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1.
Clin Pharmacol Ther ; 114(1): 118-126, 2023 07.
Article in English | MEDLINE | ID: covidwho-2243331

ABSTRACT

Despite (repeated) boosting, kidney transplant recipients (KTRs) may remain at increased risk of severe COVID-19 since a substantial number of individuals remain seronegative or with low antibody titers. In particular, mycophenolic acid use has been shown to affect antibody formation negatively and may be an important modifiable risk factor. We investigated the exposure-response relationship between mycophenolic acid 12-hour area under the curve (AUC0-12h ) exposure and seroconversion including antibody titers after vaccination using mRNA-1273 SARS-CoV-2 vaccine (Moderna) in 316 KTRs from our center that participated in the national Dutch renal patients COVID-19 vaccination - long term efficacy and safety of SARS-CoV-2 vaccination in kidney disease patients vaccination study. After two vaccination doses, 162 (51%) KTRs seroconverted. KTRs treated with mycophenolic acid showed less seroconversion and lower antibody titers compared with KTRs without mycophenolic acid (44% vs. 77%, and 36 binding antibody units (BAU)/mL vs. 340 BAU/mL; P < 0.001). The mean mycophenolic acid AUC0-12h exposure was significantly lower in KTRs who seroconverted compared with KTRs who did not (39 vs. 29 mg⋅h/L; P < 0.001). High mycophenolic acid exposure (±90 mg⋅h/L) and no exposure to mycophenolic acid resulted in a seroconversion rate ranging from 10% to 80%. Every 10 mg⋅h/L increase in mycophenolic acid AUC0-12h gave an adjusted odds ratio for seroconversion of 0.87 (95% confidence interval (CI), 0.79-0.97; P = 0.010) and 0.89 (95% CI, 0.85-0.93; P < 0.001) for KTRs on dual and triple maintenance immunosuppressive therapy, respectively. Higher mycophenolic acid AUC0-12h correlated with lower antibody titers (R = 0.44, P < 0.001). This study demonstrates the exposure-response relationship between gold standard mycophenolic acid exposure and antibody formation to support interventional studies investigating mycophenolic acid adjustment to improve antibody formation after further boosting.


Subject(s)
COVID-19 Vaccines , COVID-19 , Kidney Transplantation , Mycophenolic Acid , Humans , Antibodies , Antibody Formation , Cohort Studies , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Kidney Transplantation/adverse effects , Mycophenolic Acid/adverse effects , SARS-CoV-2 , Vaccination
2.
Transplantation ; 106(10): e441-e451, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-2051786

ABSTRACT

BACKGROUND: The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19-associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes. METHODS: This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed. RESULTS: Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA. CONCLUSIONS: This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.


Subject(s)
COVID-19 , Kidney Transplantation , Azathioprine , Calcineurin Inhibitors/adverse effects , Enzyme Inhibitors , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Mycophenolic Acid/adverse effects , Sirolimus/adverse effects , TOR Serine-Threonine Kinases
3.
Transplantation ; 106(10): 2068-2075, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-1909080

ABSTRACT

BACKGROUND: The rapid development and universal access to vaccines represent a milestone in combating the coronavirus disease 2019 (COVID-19) pandemic. However, there are major concerns about vaccine response in immunocompromised populations in particular transplant recipients. In the present study, we aim to comprehensively assess the humoral response to COVID-19 vaccination in both orthotopic organ transplant and allogeneic hematopoietic stem cell transplant recipients. METHODS: We performed a systematic review and meta-analysis of 96 studies that met inclusion criteria. RESULTS: The pooled rates of seroconversion were 49% (95% confidence interval [CI], 43%-55%) in transplant recipients and 99% (95% CI, 99%-99%) in healthy controls after the second dose of vaccine. The pooled rate was 56% (95% CI, 49%-63%) in transplant recipients after the third dose. Immunosuppressive medication is the most prominent risk factor associated with seroconversion failure, but different immunosuppressive regimens are associated with differential outcomes in this respect. Calcineurin inhibitors, steroids, or mycophenolate mofetil/mycophenolic acid are associated with an increased risk of seroconversion failure, whereas azathioprine or mammalian target of rapamycin inhibitors do not. Advanced age, short interval from receiving the vaccine to the time of transplantation, or comorbidities confers a higher risk for seroconversion failure. CONCLUSIONS: Transplant recipients compared with the general population have much lower rates of seroconversion upon receiving COVID-19 vaccines. Immunosuppressants are the most prominent factors associated with seroconversion, although different types may have differential effects.


