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1.
J Hepatol ; 77(1): 152-162, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1734733

ABSTRACT

BACKGROUND & AIMS: The long-term immunogenicity of anti-SARS-CoV-2 vaccines in liver transplant (LT) recipients is unknown. We aimed to assess the long-term antibody response of the Pfizer-BioNTech® BNT162b2 vaccine in LT recipients compared to controls. METHODS: LT recipients underwent anti-SARS-CoV-2 anti-receptor-binding domain protein IgG (anti-RBD) and anti-nucleocapsid protein IgG antibody (anti-N) measurements at the first and 1, 4 and 6 months after the second vaccination dose. RESULTS: One hundred forty-three LT recipients and 58 controls were enrolled. At baseline, 131/143 (91.6%) LT recipients tested anti-N negative (COVID-19 naïve), and 12/143 (8.4%) tested positive (COVID-19 recovered) compared to negative controls. Among COVID-19 naïve, 22.1% were anti-RBD positives 1 month after the first vaccine dose, while 66.4%, 77%, and 78.8% were 1, 4 and 6 months following the second vaccine dose. In contrast, 100% of controls were positive at 4 months (p <0.001). The median anti-RBD titer 4 months after the second vaccine dose was significantly lower (32 U/ml) in COVID-19 naïve than in controls (852 U/ml, p <0.0001). A higher daily dose of mycophenolate mofetil (MMF) (p <0.001), higher frequency of ascites (p = 0.012), and lower serum leukocyte count (p = 0.016) were independent predictors of anti-RBD negativity at 6 months. All COVID-19 recovered patients tested positive for anti-RBD at each time point. The median antibody titer was similar in those taking MMF (9,400 U/ml, 11,925 U/ml, 13,305 U/ml, and 10,095 U/ml) or not taking MMF (13,950 U/ml, 9,575 U/ml, 3,500 U/ml, 2,835 U/ml, p = NS) 3 weeks after the first and 1, 4 and 6 months after the second vaccine dose, respectively. CONCLUSIONS: In COVID-19-naïve LT recipients, the immunogenicity of anti-SARS-CoV-2 vaccination was significantly lower than that in controls. MMF was the main determinant of vaccination failure in SARS-CoV-2-naïve patients. LAY SUMMARY: The immunogenicity of anti-SARS-CoV-2 vaccination in liver transplant recipients is currently unknown. Herein, we show that liver transplant recipients who have not previously had COVID-19 are less likely to mount effective antibody responses to vaccination than a control population. The main determinant of vaccination failure was the use of the immunosuppressive drug mycophenolate mofetil.


Subject(s)
COVID-19 , Liver Transplantation , Antibodies, Viral , COVID-19/prevention & control , Humans , Immunoglobulin G , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/therapeutic use , SARS-CoV-2 , Transplant Recipients , Vaccination
2.
J Autoimmun ; 125: 102743, 2021 12.
Article in English | MEDLINE | ID: covidwho-1568811

ABSTRACT

OBJECTIVES: To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. METHODS: A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. RESULTS: Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. CONCLUSIONS: In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.


Subject(s)
/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Autoimmune Diseases/immunology , Hereditary Autoinflammatory Diseases/immunology , Rheumatic Diseases/immunology , /adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/drug therapy , COVID-19/prevention & control , Female , Greece , Hereditary Autoinflammatory Diseases/drug therapy , Humans , Immunoglobulin G/blood , Male , Methotrexate/adverse effects , Methotrexate/therapeutic use , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Prospective Studies , Rheumatic Diseases/drug therapy , Rituximab/adverse effects , Rituximab/therapeutic use , SARS-CoV-2/immunology , Young Adult
3.
EBioMedicine ; 74: 103705, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1540597

ABSTRACT

BACKGROUND: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. METHODS: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. FINDINGS: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. INTERPRETATION: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity. FUNDING: Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.


