as outpatient. 194 (61.3%) were male, median age 61 years old (IQR: 48-69), predominantly Hispanic (56.2%) and African American (29.5%). 75% received a deceased-donor renal transplant, 58% received anti-thymocyte induction. Most patients were on triple immunosuppression (95% on calcineurin inhibitors, 87% on anti-metabolite, and 97% on prednisone). Hypertension was the most common comorbidity followed by diabetes mellitus, heart disease and lung disease. A total of 65 patients (20.5%) died. The mortality rate was 37 % (47/128) in patients diagnosed between March 16 and April 30, 2020. From May 1, 2020 to end of December 2020 mortality rate has significantly decreased to 11% (7/61). Since the beginning of 2021 till November 5, 2021 the mortality rate is 7.7% (10/129). Twenty-seven patients were diagnosed with COVID-19 despite being partially of fully vaccinated (25 fully vaccinated, 2 after one dose of vaccine). 13/27 (48%) were managed at home while 14/27 (52%) were hospitalized and 2 (7%) of them died. Twenty-eight patients received treatment with casirivimab and imdevimab post diagnosis of SARS-CoV-2 starting 2021 and none of those patients have died. Conclusion(s): In summary, mortality from SARS-CoV-2 infection in kidney transplant recipients was higher earlier at the pandemic and has significantly decreased over time. This could be explained by initial exposure of the patients with higher viral load due to lack of personal protection and social distancing. However, since the judicious use of monoclonal antibodies and vaccination, in addition to social distancing protocols and use of facemask, the mortality in kidney transplant recipients has decreased over time.

Association Between Maintenance Immunosuppressive Regimens and COVID-19 Mortality in Kidney Transplant Recipients

Purpose: Kidney transplant recipients (KTR) are at increased risk of mortality from COVID-19. We conducted a cohort study among KTR from the French Solid Organ Transplant COVID-19 (SOT COVID) registry to investigate the association between maintenance immunosuppressive drugs and 60-day mortality in KTR with COVID-19. Method(s): Data from all KTR with COVID-19 included in SOT COVID 02/28/2020 and 12/30/2020 were retrieved. Among them, 116 were excluded because of missing data on immunosuppressive therapy. We evaluated associations between immunosuppressive drugs and death <=60 days of 1st symptoms using logistic regression, with all baseline characteristics considered to influence outcome or immunosuppressive regimen. Benjamini-Hochberg correction was used for controlling false positive rate;40 multiple imputations were performed. Adjusted p-value <0.05 was considered statistically significant. Result(s): There were 1,451 KTR included. Median age was 58 years, 963 (66.4%) were men. Most frequent comorbidities were hypertension (n=1188, 81.9%), diabetes (501, 34.5%), cardiovascular disease (428, 29.5%). Median time since transplant was 71 months. Maintenance immunosuppression regimen included calcineurin inhibitors (1295, 89.2%), antimetabolites (1205, 83%), corticosteroids (1094, 75.4%), Mammalian Target of Rapamycin inhibitors (144, 9.9%) and belatacept (58, 4.0%). Among 1,451 KTR, 201 (13.9%) died <=60 days. Older age and baseline creatininemia were associated with mortality (OR: 1.09 [1.07-1.11];1.01 [1.005- 1.009], p<0.001). Corticosteroid-free regimens were associated with a significantly lower risk of death (OR: 0.48 [0.31;0.76], p=0.011). All other variables yielded non-significant adjusted p-values. Conclusion(s): Corticosteroid-free regimens were associated with a lower risk of death in KTR with COVID-19. While a short course of high-dose corticosteroids is beneficial in severely ill COVID-19 patients, prolonged maintenance corticosteroids expose to chronic immune disorders that may predispose KTR to severe forms of COVID-19.

