The solid organ transplant recipient with SARS-CoV-2 infection.

PURPOSE OF REVIEW: The COVID-19 pandemic is a major challenge to global health, particularly among vulnerable populations. Here, we describe the emerging epidemiology and relevant data on treatment options for COVID-19. We discuss the implications of current knowledge for solid organ transplant (SOT) recipients. RECENT FINDINGS: Risk factors and outcomes of COVID-19 among SOT recipients remain uncertain, but recent data suggest similar outcomes to the general population. Case reports of donor-derived SARS-CoV-2 infection are emerging. Few studies on treatment of COVID-19 among SOT recipients are available, and therefore, general recommendations are similar to the general population. Vaccine efficacy in the SOT population is uncertain. SUMMARY: COVID-19 remains a significant threat to SOT recipients and studies on treatment and prevention specific to this population are urgently needed. Although vaccines represent the greatest hope to control this pandemic, their efficacy in this immunocompromised population is uncertain.

Evaluating the antibody response to SARS-COV-2 vaccination amongst kidney transplant recipients at a single nephrology centre.

BACKGROUND AND OBJECTIVES: Kidney transplant recipients are highly vulnerable to the serious complications of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infections and thus stand to benefit from vaccination. Therefore, it is necessary to establish the effectiveness of available vaccines as this group of patients was not represented in the randomized trials. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 707 consecutive adult kidney transplant recipients in a single center in the United Kingdom were evaluated. 373 were confirmed to have received two doses of either the BNT162b2 (Pfizer-BioNTech) or AZD1222 (Oxford-AstraZeneca) and subsequently had SARS-COV-2 antibody testing were included in the final analysis. Participants were excluded from the analysis if they had a previous history of SARS-COV-2 infection or were seropositive for SARS-COV-2 antibody pre-vaccination. Multivariate and propensity score analyses were performed to identify the predictors of antibody response to SARS-COV-2 vaccines. The primary outcome was seroconversion rates following two vaccine doses. RESULTS: Antibody responders were 56.8% (212/373) and non-responders 43.2% (161/373). Antibody response was associated with greater estimated glomerular filtration (eGFR) rate [odds ratio (OR), for every 10 ml/min/1.73m2 = 1.40 (1.19-1.66), P<0.001] whereas, non-response was associated with mycophenolic acid immunosuppression [OR, 0.02(0.01-0.11), p<0.001] and increasing age [OR per 10year increase, 0.61(0.48-0.78), p<0.001]. In the propensity-score analysis of four treatment variables (vaccine type, mycophenolic acid, corticosteroid, and triple immunosuppression), only mycophenolic acid was significantly associated with vaccine response [adjusted OR by PSA 0.17 (0.07-0.41): p<0.001]. 22 SARS-COV-2 infections were recorded in our cohort following vaccination. 17(77%) infections, with 3 deaths, occurred in the non-responder group. No death occurred in the responder group. CONCLUSION: Vaccine response in allograft recipients after two doses of SARS-COV-2 vaccine is poor compared to the general population. Maintenance with mycophenolic acid appears to have the strongest negative impact on vaccine response.

Increasing Living Donor Liver Transplantation Using Liver Paired Exchange.

BACKGROUND: Living donor liver transplantation (LDLT) continues to be the primary modality of liver transplantation in Asia, but it accounts for about 5% of all liver transplantations in the US. ABO incompatibility is the primary reason motivated donors are declined. Although kidney paired exchanges are common, liver paired exchange (LPE) is still evolving in the US. STUDY DESIGN: This is a retrospective review (between January 1, 2019, and July 31, 2021) of our initial experience with LPE. RESULTS: A total of 10 LPEs (20 LDLTs) were performed during the study period. Seven LPEs were initiated by a nondirected O donor. The other 3 pair sets involved 1 ABO compatible and 1 ABO incompatible pair. Transplantations in a pair set were completed within a mean of 4.8 (range 1-14) days of each other. All 20 donors are doing well with no major complications at 12.7 (range 1-20) months. Seventeen of 20 recipients are alive and have good allograft function. One recipient died in the early postoperative period. Two late deaths of patients with functioning allografts were due to COVID-19 (at 8 months) and peritoneal carcinomatosis and gram-negative sepsis (at 9 months). CONCLUSIONS: LPE is feasible in a high-volume LDLT center and is a useful option to increase LDLT by overcoming ABO incompatibility. Nondirected donors can be utilized to initiate an LPE.

Better Outcome of Coronavirus Disease 2019 Infection in Kidney Transplant Recipients: A Case Series from Eastern India.

