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1.
J Am Soc Nephrol ; 32(3): 708-722, 2021 03.
Article in English | MEDLINE | ID: covidwho-1496675

ABSTRACT

BACKGROUND: Late antibody-mediated rejection (ABMR) is a leading cause of transplant failure. Blocking IL-6 has been proposed as a promising therapeutic strategy. METHODS: We performed a phase 2 randomized pilot trial to evaluate the safety (primary endpoint) and efficacy (secondary endpoint analysis) of the anti-IL-6 antibody clazakizumab in late ABMR. The trial included 20 kidney transplant recipients with donor-specific, antibody-positive ABMR ≥365 days post-transplantation. Patients were randomized 1:1 to receive 25 mg clazakizumab or placebo (4-weekly subcutaneous injections) for 12 weeks (part A), followed by a 40-week open-label extension (part B), during which time all participants received clazakizumab. RESULTS: Five (25%) patients under active treatment developed serious infectious events, and two (10%) developed diverticular disease complications, leading to trial withdrawal. Those receiving clazakizumab displayed significantly decreased donor-specific antibodies and, on prolonged treatment, modulated rejection-related gene-expression patterns. In 18 patients, allograft biopsies after 51 weeks revealed a negative molecular ABMR score in seven (38.9%), disappearance of capillary C4d deposits in five (27.8%), and resolution of morphologic ABMR activity in four (22.2%). Although proteinuria remained stable, the mean eGFR decline during part A was slower with clazakizumab compared with placebo (-0.96; 95% confidence interval [95% CI], -1.96 to 0.03 versus -2.43; 95% CI, -3.40 to -1.46 ml/min per 1.73 m2 per month, respectively, P=0.04). During part B, the slope of eGFR decline for patients who were switched from placebo to clazakizumab improved and no longer differed significantly from patients initially allocated to clazakizumab. CONCLUSIONS: Although safety data indicate the need for careful patient selection and monitoring, our preliminary efficacy results suggest a potentially beneficial effect of clazakizumab on ABMR activity and progression.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Graft Rejection/therapy , Interleukin-6/antagonists & inhibitors , Kidney Transplantation/adverse effects , Adult , Allografts , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind Method , Female , Glomerular Filtration Rate , Graft Rejection/immunology , Graft Rejection/physiopathology , Humans , Infections/etiology , Interleukin-6/immunology , Isoantibodies/blood , Male , Middle Aged , Tissue Donors , Treatment Outcome , Young Adult
3.
Transplantation ; 105(11): e234-e243, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1494154

ABSTRACT

BACKGROUND: Data about SARS-CoV-2 vaccines efficacy in renal transplant recipients (RTR) are lacking. METHODS: To reveal predictors for humoral response to BNT162b2 vaccine among RTR, patients were divided into positive (N = 42) and negative (N = 78) response groups based on receptor-binding domain (RBD) immunoglobulin G (IgG) ≥1.1 and neutralizing antibodies (NA) ≥16 dilution versus RBD IgG <1.1 or NA <16, respectively. NA were detected using a SARS-CoV-2 pseudo-virus. RESULTS: NA were detected in only 42 of 120 (35%) of RTR versus 197 of 202 (97.5%) immunocompetent controls (P < 0.001). NA geometric mean titers in RTR were significantly lower versus the control group {83.7 (95% confidence interval [CI], 50.5-138.8) versus 482 (95% CI, 411-566), P < 0.001}. In a multivariable analysis, mycophenolic acid (MPA) dose and hemoglobin level were found to be independent predictors for antibody response in RTR. A positive response rate of 27% versus 63% was observed in patients on and off MPA, respectively. An increase in MPA dose by 1 mg/kg weight reduced the odds for a positive response by 17% (odds ratio = 0.83; 95% CI, 0.75-0.92; P < 0.001). Geometric mean titers for RBD IgG were significantly reduced as MPA daily dose increased. Hemoglobin blood level <13 g/dL reduced the antibody response by 63% (P = 0.04). Pain at the injection site after the second vaccine dose was significantly higher in the responders versus nonresponders (20.5% versus 5.5%, P = 0.01). CONCLUSIONS: Only 35% of RTR develop NA to the BNT162b2 mRNA vaccine. MPA is a major suppressor of antibody response in RTR.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunity, Humoral/drug effects , Immunogenicity, Vaccine/drug effects , Kidney Transplantation/adverse effects , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Cohort Studies , Dose-Response Relationship, Drug , Female , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , SARS-CoV-2/immunology
4.
Front Immunol ; 12: 753558, 2021.
Article in English | MEDLINE | ID: covidwho-1463476

