ABSTRACT
Background/Aims Patients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and are prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-We aim to fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine's immunogenicity. Methods Humoral, CD4 and CD8 immune responses were investigated in 147 SARS-Cov2-naive patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and diseasematched IMRD patients not receiving immunosuppressors and with healthy controls Results IMRD patients showed decreased seroconversion rates (63% vs 100%, p=0.04) and cellular immune responses (59% vs 100%, p=0.007). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept deeply affected humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed severely impaired humoral responses but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide. Conclusion IMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show the most deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine's immunogenicity.
ABSTRACT
Objectives: To assess humoral and cellular immune responses and safety profiles after two doses of different mRNA vaccine against SARS-CoV- 2;BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in patients with rheumatic musculoskeletal disease (RMD). Method(s): We enrolled consecutive, previously uninfected RMD patients with inflammatory rheumatic diseases receiving mRNA vaccine including BNT162b2 and mRNA-1273. Healthy participants all receiving BNT162b2 were recruited as control. Blood samples were obtained 3weeks after second dose of vaccines. We measured titres of neutralizing antibodies against SARS-CoV- 2 with chemiluminescent enzyme immunoassay to evaluate humoral responses and assessed T-cell immunity responses with interferon releasing assay against SARS-CoV- 2 in a part of the patients. Adverse reaction symptoms were obtained from participants through questionnaire. Result(s): A total of 1040 RMD patients and healthy 621 control participants were enrolled. Among RMD patients with immunosuppressants, 704 were received BNT162b2 and 156 were received mRNA-1273. Neutralizing antibody titres 3 weeks after vaccination and positive seroconversion rates were significantly higher in healthy participants with BNT162b2 and RMD patients with mRNA-1273 compared with RMD patients with BNT162b2;neutralizing antibody titre, 23.9 +/- 14.2 IU/mL vs 29.4 +/- 33.9 IU/mL vs 10.8 +/- 16.5 IU/mL, p < 0.001;seroconversion rates, 99.5% vs 99.4% vs 80.2%, p < 0.001, respectively, We identified that age, glucocorticoid (prednisolone dose > 7.5mg/day), and use of immunosuppressants including methotrexate, mycophenolate and rituximab, are associated with attenuation of humoral responses in patients with BNT162b2. T cell reaction against SARS-CoV- 2 were also higher in patients with RMD vaccinated with mRNA-1273 than those with BNT162b2 (Interferon gamma levels for antigen 1, 3.2 +/- 6.5 IU/mL vs 0.6 +/- 1.3 IU/mL, p = 0.002;for antigen 2, 3.2 +/- 6.3 IU/mL vs 1.0 +/- 2.1 IU/mL, p = 0.021, respectively). Regarding adverse reaction of mRNA vaccine, the proportion of systemic adverse reactions including fever and general fatigue are significantly higher in healthy controls and RMD patients with mRNA-1273 than those with BNT162b2;fever, 46.2% vs 56.7% vs 14.3%, p < 0.001;general fatigue, 62.6% vs 73.0% vs 38.5%, p < 0.001, respectively, while the frequency of background RMD flare after vaccination were not significantly different between mRNA-1273 and BNT162b2 (5.2% [n = 8] vs. 3.7% [n = 26], p = 0.41) Conclusion(s): We demonstrated higher humoral, cellular immunogenicity of the SARS-CoV- 2 mRNA-1273 (Moderna) compared with the BNT162b2 (Pfizer-BioNTech) in RMD patients. Although reactogenicity including systemic adverse reaction including fever and fatigue were observed mRNA1273 vaccinated patients, proportion of RMD relapse were similar between the patients with mRNA-1273 and BNT162b2.
ABSTRACT
Patients with immune mediated rheumatic and musculoskeletal diseases (RMD), including lupus, may develop more severe COVID 19 infection than the general population. Several medicines used in treatment of systemic lupus erythematosus (SLE), such as glucocorticoid, increases the risk of Covid 19 infection, especially at dose higher than 10 mg. The use of immunosuppression may have a role in altering the immune response to infection, therefore the experts recommend to use the good but safe alternatives, if available. However in manage acute or critical condition, established therapies may be more beneficial then alternatives to control the disease activity. Evidence for discontinuing immunosuppressants in RMD patients with COVID-19 is low, but the experts strongly recommended discontinuing them and weakly recommended to re-introduce them at least 2 weeks after recovery from acute COVID-19, but this may need to be individualized based on the clinical scenario and the judgment of physician. Lupus patients are recommended to receive SARS-CoV- 2 vaccine, as long as they do not have an allergy to vaccine components. Several studies revealed that there was no significant change in lupus disease activity after vaccination, however a study using BNT162b2 COVID-19 vaccine reported mild local reactogenicity in SLE and RA patients, such as redness and swelling. More frequent systemic reactogenicity, such as fever, fatigue, headache, chills, muscle and join pain, and vomiting, however, not more severe compared to healthy controls. This study adds to the notion that the vaccine is safe and well tolerated in patients with SLE and RA. Neutralizing antibody levels after COVID-19 vaccination were significantly lower than control population. The risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, mycophenolate, rituximab and abatacept, and type of vaccines. Adjusting the immunosuppression dosage schedule was suggested and considered an individual condition. A COVID-19 vaccine booster is encouraged for patients with autoimmune inflammatory rheumatic disease, including lupus. If they have completed the primary COVID vaccine series of 3 doses and are expected to have mounted an inadequate vaccine response, they should receive supplemental doses (e.g., >=2 additional boosters, for a total of five doses) as recommended by the CDC for immunocompromised individuals.
ABSTRACT
Kidney transplant recipients (KTRs) have a suboptimal immune response to COVID-19 vaccination due to the effects of immunosuppression, mostly mycophenolic acid (MPA). This study investigated the benefits of switching from the standard immunosuppressive regimen (tacrolimus (TAC), MPA, and prednisolone) to a regimen of mammalian target of rapamycin inhibitor (mTORi), TAC and prednisolone two weeks pre- and two weeks post-BNT162b2 booster vaccination. A single-center, opened-label pilot study was conducted in KTRs, who received two doses of ChAdOx-1 and a single dose of BNT162b2. The participants were randomly assigned to continue the standard regimen (control group, n = 14) or switched to a sirolimus (an mTORi), TAC, and prednisolone (switching group, n = 14) regimen two weeks before and two weeks after receiving a booster dose of BNT162b2. The anti-SARS-CoV-2 S antibody level after vaccination in the switching group was significantly greater than the control group (4051.0 [IQR 3142.0-6466.0] BAU/mL vs. 2081.0 [IQR 1077.0-3960.0] BAU/mL, respectively; p = 0.01). One participant who was initially seronegative in the control group remained seronegative after the booster dose. These findings suggest humoral immune response benefits of switching the standard immunosuppressive regimen to the regimen of mTORi, TAC, and prednisolone in KTRs during vaccination.