Subject(s)
/adverse effects , Immunocompromised Host/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adenine/adverse effects , Adenine/analogs & derivatives , Adenine/therapeutic use , Antibodies, Viral/blood , COVID-19/prevention & control , Female , Hematopoietic Stem Cell Transplantation , Humans , Immunotherapy, Adoptive , Leukemia, Lymphocytic, Chronic, B-Cell , Male , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Organ Transplantation , Piperidines/adverse effects , Piperidines/therapeutic use , Primary Immunodeficiency Diseases/immunology , Prospective Studies , Seroconversion , Spike Glycoprotein, Coronavirus/immunology , Vaccination/adverse effects
4.
Cornea ; 41(2): 252-253, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1505854

ABSTRACT

PURPOSE: The purpose of this study was to report a case of acute corneal epithelial rejection of living-related conjunctival limbal allograft (LR-CLAL) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. OBSERVATIONS: A 27-year-old woman developed acute epithelial rejection of LR-CLAL 2 weeks after receiving the SARS-CoV-2 vaccine. She received the LR-CLAL transplant 4 years and 7 months previously and had a stable clinical course with no history of rejection. She had an ABO blood group and human leukocyte antigen compatible donor, no systemic comorbidities, and no rejection risk factors. CONCLUSIONS: The novel SARS-CoV-2 vaccine upregulates the immune system to produce an adaptive immune response. The SARS-CoV-2 vaccine may potentially be associated with increased risk of rejection in those with ocular surface transplants.


Subject(s)
/adverse effects , Epithelium, Corneal/pathology , Graft Rejection/etiology , Limbus Corneae/cytology , Living Donors , Stem Cell Transplantation , Vaccination/adverse effects , Acute Disease , Administration, Ophthalmic , Administration, Oral , Adult , Allografts , COVID-19/prevention & control , Conjunctiva/cytology , Female , Glucocorticoids/therapeutic use , Graft Rejection/diagnosis , Graft Rejection/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/therapeutic use , Ophthalmic Solutions , Slit Lamp Microscopy , Tacrolimus/therapeutic use , Visual Acuity/physiology
5.
Am J Transplant ; 22(2): 634-639, 2022 02.
Article in English | MEDLINE | ID: covidwho-1434623

ABSTRACT

Kidney transplant recipients (KTRs) are extremely vulnerable to SARS-CoV-2 infection and show an impaired immune response to SARS-CoV-2 vaccination. We analyzed factors related to vaccination efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against SARS-CoV-2 spike S1 subunit and their neutralization capacity after SARS-CoV-2 vaccination were analyzed in 225 KTRs and compared to 176 controls. After the vaccination, 56 (24.9%) KTRs became seropositive of whom 68% had neutralizing antibodies. This immune response was significantly lower compared to controls (239 [78-519] BAU/ml versus 1826 [560-3180] BAU/ml for KTRs and controls, p < .0001). The strongest predictor for an impaired response was mycophenolate mofetil (MMF) treatment. Multivariate regression analysis revealed that MMF-free regimen was highly associated with seroconversion (OR 13.25, 95% CI 3.22-54.6; p < .001). In contrast, other immunosuppressive drugs had no significant influence. 187 out of 225 KTRs were treated with MMF of whom 26 (13.9%) developed antibodies. 23 of these seropositive KTRs had a daily MMF dose ≤1 g. Furthermore, higher trough MMF concentrations correlated with lower antibody titers (R -0.354, p < .001) supporting a dose-dependent unfavorable effect of MMF. Our data indicate that MMF dose modification could lead to an improved immune response.


Subject(s)
COVID-19 , Kidney Transplantation , Antibodies, Viral , COVID-19 Vaccines , Humans , Immunity , Kidney Transplantation/adverse effects , Mycophenolic Acid/therapeutic use , SARS-CoV-2 , Transplant Recipients , Vaccination
8.
CNS Drugs ; 35(3): 317-330, 2021 03.
Article in English | MEDLINE | ID: covidwho-1141535

ABSTRACT

BACKGROUND: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS). OBJECTIVE: The objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies. METHODS: The IBM® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database. RESULTS: 30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine. CONCLUSIONS: Comorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Adolescent , Adult , African Americans/statistics & numerical data , Aged , Aged, 80 and over , Alemtuzumab/therapeutic use , Azathioprine/therapeutic use , COVID-19/mortality , Cladribine/therapeutic use , Comorbidity , Crotonates/therapeutic use , Cyclophosphamide/therapeutic use , Cyclosporine/therapeutic use , Databases, Factual , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Humans , Hydroxybutyrates , Immunologic Factors/therapeutic use , Incidence , Interferon-beta/therapeutic use , Logistic Models , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Male , Methotrexate/therapeutic use , Middle Aged , Mitoxantrone/therapeutic use , Multiple Sclerosis/epidemiology , Mycophenolic Acid/therapeutic use , Natalizumab/therapeutic use , Nitriles , Obesity/epidemiology , Risk Factors , Rituximab/therapeutic use , SARS-CoV-2 , Toluidines/therapeutic use , United States/epidemiology , Young Adult
9.
Clin Transplant ; 35(4): e14221, 2021 04.
Article in English | MEDLINE | ID: covidwho-1043988