The coronavirus disease 2019 (COVID-19) led to a global pandemic which is still unfolding. Little is known about the presentation, course of disease, treatment, and outcome in kidney transplant recipients. In this series, we describe nine such patients who presented with COVID-19. The mean age of the patients was 41.22 years. The mean duration of kidney transplantation was 63.22 months. The most common symptom was fever (9/9), followed by malaise (7/9), cough (5/9), dyspnea (4/9), diarrhea (2/9), and hemoptysis (2/9). Five patients developed acute kidney injury. Antiproliferative was stopped in all cases. Three patients needed hospitalization due to hypoxia while others were managed at home. We observed that majority of patients could be managed at home with isolation and self-monitoring. Even patents with moderate-to-severe disease were managed with oxygen supplement, low molecular weight heparin, and remdesivir. All patients recovered without any short-term sequelae in two months follow-up.

Risk and Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Infection on Corneal Transplantation: A Case-Control Study.

PURPOSE: The purpose of this study was to evaluate the risk of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after corneal transplantation surgery, with cataract surgeries as controls, and the impact of the novel coronavirus disease pandemic in the clinical and surgical complications of corneal transplantation and cataract surgeries. METHODS: A retrospective matched case-control study of 480 consecutive individuals who underwent surgery at the Bascom Palmer Eye Institute between May 2020 and November 2020. A total of 240 patients who underwent corneal transplantation with tissue obtained from the Florida Lions Eye Bank were age, race, ethnicity, and sex matched with 240 patients who underwent cataract surgery during the same day and by the same surgical team. Only the first corneal transplant or cataract surgery during this period was considered for each individual. All donors and recipients were deemed SARS-CoV-2 negative by a nasopharyngeal polymerase chain reaction test before surgery. Postoperative SARS-CoV-2 infections were defined as previously SARS-CoV-2(-) individuals who developed symptoms or had a positive SARS-CoV-2 polymerase chain reaction test during the first postoperative month. RESULTS: Mean age, sex, race, and ethnicity were similar between groups. There were no differences between the corneal transplant and cataract groups in the rates of SARS-CoV-2 infection before (5.8% vs. 7.5%, P= 0.6) or after surgery (2.9% vs. 2.9%, P = 1). The rates of postoperative complications did not increase during the pandemic, compared with previously reported ranges. CONCLUSIONS: In this study, postoperative SARS-CoV-2 infection was similar for individuals undergoing corneal transplantation or cataract surgery. Further research is required to evaluate the transmission of SARS-CoV-2 through corneal tissue.

A propensity score-matched analysis of mortality in solid organ transplant patients with COVID-19 compared to non-solid organ transplant patients.

In the context of COVID-19 pandemic, we aimed to analyze the epidemiology, clinical characteristics, risk factors for mortality and impact of COVID-19 on outcomes of solid organ transplant (SOT) recipients compared to a cohort of non transplant patients, evaluating if transplantation could be considered a risk factor for mortality. From March to May 2020, 261 hospitalized patients with COVID-19 pneumonia were evaluated, including 41 SOT recipients. Of these, thirty-two were kidney recipients, 4 liver, 3 heart and 2 combined kidney-liver transplants. Median time from transplantation to COVID-19 diagnosis was 6 years. Thirteen SOT recipients (32%) required Intensive Care Unit (ICU) admission and 5 patients died (12%). Using a propensity score match analysis, we found no significant differences between SOT recipients and non-transplant patients. Older age (OR 1.142; 95% [CI 1.08-1.197]) higher levels of C-reactive protein (OR 3.068; 95% [CI 1.22-7.71]) and levels of serum creatinine on admission (OR 3.048 95% [CI 1.22-7.57]) were associated with higher mortality. The clinical outcomes of SARS-CoV-2 infection in our cohort of SOT recipients appear to be similar to that observed in the non-transplant population. Older age, higher levels of C-reactive protein and serum creatinine were associated with higher mortality, whereas SOT was not associated with worse outcomes.

COVID-19 in lung transplant recipients-Risk prediction and outcomes.

Patients after lung transplantation are at risk for life-threatening infections. Recently, several publications on COVID-19 outcomes in this patient population appeared, but knowledge on optimal treatment, mortality, outcomes, and appropriate risk predictors is limited. A retrospective analysis was performed in a German high-volume lung transplant center between 19th March 2020 and 18th May 2021. Impact of COVID-19 on physical and psychological health, clinical outcomes, and mortality were analyzed including follow-up visits up to 12 weeks after infection in survivors. Predictive parameters on survival were assessed using univariate and multivariate proportional hazards regression models. Out of 1,046 patients in follow-up, 31 acquired COVID-19 during the pandemic. 12 of 31 (39%) died and 26 (84%) were hospitalized. In survivors a significant decline in exercise capacity (p = 0.034), TLC (p = 0.02), and DLCO (p = 0.007) was observed at follow-up after 3 months. Anxiety, depression, and self-assessed quality of life remained stable. Charlson comorbidity index predicted mortality (HR 1.5, 1.1-2.2; p = 0.023). In recipients with pre-existing CLAD, mortality and clinical outcomes were inferior. However, pre-existing CLAD did not predict mortality. COVID-19 remains a life-threatening disease for lung transplant recipients, particularly in case comorbidities. Further studies on long term outcomes and impact on pre-existing CLAD are needed.

