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3.
Perm J ; 26(1): 123-131, 2021 Oct 29.
Article in English | MEDLINE | ID: covidwho-1863290

ABSTRACT

INTRODUCTION: Relapsing COVID-19 infections have been reported, but their etiology and severity are still unknown. In addition, there have been no cases in the literature that associate relapsing infection with immunosuppression, either from a disease course or medications. CASE PRESENTATION: This case series illustrates two patients who developed a relapsed infection, likely from recent rituximab infusions. In addition, both cases depicted a severe form of infection than the initial one. Laboratory investigations revealed these patients were unable to produce COVID-19 antibodies, even though one of the patients received convalescent plasma. CONCLUSION: Clinicians should be aware of the possibility of relapsing COVID-19, especially in immunosuppressed patients. Because rituximab induces B-cell depletion, it can also decrease the effectiveness of the COVID-19 vaccine. Therefore, these patients should receive the vaccine before their scheduled rituximab infusion.


Subject(s)
COVID-19 , Immunosuppressive Agents , Rituximab , COVID-19/diagnosis , COVID-19 Vaccines , Humans , Immunization, Passive , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Recurrence , Rituximab/adverse effects , Rituximab/therapeutic use , Treatment Outcome
5.
Curr Opin Pediatr ; 34(2): 197-202, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1853279

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is to highlight recent studies that have emerged on the topic of ANCA-associated vasculitis with some historical context. The review also discusses how the adult data is relevant to pediatric patients. RECENT FINDINGS: Pediatric studies on AAV are lacking. Therapies targeted to the inflammatory cascade specifically implicated in AAV, such as MPO inhibitors and complement mediators, are emerging. The PEXIVAS study recently called into question the routine use of plasma exchange (PLEX) in severe AAV, with no difference in ESKD or mortality found between patients who did or did not receive PLEX. Longer maintenance duration of nearly 48 months is preferred as compared with shorter duration in patients who are not on dialysis because of higher relapse rates in children with AAV. SUMMARY: Current treatment in AAV includes corticosteroids, rituximab, and cyclophosphamide for induction. Maintenance therapy commonly consists of azathioprine or rituximab. Plasma exchange (PLEX) is no longer recommended for induction therapy for AAV but some experts still consider this as an option for patients who are not responding to therapy or have severe disease at presentation. However, emerging novel therapies may be on the horizon.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/therapy , Azathioprine , Child , Humans , Immunosuppressive Agents/therapeutic use , Kidney , Plasma Exchange , Rituximab/therapeutic use
6.
J Infect Chemother ; 28(8): 1153-1158, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1851525

ABSTRACT

BACKGROUND: To date, reports addressing the antibody response following mRNA SARS-CoV-2 vaccination in lung transplant (LTX) recipients are limited. Thus, the aim of this clinical study was to investigate the efficacy and safety of the vaccines in LTX recipients compared to controls. METHODS: An open-label, nonrandomized prospective study was conducted at Tohoku University Hospital. LTX recipients and controls who received either the BNT162b2 vaccine or the mRNA-1273 vaccine were recruited, and SARS-CoV-2 IgG was measured before and after vaccination. The adverse events were reviewed. Predictors of negative serology after vaccination were evaluated with logistic regression. RESULTS: Forty-one LTX recipients and 24 controls were analyzed. Although all controls had a positive antibody response to a SARS-CoV-2 mRNA vaccine, antibody response was found in 24.4% of LTX recipients (p < .0001). The amount of SARS-CoV-2 IgG following the 2nd dose significantly climbed to 6557 AU/mL in controls, whereas the increase in IgG in LTX recipients was 8.3 AU/mL (p < .0001). Fewer LTX recipients developed systemic fever than controls (p < .0001) despite equivalent overall adverse event percentages in both groups. A higher plasma concentration of mycophenolate was a significant predictor of negative serology (p = .032). CONCLUSIONS: An impaired antibody response to mRNA vaccines was significantly found in LTX recipients compared to controls and was associated with the plasma concentration of mycophenolate. While repeating mRNA vaccination may be one of the strategies to improve antibody response given the safety of the vaccines, emerging data on humoral immune responses based on immunosuppression regimens in LTX recipients should be studied (jRCT1021210009).