ABSTRACT

The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04-4.04), peak D-dimer (OR = 1.20; 1.04-1.39), and peak white blood cell count (OR = 1.11; 1.02-1.21) were all associated with mortality among KTRs hospitalized for COVID-19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p < .01). Conversely, immunosuppression intensity and degree of reduction following COVID-19 diagnosis were not associated with either survival or acute allograft rejection. Our findings potentially support a strategy of individualization of immunosuppression targets based on patient-specific risk factors, rather than universal immunosuppression reduction for KTRs at risk from COVID-19.


Subject(s)
COVID-19/mortality , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/mortality , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Female , Graft Rejection/epidemiology , HIV Infections , Humans , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Retrospective Studies , Risk Factors , Tacrolimus/therapeutic use , Transplant Recipients
10.
Transplant Proc ; 53(4): 1207-1210, 2021 May.
Article in English | MEDLINE | ID: covidwho-989339

ABSTRACT

Immunocompromised populations are at great risk of the current 2020 global emergency of coronavirus disease 2019 (COVID-19), and treatment of kidney transplant recipients with COVID-19 is currently not declared. Hence, the purpose of the study is to set a clear treatment regimen. We report here a therapeutic course of 2 patients who underwent transplant surgery in March 2020 and got infected soon after. Since the transplant, these 2 patients have received triple maintenance immunosuppressive therapy with oral tacrolimus, mycophenolate mofetil (MMF), and prednisone, and they have been regularly followed up at our hospital. The tacrolimus trough level was between 10 and 12 ng/mL. After the diagnosis of COVID-19, MMF was stopped and the tacrolimus dose was reduced so that blood level was between 4 and 6 ng/mL. The first patient was a 30-year-old man who, despite being treated with hydroxychloroquine, favipiravir, oseltamivir, and azithromycin therapy, died because of the presence of other comorbidities. The second case was a 58-year-old man who fully recovered from COVID-19 pneumonia with treatment with methylprednisolone, MMF, azithromycin, favipiravir, hydroxychloroquine, and reduction in immunosuppression dosage. This reflects the importance of using glucocorticoids in the treatment of COVID-19 along with other medications and the decreased mortality rate associated with their use.


Subject(s)
COVID-19/diagnosis , Kidney Transplantation , Adult , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Glucocorticoids/therapeutic use , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Mycophenolic Acid/therapeutic use , SARS-CoV-2/isolation & purification , Tacrolimus/therapeutic use , Withholding Treatment
11.
Turk J Med Sci ; 51(2): 428-434, 2021 04 30.
Article in English | MEDLINE | ID: covidwho-922877

ABSTRACT

Background/aim: We aimed to identify clinical settings of renal transplant patients with COVID-19. Materials and methods: In this retrospective study, we included kidney transplant inpatients with laboratory confirmed COVID-19 who had been discharged or had died by October 1st, 2020. Characteristics of the patients, including basal and last outpatient biochemical parameters were recorded. Discontinuation or dosage reduction of immunosuppressives and other treatment information was documented. Results: Twenty patients were included in this study, of whom 18 were discharged and 2 died in hospital. The mean duration of hospitalization and follow-up were 9.7 ± 6.4 days and 4.5 ± 2.0 months, respectively. Fourteen patients (70%) were male and mean age was 48.0 ± 10.3 years. At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/ day (50%) or dexamethasone (50%). Tacrolimus/m-TOR inhibitors were reduced by 50% and all antimetabolites were discontinued. Hemodialysis was needed for 10% of patients. Acute kidney injury was detected in 25% of the patients. With respect to hospitalization time and complications, there was no significant difference between patients who used dexamethasone and those who did not (P > 0.05). The discontinued immunosuppressives were resumed within 2 to 4 weeks after discharge according to the severity of disease. No rehospitalization or acute rejection was detected during the follow-up of the patients. Conclusion: Renal transplant patients are considered a high risk group for COVID-19. It can be said that discontinuation or reducing dosages of immunosuppressives may be effective and safe in kidney transplant patients.