Subject(s)
COVID-19 Vaccines , COVID-19 , Transplant Recipients , Antibodies, Viral , Azathioprine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Calcineurin Inhibitors/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , Mycophenolic Acid/adverse effects , TOR Serine-Threonine Kinases
4.
Transplant Proc ; 54(6): 1561-1563, 2022.
Article in English | MEDLINE | ID: covidwho-1641699

ABSTRACT

BACKGROUND: Casirivimab-imdevimab is a cocktail of 2 monoclonal antibodies designed to prevent infection by SARS-CoV-2, the virus that causes COVID-19. Casirivimab-imdevimab has been approved in Japan for treating mild to moderate COVID-19; however, to our knowledge, there are no reports of its use after kidney transplant from a live donor. Everolimus, an antineoplastic chemotherapy drug, is expected to be effective in inhibiting the spread of SARS-CoV-2 and preventing its replication, which may facilitate treatment. Here, we report a case of COVID-19 infection after kidney transplant that was initially treated with casirivimab-imdevimab and mycophenolate mofetil but was later changed to everolimus. CASE REPORT: A 47-year-old man underwent living donor kidney transplant from his mother in 2017. Immunosuppression therapy was underway through the administration of tacrolimus, mycophenolate mofetil, and methylprednisolone. In early September 2021, he was diagnosed as having COVID-19 and was hospitalized on day 3. On hospitalization, mycophenolate mofetil was discontinued and casirivimab-imdevimab and heparin were started. The patient started an everolimus regimen on day 5. The clinical course was successful without rejection. There was no exacerbation of COVID-19; the patient's serum creatinine levels and renal function had otherwise remained stable. CONCLUSIONS: We could safely treat a patient with casirivimab-imdevimab after kidney transplant. It is suggested that casirivimab-imdevimab can prevent COVID-19 from becoming severe and can be administered without worsening renal function. In addition, everolimus may have inhibited the spread of the virus and prevented it from replicating.


Subject(s)
COVID-19 , Kidney Transplantation , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Creatinine , Everolimus/adverse effects , Graft Rejection , Heparin , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Male , Methylprednisolone/therapeutic use , Middle Aged , Mycophenolic Acid/adverse effects , SARS-CoV-2 , Tacrolimus/therapeutic use
6.
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)
2019-nCoV Vaccine mRNA-1273/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Autoimmune Diseases/immunology , BNT162 Vaccine/immunology , Hereditary Autoinflammatory Diseases/immunology , Rheumatic Diseases/immunology , 2019-nCoV Vaccine mRNA-1273/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/drug therapy , BNT162 Vaccine/adverse effects , 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
7.
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)
BNT162 Vaccine/adverse effects , BNT162 Vaccine/immunology , 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 , Vaccine Efficacy
8.
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 , BNT162 Vaccine , 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
9.
Ann Rheum Dis ; 81(4): 575-583, 2022 04.
Article in English | MEDLINE | ID: covidwho-1450597

ABSTRACT

OBJECTIVES: Our aim was to evaluate systemic lupus erythematosus (SLE) disease activity and SARS-CoV-2-specific immune responses after BNT162b2 vaccination. METHODS: In this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine until day 15 after the second dose in 126 patients with SLE. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T cell responses were quantified by interferon-γ release assay after the second dose. RESULTS: BNT162b2 was well tolerated and no statistically significant variations of BILAG (British Isles Lupus Assessment Group) and SLEDAI (SLE Disease Activity Index) scores were observed throughout the study in patients with SLE with active and inactive disease at baseline. Mycophenolate mofetil (MMF) and methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody response (ß=-78, p=0.007; ß=-122, p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total immunoglobulin G serum levels, naïve B cell frequencies (ß=2, p=0.018; ß=2.5, p=0.003) and SARS-CoV-2-specific T cell response (r=0.462, p=0.003). In responders, serum neutralisation activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients. CONCLUSION: MMF, MTX and poor baseline humoral immune status, particularly low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating patients with SLE who might need adapted vaccine regimens and follow-up.