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunoglobulin G , Immunosuppressive Agents , Lung , Prospective Studies , RNA, Messenger , SARS-CoV-2/genetics , Transplant Recipients , Vaccines, Synthetic
8.
Front Immunol ; 13: 860891, 2022.
Article in English | MEDLINE | ID: covidwho-1834406

ABSTRACT

Immunosuppressant conditions such as hematological malignancies increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It has been described in the literature that patients on anti-CD20 maintenance therapies for lymphoid malignancies are susceptible to having recurrent flares together with viral replication or reinfections, although these cases are scarce. These patients are not well represented in randomized controlled trials, and as a consequence, the evidence for the use of certain treatments in this scenario is lacking. We present two cases of patients with B-cell lymphoma on remission and treated with rituximab on maintenance. They developed at least 1 flare of coronavirus disease 2019 (COVID-19) after acute infection and always after receiving rituximab. RT-PCR was positive in the nasopharyngeal swab and also in plasma. Patients were treated during flares with remdesivir, hyperimmune plasma, and corticosteroids. These two cases showed the unresolved problem of COVID-19 in immunosuppressant patients and showed that despite the vast amount of information available on SARS-CoV-2, information in this subgroup of patients is lacking.


Subject(s)
COVID-19 , Lymphoma, B-Cell , Antibodies, Monoclonal , COVID-19/drug therapy , Humans , Immunocompromised Host , Immunosuppressive Agents , Lymphoma, B-Cell/drug therapy , Rituximab/therapeutic use , SARS-CoV-2
9.
Sci Rep ; 12(1): 6850, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1815593

ABSTRACT

Immunocompromised patients, especially those who undergo kidney transplantation, have lower antibody levels following SARS-CoV-2 mRNA vaccination. The situation of transplant treatment, such as transplant source and immunosuppressive drugs, is different in Japan than that in other countries. Therefore, it is necessary to clarify whether antibody acquisition rates differ between Japan and other countries. This retrospective study included patients with post-kidney transplant who were attending at the Nagoya University Hospital. The anti-SARS-CoV-2 IgG antibody titers were measured between 3 weeks and 3 months after vaccination. Seventy-three patients (45 men and 28 women) were included. Of these, 23 (31.5%) showed antibody presence, and the rates of antibody acquisition were very low than those in the control group (100.0% vs. 31.5%, P < 0.05). Antibody acquisition rates were associated with body mass index (odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.04-1.39, P < 0.05) and the duration between transplantation and vaccination (OR: 1.01, 95% CI: 1.00-1.02, P < 0.05). The immunosuppressive drugs used were: prednisolone in all cases, tacrolimus in 89.0%, cyclosporine in 9.6%, and mofetil mycophenolate in 97.3%. None of the patients were excluded from receiving two doses of the vaccine due to adverse effects. The study indicated that vaccination-induced antibody acquisition rates against SARS-CoV-2 were extremely low in Japanese patients who underwent post-kidney transplantation. Thus, despite two doses of vaccination, it is necessary to closely monitor infection control in such patients.


Subject(s)
COVID-19 , Kidney Transplantation , Antibody Formation , COVID-19/prevention & control , Female , Humans , Immunosuppressive Agents/pharmacology , Japan , Kidney Transplantation/adverse effects , Male , RNA, Messenger , Retrospective Studies , SARS-CoV-2/genetics , Vaccination
10.
Ann Palliat Med ; 11(4): 1308-1316, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1811755

