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BackgroundVaccination has been recommended in the midst of the COVID-19 pandemic, but some patients are not vaccinated due to concerns about adverse reactions.ObjectivesThe purpose of this study is to investigate the adverse reactions in rheumatic diseases and to guide the decision-making of patients and physicians.MethodsA questionnaire was sent to patients with rheumatic diseases, and patients who could be counted as of September 2021, when they consented to this study, were surveyed.ResultsThe subjects were 123 (male:female=10:113), 84 with rheumatoid arthritis and 39 with other immune diseases. The therapeutic agents used were PSL 31(25.2%), MTX 65(52.8%), NSAID/COX inhibitors 28(22.8%), bDMARDs 42(34.1%). adverse reactions after the first and second vaccination were fever 17(13.8%)/50(40.7%), joint symptoms 7(5.7%)/22(17.9%), local injection reactions (pain/irritation) 22(17.9%), local injection reactions (pain/erythema) 93(75.6)/98(79.7), systemic skin symptoms 0(0%)/2(1.6%), other symptoms (malaise, myalgia, etc.) 59(48.0%)/85(69.1%), and treatment intensification 5(4.1%)/12(9.7%). These responses differed in occurrence only for fever with and without PSL medication (22.5%: 47.3% (p=0.02)).The odds ratio for disease worsening after the first dose of vaccine and again after the second dose was 33.5 (p<0.01).ConclusionNo specific adverse reactions other than the commonly known ones were observed, but some patients experienced worsening of symptoms after vaccination, requiring intensified treatment. Based on the results of this study, we believe that adverse reactions to vaccination are acceptable. We plan to accumulate more cases and analyze them in the future.The exacerbation of disease after the first vaccination would predict the exacerbation after the second vaccination.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Rationale: Individuals with COPD who develop COVID-19 are at increased risk of hospitalization, ICU admission and death. COPD is associated with increased airway epithelial expression of ACE2, the receptor mediating SARS-CoV-2 entry into cells. Hypercapnia commonly develops in advanced COPD and is associated with frequent and potentially fatal pulmonary infections. We previously reported that hypercapnia increases viral replication, lung injury and mortality in mice infected with influenza A virus. Also, global gene expression profiling of primary human bronchial epithelial (HBE) cells showed that elevated CO2 upregulates expression of cholesterol biosynthesis genes, including HMGCS1, and downregulates ATP-binding cassette (ABC) transporters that promote cholesterol efflux. Given that cellular cholesterol is important for entry of viruses into cells, in the current study we assessed the impact of hypercapnia on regulation of cellular cholesterol levels, and resultant effects on expression of ACE2 and entry of Pseudo-SARS-CoV-2 in cultured HBE, BEAS-2B and VERO cells, and airway epithelium of mice. Methods: Differentiated HBE, BEAS-2B or VERO cells were pre-incubated in normocapnia (5% CO2, PCO2 36 mmHg) or hypercapnia (15% CO2, PCO2 108 mmHg), both with normoxia, for 4 days. Expression of ACE2 and sterol regulatory element binding protein 2 (SREPB2), the master regulator of cholesterol synthesis, was assessed by immunoblot or immunofluorescence. Cholesterol was measured in cell lysates by Amplex red assay. Cells cultured in normocapnia or hypercapnia were also infected with Pseudo SARS-CoV-2, a Neon Green reporter baculovirus. For in vivo studies, C57BL/6 mice were exposed to normoxic hypercapnia (10% CO2/21% O2) for 7 days, or air as control, and airway epithelial expression of ACE2, SREBP2, ABCA1, ABCG1 and HMGCS1 was assessed by immunofluorescence. SREBP2 was blocked using the small molecules betulin or AM580, and cellular cholesterol was disrupted using MβCD. Results: Hypercapnia increased expression and activation of SREBP2 and decreased expression of ABC transporters, thereby augmenting epithelial cholesterol levels. Elevated CO2 also augmented ACE2 expression and Pseudo-SARSCoV- 2 entry into epithelial cells in vitro and in vivo. These effects were all reversed by blocking SREBP2 or disrupting cellular cholesterol. Conclusion: Hypercapnia augments cellular cholesterol levels by altering expression of cholesterol biosynthetic enzymes and efflux transporters, leading to increased epithelial expression of ACE2 and entry of Pseudo-SARS-CoV-2 into cells. These findings suggest that ventilatory support to limit hypercapnia or pharmacologic interventions to decrease cellular cholesterol might reduce viral burden and improve clinical outcomes of SARSCoV- 2 infection in advanced COPD and other severe lung diseases.
