ABSTRACT
Reduction in immunosuppression (IS) is universally recommended in the setting of infection, but its effect on outcomes in the setting of COVID-19 has not been established. The purpose of this study is to characterize the impact of IS reduction strategies on disease severity and outcomes of COVID infection in heart transplant patients (HTPs). This was a single center, retrospective review of HTPs with COVID infection managed inpatient or outpatient, examined in cohorts by approach to IS reduction. Demographics, severity at diagnosis and peak based on NIH Classification of COVID Illness Severity, and secondary clinical outcomes were collected (Table 1). The primary outcome was the difference in COVID severity score after IS regimen changes at time of diagnosis. Descriptive statistics, ANOVA, independent t-tests, and chi square analyses were used to evaluate baseline characteristics, primary outcome, and secondary outcomes. Data was collected for 110 patients with 113 COVID infections between March 2020 and June 2022. Patients were on average 54 years old, 75% white, 15% Hispanic ethnicity, and 5 years post HT at the time of their infection. Approaches to IS changes were antimetabolite (antiM) reduction (62%), all IS reduced (6%), or no change (32%). There was a significant difference in clinical severity from diagnosis to peak across all groups (p = 0.004), contributed largely by the All IS Reduced group with significantly higher peak severity (p = 0.002) leading to drastic IS reductions. In a sub-analysis to compare the protocolized approach of antiM reduction to no change in IS, no difference was noted in mortality, superimposed infections, or treated graft rejection (Table 1). Change in severity of infection over time is noted by variant in Figure 1. As COVID vaccination and therapeutic agents evolve, drastic IS modifications may not be necessary if baseline infection is mild. However, reduced duration IS reduction did not lead to more treated graft rejection. [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.)
ABSTRACT
Infections are major cause of morbidity and mortality after transplantation. Although many infections are common worldwide, there are differences in various geographic locations. South Asia and India, in particular, has a very active transplant program for kidney and liver transplantation, however, there are no guidelines as how to screen and provide prophylaxis to solid organ transplant (SOT) recipients and donors for both specific infections prevalent in this region along with usual infections. Keeping this in mind, a working group was created comprising transplant physicians, surgeons, and infectious disease specialists from South Asia as well as experts from other countries. This working group developed guidelines based on published evidence, unpublished data from large centers in this region, along with expert opinion. This section of the guidelines deals with pretransplant screening of donors and recipients, which should be useful in dealing with transplants performed in this region for patients belonging to these countries, for those coming for transplantation from other countries, and for programs outside of South Asia who are screening donors and recipients from this region or who have spent significant time in this region. Copyright © 2022 Indian Journal of Transplantation Published by Wolters Kluwer - Medknow.
ABSTRACT
Infections are common after solid organ transplantation (SOT) and are an important cause of significant morbidity and mortality. Many of these infections can be prevented or their severity reduced by vaccination in pre and posttransplantation period. It is better to complete the vaccination before transplantation as protection and seroconversion is better, and live vaccines are mostly contraindicated after SOT. Live vaccines should be given at least 4 weeks before transplantation but killed vaccines can be given up to 2 weeks before the planned transplantation. Vaccination for some diseases which are endemic in South Asia should be given, along with usual vaccinations. Serological monitoring is required for some vaccines to check their efficacy. Similarly, some vaccines are recommended for SOT recipients traveling to various endemic regions. Copyright © 2022 Indian Journal of Transplantation Published by Wolters Kluwer - Medknow.
