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Organ transplant recipients receive immunosuppressive drugs and hence are at high risk for COVID-19 due to their compromised immunity. This study assessed 1,370 liver transplant recipients who were followed at our hospital. A total of 12 patients got COVID-19: 5 recipients <50-years-old had mild disease, 7 recipients >60-years-old had moderate to severe disease, and 2 patients died. In addition, not all patients received 2 vaccinations, suggesting that the immunization is important for COVID-19 prophylaxis even in this patient population. One recipient was successfully treated with a combination of a reduced dose of immunosuppressive drugs, dexamethasone, remdesivir, and antibiotics, which is being established as an effective therapy for COVID-19.Copyright © 2022 The Japan Society of Hepatology.
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We propose a method that uses an emotion analysis for PBL education. The emotion analysis is a method of analyzing a person's emotions from the person's remarks or facial expressions. In this method, teachers understand the situation of students from the results of the emotion analysis and give accurate advice. PBL education often involves group activities. The students conducted groups discuss, propose ideas, select ideas, and make the products. However, not all students are able to participate in discussions and express their opinions. It is the teacher's duty to provide guidance to such students. Therefore, we propose the use of the emotion analysis techniques to identify and guide students who have problems, such as those who cannot participate in discussions. The method is possible for one teacher to grasp multiple groups at the same time and to help developing the students' ability to learn. Under COVID-19, face-to-face classes were restricted. Online classes using Zoom etc. have also been introduced in PBL education. In online classes, it is difficult to grasp the situation of students. This was a big difference from face-to-face classes. So we looked at ways to keep track of the situation for all students. This is because the gap between students who are willing to take classes and those who are reluctant to take classes has widened due to the shift to online classes. As a result of the adaption to the classes, the number of students who actively participate in the classes has increased. The effectiveness of the proposed method was confirmed. © 2022 SEFI 2022 - 50th Annual Conference of the European Society for Engineering Education, Proceedings. All rights reserved.
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Background: Atezo + Bev has been approved as first-line treatment in pts with uHCC based on a global phase 3 study (IMbrave 150). However, there is a lack of real-world data worldwide. Thus, we conducted the ELIXIR study to evaluate the safety and efficacy of Atezo + Bev prospectively in 500 real-world Japanese pts. Here, we report the first pre-planned safety assessment in 105 initially registered pts out of 500 pts. Method(s): In this prospective, multicenter, observational study, 500 systemic treatment-naive pts with uHCC and Child-Pugh A received Atezo 1200 mg IV q3w + Bev 15 mg/kg IV q3w. The primary endpoint was adverse events of special interest (AESI). Efficacy outcomes including progression-free survival (PFS) and objective response rate (ORR) were assessed in this analysis. Result(s): A total of 500 pts were enrolled between Apr 2021 and Feb 2022. One hundred and five initially registered pts finished enrollment by Aug 2021 and the median follow-up time was 6.4 mo. A total of 49 AESIs and 35 AESIs Grade >=3 were observed in these pts (Table). Median PFS was 6.0 mo (95% CI, 5.1, 6.7) per RECIST 1.1 and 6.5 mo (95% CI, 5.2, 8.0) per modified RECIST (mRECIST). ORR was 23.8% (95% CI, 16.0, 33.1) per RECIST 1.1 and 34.3% (95% CI, 25.3, 44.2) per mRECIST. [Formula presented]. Conclusion(s): In this analysis, additional safety signals were not observed in Japanese pts. Efficacy data could be underestimated at this time. The ELIXIR study showed that Atezo + Bev is a promising first-line treatment for Japanese pts with uHCC in the real world. Clinical trial identification: UMIN000043463. Editorial acknowledgement: Medical writing assistance for this was provided by Tetsuji Asao, PhD, of SunFlare Co., Ltd. Legal entity responsible for the study: Chugai Pharmaceutical Co., Ltd. Funding(s): Chugai