Clinical experience of coronavirus disease 2019 in hematopoietic cell transplant and chimeric antigen receptor T-cell recipients.

PURPOSE OF REVIEW: To discuss the clinical experience of coronavirus disease 2019 (COVID-19) in hematopoietic cell transplant and chimeric antigen receptor T-cell therapy recipients over the past year and to identify key knowledge gaps for future research. RECENT FINDINGS: Immunocompromised individuals and those with chronic health conditions are especially susceptible to infections, which have had a disproportionate impact on health outcomes during the COVID-19 pandemic. Several studies have evaluated the clinical characteristics and outcomes of transplant and cellular therapy (TCT) recipients who developed COVID-19. Age, sex, comorbid conditions, and social determinants of health are important predictors of the risk of severe acute respiratory syndrome coronavirus 2 infection and of the eventual severity of the disease. Various treatment approaches have been investigated over the last year. The paradigm of management strategies continues to evolve as more experience is accumulated. SUMMARY: In this review, we summarize some important findings as they relate to the clinical characteristics of TCT recipients who develop COVID-19. We also discuss some treatment approaches that are currently recommended and opine on vaccination in this population.

The new world: hematopoietic stem cell transplant during a pandemic.

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted every facet of hematopoietic cell transplantation. This article reviews the adjustments to recipient and donor care that occurred in response to this unprecedented event. RECENT FINDINGS: Transplant centers modified algorithms, patient flow, education, and how we provided care. Our donor center partners reworked how donors were evaluated and products delivered to the transplant center. Our professional societies provided guidelines for patient and donor care and rapidly modified these based upon the never-ending stream of new data learned about SARS-CoV-2. Our research organizations provided rapid analyses to ensure the care modifications necessitated did not have a profound negative impact on our patients or donors. SUMMARY: The efforts of transplant providers and donor centers worldwide allowed patients to receive the transplant needed with assurances that they were receiving the best care available despite the worldwide challenge.

Serological Response to the BNT162b2 COVID-19 mRNA Vaccine in Adolescent and Young Adult Kidney Transplant Recipients.

BACKGROUND: Initial reports in adult kidney transplant recipients (KTR) indicate low immunogenicity after 2 doses of the BNT162b2 COVID-19 mRNA vaccine. We describe the immunogenicity of this vaccine compared to the serologic response in naturally infected COVID-19 positive adolescent and young adult KTR. METHODS: For this prospective observational study, the study group included 38 KTR who received 2 doses of the tested vaccine, and the control group included 14 KTR who had a previous polymerase chain reaction-confirmed COVID-19 infection. RESULTS: The mean age was 18 ± 3 y. Positive serologic responses were observed in 63% and 100% of the study and control groups, respectively (P = 0.01). Antibody titers were almost 30-fold higher in the control than the study group (median [interquartile range (IQR)]: 2782 [1908-11 000] versus 100.3 [4.7-1744] AU/mL, P < 0.001), despite the longer time from the COVID-19 infection to serologic testing compared to time from vaccination (median [IQR]: 157.5 [60-216] versus 37 [20.5-53] d, P = 0.011). Among vaccinated patients, higher proportions of those seronegative than seropositive were previously treated with rituximab (50% versus 8%, P = 0.01). Time from the second vaccine dose to serologic testing was longer in seropositive than seronegative patients (median [IQR]: 24.5 [15-40] versus 46 [27-56] d, P = 0.05). No patient developed symptomatic COVID-19 disease postvaccination. CONCLUSIONS: The BNT162b2 COVID-19 mRNA vaccine yielded higher positive antibody response in adolescent and young adult KTR than previously reported for adult KTR. Antibody titers after vaccination were significantly lower than following COVID-19 infection. Longer time may be required to mount appropriate humoral immunity to vaccination in KTR.

Consequences of the first and second COVID-19 wave on kidney transplant recipients at a large Indian transplant centre.