ABSTRACT
Purpose: Emerging SARS-CoV-2 variants may be associated with a higher risk of breakthrough infections compared to wild-type (WT) virus in kidney transplant recipients (KTRs). The purpose of this study was to evaluate antiviral immune responses against WT and Delta (B.1.617.2) variant of SARS-CoV-2 after 3 doses of SARS-CoV-2 mRNA vaccines in KTRs. Method(s): We conducted a multicenter prospective cohort study of adult KTRs who received 3 doses of BNT162b2 or mRNA-1273. Blood samples were collected from KTRs before and 4 weeks after the 3rd vaccine dose. Sera from pre-pandemic healthy controls (HCs) and pre-pandemic kidney transplant control patients (KCs) were used for comparison. A Luminex-based multiplex assay was used to measure anti-spike antibodies for the WT, Alpha, Beta, Gamma and Delta variants of SARSCoV- 2. A surrogate virus neutralization test was used to assess neutralization against the WT and Delta variant. Patients were also monitored for rejection using several non-invasive biomarkers. Result(s): 54 KTRs were enrolled in the study. The median age was 63, 44% were female and the median time post-transplantation was 42 months. 94% received BNT162b2 vaccine. After the 3rd vaccine dose, there was a significant increase in anti-spike antibody MFIs against the WT, Alpha, Beta, Gamma and Delta variants (Fig. 1A, p<0.0001 for all). For comparison, all pre-pandemic HCs and KCs had a negative result for anti-spike antibody levels (Fig. 1B). Prior to the 3rd vaccine dose, 29% of KTRs had anti-spike antibodies against the WT compared to only 2% against the Delta variant (Fig. 1C, p=0.0001). After the 3rd vaccine dose, 67% of KTRs had anti-spike antibodies against the WT compared to 25% against the Delta variant (p<0.0001, Fig. 1D). Differences between WT and other variants are shown in Figure 1C-D. After the 3rd vaccine dose, there was a 2.1-fold and 2.5-fold increase in the percentage of KTRs with neutralizing responses against the WT and Delta variant respectively (p<0.0001 for both). There was no significant change in serum creatinine, proteinuria, or donor-derived cell-free DNA levels after vaccination. No episodes of rejection occurred during follow-up. Conclusion(s): Two doses of SARS-CoV-2 mRNA vaccines in KTRs are associated with minimal anti-spike antibody response directed against the Delta variant of SARS-CoV-2. After the third dose, a quarter of KTRs developed anti-spike antibodies directed against the Delta variant of SARS-CoV-2.
ABSTRACT
Background: There is limited data on the safety and efficacy of SARS-CoV-2 mRNA vaccines in kidney transplant recipients (KTRs). Methods: We conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines to assess vaccine safety and efficacy. Primary outcome was biopsy-proven rejection within 3 months of vaccination. Secondary outcomes included adverse events, serum creatinine, proteinuria, donor-derived cell-free DNA (ddcfDNA) levels, and antibody and cellular immunity generation against SARSCoV-2. Results: Median age was 62 with 41% females. Median time post-transplantation was 48 months. Only one patient (2%) developed acute cellular rejection though patient had been recently converted to belatacept. There were no severe adverse events or deaths during follow-up. Two patients (3%) developed SARS-CoV-2 infection, one of whom required hospitalization. There was no significant change in serum creatinine, proteinuria or ddcfDNA during the study. Following vaccination, 36%, 25% and 20% of KTRs developed anti-spike, anti-S1 and anti-RBD antibodies. KTRs on mycophenolate-based and steroid-maintenance regimens were less likely to develop an anti-spike antibody response. 100% of KTRs with anti-spike and anti-RBD antibodies had a neutralizing response, compared to 44% in KTRs with anti-spike but without anti-RBD antibodies (RR 2.25, 95% CI 1.08-4.67). There was a significant increase in IFN-gamma spots per 106 PBMCs incubated with S1 peptides following vaccination (p=0.0143). Conclusions: SARS-CoV-2 vaccination in KTRs was safe and associated with the generation of cellular immune response and in a third of patients with anti-spike antibody response. The degree of protection gained by these responses needs to be evaluated in future studies.