Safety and Efficacy of Peri-Vaccination Antimetabolite Hold to Augment Third SARS-CoV-2 Vaccine Dose Response in Lung Transplant Recipients

Purpose: Lung transplant recipients (LTRs) are less likely than other solid organ transplant recipients (SOTRs) to develop an antibody response to SARS-CoV-2 vaccination. Mycophenolate has been associated with impaired humoral response to SARS-CoV-2 vaccination, leaving these patients vulnerable to infection. Perivaccination antimetabolite hold has been an effective strategy for some patients with rheumatic and musculoskeletal diseases. In this study, we describe the safety and efficacy of a peri-vaccination antimetabolite hold in LTRs on SARS-CoV-2 anti-spike protein development following a third vaccine dose. Method(s): We studied LTRs on mycophenolate or azathioprine based antimetabolite therapy (AMT) >1-year post-LT with no history of acute cellular or humoral rejection who received SARS-CoV-2 vaccine Dose 3 (D3) May-October 2021. Patients were instructed to hold AMT 1 week before and 2 weeks after D3. Antibody titers were measured pre- and post-D3 (Roche Elecsys or DiaSorin Liaison anti-S EIA). Safety was evaluated using donor specific antibody (DSA) trend and lung biopsy results. Result(s): Of 40 participants, 30 held AMT and 10 did not hold AMT. Median (IQR) time since transplant was 3.9 years (1.9-7.3). Median (IQR) time between vaccine dose 2 and D3 was 163 days (143- 180). Among participants seronegative pre-D3, seroconversion post-D3 occurred in 52% (12/23) who held AMT vs. 57% (4/7) who did not hold AMT (p>0.9). Among patients with pre- and post-D3 DSA levels (N=19), increasing or de novo positive DSA was seen in 8.3% (1/12) of patients who held AMT vs. 0% of patients who did not hold AMT. For patients who underwent lung biopsy post-D3 (N=8), abnormal biopsy was seen in 0% (0/1) of patients holding AMT vs. 28.6% (2/7) not holding AMT. Conclusion(s): A three-week AMT hold by LTRs was not associated with increased rejection but also showed no significant difference in seroconversion compared to LTRs who did not hold AMT, suggesting this hold protocol is safe but not effective. Further investigation of alternative strategies is needed to protect LTRs from COVID-19 infection who do not mount effective immunoprotection following SARS COV-2 vaccination. (Table Presented).

Effects of Race, Previous CoV2 Exposure and the Length and Type of Maintenance Immunosuppression on Protective Immunity to COVID19 Vaccine in Solid Organ Transplant Recipients

Purpose: The diverse factors affecting the vaccine induced neutralizing antibody response in solid organ transplant recipients and their immunity against CoV2 variants are needed to be well characterize to understand how we improve the vaccine efficacy. Method(s): Anti-CoV2 receptor binding domain (RBD) plasma antibody response and their neutralization potency in 29 kidney and 22 heart transplant patients was determined with recombinant RBD protein binding ELISA and by calculating the 50% virus neutralization titer of the plasma antibody with ACE2-Hu-HeLa cell based pseudo virus neutralization assay against CoV2 wild type and delta variant. Result(s): We detected strong binding and protective neutralizing plasma antibody response in SOTR who were infected with CoV-2 either prior to or after the first dose of vaccine (n=8), who showed high median IC50 value > 10,000 against both the CoV2 wild type strain and the more transmissible delta variant. In contrast to this, the CoV2 uninfected and vaccinated SOTR ( naive vaccinees, n=43) had considerably lower anti-RBD plasma antibody binding titers, and only 19% of this population possessed minimally protective neutralizing antibody titer (IC50 >50) against the wild type CoV2 strain, which further decreased to 10% against the delta variant. While IgG and IgA were dominant isotypes of anti-RBD antibody induced by the CoV2 vaccines and correlated significantly (r=0.84, p=<0.001) with the CoV2 neutralization. The COV2 uninfected SOTR vaccinees who were within 1.5 years from transplantation or African American ethnicity were less likely to have detectable vaccine induced neutralizing antibody responses than the other populations. In the naive vaccinees, administration of corticosteroids in combination with calcineurin or mTOR inhibitors and antimetabolites also negatively affected the CoV2 antibody responses, while female and younger organ transplant recipients tended towards higher IgM and IgA titers. Kidney transplant recipients showed better IgG responses vs heart transplant recipients and elevated serum creatinine levels correlated with poorer antibody response to the vaccines in both kidney and heart transplant groups. Conclusion(s): These results suggest that in the absence of immunity due to CoV2 infection, vaccination in SOTRs induces much lower protective antibody levels than in healthy controls and identifies African-American ethnicity, less than 1.5 years post transplantation as additional risk factors that further exacerbate these effects. Poor kidney function negatively affected the vaccine induced antibody response.