Pharmaceutical Co., Ltd. Disclosure: M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, NIHON Servier, Novartis, Ono, Takeda, GlaxoSmithKline;Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Eli Lilly Japan, Eisai, NIHON SERVIER, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Abbott Japan, Fujifilm Toyama Chemical, Incyte Biosciences Japan, ASLAN, Chugai, NIHON SERVIER, Takeda;Financial Interests, Institutional, Invited Speaker: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, Merck Serono, MSD, Ono, Yakult, Novartis, Takeda, J-Pharma, Pfizer, Chiome Bioscience, NIHON SERVIER, Delta-Fly Pharma, Syneos Health, Merus.N.V. N. Kato: Financial Interests, Personal, Invited Speaker: Gilead Sciences Inc., AbbVie G.K., Ohtsuka Pharmaceutical Co., Ltd., Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Olympus Corporation, Eisai Co., Ltd., Aska Pharmaceutical Co., Ltd., Tsumura & Co., Mochida Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co., Ltd., Covidien Japan Inc., Eli Lilly Japan K.K., Nobelpharma Co., Ltd., Kowa Company, Ltd., Incyte Biosciences Japan GK, Yakult Honsha Co.,Ltd., Olympus Marketing, Inc., Taisho Pharmaceutical Co.,Ltd., Janssen Pharmaceutical K.K.;Financial Interests, Institutional, Research Grant: AbbVie G.K., Ohtsuka Pharmaceutical Co., Ltd., Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Shionogi & Co., Ltd., Eisai Co., Ltd., Tsumura & Co., Nippon Kayaku Co., Ltd., JIMRO Co., Ltd., Kowa Company, Ltd. T. Kagawa: Financial Interests, Personal, Invited Speaker: AbbVie, Eisai, Chugai, Sumitomo Pharma, Gilead, EA Pharma, Asuka, Takeda, Miyarisan, Otsuka, Eli Lilly, Kowa, Bayer;Financial Interests, Personal, Funding: AbbVie, Chugai, Sumitomo Pharma, Diichi Sankyo, Tanabe Mitsubishi, Takeda, MSD, Eisai, Shionogi, EA Pharma, Otsuka, Kyowa Kirin, Sanofi, Teijin, Eli Lilly. T. Yamashita: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Lilly, Bayer;inancial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, MSD, Ono. M. Moriguchi: Financial Interests, Personal, Invited Speaker: Eisai Co., Ltd., Bayer Yakuhin, Ltd., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd.;Financial Interests, Personal, Advisory Board: Eisai Co., Ltd., Bayer Yakuhin, Ltd., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd.;Financial Interests, Institutional, Funding: MSD K.K. Eisai Co., Ltd., Bristol Myers Squibb K.K., Bayer Yakuhin, Ltd. H. Iijima: Financial Interests, Institutional, Funding: Canon Medical systems, GE healthcare. K. Ohkawa: Financial Interests, Personal, Invited Speaker: Gilead, Eisai, Century Medical, Takeda;Financial Interests, Personal, Research Grant: Towa, Sumitomo Chemical. R. Sugimoto: Financial Interests, Personal, Invited Speaker, Speaker and moderator fees: Eisai Co, Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd.;Financial Interests, Personal, Invited Speaker, Speaker fees: Gilead Sciences, Chugai Pharmaceutical Co., Ltd.;Financial Interests, Personal, Invited Speaker, Speaker fees: Bayer Yakuhin Ltd, Nobelpharma Co., Ltd., Takeda Pharmaceutical Company Limited. T. Takehara: Financial Interests, Personal, Invited Speaker: Chugai;Financial Interests, Institutional, Research Grant: Chugai. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Bayer, Takeda, MSD;Financial Interests, Institutional, Research Grant: Otsuka, Sumitomo Dainippon Pharma, EA Pharma, Taiho, Eisai, AbbVie, Gilead Sciences, Takeda, GE Healthcare, Chugai. K. Yamamoto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, CMIC holdings, Johokiko, Triceps, Kanagawa Medical Practitioners Association;Financial Interests, Personal, Other, Statistical analysis: Otsuka Pharmaceutical;Financial Interests, Personal, Other, Statistical consultation: J-Pharma, Craif, Kanagawa Prefectural Hospital Organization;Financial Interests, Institutional, Other, unlimited grant: Taiho Pharmaceutical;Financial Interests, Institutional, Other, Unlimited grant: Boehringer Ingelheim, Ono Pharmaceutical, Takeda Pharmaceutical, Bayer Yakuhin, Daiichi-Sankyo, Astellas, Kyowa Kirin, Data Vehicle Inc., EP Croit. All other authors have declared no conflicts of interest. Copyright © 2022