ABSTRACT

BACKGROUND: There is uncertainty of the effect of immunosuppression, including corticosteroids, before COVID-19 infection on COVID-19 outcomes. The aim of this study was to investigate the relationship between prehospitalization immunosuppressants use (exposure) and COVID-19 patient outcomes. METHODS: We conducted a population-based retrospective cohort study using a nationwide healthcare claims database of South Korea as of May 15, 2020. Confirmed COVID-19 infection in hospitalized individuals aged 40 years or older were included for analysis. We defined exposure variable by using inpatient and outpatient prescription records of immunosuppressants from the database. Our primary endpoint was a composite endpoint of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Inverse probability of treatment weighting (IPTW)-adjusted logistic regression analyses were used, to estimate odds ratio (OR) and 95% confidence intervals (CI), comparing immunosuppressants users and non-users. RESULTS: We identified 4,349 patients, for which 1,356 were immunosuppressants users and 2,993 were non-users. Patients who used immunosuppressants were at increased odds of the primary endpoint of all-cause death, ICU admission and mechanical ventilation use (IPTW OR =1.32; 95% CI: 1.06-1.63), driven by higher odds of all-cause mortality (IPTW OR =1.63; 95% CI: 1.21-2.26). Patients who used corticosteroids (n=1,340) were at increased odds of the primary endpoint (IPTW OR =1.33; 95% CI: 1.07-1.64). CONCLUSIONS: Immunosuppressant use was associated with worse outcomes among COVID-19 patients. These findings support the latest guidelines from the CDC that people on immunosuppressants are at high risk of severe COVID-19 and that immunocompromised people may benefit from booster COVID-19 vaccinations.


Subject(s)
COVID-19 , Cohort Studies , Hospitalization , Humans , Immunosuppressive Agents/adverse effects , Intensive Care Units , Retrospective Studies
11.
J Immunol Res ; 2022: 5545319, 2022.
Article in English | MEDLINE | ID: covidwho-1807699

ABSTRACT

Coronavirus disease 2019 (COVID-19) has been raised as a pandemic disease since December 2019. Immunosuppressive cells including T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are key players in immunological tolerance and immunoregulation; however, they contribute to the pathogenesis of different diseases including infections. Tregs have been shown to impair the protective role of CD8+ T lymphocytes against viral infections. In COVID-19 patients, most studies reported reduction, while few other studies found elevation in Treg levels. Moreover, Tregs have a dual role, depending on the different stages of COVID-19 disease. At early stages of COVID-19, Tregs have a critical role in decreasing antiviral immune responses, and consequently reducing the viral clearance. On the other side, during late stages, Tregs reduce inflammation-induced organ damage. Therefore, inhibition of Tregs in early stages and their expansion in late stages have potentials to improve clinical outcomes. In viral infections, MDSC levels are highly increased, and they have the potential to suppress T cell proliferation and reduce viral clearance. Some subsets of MDSCs are expanded in the blood of COVID-19 patients; however, there is a controversy whether this expansion has pathogenic or protective effects in COVID-19 patients. In conclusion, further studies are required to investigate the role and function of immunosuppressive cells and their potentials as prognostic biomarkers and therapeutic targets in COVID-19 patients.


Subject(s)
COVID-19 , Myeloid-Derived Suppressor Cells , Humans , Immune Tolerance , Immunosuppressive Agents , Pandemics , T-Lymphocytes, Regulatory
12.
Dtsch Med Wochenschr ; 147(8): 470-480, 2022 04.
Article in German | MEDLINE | ID: covidwho-1805699

ABSTRACT

Autoimmune hepatitis is a rare but chronic autoimmune-mediated liver disease. Key features are elevated transaminases, hypergammaglobulinemia, presence of specific autoantibodies and typical histological features. Diagnostic scores are helpful in establishing the diagnosis. Immunosuppressive therapy should be initiated in every patient with inflammatory activity. First-line therapy includes steroids and azathioprine and results in biochemical and histological remission in the majority of patients. In most cases, lifelong therapy is required. Every patient should receive regular follow-up surveillance including biochemical parameters as well as sonography and elastography.