ABSTRACT

To date there is limited data on the immune profile and outcomes of solid organ transplant recipients who encounter COVID-19 infection early post-transplant. Here we present a unique case where the kidney recipient's transplant surgery coincided with a positive SARS-CoV-2 test and the patient subsequently developed symptomatic COVID-19 perioperatively. We performed comprehensive immunological monitoring of cellular, proteomic, and serological changes during the first 4 critical months post-infection. We showed that continuation of basiliximab induction and maintenance of triple immunosuppression did not significantly impair the host's ability to mount a robust immune response against symptomatic COVID-19 infection diagnosed within the first week post-transplant.


Subject(s)
Basiliximab/therapeutic use , COVID-19/immunology , Glomerulonephritis, IGA/therapy , Graft Rejection/immunology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , SARS-CoV-2/physiology , Adult , Humans , Immune Tolerance , Immunity , Male , Perioperative Period , Transcriptome
5.
Front Immunol ; 12: 645989, 2021.
Article in English | MEDLINE | ID: covidwho-1389177

ABSTRACT

We describe the unique disease course and cure of SARS-CoV-2 infection in a patient with SCID and graft failure. In absence of a humoral immune response, viral clearance was only achieved after transfusion of convalescent plasma. This observation underscores the necessity of the humoral immune response for SARS-CoV-2 clearance.


Subject(s)
COVID-19/therapy , SARS-CoV-2/physiology , Severe Combined Immunodeficiency/complications , Adult , Antibodies, Viral/blood , COVID-19/complications , COVID-19/immunology , COVID-19/virology , Female , Graft Rejection/complications , Graft Rejection/immunology , Graft Rejection/virology , Humans , Immunization, Passive , Severe Combined Immunodeficiency/immunology , Severe Combined Immunodeficiency/virology , Sustained Virologic Response , Viral Load , Virus Replication
6.
Transplantation ; 105(11): e226-e233, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1354364

ABSTRACT

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.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host , Kidney Transplantation/adverse effects , SARS-CoV-2/immunology , Adolescent , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19 Nucleic Acid Testing , COVID-19 Vaccines/administration & dosage , Case-Control Studies , Child , Female , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Immunogenicity, Vaccine/drug effects , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Prospective Studies , SARS-CoV-2/isolation & purification , Transplant Recipients/statistics & numerical data , Young Adult
9.
Transplantation ; 105(6): 1372-1380, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1249353

ABSTRACT

BACKGROUND: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown. METHODS: We enumerated SARS-CoV-2-specific interferon-γ-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6. RESULTS: Detectable (≥0.1%) SARS-CoV-2-specific CD4+ T-cell response was found in 57.1% and 47.4% of patients at months 4 and 6. Corresponding rates for CD8+ T cells were 19.0% and 42.1%, respectively. Absolute SARS-CoV-2-specific T-cell counts increased from month 4 to month 6 in CD8+ (P = 0.086) but not CD4+ subsets (P = 0.349). Four of 10 patients with any detectable response at month 4 had lost SARS-CoV-2-CMI by month 6, whereas 5 of 9 patients mounted SARS-CoV-2-CMI within this period. All but 2 patients (89.5%) tested positive for SARS-CoV-2 IgG. Patients lacking detectable SARS-CoV-2-specific CD4+ response by month 6 were more likely to be under tacrolimus (100.0% versus 66.7%; P = 0.087) and to have received tocilizumab for the previous COVID-19 episode (40.0% versus 0.0%; P = 0.087). CONCLUSIONS: Although still exploratory and limited by small sample size, the present study suggests that a substantial proportion of KT recipients exhibited detectable SARS-CoV-2-CMI after 6 months from COVID-19 diagnosis.


