RESUMEN
BackgroundAmid the coronavirus disease 2019 (COVID-19) crisis, two messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have benefited most people worldwide. While healthy people can acquire sufficient humoral immunity against COVID-19 even in the elderly by vaccination with three doses of vaccine., recent studies have shown that complex factors other than age, including the type of vaccines and immunosuppressive drugs, are associated with immunogenicity in patients with rheumatic musculoskeletal disease (RMD). Identifying factors that contribute to the vulnerability of those patients to acquire not only humoral but also cellular immunity to SARS-CoV-2 despite multiple vaccinations is crucial for establishing an appropriate booster vaccine strategy.ObjectivesTo assess humoral,and T cell immune responses after third doses of mRNA vaccines against SARS-CoV-2.MethodsThis prospective observational study included consecutive RMD patients treated with immunosuppressant who received three doses of mRNA vaccines including BNT162b2 and mRNA-1273. Blood samples were obtained 2-6 weeks after second and third dose of mRNA vaccines. We measured neutralizing antibody titres, which against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 and seroconversion rates to evaluate the humoral responses. We also assessed T-cell immunity responses using interferon releasing assay against SARS-CoV-2.ResultsA total of 586 patients with RMD treated with mmunosuppressive treatments were enrolled. The mean age was 54 years, and 70% of the patients were female. Seroconversion rates and neutralizing antibody titres after third vaccination of SARS-CoV-2 were significantly higher compared to those after second vaccination (seroconversion rate, 94.5% vs 83.6%, p<0.001;titres of neutralizing antibody, 48.2 IU/mL vs 11.0 IU/mL, p<0.001, respectively). Interferon releasing assay after third vaccinations demonstrated that T cell reaction against SARS-CoV-2 was also increased from that of second vaccination (interferon for antigen 1, 1.11.9 vs 0.61.9, p=0.004,interferon for antigen 2, 1.72.6 vs 0.82.3, p=0.004). Humoral and cellular immunogenicity did not differ between the types of third vaccination including full dose of BNT162 and half dose of mRNA1273.(neutralizing antibody titers, 47.8±76.1 IU/mL vs 49.0±60.1 IU/mL, p<0.001;interferon for antigen 1, 1.12.0 vs 1.01.5, p=0.004, respectively). Attenuated humoral response to third vaccination was associated with BNT162b2 as second vaccination age (>60 years old), glucocorticoid (equivalent to prednisolone > 7.5 mg/day), and immunosuppressant use including mycophenolate, and rituximab. On another front, use of mycophenolate and abatacept or tacrolimus but not rituximab were identified as negative factors for T-cell reactions against SARS-CoV-2. Although 53 patients (9.0%) who had been immunised with third-vaccination contracted COVID-19 during Omicron pandemic phase, no one developed severe pulmonary disease that required corticosteroid therapy.ConclusionOur results demonstrated third mRNA vaccination booster of SARS-CoV-2 contributed to restore both humeral and cellular immunity in RMD patients with immunosuppressants. We also identified that certain immunosuppressive therapy with older RMD patients having BNT162b2 as a second vaccination may need additional booster vaccination.Reference[1]Furer V, Eviatar T, Freund T, et al. Ann Rheum Dis. 2022 Nov;81(11):1594-1602. doi: 10.1136/ard-2022-222550.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
RESUMEN
Background. Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibited the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. To evaluate the efficacy and safety of nelfinavir, we conducted a randomized controlled trial. Methods. Adult patients testing positive for SARS-CoV-2 infection within 3 days were eligible for the study if they had no or mild symptoms of coronavirus disease 2019. Exclusion criteria included the followings: onset of symptoms >= 8 days before enrollment;oxygen saturation of 95% or less on room air;and vaccinated patients. Patients were randomly assigned (1:1) to receive oral nelfinavir 750 mg (x3 times daily) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to clearance of SARS-CoV-2. Saliva was collected every day and viral load was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Nelfinavir was administered for 14 days. However, the treatment could be discontinued by the decision of investigator, if patients had 2 consecutive negative test results by qRT-PCR. Clinical course and safety information were collected through day 28. The study is registered with the Japan Registry of Clinical Trials (number, jRCT2071200023). Results. Between July 2020 and October 2021, 123 patients (63 in the nelfinavir group and 60 in the control group) were enrolled into the study and included in the analysis. The median time to viral clearance was 8.0 (95% confidence interval [CI] 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI 7.0 to 10.0) days in the control group without statistically significant difference between the treatment group (hazard ratio 0.815, 95% CI 0.563 to 1.182;P = 0.1870). Adverse events were reported in 47 (74.6%) patients in the nelfinavir group and 20 (33.3%) in the control group. The most common adverse events in the nelfinavir group were diarrhea (49.2%) and nausea (6.3%). Conclusion. Nelfinavir did not reduce the time to viral clearance in this setting.