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Purpose: For purpose of SARS-CoV-2 infection control, vaccination was started in worldwide, however, low reactivity of antibody production after vaccination is a concern for solid organ transplant (SOT) recipients. In general, antibody titers would be peaked within one month after vaccination for the healthy population, there are few report about SOT recipients vaccination. We explored antibody transitions in SOT recipients after vaccination. Method(s): A total of 641 solid organ transplant recipients were enrolled (481 kidney, 51 liver, 54 heart, 20 lung, and 35 simultaneous pancreas-kidney). All participants were administered the two-dose regimen mRNA vaccine (BNT162b2, Pfizer or mRNA-1273, Moderna), as indicated. SARS-CoV-2 antibodies were measured total 5 times throughout vaccination (Elecsys, Roche). Result(s): The antibody titer and positive rate were both elevated until three months and declined at six months after vaccination (positive rate;10.4%, 41.2%, 68.6%, 56.9%, in each) (Fig.1). Lung and kidney-pancreas transplant recipients showed poor antibody titer elevation compared with other organ transplantation (Fig. 2). Antibody titers be significant low by more than 60 years old compared with other ages (Fig.3). Conclusion(s): The antibody titer and positive rate transition of SOT recipients were quite different compared with the health population. The acquisition of antibody was different depends on type of SOT. (Figure Presented).
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Organ transplant recipients receive immunosuppressive drugs and hence are at high risk for COVID-19 due to their compromised immunity. This study assessed 1,370 liver transplant recipients who were followed at our hospital. A total of 12 patients got COVID-19: 5 recipients <50-years-old had mild disease, 7 recipients >60-years-old had moderate to severe disease, and 2 patients died. In addition, not all patients received 2 vaccinations, suggesting that the immunization is important for COVID-19 prophylaxis even in this patient population. One recipient was successfully treated with a combination of a reduced dose of immunosuppressive drugs, dexamethasone, remdesivir, and antibiotics, which is being established as an effective therapy for COVID-19.
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This paper proposes a word clustering method using graphical lasso-guided principal component analysis (PCA) for trend analysis of coronavirus disease (COVID-19). We define changes in daily frequencies of words on Twitter as trends, and clustering denotes to find similar trends. There is a problem that trends based on indirect correlations degrade the clustering performance. To address this problem, we newly develop graphical lasso-guided PCA. Specifically, graphical lasso is able to obtain a partial correlation matrix (a graph that represents direct correlations between trends). By calculating loadings of PCA to the partial correlation matrix (authority scores calculated by a hyperlink-induced topic search algorithm), accurate clustering becomes feasible. We conducted experiments by collecting Japanese tweets about COVID-19 from March 1, 2020 to April 30, 2020. The results show that our graphical lasso-guided PCA can distinguish two clusters before and after a state of emergency, unlike comparative method using indirect correlations. © 2021 IEEE.
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The COVID-19 pandemic caused by the SARS-CoV-2 epidemic now requires the deployment of fast, sensitive and inexpensive diagnostic methods to facilitate disease management and containment worldwide. The real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay is currently the standard method for detecting SARS-CoV-2 virus. However, lack of access to laboratory resources (including rRT-PCR instrumentation, reagents, or even trained laboratory technicians) limits rRT-PCR assays from being a field-deployable and rapid diagnostic tool, especially in resource-constrained pandemic zones. Given this limitation and the necessity of expediting the diagnostic procedures, there is a strong need to develop an accurate point-of-care (POC) testing platform for COVID-19 with quick turnaround times. A POC community-level quick test (used as an initial screening test before subsequent confirmation by rRT-PCR in a central laboratory) can significantly improve diagnostic utility and ultimately reduce the burden on medical resources. CRISPR-Cas technology has now surfaced as a promising diagnostic tool with rewarding prospects of rapid detection and low cost, thereby serving as a POC one-stop platform to detect COVID 19 infection and loads. Herein, we review various hitherto CRISPR–Cas-based methodologies for the detection of SARS-CoV-2 viral RNA.
