Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.

Antibody acquisition after second and third SARS-CoV-2 vaccinations in Japanese kidney transplant patients: a prospective study.

BACKGROUND: Kidney transplant patients have lower antibody acquisition after SARS-CoV-2 vaccination. The efficacy of vaccines in Japanese kidney transplant patients with specific characteristics, such as predominant living-donor, ABO-incompatible kidney transplant, and low-dose immunosuppression, requires verification. METHODS: We conducted a prospective study to estimate anti-SARS-CoV-2 antibody levels in 105 kidney transplant patients and 57 controls. Blood samples were obtained before vaccination, 1, 3, and 6 months after second vaccination, and 1 month after third vaccination. We investigated antibody acquisition rates, antibody levels, and factors associated with antibody acquisition. RESULTS: One month after second vaccination, antibody acquisition was 100% in the controls but only 36.7% in the kidney transplant group (P < 0.001). Antibody levels in positive kidney transplant patients were also lower than in the controls (median, 4.9 arbitrary units vs 106.4 arbitrary units, respectively, P < 0.001). Years after kidney transplant (odds ratio 1.107, 95% confidence interval 1.012-1.211), ABO-incompatible kidney transplant (odds ratio 0.316, 95% confidence interval 0.101-0.991) and mycophenolate mofetil use (odds ratio 0.177, 95% confidence interval 0.054-0.570) were significant predictors for antibody acquisition after second vaccination. After third vaccination, antibody positivity in the kidney transplant group increased to 75.3%, and antibody levels in positive patients were 71.7 arbitrary units. No factors were associated with de novo antibody acquisition. CONCLUSIONS: In Japanese kidney transplant patients, years after kidney transplant, ABO-incompatible kidney transplant and mycophenolate mofetil use were predictors for antibody acquisition after second vaccination. Third vaccination improves antibody status even in patients who were seronegative after the second vaccination.

Outcome of COVID-19 in patients with rheumatic and inflammatory diseases treated with mycophenolic acid: data from the French RMD COVID-19 cohort.

BACKGROUND: Patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) receiving mycophenolic acid (MPA) may have a less favourable outcome from COVID-19 infection. Our aim was to investigate whether MPA treatment is associated with severe infection and/or death. METHODS: IRMD patients with and without MPA treatment with highly suspected/confirmed COVID-19 were included in this observational multicentre study. The primary outcome was death rate from COVID-19 with secondary objectives to determine the severity of infection and length of hospital stay. Outcome comparisons were made using regression models with and without adjustment on prespecified confounding factors. ORs, sub-HR (sHR) and 95% CIs were calculated using patients not treated with MPA as a reference group. RESULTS: Of the 1977 patients, 1928 were not treated with MPA (393 were MPA eligible), and 49 patients were treated with MPA. MPA-treated patients had more severe disease, longer hospital stays and higher death rate from COVID-19 than non-MPA patients (OR 8.02 (95% CI 3.35 to 19.20), p<0.001; sHR 0.57 (95% CI 0.33 to 0.98), p=0.040; OR 11.58 (95% CI 4.10 to 32.69), p<0.001). In adjusted analyses, however, no outcome was independently associated with MPA treatment. Death rate, severity and length of hospital stay of MPA-treated patients were not significantly different from those of not treated but MPA-eligible patients. CONCLUSION: MPA therapy is not associated with a more severe COVID-19 infection. However, due to increased vulnerability of developing a severe form of COVID-19, careful consideration should be taken with iRMD patients likely to be treated with MPA. TRIAL REGISTRATION NUMBER: NCT04353609.

Immunogenicity and safety of the mRNA-based BNT162b2 vaccine in systemic autoimmune rheumatic diseases patients.