Subject(s)
Hepatitis, Autoimmune , Liver Diseases , Autoantibodies , Azathioprine/therapeutic use , Glucocorticoids/therapeutic use , Hepatitis, Autoimmune/diagnosis , Hepatitis, Autoimmune/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Liver Diseases/drug therapy
13.
Hepatol Int ; 16(2): 257-268, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1797505

ABSTRACT

The world has made significant progress in developing novel treatments for COVID-19 since the pandemic began. Some treatments target the patient's dysregulated inflammatory response during COVID-19 infection and may cause hepatitis B reactivation (HBVr) in patients with current or past hepatitis B virus (HBV) infection. This review summarizes the risk and management of HBVr due to different treatments of COVID-19 in patients who have current or past HBV infection. Abnormal liver function tests are common during COVID-19 infection. Current evidence suggests that current or past HBV infection is not associated with an increased risk of liver injury and severe disease in COVID-19 patients. Among patients who received high-dose corticosteroids, various immunosuppressive monoclonal antibodies and inhibitors of Janus kinase, the risk of HBVr exists, especially among those without antiviral prophylaxis. Data, however, remain scarce regarding the specific use of immunosuppressive therapies in COVID-19 patients with HBV infection. Some results are mainly extrapolated from patients receiving the same agents in other diseases. HBVr is a potentially life-threatening event following profound immunosuppression by COVID-19 therapies. Future studies should explore the use of immunosuppressive therapies in COVID-19 patients with HBV infection and the impact of antiviral prophylaxis on the risk of HBVr.


Subject(s)
COVID-19 , Hepatitis B , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Hepatitis B/prevention & control , Hepatitis B Surface Antigens , Hepatitis B virus , Humans , Immunosuppressive Agents/adverse effects , Virus Activation/physiology
14.
BMJ Open ; 12(4): e061864, 2022 04 15.
Article in English | MEDLINE | ID: covidwho-1794490

ABSTRACT

INTRODUCTION: Regulatory T cell (Treg) therapy has been demonstrated to facilitate long-term allograft survival in preclinical models of transplantation and may permit reduction of immunosuppression and its associated complications in the clinical setting. Phase 1 clinical trials have shown Treg therapy to be safe and feasible in clinical practice. Here we describe a protocol for the TWO study, a phase 2b randomised control trial of Treg therapy in living donor kidney transplant recipients that will confirm safety and explore efficacy of this novel treatment strategy. METHODS AND ANALYSIS: 60 patients will be randomised on a 1:1 basis to Treg therapy (TR001) or standard clinical care (control). Patients in the TR001 arm will receive an infusion of autologous polyclonal ex vivo expanded Tregs 5 days after transplantation instead of standard monoclonal antibody induction. Maintenance immunosuppression will be reduced over the course of the post-transplant period to low-dose tacrolimus monotherapy. Control participants will receive a standard basiliximab-based immunosuppression regimen with long-term tacrolimus and mycophenolate mofetil immunosuppression. The primary endpoint is biopsy proven acute rejection over 18 months; secondary endpoints include immunosuppression burden, chronic graft dysfunction and drug-related complications. ETHICS AND DISSEMINATION: Ethical approval has been provided by the National Health Service Health Research Authority South Central-Oxford A Research Ethics Committee (reference 18/SC/0054). The study also received authorisation from the UK Medicines and Healthcare products Regulatory Agency and is being run in accordance with the principles of Good Clinical Practice, in collaboration with the registered trials unit Oxford Clinical Trials Research Unit. Results from the TWO study will be published in peer-reviewed scientific/medical journals and presented at scientific/clinical symposia and congresses. TRIAL REGISTRATION NUMBER: ISRCTN: 11038572; Pre-results.