ABSTRACT
Purpose Outcomes of lung transplant recipients (LTR) hospitalized for COVID-19 and comparisons to non-lung solid organ transplant recipients (SOTR) are incompletely described. Methods Using a multicenter prospective registry of SOTR, we examined 28-day outcomes (mortality [primary outcome], intensive care unit (ICU) admission, mechanical ventilation, and bacterial pneumonia) among both LTR and non-lung SOTR hospitalized with laboratory-confirmed COVID-19 diagnosed between March 1, 2020 and September 21, 2020. Data were analyzed using Stata (StataCorp, College Station, TX);chi-square tests were used to compare categorical variables and multivariable logistic regression was used to assess risk factors for mortality. Results The cohort included 72 LTR and 392 non-lung SOTR (Table 1). Overall, 28-day mortality trended higher in LTR vs. non-lung SOTR (27.8% vs. 19.9%, P=0.136). Other 28-day outcomes were similar between LTR and non-lung SOTR: ICU admission (45.8% vs. 39.1%, P=0.28), mechanical ventilation (32.9% vs. 31.1%, P=0.78), and bacterial pneumonia (15.3% vs. 8.2%, P=0.063). Congestive heart failure, diabetes, age >65 years, and obesity (BMI >= 30) were independently associated with mortality in non-lung SOTR, but not in LTR (Table 2). Conclusion In this large prospective cohort comparing lung and non-lung SOTR hospitalized for COVID-19, there were high but not significantly different rates of short-term morbidity and mortality. Baseline comorbidities appeared to drive mortality in non-lung SOTR but not LTR. Further studies are needed to identify risk factors for mortality among LTR.
ABSTRACT
Background: Early reports suggest a possible increased risk of serious complications and death in COVID-19patients with cancer. However, rigorous comparisons with non-cancer control patients with COVID-19 are lacking. Methods: We systematically identified all patients with a history of cancer admitted to two major academic medicalcenters in Boston with symptomatic COVID-19 infections between 03/13/2020 and 05/10/2020. 162 cases wereidentified, and matched 1:2 by age, gender, race, and admission date with systematically identified controls withouta cancer history. Sociodemographics, comorbidities, presenting symptoms, hospital course, and COVID-19outcomes were extracted from medical records for all patients. Cancer history and treatments were documented forcases. Clinical characteristics and outcomes were compared between cases and controls using conditional logisticregression. Among cancer patients, logistic regression models were fit to identify predictors of death/discharge tohospice. Results: As of 06/05/2020, among 162 cancer patients (median time since diagnosis, 35.6 [range 0.39-435]months;80% with solid tumor, 20%, hematologic diagnosis), 27.8% died or were discharged to hospice and 4.3%were still hospitalized. Among the 324 controls, 25.6% died or were discharged to hospice, and 3.1% were stillhospitalized. Median duration of hospitalization was 9 days for both cases and controls. The proportion of controlswho were intubated (36.1%) was higher than cases (27.2%). The odds of mortality/discharge to hospice (vs.discharge to home/facility) were similar between cancer cases and matched controls (univariable OR: 1.15, 95% CI:0.73-1.82;multivariable OR: 1.54, 95% CI: 0.90-2.65). In multivariable analyses, cancer patients were more likely tobe immunosuppressed (OR: 4.21, 95% CI: 2.42-7.34), to have presented at hospital admission with fatigue (OR:1.71, 95% CI: 1.05-2.78), and were less likely to have a premorbid neurologic condition (OR: 0.37, 95% CI: 0.16-0.82). Among cancer cases, patients with metastatic disease or who had received cancer-directed therapy in thelast 6 months (n=74, 46%) did not have higher odds of death/discharge to hospice following their hospital course(univariable OR: 1.37, 95% CI: 0.68-2.75;multivariable OR: 1.77, 95% CI: 0.80-3.93) compared to patients with noevidence of disease and no treatment within 6 months. Conclusions: Patients with a history of cancer hospitalized for COVID-19 had similar hospital course and mortalityto matched hospitalized COVID-19+ controls without cancer. Additionally, we did not find an association betweenhaving metastatic disease or recent cancer treatment and experiencing an adverse outcome. During the onset andsurge peak of the COVID-19 crisis in Boston, people with a history of cancer admitted to two large teachinghospitals for COVID-19 infection fared no worse than those without a history of cancer.