Subject(s)
Antirheumatic Agents/adverse effects , BNT162 Vaccine/immunology , Immunity, Humoral/drug effects , Lupus Erythematosus, Systemic/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/immunology , Antirheumatic Agents/immunology , COVID-19/prevention & control , Female , Humans , Immunogenicity, Vaccine/drug effects , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/virology , Male , Methotrexate/adverse effects , Methotrexate/immunology , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/immunology , Prospective Studies , Severity of Illness Index
10.
Transpl Infect Dis ; 23(2): e13524, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-991692

ABSTRACT

Kidney transplant (KT) recipients are at an increased risk for severe COVID-19 because of their immunosuppressed state. A 42-year-old KT patient was diagnosed with COVID-19 three months after KT. Despite lymphopenia and several risk factors, he had a mild disease course. Nasopharyngeal real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 became negative 48 days after detection. SARS-CoV-2 IgG antibodies became negative after day 40. TTV DNA load increased with the onset COVID-19 and reduced after its resolution. This is the first report where TTV DNA load was measured during the course of COVID-19.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , DNA Virus Infections/immunology , DNA, Viral/metabolism , Immunocompromised Host , Immunoglobulin G/immunology , Kidney Transplantation , Torque teno virus/genetics , Adult , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Comorbidity , Diabetes Mellitus/epidemiology , Glucocorticoids/therapeutic use , Graft Rejection/prevention & control , Humans , Hypertension/epidemiology , Immunoglobulin M/immunology , Immunosuppressive Agents/adverse effects , Kinetics , Lymphopenia/immunology , Male , Mycophenolic Acid/adverse effects , Obesity/epidemiology , Prednisolone/therapeutic use , SARS-CoV-2/immunology , Severity of Illness Index , Tacrolimus/adverse effects , Viral Load
11.
Transpl Infect Dis ; 23(2): e13501, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-949310

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might increase the risk of invasive pulmonary aspergillosis (IPA). Although several case reports and small series have been reported in the general population, scarce information is available regarding coronavirus disease 2019 (COVID-19)-associated IPA in the setting of solid organ transplantation. We describe a case of a kidney transplant recipient with severe COVID-19 that was subsequently diagnosed with probable IPA on the basis of the repeated isolation of Aspergillus fumigatus in sputum cultures, repeatedly increased serum (1 â†’ 3)-ß-d-glucan levels, and enlarging cavitary nodules in the CT scan. The evolution was favorable after initiation of isavuconazole and nebulized liposomal amphotericin B combination therapy and the withdrawal of immunosuppression.


Subject(s)
Antifungal Agents/therapeutic use , COVID-19/therapy , Immunosuppressive Agents/adverse effects , Invasive Pulmonary Aspergillosis/drug therapy , Kidney Failure, Chronic/therapy , Kidney Transplantation , Acute Kidney Injury , Administration, Inhalation , Amphotericin B/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Azithromycin/therapeutic use , COVID-19/complications , COVID-19/immunology , Ceftriaxone/therapeutic use , Deprescriptions , Female , Glucocorticoids/adverse effects , Graft Rejection/prevention & control , Humans , Hydroxychloroquine/therapeutic use , Hyperoxaluria, Primary/complications , Hyperoxaluria, Primary/diagnosis , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Invasive Pulmonary Aspergillosis/complications , Invasive Pulmonary Aspergillosis/diagnostic imaging , Invasive Pulmonary Aspergillosis/immunology , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/pathology , Middle Aged , Mycophenolic Acid/adverse effects , Nitriles/therapeutic use , Oxygen Inhalation Therapy , Prednisone/adverse effects , Pyridines/therapeutic use , Renal Dialysis , SARS-CoV-2 , Sputum , Tacrolimus/adverse effects , Tomography, X-Ray Computed , Triazoles/therapeutic use
12.
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 , Immunosuppression Therapy/adverse effects , 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 , Immunosuppression Therapy/methods , 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 , COVID-19 Drug Treatment
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