Subject(s)
Kidney Transplantation , T-Lymphocytes, Regulatory , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/methods , Living Donors , Randomized Controlled Trials as Topic , State Medicine , Tacrolimus/therapeutic use
15.
Front Immunol ; 12: 752557, 2021.
Article in English | MEDLINE | ID: covidwho-1789371

ABSTRACT

Objective: To analyze and compare different clinical, laboratory, and magnetic resonance imaging characteristics between pediatric and adult patients with first-attack myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and to explore predictive factors for severity at disease onset. Methods: Patients diagnosed with MOGAD at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2021 were enrolled in this retrospective study. Age at disease onset, sex, comorbidities, laboratory tests, magnetic resonance imaging (MRI) characteristics, and Expanded Disability Status Scale (EDSS) scores were collected and analyzed. The association between risk factors and initial EDSS scores at disease onset was analyzed using logistic regression models and Spearman correlation analyses. A receiver-operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of the uric acid and homocysteine (Hcy) levels for the severity of neurological dysfunction at the onset of MOGAD. Results: Sixty-seven patients (female, n=34; male, n=33) with first-attack MOGAD were included in this study. The mean age at onset was 26.43 ± 18.22 years (range: 3-79 years). Among patients <18 years of age, the most common presenting symptoms were loss of vision (36.0%), and nausea and vomiting (24.0%), and the most common disease spectrum was acute disseminated encephalomyelitis (ADEM) (40.0%). Among patients aged ≥18 years, the most common presenting symptoms were loss of vision (35.7%), paresthesia (33.3%), and paralysis (26.2%), and the most common disease spectrum was optic neuritis (35.7%). The most common lesions were cortical gray matter/paracortical white matter lesions in both pediatric and adult patients. Uric acid [odds ratio (OR)=1.014; 95% confidence interval (CI)=1.006-1.022; P=0.000] and serum Hcy (OR=1.125; 95% CI=1.017-1.246; P=0.023) levels were significantly associated with the severity of neurological dysfunction at disease onset. Uric acid levels (r=0.2583; P=0.035) and Hcy levels (r=0.3971; P=0.0009) were positively correlated with initial EDSS scores. The areas under the ROC curve were 0.7775 (95% CI= 0.6617‒0.8933; P<0.001) and 0.6767 (95% CI=0.5433‒0.8102, P=0.014) for uric acid and Hcy levels, respectively. Conclusion: The clinical phenotype of MOGAD varies in patients of different ages. The most common disease spectrum was ADEM in patients aged<18 years, while optic neuritis was commonly found in patients aged ≥18 years. The uric acid and Hcy levels are risk factors for the severity of neurological dysfunction at disease onset in patients with first-attack MOGAD.


Subject(s)
Autoantibodies/immunology , Autoimmune Diseases of the Nervous System/epidemiology , Myelin-Oligodendrocyte Glycoprotein/immunology , Adolescent , Adult , Age of Onset , Aged , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnosis , Autoimmune Diseases of the Nervous System/diagnostic imaging , Autoimmune Diseases of the Nervous System/immunology , Autoimmune Diseases of the Nervous System/metabolism , Biomarkers , Central Nervous System/diagnostic imaging , Cerebrospinal Fluid Proteins/analysis , Child , Child, Preschool , China/epidemiology , Comorbidity , Diagnosis, Differential , Female , Follow-Up Studies , Homocysteine/blood , Humans , Immunosuppressive Agents/therapeutic use , Magnetic Resonance Imaging , Male , Middle Aged , Risk Factors , Severity of Illness Index , Single-Blind Method , Uric Acid/blood , Young Adult
17.
Arthritis Rheumatol ; 74(6): 927-933, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1777528