Subject(s)
COVID-19/immunology , Immunity, Cellular , Immunocompromised Host , Kidney Transplantation/adverse effects , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , COVID-19/blood , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Testing , Female , Follow-Up Studies , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/adverse effects , Interferon-gamma/metabolism , Male , Middle Aged , Transplant Recipients
10.
Transplantation ; 105(9): 2119-2123, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1240980

ABSTRACT

BACKGROUND: Belatacept may impair humoral immunity, impacting the effectiveness of SARS-CoV-2 mRNA vaccines in transplant recipients. We investigated immunogenicity after SARS-CoV-2 mRNA vaccines in kidney transplant recipients who are and are not taking belatacept. METHODS: Participants were recruited between December 9, 2020, and April 1, 2021. Blood samples were collected after dose 1 and dose 2 (D1, D2) and analyzed using either an anti-SARS-CoV-2 enzyme immunoassay against the S1 domain of the SARS-CoV-2 spike protein or immunoassay against the receptor-binding domain of the SARS-CoV-2 spike protein. Stabilized inverse probability of treatment weights was used to compare immunogenicity, and a weighted logistics regression was used to calculate fold change of positive response. RESULTS: Among the 609 participants studied, 24 (4%) were taking belatacept. After dose 1, 0/24 (0%) belatacept patients had detectable antibodies, compared with 77 of 568 (14%) among the equivalent nonbelatacept population (P = 0.06). After dose 2, 1/19 (5%) belatacept patients had detectable antibodies, compared with 190/381 (50%) among the equivalent nonbelatacept population (P < 0.001). Belatacept use was associated with 16.7-fold lower odds of having a positive post-D2 titer result (P < 0.01). CONCLUSIONS: Additional measures need to be explored to protect kidney transplant recipients taking belatacept. Best safety practices should be continued despite vaccination among this population.


Subject(s)
Abatacept/pharmacology , COVID-19/epidemiology , Graft Rejection/immunology , Immunity, Humoral , Kidney Transplantation/adverse effects , RNA, Viral/analysis , Renal Insufficiency/surgery , Aged , Antibodies, Viral/blood , Comorbidity , Female , Follow-Up Studies , Graft Rejection/drug therapy , Humans , Immunosuppressive Agents/pharmacology , Male , Middle Aged , Pandemics , Renal Insufficiency/epidemiology , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology
11.
Ann Transplant ; 26: e929279, 2021 Mar 12.
Article in English | MEDLINE | ID: covidwho-1154830

ABSTRACT

Coronavirus disease 19 (COVID-19) has been an ongoing pandemic since December 2019. Unfortunately, kidney transplant recipients are a high-risk group during the disease course, and scientific data are still limited in this patient group. Beyond the dosage of immunosuppressive drugs, pharmacological immunosuppression may also alter the infection response in the COVID-19 course. The effects of immunosuppressive agents on the development and process of infection should not be decided only by determining how potent they are and how much they suppress the immune system; it is also thought that the direct effect of the virus, increased oxidative stress, and cytokine storm play a role in the pathogenesis of COVID-19 disease. There are data about immunosuppressive drugs like calcineurin inhibitors (CNI) or mammalian target of rapamycin inhibitors (mTORi) therapy related to their beneficial effects during any infection course. Limited data suggest that the use of CNI or mTORi may have beneficial effects on the process. In this hypothetical review, the probable impacts of CNI and mTORi on the pathogenesis of the COVID-19 were investigated.


Subject(s)
COVID-19/immunology , Calcineurin Inhibitors/therapeutic use , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Postoperative Complications/immunology , Protein Kinase Inhibitors/therapeutic use , Adaptive Immunity/drug effects , COVID-19/diagnosis , Calcineurin Inhibitors/pharmacology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/prevention & control , Cytokine Release Syndrome/virology , Graft Rejection/immunology , Humans , Immunity, Innate/drug effects , Immunocompromised Host , Immunosuppressive Agents/pharmacology , Oxidative Stress/drug effects , Oxidative Stress/immunology , Postoperative Complications/diagnosis , Postoperative Complications/virology , Protein Kinase Inhibitors/pharmacology , TOR Serine-Threonine Kinases/antagonists & inhibitors
13.
Clin Transplant ; 35(1): e14150, 2021 01.
Article in English | MEDLINE | ID: covidwho-1057980