Subject(s)
COVID-19/physiopathology , Glucocorticoids/therapeutic use , Graft Rejection/prevention & control , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Acute Kidney Injury/physiopathology , Acute Kidney Injury/therapy , Adult , COVID-19/immunology , COVID-19/therapy , Deprescriptions , Dexamethasone/therapeutic use , Disease Progression , Everolimus/therapeutic use , Female , Hospital Mortality , Hospitalization , Humans , Length of Stay , Male , Methylprednisolone/therapeutic use , Middle Aged , Mycophenolic Acid/therapeutic use , Renal Dialysis , Respiration, Artificial , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2 , Sepsis/physiopathology , Tacrolimus/therapeutic use
12.
Transpl Infect Dis ; 23(2): e13500, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-916948

ABSTRACT

There is still no consensus on the optimal management of COVID-19 within the general population due to the emerging evidence base. High-risk groups, including kidney transplant recipients living with HIV present unique additional challenges. Here we discuss two kidney transplant recipients living with HIV with SARS-CoV-2 infection and their clinical course, and review the existing literature for this subset of challenging patients.


Subject(s)
Anti-HIV Agents/therapeutic use , COVID-19/therapy , Glucocorticoids/therapeutic use , Graft Rejection/prevention & control , HIV Infections/drug therapy , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Adult , Anti-Bacterial Agents/therapeutic use , Atovaquone/therapeutic use , CD4 Lymphocyte Count , CD4-CD8 Ratio , COVID-19/complications , COVID-19/immunology , Dideoxynucleosides/therapeutic use , Female , HIV Infections/complications , HIV Infections/immunology , HIV-1/genetics , Humans , Immunocompromised Host/immunology , Lamivudine/therapeutic use , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Pneumonia, Pneumocystis/prevention & control , Prednisolone/therapeutic use , RNA, Viral , Raltegravir Potassium/therapeutic use , SARS-CoV-2 , Tacrolimus/therapeutic use , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
13.
J Hepatol ; 74(1): 148-155, 2021 01.
Article in English | MEDLINE | ID: covidwho-709265

ABSTRACT

BACKGROUND & AIMS: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. METHODS: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression. RESULTS: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit. CONCLUSIONS: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged. LAY SUMMARY: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.


Subject(s)
COVID-19/epidemiology , Liver Transplantation , Transplant Recipients , Aged , COVID-19/mortality , Calcineurin Inhibitors/therapeutic use , Female , Hospitalization , Humans , Immunosuppressive Agents/therapeutic use , Incidence , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Prospective Studies , Spain/epidemiology
14.
Clin Rheumatol ; 39(9): 2803-2810, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-679748

ABSTRACT

COVID-19 has become a global concern. A large number of reports have explained the clinical characteristics and treatment strategies of COVID-19, but the characteristics and treatment of COVID-19 patient with systemic lupus erythematosus (SLE) are still unclear. Here, we report the clinical features and treatment of the first SLE patient with confirmed COVID-19 pneumonia. This was a 39-year-old woman, diagnosed with SLE 15 years ago, whose overall clinical characteristics (symptoms, laboratory tests, and chest CTs) were similar to those of the general COVID-19 patients. She continued to take the previous SLE drugs (doses of glucocorticoids, hydroxychloroquine, and immunosuppressive agents were not reduced) and was treated with strict antiviral and infection prevention treatment. After the first discharge, she got a recurrence of COVID-19 during her home isolation, and then returned to hospital and continued the previous therapy. Finally, this long-term immune suppressive patient's COVID-19 was successfully cured. The successful recovery of this case has significant reference value for the future treatment of COVID-19 patients with SLE. Key Points • COVID-19 patients with SLE is advocated to continue the medical treatment for SLE. • Hydroxychloroquine may have potential benefits for COVID-19 patients with SLE. • COVID-19 patients with SLE is prone to relapse, and multiple follow-ups are necessary.