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In recent years, the number of users and the waves of the communication on the Internet such as SNS (Social Networking Service) is increasing. However, the problem on SNS is pointed out the flood of uncertain information as hoax, rumors and fake news. This study proposes the algorithm of visualization to judge true and false using LSTM for news posted on the Internet. © 2021 IEEE.
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Rationale: Individuals with chronic obstructive pulmonary disease (COPD) who develop 2019 coronavirus disease (COVID-19) are at increased risk of hospitalization, intensive care unit admission and death. COPD is associated with increased airway epithelial expression of angiotensin converting enzyme 2 (ACE2), the cell surface receptor to which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds and which mediates entry of the virus into cells. Hypercapnia, the elevation of CO2 in blood and tissue, commonly develops in advanced COPD and is associated with frequent and potentially fatal pulmonary infections. We previously showed that normoxic hypercapnia alters expression of innate immune genes, including multiple viral response genes, in primary human bronchial epithelial (HBE) cells (Sci Reports 8:13508, 2018). Thus, in the current study, we explored the effect of hypercapnia on expression of ACE2 and uptake of a Pseudo-SARS-CoV-2 baculovirus by airway epithelial cells. Methods: HBE cells (Lonza) differentiated at air-liquid interface or immortalized BEAS-2B cells were pre-incubated in normocapnia (NC, 5% CO2, PCO2 36 mmHg) or normoxic hypercapnia (HC, 15% CO2, PCO2 108 mmHg) for 4 days. ACE2 protein expression was assessed by immunoblot or immunofluorescence (IF). In addition, BEAS-2B cells pre-exposed to NC or HC for 2 days were infected with Pseudo SARS-CoV-2 for an additional 2 days. Pseudo SARS-CoV-2 (Montana Molecular) is a reporter baculovirus whose surface is decorated with SARS-CoV-2 spike protein, and which induces expression of Neon Green protein in the nucleus of host cells 24 h after viral entry. For in vivo studies, C57BL/6 mice were pre-exposed to normoxic hypercapnia (10% CO2/21% O2) for 7 days, or air as control, and ACE2 expression in lung tissue was assessed by IF. Results: Compared to culture in NC, HC increased ACE2 protein expression by ∼4-fold in HBE cells and ∼2.5-fold in BEAS-2B cells. Likewise exposure of mice for 7 days to 10% CO2, as compared to air, markedly increased airway epithelial cell expression of ACE2 (Figure 1). Additionally, culture in HC, as compared to NC, increased Pseudo SARS-CoV-2 entry to BEAS-2B cells. Conclusion: Elevated CO2 increases airway epithelial cell expression of the SARS-CoV-2 receptor, ACE2, in vitro and in vivo. This may lead to a greater burden of SARS-CoV-2 infection in patients with hypercapnia, and in part account for worse clinical outcomes of COVID-19 pneumonia in advanced COPD and other severe lung diseases.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease (COVID-19) which has spread rapidly worldwide to cause a global pandemic. The SARS-CoV-2 genome shows a lower mutation rate than other RNA viruses. However, because of the ongoing rapid worldwide transmission among humans, the genetic diversity of the SARS-CoV-2 genome has increased. In Japan, a previous study suggested that the distinct viral clades L, S, G and GR of SARS-CoV-2 had been imported from overseas and begun to circulate domestically by April 2020. However, little is known about molecular epidemiology of SARS-CoV-2 since then, because of the lack of sufficient information on the viral genome sequence information in Japan. Herein, to probe the molecular epidemiological trends in Japan, we determined the full genome sequences of SARS-CoV-2 (n=55) derived from patients admitted to our hospital and performed a comparative analysis with domestic and international sequence information available from GISAID and GenBank. The results showed that the dominant domestic genotypes, including our determined sequences, had shifted from clades S and L to clades G and GR, and dispersed widely during the first infection peak period (March to April). In contrast, all the SARS-CoV-2 genotypes after May 2020 are highly clustered as unique clade GR genotypes that are not detected outside Japan. This genetic clustering occurred during the period under which restrictions were placed on overseas travel in Japan. Similar trends of viral genotype clustering have also been observed worldwide, with regional disparities. Under these circumstances, we should adopt adequate preventive measures to prevent the viral genetic diversity from increasing, and also further extend the molecular epidemiological survey of SARS-CoV-2 genotypes in Japan. These efforts will aid in ensuring successful use of the novel vaccines and antiviral drugs in the near future.