ABSTRACT

There is uncertainty about the safety of kidney transplantation during the SARS-CoV-2 pandemic due to the risk of donor transmission, nosocomial infection and immunosuppression use. We describe organ donation and transplant practice in the UK and assess whether kidney transplantation conferred a substantial risk of harm. Data from the UK transplant registry were used to describe kidney donation and transplant activity in the UK, and a detailed analysis of short-term, single-center, patient results in two periods: during the pre-pandemic era from 30th December 2019 to 8th March 2020 ("Pre-COVID era") and the 9th March 2020 to 19th May 2020 ("COVID era"). Donor and recipient numbers fell by more than half in the COVID compared to the pre-COVID era in the UK, but there were more kidney transplants performed in our center (42 vs. 29 COVID vs. pre-COVID respectively). Overall outcomes, including re-operation, delayed graft function, primary non-function, acute rejection, length of stay and graft survival were similar between COVID and pre-COVID era. 6/71 patients became infected with SARS-CoV-2 but all were discharged without critical care requirement. Transplant outcomes have remained similar within the COVID period and no serious sequelae of SARS-CoV-2 infection were observed in the peri-transplant period.


Subject(s)
COVID-19/complications , Graft Rejection/epidemiology , Hospitals, High-Volume/statistics & numerical data , Kidney Transplantation/adverse effects , SARS-CoV-2/isolation & purification , Transplant Recipients/statistics & numerical data , Adult , COVID-19/immunology , COVID-19/virology , Female , Graft Rejection/immunology , Graft Rejection/virology , Humans , Male , Middle Aged , Retrospective Studies , United Kingdom/epidemiology
15.
World J Gastroenterol ; 26(44): 7076-7084, 2020 Nov 28.
Article in English | MEDLINE | ID: covidwho-972402

ABSTRACT

BACKGROUND: Coronavirus disease (COVID) is a new and highly contagious infectious disease caused by the coronavirus (COVID-19 or severe acute respiratory syndrome coronavirus 2). There is limited data regarding the incidence and management of COVID-19 in immunocompromised patients' post-transplantation. In the pre-COVID-19 era, these patients were already at an increased risk of developing opportunistic infections. These often manifested with atypical symptoms. CASE SUMMARY: We report another case of uneventful COVID-19 pneumonia in a 58-year old male who was 18 mo' post liver transplantation. He received tacrolimus monotherapy since July 2019. The clinical manifestations included only epigastric pain radiating to the right hypochondrium, nausea and vomiting. He had no fevers, cough, shortness of breath, anosmia or dysgeusia even if the chest computed tomography scan revealed an extension of the multiple patchy ground-glass density shadows to the upper lobe of the left lung too. He was hospitalised and received a course of oral chloroquine (200 mg × 3 per day) for a period of 10 d. Interestingly, the COVID 19 infection was uneventful though there were no modifications to his tacrolimus dosing. He was successfully discharged. We performed subsequent follow-up via telemedicine. CONCLUSION: In light of the current pandemic, it is even more important to identify how the liver recipient's patients present and are managed, especially for immunosuppression treatment.


Subject(s)
COVID-19/diagnosis , Graft Rejection/prevention & control , Liver Transplantation/adverse effects , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Graft Rejection/immunology , Humans , Immunocompromised Host , Lung/diagnostic imaging , Lung/immunology , Lung/virology , Male , Middle Aged , SARS-CoV-2/isolation & purification , Severity of Illness Index , Tomography, X-Ray Computed
16.
Biol Blood Marrow Transplant ; 26(7): e161-e166, 2020 07.
Article in English | MEDLINE | ID: covidwho-799190