ABSTRACT

OBJECTIVE: Antibody response to the messenger RNA (mRNA) COVID-19 vaccine has been shown to be diminished in rituximab (RTX)-treated patients. We undertook this study to compare humoral and T cell responses between healthy controls, patients with autoimmune diseases treated with RTX, and those treated with other immunosuppressants, all of whom had been vaccinated with 2 doses of the mRNA COVID-19 vaccine. METHODS: We performed anti-spike IgG and neutralization assays just before and 28 days after the second BNT162b2 (Pfizer-BioNTech) vaccine dose. The specific T cell response was assessed in activated CD4 and CD8 T cells using intracellular flow cytometry staining of cytokines (interferon-γ, tumor necrosis factor, and interleukin-2) after stimulation with SARS-CoV-2 spike peptide pools. RESULTS: A lower proportion of responders with neutralizing antibodies to the vaccine was observed in the RTX group (29%; n = 24) compared to the other immunosuppressants group (80%; n = 35) (P = 0.0001) and the healthy control group (92%; n = 26) (P < 0.0001). No patients treated with RTX in the last 6 months showed a response. Time since last infusion was the main factor influencing humoral response in RTX-treated patients. The functional CD4 and CD8 cellular responses to SARS-CoV-2 peptides for each single cytokine or polyfunctionality were not different in the RTX group compared to the other immunosuppressants group or the control group. In RTX-treated patients, the T cell response was not different between patients with and those without a humoral response. CONCLUSION: RTX induced a diminished antibody response to the mRNA COVID-19 vaccine, but the functional T cell response was not altered compared to healthy controls and autoimmune disease patients treated with other immunosuppressants. Further work is needed to assess the clinical protection granted by a functionally active T cell response in the absence of an anti-spike antibody response.


Subject(s)
Antibodies, Viral/immunology , Autoimmune Diseases , COVID-19 Vaccines/immunology , COVID-19 , Autoimmune Diseases/drug therapy , COVID-19/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , RNA, Messenger , Rituximab/therapeutic use , SARS-CoV-2
19.
Exp Clin Transplant ; 20(3): 285-292, 2022 03.
Article in English | MEDLINE | ID: covidwho-1771685

ABSTRACT

OBJECTIVES: With the declaration of the COVID-19 pandemic and the increased COVID-19 risk shown in transplant recipients, the prevalence, clinical course, and outcomes of COVID-19 infections among liver transplant recipients were assessed. MATERIALS AND METHODS: A questionnaire was designed and used to survey medical services for liver transplant recipients seen at our center in terms of COVID-19 infection. RESULTS: Twenty-five patients infected with COVID-19 were identified from 265 liver transplant recipients. Most patients were male and had COVID-19 despite quarantine at home. All patients received modified immunosuppressive drugs during infection with COVID-19 with minor changes in routine immunosuppressive therapy. Among the identified patients, 21 recovered and 4 patients died. One of the dead patients, in addition to having a liver transplant, had brain cancer with metastasis to the lungs. CONCLUSIONS: In liver transplant recipients infected with COVID-19, immunosuppressive drugs seemed to cause only mild to moderate illnesses or even helped them recover from the disease. However, more evidence is needed to prove this hypothesis. It is also recommended that transplant recipients should be warned about personal hygiene and be monitored closely by organ transplant centers.


Subject(s)
COVID-19 , Kidney Transplantation , Liver Transplantation , Humans , Immunosuppressive Agents/adverse effects , Iran/epidemiology , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Male , Pandemics , Registries , SARS-CoV-2 , Transplant Recipients , Treatment Outcome
20.
JCI Insight ; 7(9)2022 May 09.
Article in English | MEDLINE | ID: covidwho-1765224

ABSTRACT

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus-neutralizing capacity. Interestingly, 21/25 (84%) calcineurin inhibitor-treated patients responded, but only 1/4 belatacept-treated patients responded. In line with humoral responses, counts and relative frequencies of spike receptor binding domain-specific (RBD-specific) B cells were markedly increased on day 7 after vaccination, with an increase in RBD-specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo-activated programmed cell death 1-positive T cells significantly increased after revaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, antimetabolite hold augmented all arms of immunity during booster vaccination. These data suggest further studies of antimetabolite hold in kidney transplant recipients.


Subject(s)
Antimetabolites , COVID-19 Vaccines , COVID-19 , Kidney Transplantation , Antibodies, Viral , Antimetabolites/therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , Immunity, Cellular , Immunity, Humoral , Immunosuppressive Agents/therapeutic use , SARS-CoV-2 , Transplant Recipients , Vaccination
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