ONE MORE FEATHER IN THE CAP (DECITABINE): YET ANOTHER CASE OF CHEMOTHERAPY-INDUCED LUNG INJURY

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Lung toxicity due to antineoplastic therapy is reported with both cytotoxic and molecularly targeted agents [1]. We present one such case of lung injury induced by capecitabine. CASE PRESENTATION: A 79-year-old female with history of triple negative infiltrating duct carcinoma of the right breast (status post mastectomy and adjuvant chemotherapy with docetaxel and cyclophosphamide 3 years prior) presented to the hospital with dyspnea on exertion following her fourth cycle of capecitabine therapy for breast cancer recurrence. Patient developed nausea, vomiting, and malaise with cycles 1, 2, and 3 of capecitabine therapy with onset of severe dyspnea on exertion, cough, and hypoxia following cycle 4. Computed tomography (CT) scan of the chest on admission showed consolidative opacities in the right upper, right middle, and anterior right lower lobe along with smaller opacities in the left lung apex and small subcentimeter nodules;no pulmonary embolism. Antibiotics were given for a short duration for suspected pneumonia without improvement. Capecitabine was held on discharge. She presented again to the emergency room with worsening shortness of breath, diarrhea, fatigue, and dizziness. COVID test was negative. Chest x-ray redemonstrated patchy airspace disease involving the right apical, lateral, mid lower lung field. Oral steroids were recommended for suspected organizing pneumonia, but the patient refused due to concerns about side effects. Her hospital course was complicated by Clostridium difficile infection (treated with oral vancomycin) and left lower extremity deep venous thrombosis (treated with anticoagulation). Subsequently she followed up with pulmonology outpatient. Repeat imaging showed evolving infiltrates in the same areas with elevated aspergillus IgG level (18.0 mcg/ml) and IgE (178 kU/L) but negative galactomannan and sputum bacterial/fungal/acid fast cultures. Oral steroids were initiated with clinical and symptomatic improvement. DISCUSSION: Capecitabine is a prodrug of fluorouracil (antimetabolite). It is used as a chemotherapy agent in multiple types of cancer including breast cancer. Respiratory side effects include cough (<7%) and bronchitis (<5%). Lung injury/pneumonitis is a rare complication with only a few cases reported to date [2,3]. The timing of symptoms with chemotherapy administration and the negative infectious work-up supports capecitabine as the inciting etiology of lung injury. Withholding chemotherapy and starting systemic steroids were effective treatments in this case of chemotherapy induced lung toxicity. CONCLUSIONS: Capecitabine induced lung injury is a rare but important entity and should always be kept in mind while evaluating dyspnea in cancer patients. Reference #1: Capri G, Chang J, et al. An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer. Ann Oncol. 2010;21(3):474. Epub 2009 Oct 8. DOI: 10.1093/annonc/mdp373 Reference #2: C. J. Benthin, G. Allada. Capecitabine-Induced Lung Injury. American Journal of Respiratory and Critical Care Medicine 2016;193:A1653. Reference #3: Andrew K Chan, Bok A Choo, John Glaholm. Pulmonary toxicity with oxaliplatin and capecitabine/5-Fluorouracil chemotherapy: a case report and review of the literature. Onkologie. 2011;34(8-9):443-6. doi: 10.1159/000331133. Epub 2011 Aug 19. DISCLOSURES: No relevant relationships by William Karkowsky No relevant relationships by Chahat Puri No relevant relationships by Sahib Singh