ABSTRACT

With the COVID-19 pandemic and the ensuing barriers to the collection and transport of donor cells, it is often necessary to collect and cryopreserve grafts before initiation of transplantation conditioning. The effect on transplantation outcomes in nonmalignant disease is unknown. This analysis examined the effect of cryopreservation of related and unrelated donor grafts for transplantation for severe aplastic anemia in the United States during 2013 to 2019. Included are 52 recipients of cryopreserved grafts who were matched for age, donor type, and graft type to 194 recipients who received noncryopreserved grafts. Marginal Cox regression models were built to study the effect of cryopreservation and other risk factors associated with outcomes. We recorded higher 1-year rates of graft failure (hazard ratio [HR], 2.26; 95% confidence interval, 1.17 to 4.35; P = .01) and of 1-year overall mortality (HR, 3.13; 95% CI, 1.60 to 6.11; P = .0008) after transplantation of cryopreserved compared with noncryopreserved grafts, with adjustment for sex, performance score, comorbidity, cytomegalovirus serostatus, and ABO blood group match. The incidence of acute and chronic graft-versus-host disease did not differ between the 2 groups. Adjusted probabilities of 1-year survival were 73% (95% CI, 60% to 84%) in the cryopreserved graft group and 91% (95% CI, 86% to 94%) in the noncryopreserved graft group. These data support the use of noncryopreserved grafts whenever possible in patients with severe aplastic anemia.


Subject(s)
Anemia, Aplastic/therapy , Bone Marrow Transplantation/methods , Coronavirus Infections/epidemiology , Cryopreservation/methods , Graft Rejection/pathology , Graft vs Host Disease/pathology , Peripheral Blood Stem Cell Transplantation/methods , Pneumonia, Viral/epidemiology , Acute Disease , Adolescent , Adult , Aged , Anemia, Aplastic/immunology , Anemia, Aplastic/mortality , Anemia, Aplastic/pathology , COVID-19 , Child , Child, Preschool , Female , Graft Rejection/immunology , Graft Rejection/mortality , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Histocompatibility Testing , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , Siblings , Survival Analysis , Transplantation Conditioning/methods , United States/epidemiology , Unrelated Donors
17.
Pediatr Transplant ; 25(3): e13868, 2021 05.
Article in English | MEDLINE | ID: covidwho-781008

ABSTRACT

The clinical course of COVID-19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi-center, multi-organ cohort analysis of COVID-19-positive transplant recipients ≤ 18 years at time of transplant. Data were collected via institutions' respective electronic medical record systems. Local review boards approved this cross-institutional study. Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. Six were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n = 12 (46%)), fever (n = 9 (35%)), dry/sore throat (n = 3 (12%)), rhinorrhea (n = 3 (12%)), anosmia (n = 2 (8%)), chest pain (n = 2 (8%)), diarrhea (n = 2 (8%)), dyspnea (n = 1 (4%)), and headache (n = 1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post-transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Our multi-institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID-19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required.


Subject(s)
COVID-19/complications , COVID-19/immunology , Graft Rejection/prevention & control , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Organ Transplantation , Perioperative Care/methods , Adolescent , COVID-19/diagnosis , COVID-19/therapy , Child , Child, Preschool , Female , Graft Rejection/immunology , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Perioperative Care/statistics & numerical data , Severity of Illness Index , Treatment Outcome
18.
Am J Transplant ; 20(11): 3210-3215, 2020 11.
Article in English | MEDLINE | ID: covidwho-703598

ABSTRACT

The optimal management in transplant recipients with coronavirus disease 2019 (COVID-19) remains uncertain. The main concern is the ability of immunosuppressed patients to generate sufficient immunity for antiviral protection. Here, we report on immune monitoring facilitating a successful outcome of severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated pneumonia, meningoencephalitis, gastroenteritis, and acute kidney and pancreas graft failure in a pancreas-kidney transplant recipient. Despite the very low numbers of circulating B, NK, and T cells identified in follow-up, a strong SARS-CoV-2 reactive T cell response was observed. Importantly, we detected T cells reactive to Spike, Membrane, and Nucleocapsid proteins of SARS-CoV-2 with majority of T cells showing polyfunctional proinflammatory Th1 phenotype at all analyzed time points. Antibodies against Spike protein were also detected with increasing titers in follow-up. Neutralization tests confirmed their antiviral protection. A correlation between cellular and humoral immunity was observed underscoring the specificity of demonstrated data. We conclude that analyzing the kinetics of nonspecific and SARS-CoV-2-reactive cellular and humoral immunity can facilitate the clinical decision on immunosuppression adjustment and allow successful outcome as demonstrated in the current clinical case. Although the antiviral protection of the detected SARS-CoV-2-reactive T cells requires further evaluation, our data prove an ability mounting a strong SARS-CoV-2-reactive T cell response with functional capacity in immunosuppressed patients.