BACKGROUND: The COVID-19 outbreak has led to the rapid development and administration of the COVID-19 vaccines worldwide. Data about the immunogenicity and adverse effects of the vaccine on patients with systemic autoimmune rheumatic diseases (SARDs) is emerging. AIM: To evaluate Pfizer/BioNTech (BNT162b2) mRNA-based vaccine second-dose immunogenicity and safety, and the relation between them, in patients with SARDs. METHODS: A total of one hundred forty tow adults who received two doses of the BNT162b2 vaccine were included in the study. The SARDs group included Ninety-nine patients and the control group (forty-three participants) comprised a mixture of healthy participants and patients who were seen at the rheumatology clinic for non-SARDs. Anti-SARS-CoV-2 IgG antibodies against the Spike protein were evaluated using a SARS-CoV-2 IgG immunoassay. A level of > 150 AU/mL was considered positive. An adverse effects questionnaire was given to the participants upon their first visit to the clinic after their BNT162b2 vaccination. RESULTS: Of the 142 participants, 116 were seropositive (81.7%) and 26 (18.3%) were seronegative. Of the seronegative participants, 96.2% were SARDs patients. The proportion of seropositivity in the SARDs patients treated with any immunosuppressant was significantly lower (69.9%) compared to the control group and SARDs patients not receiving immunosuppressants (96.8%). A significant negative correlation between seronegativity and treatment with rituximab, mycophenolate mofetil (MMF), and prednisone was found in the SARDs group (p = 0.004, 0.044, 0.007 respectively). No fever was observed following the BNT162b2 vaccine in seronegative patients, and the frequency of musculoskeletal adverse effects upon the second dose of the BNT162b2 vaccine was significantly higher in seropositive compared to seronegative patients and in the control group compared to the SARDs patients (p = 0.045, p = 0.02 respectively). CONCLUSION: A decline in the immunogenicity to the second dose of BNT162b2 mRNA is seen in patients with SARDs, especially in patients treated with rituximab, MMF, and prednisone. Adverse effects of the vaccine including fever and musculoskeletal symptoms might be a signal for the acquisition of immunity in those patients. KEY POINTS: • BNT162b2 mRNA vaccine is less immunogenic in SARDs patients compared to the control group. • Rituximab, prednisone, and mycophenolate mofetil significantly reduced immunogenicity to the vaccine. • There is a correlation between immunogenicity and adverse effects of the vaccine.

mTOR inhibitors, mycophenolates, and other immunosuppression regimens on antibody response to SARS-CoV-2 mRNA vaccines in solid organ transplant recipients.

A recent study concluded that SARS-CoV-2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression- and machine learning-based analyses to compare antibody responses by immunosuppressive agents in a national cohort (n = 1037). MMF was associated with significantly lower odds of positive antibody response (aOR = 0.09 0.130.18 ). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = 1.00 1.452.13 ); however, importantly, this seemingly protective tendency disappeared (aOR = 0.47 0.731.12 ) after adjusting for MMF. We repeated this comparison by combinations of immunosuppression agents. Compared to MMF + tacrolimus, MMF-free regimens were associated with higher odds of positive antibody response (aOR = 2.39 4.267.92 for mTORi+tacrolimus; 2.34 5.5415.32 for mTORi-only; and 6.78 10.2515.93 for tacrolimus-only), whereas MMF-including regimens were not, regardless of mTORi use (aOR = 0.81 1.542.98 for MMF + mTORi; and 0.81 1.512.87 for MMF-only). We repeated these analyses in an independent cohort (n = 512) and found similar results. Our study demonstrates that the recently reported findings were confounded by MMF, and that mTORi is not independently associated with improved vaccine responses.

A pilot randomized controlled trial of de novo belatacept-based immunosuppression following anti-thymocyte globulin induction in lung transplantation.

The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a two-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial. Twenty-seven participants were randomized to Control (Tacrolimus, Mycophenolate Mofetil, and prednisone, n = 14) or Belatacept-based immunosuppression (Tacrolimus, Belatacept, and prednisone until day 89 followed by Belatacept, Mycophenolate Mofetil, and prednisone, n = 13). All participants were treated with rabbit anti-thymocyte globulin for induction immunosuppression. We permanently stopped randomization and treatment with Belatacept after three participants in the Belatacept arm died compared to none in the Control arm. Subsequently, two additional participants in the Belatacept arm died for a total of five deaths compared to none in the Control arm (log rank p = .016). We did not detect a significant difference in DSA development, acute cellular rejection, or infection between the two groups. We conclude that the investigational regimen used in this study is associated with increased mortality after lung transplantation.

Coronavirus Disease 2019 Positivity Immediately After Lung Transplantation: A Case Report.

Management of COVID-19 in lung transplant recipients is challenging. We report a case of a 71-year-old male who underwent bilateral lung transplantation with an unexpected case of COVID-19. The patient had been fully vaccinated. The patient and donor tested negative for pretransplant COVID-19. On routine bronchoscopy on day 1 after transplant, the COVID-19 test was positive. Mycophenolic mofetil and the second dose of basiliximab were skipped, but tacrolimus and prednisone were continued. He was treated with casirivimab/imdevimab and remdesivir. He was discharged on day 14 and has had no episodes of acute rejection during the 3 months.