Subject(s)
Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Glucocorticoids/therapeutic use , Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/therapeutic use , Lopinavir/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Pneumonia, Viral/drug therapy , RNA, Viral , Ritonavir/therapeutic use , Adult , Anti-Bacterial Agents/therapeutic use , Betacoronavirus , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Drug Combinations , Female , Humans , Lung/diagnostic imaging , Lupus Erythematosus, Systemic/complications , Moxifloxacin/therapeutic use , Mycophenolic Acid/therapeutic use , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Prednisone/therapeutic use , Recurrence , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed
15.
Clin Dermatol ; 38(6): 775-780, 2020.
Article in English | MEDLINE | ID: covidwho-659114

ABSTRACT

The emergence of the COVID-19 pandemic has led to significant uncertainty among physicians and patients about the safety of immunosuppressive medications used for the management of dermatologic conditions. We review available data on commonly used immunosuppressants and their effect on viral infections beyond COVID-19. Notably, the effect of some immunosuppressants on viruses related to SARS-CoV2, including SARS and MERS, has been previously investigated. In the absence of data on the effect of immunosuppressants on COVID-19, these data could be used to make clinical decisions on initiation and continuation of immunosuppressive medications during this pandemic. In summary, we recommend considering the discontinuation of oral Janus kinase (JAK) inhibitors and prednisone; considering the delay of rituximab infusion; and suggesting the careful continuation of cyclosporine, mycophenolate, azathioprine, methotrexate, and biologics in patients currently benefitting from such treatments.


Subject(s)
COVID-19/complications , Immunosuppressive Agents/therapeutic use , Skin Diseases/drug therapy , Azathioprine/therapeutic use , Biological Products/therapeutic use , Cyclosporine/therapeutic use , Evidence-Based Medicine , Humans , Janus Kinase Inhibitors/therapeutic use , Methotrexate/therapeutic use , Mycophenolic Acid/therapeutic use , Prednisone/therapeutic use , Rituximab/therapeutic use , SARS-CoV-2 , Severe Acute Respiratory Syndrome/complications , Skin Diseases/complications
16.
Nephrol Dial Transplant ; 35(7): 1250-1261, 2020 07 01.
Article in English | MEDLINE | ID: covidwho-652871

ABSTRACT

BACKGROUND: Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies. METHODS: We performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate. RESULTS: Of the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients. CONCLUSIONS: Data from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Graft Rejection/therapy , Hydroxychloroquine/therapeutic use , Kidney Transplantation , Mycophenolic Acid/therapeutic use , Pneumonia, Viral/complications , Adult , Aged , Aged, 80 and over , Allografts , Antimalarials/therapeutic use , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Enzyme Inhibitors/therapeutic use , Female , Graft Rejection/complications , Graft Rejection/epidemiology , Humans , Immunosuppressive Agents/therapeutic use , Incidence , Male , Middle Aged , New York City/epidemiology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Retrospective Studies , SARS-CoV-2 , Transplant Recipients
17.
Gastroenterol Hepatol ; 43(8): 457-463, 2020 Oct.
Article in English, Spanish | MEDLINE | ID: covidwho-639589

ABSTRACT

SARS-CoV-2 infection has produced a pandemic with serious consequences for our health care system. Although liver transplant patients represent only a minority of the population, the hepatologists who follow these patients have tried to coordinate efforts to produce a protocol the management of immunosuppression during SARS-CoV-2 infection. Although there are no solid studies to support general recommendations, experiences with other viral infections (hepatitis C, cytomegalovirus) suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors (drugs that are also associated with leukopenia and lymphopenia) may be beneficial. It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID 19 (lopinavir/ritonavir, azithromycin). Finally, the immunosuppressive effect of immunomodulating drugs (tocilizumab and similar) administered to patients with severe lung disease should be taken into account. The mechanisms of action of the different immunosuppressive drugs are reviewed in this article, as well as their potential effect on SARS-CoV-2 infection, and suggests guidelines for the management of immunosuppression.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Immunosuppressive Agents/adverse effects , Liver Transplantation , Pandemics , Pneumonia, Viral/epidemiology , Adaptive Immunity , Antiviral Agents/pharmacology , Betacoronavirus/immunology , Betacoronavirus/physiology , COVID-19 , Calcineurin Inhibitors/adverse effects , Calcineurin Inhibitors/pharmacology , Calcineurin Inhibitors/therapeutic use , Contraindications, Drug , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Disease Susceptibility , Drug Interactions , Everolimus/adverse effects , Everolimus/pharmacology , Everolimus/therapeutic use , Glucocorticoids/adverse effects , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , Humans , Immunity, Innate , Immunocompromised Host , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/adverse effects , Mycophenolic Acid/pharmacology , Mycophenolic Acid/therapeutic use , Pneumonia, Viral/immunology , Postoperative Complications/immunology , Postoperative Complications/prevention & control , SARS-CoV-2 , Sirolimus/adverse effects , Sirolimus/pharmacology , Sirolimus/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors
19.
Transpl Infect Dis ; 22(6): e13367, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-596059