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This paper proposes the project-based learning (PBL) education system which uses Artificial Intelligence (AI) instead of teachers’ direct instruction. Kanazawa Institute of Technology (KIT) applies PBL to its design and engineering programme as Project Design (PD) Programme. Students form small groups to discuss real-life problems and sometimes collaborate with local communities. However, in order to prevent COVID-19 infection, students cannot go to school. Instead, e-Syllabus and the web meeting Zoom (videoconferencing software) are used to take lectures at home. Adding to the PBL class implementation experience under the impact of COVID-19 and to the review results of the progress of digital technology, the outline, and the feature of the on-line PBL education system using chatbot and AI is proposed. Although the system is still under development, some of the components are introduced. © PDE 2021.
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BACKGROUND AND AIMS: Hyponatremia is associated with aggravation of inflammation in COVID-19 patients. However, to the best of our knowledge, no study has used longitudinal data and investigated the association between hyponatremia and COVID-19. Therefore, we analyzed COVID-19 patients' changes in serum sodium (Na) levels from admission to discharge. METHOD: We conducted a retrospective, single-center, observational cohort study, involving adult COVID-19 patients who were admitted to Japan Self-Defense Forces Central Hospital between April 1 and May 31, 2020. Serum Na level of < 135 mEq/L was defined as hyponatremia, 135-145 mEq/L as normonatremia, and > 145 mEq/L as hypernatremia. Inflammation was assessed by serum C-reactive protein (CRP) levels. Univariate logistic regression analyses were used to assess associations between hyponatremia at admission and need for oxygen or death during hospitalization. A comparison of serum Na levels at admission and discharge was tested using a paired ttest. Cross-sectional associations between serum Na and CRP levels at admission or days from onset to admission were analyzed using multivariate linear regression analyses. A restricted cubic spline (RCS) curve incorporated in one of these multivariate linear regression analyses was used to identify when serum Na levels were the lowest. In addition, we employed a mixed-effect model to examine the longitudinal association between changes in serum Na and CRP levels during hospitalization. RESULTS: Ninety-eight patients were enrolled, of whom 53 (54%) were male and 39 (40%) had a smoking history. Mean (SD) or median (IQR) of age, eGFR, body mass index (BMI), serum Na, and CRP at admission were 50 (17) years, 82 (20) mL/min/ 1.73m2, 23.3 (5.5), 138 (3.7) mEq/L, and 1.8 (0.2-6.0) mg/dL, respectively. It took an mean of 8.9 (3.7) days from onset to admission due to social disruption. According to government policies, during observation period, patients diagnosed with COVID-19 have to be hospitalized, even if they have minor or improving clinical symptoms. At admission, hyponatremia was observed in 11 (11.2%) patients;the rest of the patients had normonatremia. Twenty-seven (27.6%) patients received oxygen, and 4 (4.1%) died during hospitalization. Hyponatremia at admission was significantly associated with the need for oxygen (odds ratio: 41.2;95% CI: 4.9-344;P=0.001) and death (odds ratio: 32.3;95% CI: 3.0-347;P=0.004). Irrespective of hyponatremia at admission, the serum Na levels at discharge were significantly higher than those at admission (Fig. 1). In both cross-sectional and longitudinal analyses, serum Na levels were negatively associated with serum CRP levels after adjustment for age, sex, eGFR, BMI, and smoking history (P<0.001), which suggests that serum Na levels may reflect the activity of COVID-19. Furthermore, the serum Na levels at admission were positively associated with days from onset to admission after adjustment for age, sex, eGFR, BMI, smoking history, and serum CRP levels (P=0.035), and the RCS curve showed that the serum Na levels tended to be the lowest around the 7th day after onset (Fig. 2). CONCLUSION: Hyponatremia in COVID-19 may occur secondarily, and a condition called 'COVID-19-induced hyponatremia' might exist.