Subject(s)
Antibodies, Viral/immunology , COVID-19/epidemiology , Immunity, Humoral , Kidney Transplantation , Monitoring, Immunologic/methods , Pancreas Transplantation/methods , SARS-CoV-2/immunology , COVID-19/virology , Clinical Decision-Making , Comorbidity , Graft Rejection/epidemiology , Graft Rejection/immunology , Humans , Immunocompromised Host , Pandemics
19.
Immun Inflamm Dis ; 8(4): 534-543, 2020 12.
Article in English | MEDLINE | ID: covidwho-696607

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an ongoing outbreak of respiratory illness called coronavirus disease 2019 (COVID-19). The clinical course could be ranging from mild to severe illness especially the individuals with an immunocompromised condition such as solid organ transplant recipients. METHOD: We described a family cluster of COVID-19 patients who were admitted during 3rd April 2020 to 30th April 2020. COVID-19 was confirmed by a presence of SARS-CoV-2 ribonucleic acid in the respiratory specimens detected by a qualitative, real-time reverse transcription-polymerase chain reaction. The study focused on the clinical course and management of our cases. RESULTS: A family cluster of four laboratory-confirmed COVID-19 patients, one of those carried an underlying kidney transplant (KT) receiving immunosuppressants. Clinical presentation and severity of our case series are variable depending on each individual immune status. By far, a KT recipient seems to develop more severity despite antiviral therapy, cessation of immunosuppressant, and aggressive intensive care support. CONCLUSION: Our case series plausibly affirmed a person-to-person transmission and potentially severe disease in the transplant population. Clinicians who are encountering with transplant recipients should be aware of possible transmission among family members.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Graft Rejection/prevention & control , Kidney Transplantation/adverse effects , Pneumonia, Viral/immunology , Adult , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Coronavirus Infections/virology , Family , Female , Graft Rejection/etiology , Graft Rejection/immunology , Humans , Immunosuppressive Agents/adverse effects , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Radiography , SARS-CoV-2 , Thailand
20.
Transpl Infect Dis ; 22(5): e13371, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-640837

ABSTRACT

INTRODUCTION: Management of COVID-19 in kidney transplant recipients should include treatment of the infection, regulation of immunosuppression, and supportive therapy. However, there is no consensus on this issue yet. This study aimed to our experiences with kidney transplant recipients diagnosed with COVID-19. MATERIAL AND METHODS: Kidney transplant recipients diagnosed with COVID-19 from five major transplant centers in Istanbul, Turkey, were included in this retrospective cohort study. Patients were classified as having moderate or severe pneumonia for the analysis. The primary endpoint was all-cause mortality. The secondary endpoints were acute kidney injury, the average length of hospital stay, admission to intensive care, and mechanical ventilation. RESULTS: Forty patients were reviewed retrospectively over a follow-up period of 32 days after being diagnosed with COVID-19. Cough, fever, and dyspnea were the most frequent symptoms in all patients. The frequency of previous induction and rejection therapy was significantly higher in the group with severe pneumonia compared to the moderate pneumonia group. None of the patients using cyclosporine A developed severe pneumonia. Five patients died during follow-up in the intensive care unit. None of the patients developed graft loss during follow-up. DISCUSSION: COVID-19 has been seen to more commonly cause moderate or severe pneumonia in kidney transplant recipients. Immunosuppression should be carefully reduced in these patients. Induction therapy with lymphocyte-depleting agents should be carefully avoided in kidney transplant recipients during the pandemic period.


Subject(s)
COVID-19/therapy , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/immunology , COVID-19 Nucleic Acid Testing , Critical Care/methods , Critical Care/standards , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Female , Follow-Up Studies , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , /methods , Immunosuppressive Agents/administration & dosage , Intensive Care Units/standards , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Male , Middle Aged , Patient Admission/standards , Practice Guidelines as Topic , Respiration, Artificial/standards , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severity of Illness Index , Transplant Recipients , Treatment Outcome , Turkey
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