ABSTRACT

The clinical course and outcomes of immunocompromised patients, such as transplant recipients, with COVID-19 remain unclear. It has been postulated that a substantial portion of the disease burden seems to be mediated by the host immune activation to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present a simultaneous heart-kidney transplant (SHKT) recipient who was hospitalized for the management of respiratory failure from volume overload complicated by failure to thrive, multiple opportunistic infections, and open non-healing wounds in the setting of worsening renal dysfunction weeks prior to the first case of SARS-CoV-2 being detected in the state of Connecticut. After his third endotracheal intubation, routine nucleic acid testing (NAT) for SARS-CoV-2, in anticipation of a planned tracheostomy, was positive. His hemodynamics, respiratory status, and ventilator requirements remained stable without any worsening for 4 weeks until he had a negative NAT test. It is possible that the immunocompromised status of our patient may have prevented significant immune activation leading up to clinically significant cytokine storm that could have resulted in acute respiratory distress syndrome and multisystem organ failure.


Subject(s)
COVID-19/immunology , Cardiomyopathy, Dilated/surgery , Heart Transplantation , Immunocompromised Host/immunology , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation , Malnutrition/immunology , Opportunistic Infections/immunology , Antibiotics, Antineoplastic/adverse effects , BK Virus , Bacteremia/complications , Bacteremia/immunology , COVID-19/complications , COVID-19 Nucleic Acid Testing , Cardiomyopathy, Dilated/chemically induced , Cardiomyopathy, Dilated/complications , Cardiotoxicity , Doxorubicin/adverse effects , Graft Rejection/prevention & control , Gram-Positive Bacterial Infections/complications , Gram-Positive Bacterial Infections/immunology , Humans , Incidental Findings , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Malnutrition/complications , Methicillin-Resistant Staphylococcus aureus , Middle Aged , Mycophenolic Acid/therapeutic use , Opportunistic Infections/complications , Polyomavirus Infections/complications , Polyomavirus Infections/immunology , Postoperative Complications/therapy , Prednisone/therapeutic use , Renal Dialysis , SARS-CoV-2 , Staphylococcal Infections/complications , Staphylococcal Infections/immunology , Surgical Wound Infection/complications , Surgical Wound Infection/immunology , Tacrolimus/therapeutic use , Tracheostomy , Tumor Virus Infections/complications , Tumor Virus Infections/immunology , Vancomycin-Resistant Enterococci , Viremia/complications , Viremia/immunology , Water-Electrolyte Imbalance/complications , Water-Electrolyte Imbalance/therapy
20.
J Investig Med High Impact Case Rep ; 8: 2324709620933438, 2020.
Article in English | MEDLINE | ID: covidwho-535847

ABSTRACT

In this article, we present a case of a young female patient with previously diagnosed lupus pneumonitis, now with a flare and new superimposed COVID-19 infection that was treated with intravenous steroids. On computed tomography scans, she had extensive interstitial lung fibrosis in addition to a positive COVID-19 polymerase chain reaction test requiring 6 L of oxygen via nasal cannula on admission. After administration of methylprednisolone, the patient improved and was weaned off her oxygen requirements and was discharged home.


Subject(s)
Coronavirus Infections/complications , Lupus Erythematosus, Systemic/complications , Pneumonia, Viral/complications , Pneumonia/complications , Antibodies, Antinuclear/immunology , Antirheumatic Agents/therapeutic use , Betacoronavirus , COVID-19 , Cardiac Tamponade , Complement C3/immunology , Complement C4/immunology , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , DNA , Disease Progression , Enzyme Inhibitors/therapeutic use , Female , Fibrin Fibrinogen Degradation Products , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Lung/diagnostic imaging , Lupus Erythematosus, Systemic/diagnostic imaging , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/immunology , Lupus Nephritis , Lymphopenia/etiology , Methylprednisolone/therapeutic use , Mycophenolic Acid/therapeutic use , Oxygen Inhalation Therapy , Pandemics , Pneumonia/diagnostic imaging , Pneumonia/immunology , Pneumonia/therapy , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
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