BACKGROUND: There is a scarcity of data comparing the consequences of first and second COVID-19 waves on kidney transplant recipients (KTRs) in India. METHODS: We conducted a single-centre retrospective study of 259 KTRs with COVID-19 to compare first wave (March 15-December 31 2020, n = 157) and second wave (April 1-May 31 2021, n = 102). RESULTS: KTRs during second wave were younger (43 vs. 40 years; p-value .04) and also included paediatric patients (0 vs. 5.9%; p-value .003). Symptoms were milder during the second wave (45 vs. 62.7%; p-value .007); COVID-19 positive patients had less frequent cough (32 vs. 13.8%; p-value .001), fever was less frequent (58 vs. 37%; p-value .001), and we observed fewer co-morbidities (11 vs. 20.6%; p-value .04). The percentages of neutrophils (77 vs. 83%; p-value .001) and serum ferritin (439 vs. 688; p-value .0006) were higher during second wave, while lymphocyte counts were reduced (20 vs. 14%; p-value .0001). Hydroxychloroquine (11 vs. 0%; p-value .0001) and tocilizumab (7 vs. 0%; p-value .004) were more frequently prescribed during first wave, while utilization of dexamethasone (6 vs. 27%; p-value .0001) and remdesivir (47 vs. 65%; p-value .03) increased during the second wave. Mucormycosis (1.3 vs. 10%; p-value .01) and ICU admissions (20 vs. 37.2%; p-value .002) were more frequent during second wave. The 28-day mortality rate (9.6 vs. 10%; p-value 1) was not different. CONCLUSIONS: There has been a different clinical spectrum of COVID-19 amongst KTR with similar mortality between the two waves at a large Indian transplant centre.

High mortality among kidney transplant recipients diagnosed with coronavirus disease 2019: Results from the Brazilian multicenter cohort study.

BACKGROUND: Kidney transplant (KT) recipients are considered a high-risk group for unfavorable outcomes in the course of coronavirus disease 2019 (COVID-19). AIM: To describe the clinical aspects and outcomes of COVID-19 among KT recipients. METHODS: This multicenter cohort study enrolled 1,680 KT recipients diagnosed with COVID-19 between March and November 2020, from 35 Brazilian centers. The main outcome was the 90-day cumulative incidence of death, for the entire cohort and according to acute kidney injury (AKI) and renal replacement therapy (RRT) requirement. Fatality rates were analyzed according to hospitalization, intensive care unit (ICU) admission, and mechanical ventilation (MV) requirement. Multivariable analysis was performed by logistic regression for the probability of hospitalization and death. RESULTS: The median age of the recipients was 51.3 years, 60.4% were men and 11.4% were Afro-Brazilian. Comorbidities were reported in 1,489 (88.6%), and the interval between transplantation and infection was 5.9 years. The most frequent symptoms were cough (54%), myalgia (40%), dyspnea (37%), and diarrhea (31%), whereas the clinical signs were fever (61%) and hypoxemia (13%). Hospitalization was required in 65.1%, and immunosuppressive drugs adjustments were made in 74.4% of in-hospital patients. ICU admission was required in 34.6% and MV in 24.9%. In the multivariable modeling, the variables related with the probability of hospitalization were age, hypertension, previous cardiovascular disease, recent use of high dose of steroid, and fever, dyspnea, diarrhea, and nausea or vomiting as COVID-19 symptoms. On the other hand, the variables that reduced the probability of hospitalization were time of COVID-19 symptoms, and nasal congestion, headache, arthralgia and anosmia as COVID-19 symptoms. The overall 90-day cumulative incidence of death was 21.0%. The fatality rates were 31.6%, 58.2%, and 75.5% in those who were hospitalized, admitted to the ICU, and required MV, respectively. At the time of infection, 23.2% had AKI and 23.4% required RRT in the follow-up. The cumulative incidence of death was significantly higher among recipients with AKI (36.0% vs. 19.1%, P < 0.0001) and in those who required RRT (70.8% vs. 10.1%, P < 0.0001). The variables related with the probability of death within 90 days after COVID-19 were age, time after transplantation, presence of hypertension, previous cardiovascular disease, use of tacrolimus and mycophenolate, recent use of high dose of steroids, and dyspnea as COVID-19 symptom. On the other hand, the variables that reduced the risk of death were time of symptoms, and headache and anosmia as COVID-19 symptoms. CONCLUSION: The patients diagnosed with COVID-19 were long-term KT recipients and most of them had some comorbidities. One in every five patients died, and the rate of death was significantly higher in those with AKI, mainly when RRT was required.

COVID-19 diagnosis and testing in pediatric heart transplant recipients.

Pediatric heart transplant recipients have been expected to be at higher risk of adverse events from developing COVID-19 infection. COVID-19 RNA PCR and antibody testing has been performed in our cohort of patients since March 15, 2020 and outcomes were reviewed. COVID-19 infection in our population of pediatric heart transplant recipients is common (21%), despite recommendations to avoid contact with others. Asymptomatic COVID-19 infection is common as well (55%). Despite the frequency of infection, COVID-19 is well tolerated in this population (5% admission from home; 0% mortality). A suppressed immune system does not significantly inhibit an antibody response in pediatric heart transplant recipients (>70% antibody seroconversion) and appears to persist, similar to those without transplantation (>90 days). Routine testing for COVID-19 via PCR and antibody testing enhances the ability to detect COVID-19 infection in asymptomatic patients and may help reduce unintended transmission to more susceptible individuals.

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies.

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.