Mycophenolate mofetil decreases humoral responses to three doses of SARS-CoV-2 vaccine in liver transplant recipients.

BACKGROUND AND AIMS: After 2 doses, the efficacy of anti-SARS-CoV-2 vaccination seems to be lower in solid organ transplant recipients than in the immunocompetent population. The objective of this study was to determine the humoral response rate after vaccination, including with a booster dose, and to identify risk factors for non-responsiveness in liver transplant recipients. METHODS: We included all patients seen in consultation in two French liver transplant centres between January 1, 2021, and March 15, 2021. RESULTS: 598 liver transplant recipients were enrolled and 327 were included for analysis. Sixteen patients received one dose, 63 patients two doses and 248 patients three doses. Anti-SARS-Cov-2 antibodies were detected in 242 out of 327 (74.0%) liver transplant patients after vaccination. Considering an optimal serologic response defined as an antibody titre >260 BAU/ml, 172 patients (52.6%) were responders. Mycophenolate mofetil (MMF) treatment was an independent risk factor for a failure to develop anti-SARS-CoV-2 antibodies after vaccination (OR 0.458; 95%CI 0.258-0.813; p = .008). Conversely, male gender (OR 2.247, 95%CI 1.194-4.227; p = .012) and receiving an mRNA vaccine (vs a non-mRNA vaccine) (OR 4.107, 95%CI 1.145-14.731; p = .030) were independent predictive factors for developing an optimal humoral response after vaccination. None of the patients who received the vaccine experienced any serious adverse events. CONCLUSIONS: Even after a third booster dose, response rate to vaccination is decreased in liver transplant recipients. MMF appears to be a major determinant of seroconversion and optimal response to vaccination in these patients.

Past COVID-19 and immunosuppressive regimens affect the long-term response to anti-SARS-CoV-2 vaccination in liver transplant recipients.

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.

Perspective on COVID-19 vaccination in patients with immune-mediated kidney diseases: consensus statements from the ERA-IWG and EUVAS.

Patients with immune-mediated kidney diseases are at increased risk of severe coronavirus disease 2019 (COVID-19). The international rollout of COVID-19 vaccines has provided varying degrees of protection and enabled the understanding of vaccine efficacy and safety. The immune response to COVID-19 vaccines is lower in most patients with immune-mediated kidney diseases; either related to immunosuppression or comorbidities and complications caused by the underlying disease. Humoral vaccine response, measured by the presence of antibodies, is impaired or absent in patients receiving rituximab, mycophenolate mofetil (MMF), higher doses of glucocorticoids and likely other immunosuppressants, such as cyclophosphamide. The timing between the use of these agents and administration of vaccines is associated with the level of immune response: with rituximab, vaccine response can only be expected once B cells start to recover and patients with transient discontinuation of MMF mount a humoral response more frequently. The emergence of new COVID-19 variants and waning of vaccine-induced immunity highlight the value of a booster dose and the need to develop mutant-proof vaccines. COVID-19 vaccines are safe, exhibiting a very low risk of de novo or relapsing immune-mediated kidney disease. Population-based studies will determine whether this is causal or coincidental. Such cases respond to standard management, including the use of immunosuppression. The Immunonephrology Working Group and European Vasculitis Society recommend that patients with immune-mediated kidney diseases follow national guidance on vaccination. Booster doses based on antibody measurements could be considered.

A prospective multicenter study assessing humoral immunogenicity and safety of the mRNA SARS-CoV-2 vaccines in Greek patients with systemic autoimmune and autoinflammatory rheumatic diseases.

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.

Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial.

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.

Acute Corneal Epithelial Rejection of LR-CLAL After SARS-CoV-2 Vaccination.

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.

Intensity of mycophenolate mofetil treatment is associated with an impaired immune response to SARS-CoV-2 vaccination in kidney transplant recipients.

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.

COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies.

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.

Influence of patient characteristics and immunosuppressant management on mortality in kidney transplant recipients hospitalized with coronavirus disease 2019 (COVID-19).

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.

Kidney Transplantation and COVID-19: Two Case Reports.

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.

Clinical course of COVID-19 disease in immunosuppressed renal transplant patients

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.