RESUMEN
BackgroundAnti-MDA5 antibody positive dermatomyositis (MDA5-DM) is characterized by high mortality due to rapid progressive ILD. MDA5 is a cytosolic protein and a family of RIG-I like receptor, which functions as a virus RNA sensor and induces the production of such as type-1 IFN. Although little is known about the pathogenesis of MDA5-DM, it is notable that the similarities were reported between COVID-19 infection and MDA5-DM. It may suggest that there is a common underlying autoinflammatory mechanism. We reported that in MDA5-DM, (1) RIG-I-like receptor signaling is enhanced and (2) antiviral responses such as type 1 IFN signaling are also enhanced as compare with anti-ARS-antibody positive DM, and (3) the key for survival is suppression of RIG-I-like and IFN signaling (EULAR2022, POS0390). We also found that a significant role for uncontrolled macrophage in the pathogenesis of ILD by our autopsy case. Recently, it has been reported that tacrolimus (TAC) and cyclophosphamide (CY) combination therapy (TC-Tx) has improved the prognosis of cases with early onset of the disease, but there are cases that cannot be saved. Therefore, we devised BRT therapy (BRT-Tx). The Tx combines baricitinib (BAR), which inhibits GM-CSF and IFN-mediated signaling and effectively suppresses uncontrolled macrophages, with rituximab (RTX) and TAC, which rapidly inhibits B and T cell interaction and ultimately prevents anti-MDA5 antibody production.ObjectivesTo determine the differences in gene expression between BRT and TC-Tx for MDA5-DM in peripheral blood.MethodsTotal of 6 MDA5-DM (TC: 3, BRT: 3) were included and all of them had multiple poor prognostic factors. Peripheral whole blood was collected at just before and 2-3 months after the treatment. RNA was extracted, and quantified using a next-generation sequencer. Differentially Expressed Genes (DEGs) were identified by pre vs. post treatment. Gene Ontology (GO), clustering and Gene Set Variation Analysis (GSVA) were performed to DEGs. As one BRT case was added since our last year's report, we also reanalyzed the surviving vs. fatal cases. The IFN signature was scored separately for Types 1, 2, and 3, and the changes between pre- and post-treatment were investigated.ResultsTwo of three cases with TC died during treatment, while all three cases on BRT recovered. The cluster analysis of the DEGs separated deaths from survivors, not by type of treatment. Comparing surviving and dead cases, GO analysis revealed that the immune system via immunoglobulins and B cells was significantly suppressed in surviving cases. GO analysis of DEGs in each therapeutic group showed that expression of B cell-related genes such as lymphocyte proliferation and B cell receptor signaling pathway were significantly suppressed in BRT-Tx. On the other hand, TC-Tx significantly suppressed such pathways as cell proliferation and cell surface receptor signaling, and was less specific for the target cells than BRT-Tx. The changes in IFN signature score after treatment showed an increase in type 2 and 3 IFN scores in all fatal cases and an increase in type 1 IFN score in one fatal case.ConclusionBRT-Tx significantly suppressed gene expression associated with B cells, while TC-Tx was characterized by low specificity of therapeutic targets and suppression of total cell proliferation. Comparison of surviving and dead cases revealed that the combination of RTX contributed to the success of treatment, as suppression of the immune system mediated by immunoglobulins and B cells is the key for survival. Analysis of the IFN signature revealed an increase in IFN score after treatment in fatal cases, indicating that the combination of BAR is beneficial. The superiority of BRT-Tx seems clear from the fact that all patients survived with BRT-Tx while only one/three patients survived with TC-Tx.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMoe Sakamoto: None declared, Yu Nakai: None declared, Yoshiharu Sato: None declared, Yoshinobu Koyama Speakers bureau: Abbvie, Asahikasei, Ayumi, BMS, Esai, Eli-Lilly, Mitsubishi Tanabe, Grant/research support from: Abbvie, GSK.
RESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of novel coro-navirus disease 2019 (COVID-19), a major cause of atypical pneumonia worldwide. Elderly individuals and those with underlying illnesses, such as cardio-vascular and pulmonary diseases, are at a high risk of experiencing severe symptoms and have high mortality rates. There is therefore a major need to develop additional vaccines, effective treatments, and complementary drugs to control this infection. Lactoferrin (LF), a naturally-occurring glycoprotein, is bioactive against viruses and other pathogens. LF has a unique immunomodulatory function and is indispensable for immunity in infants. It is thought to contribute to biological defense in individuals across all generations, not only infants. LF inhibits viral adhesion to host cell surfaces through ionic binding to glycosaminoglycans and/or specific binding to viral structures. Purified LF is cost-effective and orally available as a dietary sup-plement. Here, we review studies on the protective role of LF against common viral infections. Based on this review, we propose that LF can be a possible prophy-lactic or therapeutic agent for COVID-19 disease. © Fuji Technology Press Ltd.
RESUMEN
COVID-19 has dramatically changed the social situation in Japan. Along with the change in the real society, COVID-19 also changes the usage of social media. This study reports on findings from an analysis of onomatopoeia appears in posts on social media regarding COVID-19 to see how it has affected people's emotion. We analyzed the frequency of appearance of onomatopoeias expressing specific emotions according to the time variation, the relation between major events such as the declaration of state of emergency, and changes of co-occurrence words for the onomatopoeias. As a result of analysis, we found that the frequencies and degree of variation of onomatopoeias that belong to the same emotion group are complexly associated. The analysis results on co-occurrence words and frequency shift by events suggest that the cause of the change in emotion was different even for the onomatopoeia expressing the same emotion. The long-term emotional changes marked the peak in June 2020 during the second COVID-19 outbreak in Japan, rather than the first outbreak occurred in April 2020. At this time, as the number of infected people increased, the frequency of the use of the onomatopoeias also tended to increase. From the first case of COVID-19 in Japan (Jan 2019) to the second outbreak (Jun 2020), "anger "and "fear"were dominant emotions then they change to "peace of mind"during the second peak to the third outbreak (Nov 2020), and finally become "disgust". © 2021 ACM.