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We present a large-scale case study using an agent platform that gathered cross-class public opinions about the COVID-19 situation. Our system extracts valuable insights from users from the perspective of offering suggestions to public health policy makers about what pandemic action is required in Afghanistan. The research goal of this study is to contribute insights about the scale of the issues and their solutions for COVID-19 by facilitating crowd engagement and discussing potential factors to address future policy-making issues. We methodically used social platforms to encourage participation from private citizens and invited health experts and patients into our discussion system in collaboration with Afghanistans Ministry of Public Health. ZOOM webinars were used to host discussions on Facebook and YouTube as a way to promote COVID-related collective social awareness. Our system mediates discussions with an unlimited number of participants and extracts the insights of their opinions in real time. It can also classify discussion insights into four elements and find the relationships among them: issues, ideas, merits, and demerits. We present various kinds of statistical information from 2,046 collected opinions of 1,101 participants by both identification of Al insights and human-conducted studies. Our discourse analysis categorized the discussion elements and peoples word-usage frequency in each group. We analyzed the word frequencies of each groups discussion data based on four types of extracted IBIS elements and extracted the most frequently used keywords. In a discourses IBIS analysis, we found that a solution proposed by one class was considered an issue by another class. To the best of our knowledge, this is the first time in Afghanistan that a cross-class dialogue on COVID-19 has been organized using conversational Al as a representative application for public mediation and deliberation.
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Introduction: COVID-19 pandemic makes us realize that infectious disease a threat for humankind. Because respiratory infections such as coronaviruses are transmitted through contact and droplets, bronchoscopy is thought to be a high risk manipuration. An increased risk of virus transmission through droplets and aerosols has been reported, and strict infection control measures are essential. Healthcare providers take standard precautions, but few measures are taken on the side of patients who generates infectious droplets and aerosols.Therefore, innovative and user-friendly measures to cut droplets and aerosols are highly desirable.Method: To prevent droplets and aerosols during bronchoscopy, we created a simple, disposable, costeffective, mask for the patients who undergo bronchoscopy, with the Japanese mask industry help. The mask has a 10-mm-slit in the center for insertion of bronchoscope and a 6-mm-slit on both sides for suction catheter, which is realized with its unique pleats. The slits are closed with an electrified filter unless the tube is pierced. To evaluate the effectiveness of the prevention of droplet dispersal from the mouth, visualization of the particles with the super-highly sensitive camera and high-power light source (ViEST system) with or without the mask (bronchoscope and one suction catheter inserted) was performed and analyzed. With the quantification of droplets, and analysis of fluorescence-based image, the efficacy of prevention was evaluated. Moreover, we do the simulation with fluid dynamics software (Cradle) to visualize the spread of aerosol. The Aerosol was almost prevented with the mask. We also accessed the feasibility via the observation time of the bronchoscopy for the doctors. Results: The visualization and quantification of the droplets with ViEST system revealed that almost all the droplets are cut with the mask on bronchoscope. The simulation of the aerosol spreading indicated that the mask prevented the straightforward spreading of the aerosol from the patient's mouth. The observation time of bronchoscopy did not show the difference between with mask and without mask.In conclusion, this new mask might be useful in preventing splashes and aerosols during bronchoscopy. .