RESUMEN
Background: The SARS-CoV-2 messenger RNA (mRNA) vaccines BNT162b2 (Pfzer-BioNTech) and mRNA-1273 (Moderna) have beneftted all countries amid the coronavirus disease 2019 (COVID-19) crisis. Whereas both of them have shown efficacy in preventing COVID-19 illness in healthy participants, there is paucity of data about immunogenicity and safety of mRNA COVID-19 vaccines in patients with autoimmune, infammatory rheumatic disease. Recent observational studies evaluated mainly BNT162b2, suggesting that glucocorticoids, immunosuppressive agents impair SARS-CoV-2 vaccine responses. However, difference in immune reactions and safety between BNT162b2 and mRNA-1273 have not been clarifed in patients with infammatory rheumatic diseases. Objectives: To assess humoral and T cell immune responses and safety profiles after two doses of different mRNA vaccine against SARS-CoV-2;BNT162b2 and mRNA-1273. Methods: We enrolled consecutive, previously uninfected patients with infam-matory rheumatic diseases receiving mRNA vaccine including BNT162b2 and mRNA-1273. Healthy participants receiving BNT162b2 were also recruited as control. Blood samples were obtained 3weeks, 2 months, 3 months, 4 months, and 6 months after second dose of vaccines. We measured titres of neutralizing antibodies against SARS-CoV-2 and calculated seroconversion rates to evaluate humoral responses. We also assessed T-cell immunity responses by using interferon releasing assay against SARS-CoV-2 in a part of the patients. Answers to questionnaires about adverse reactions were obtained from participants. Results: A total of 974 patients with infammatory rheumatic diseases and healthy 630 control participants were enrolled. Among them, 796 patients received BNT162b2, 178 patients received mRNA-1273, and all control participants received BNT162b2. Seroconversion rates and neutralizing antibody titres 3 weeks after vaccination were signifcantly higher in patients with mRNA-1273 and healthy participants with BNT162b2 compared with patients with BNT162b2;seroconver-sion rates, 97.2% vs 99.5% vs 83.3%, p<0.001;titers of neutralizing antibodies, 29.4±33.9 IU/mL vs 23.9±14.2 IU/mL vs 10.8±16.5 IU/mL, p<0.001, respectively. On another front, T cell reaction against SARS-CoV-2 was similar in both patients with mRNA-1273 and BNT162b2;interferon gamma levels for antigen 1, 1.2±2.1 IU/mL vs 0.8±2.5 IU/mL, p=0.23;and for antigen 2, 1.4±1.9 IU/mL vs 1.0±2.1 IU/mL, p=0.11, respectively. Regarding adverse reaction of each mRNA vaccine, the frequency of systemic adverse reactions including fever and general fatigue are also signifcantly higher in patients with mRNA-1273 and healthy controls than patients with BNT162b2;fever, 48.0% vs 44.9% vs 10.2%, p<0.001;general fatigue, 70.4% vs 61.8% vs 31.2%, p<0.001, respectively). In longitudinal measurement, neutralizing antibody titres in patients with BNT162b2 were decreased more rapidly than those in healthy controls;3.3±3.2 IU/mL in patients with BNT162b2 at 4 months and 3.2±4.7 IU/mL in healthy controls with BNT162b2 at 6 months. We identifed age, glucocorticoid dose (prednisolone > 7.5mg), use of immunosuppressants including methotrexate, mycophenolate, cyclophosphamide, and tacrolimus are associated with rapid attenuation of humoral responses in patients with BNT162b2. Conclusion: Our results demonstrated a signifcant higher humoral immuno-genicity and frequency of systemic adverse reaction of the SARS-CoV-2 mRNA-1273 (Moderna) compared with the BNT162b2 (Pfzer-BioNTech) in infammatory rheumatic disease patients. Glucocorticoid and immunosuppressive agents impaired induction and sustention of neutralizing antibody, and earlier third booster vaccination may be required within 4 months, especially for those receiving BNT162b2.
RESUMEN
This paper presents and evaluates a new educational tool and a model for learning theory and practice of game development, by involving geographically separated and culturally different industrial and academic organizations. We propose a TRIAD education model, which is as an extension to the conventional project-based learning, by uniting industry staff, faculty members, and students in an online discussion space. This model is a two-phase cyclic model where in Phase-1) industry members and academic staff discuss the progress of PBL transparently, showing the cross-cultural gaps and advising how to solve them, and in Phase-2) students make progress on the projects. Additionally, the TRIAD model adopts asynchronous text messaging as a core communication method, which is suitable for a multi-timezone situation, as well as exchanges of self-reviews from students and feedback from instructors. The online space not only facilitates interns in overcoming the hurdles represented by the gaps between the industry and academia, but it also visualizes the students' implicit educational progress by periodically analyzing all stored data by applying quantitative text analysis methods. This paper shows the result of an empirical study by utilizing this TRIAD model and analytics tool conducted at a large-scale Japanese game company with over 2,000 employees focusing on two students from the division of game development at a university in Sweden. We applied a quantitative text analysis tool for this model during an on-going internship program to clarify how students change their thoughts and behaviors by acquiring cross-cultural professionalism in the game industry. In addition, the result indicates that this TRIAD model is resilient, even under the COVID-19 epidemic situation due to its text-based approach. © 2020 IEEE.