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The novel coronavirus disease 2019 (COVID-19) was first reported to the World Health Organization by the WHO country office in China in December 2019 and has since become a worldwide pandemic. In Japan, COVID-19 is a designated infectious disease under the Infectious Disease Control Act, meaning that hospitalization or isolation measures are required for infected persons. It has been noted that in some cases, patients show positive PCR test results even after discharge from the hospital upon meeting the discharge criteria for COVID-19. However, so far, there is a lack of substantial evidence on the pathogenesis of re-infection or relapse in patients with COVID-19. We report 4 cases of COVID-19 who showed repeat-positive PCR test results for SARS-COV-2 after discharge from the hospital, and assessed their infectivity using clinical information collected via a public epidemiological survey. All 4 cases showed a repeat-positive PCR test results within 40 days of the initial onset of symptoms. All the PCR test results showed high Ct values of 33 or higher in the repeat-positive test. In addition, neutralizing antibodies were detected in all cases within 3 days from the date of the repeat-positive test. Furthermore, an epidemiological survey was conducted in 18 persons who were in close contact with the 4 cases, and 11 of them tested negative by the PCR test, and no case of secondary infection was found. Based on these findings, the risk of secondary infection from the 4 cases was considered as low. No specimens collected at the time of the first infection or virus culture test results were available for further evaluation. Issues remain to be resolved in respect of the systems needed for cooperation with healthcare providers and the laboratory testing required for the evaluation of re-infection. In order to further elucidate the pathogenesis of COVID-19, and to provide appropriate medical care, it is essential to evaluate the infectivity of patients with a repeat-positive PCR test and to accumulate further knowledge about the disease.
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Aim: We present the study protocol of a multicenter, retrospective observational study that aims to investigate the efficacy of the actual treatment (the efficacy of conventional and Kampo medicines) of patients with mild to moderate or suspected coronavirus disease (COVID-19). Methods: This study is designed as a multicenter, retrospective observational study. Outpatients and inpatients will be recruited from Japanese hospitals. The inclusion criteria are as follows: having or suspected to have COVID-19, mild to moderate COVID-19, symptomatic, ≥20 years of age, male or female, able to communicate in Japanese, and treated with conventional and Kampo medicine. The exclusion criteria are: unable to provide informed consent due to dementia, psychosis, or psychiatric symptoms, severe COVID-19, or determined unsuitable for this study. The sample size is set at 1000, as this number of people can be treated at the collaborating medical institutions during the study period. Results: The main outcome is the number of days without fever, with a body temperature of less than 37°C. The secondary outcome is set at common cold-like symptoms other than fever (fatigue, cough, shortness of breath, sputum, diarrhea) and severity of illness and hospitalization up to 14 days after the visit. Trial registration: The trial was registered in the University Hospital Medical Information Network (Reservation No. UMIN000041301) on August 4, 2020. Conclusion: Our study will explore the contribution of conventional and Kampo medicine in the treatment of patients with mild and moderate COVID-19.
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Aim: Traditional Japanese (Kampo) medicine has been used to treat viral infectious diseases. In particular, saikatsugekito (a combination drug of kakkonto, shosaikoto, Platicodon glandiflorum root, and gypsum) has been reported to be useful during the past influenza pandemic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, causing the novel coronavirus disease (COVID-19) to emerge as a pandemic. In this article, we conducted a literature review on the pharmacological activities of the components present in saikatsugekito against viral infection and respiratory inflammation. Methods: We searched PubMed and the Cochrane Library for English articles, as well as Ichushi and J-stage for Japanese articles. Articles published until January 1, 2000 were retrieved using the keywords ‘kakkonto’, ‘shosaikoto’, ‘Platycodon’, and ‘gypsum’. We then extracted articles on basic research investigating viral infections, inflammation, cytokine, the immune response, and lung tissue damage. Results: We extracted 28 eligible articles. Kampo medicines have antiviral activities by interfering with the attachment, internalization, replication, progeny virion release, and cell-to-cell spreading of single-strand RNA viruses. They also enhance the immunomodulating activities of the host, including cytokine production, regulation of multiple immune cells, and protection from lung tissue injury. Furthermore, Kampo medicine has been found to regulate body temperature and airway mucin release. Conclusion: The results demonstrated that Kampo medicine has therapeutic activities against single-strand RNA virus infections and respiratory inflammation, and may also have activities against SARS-CoV-2. Further research is required to investigate the activity of Kampo medicines, such as saikatsugekito, against SARS-CoV-2.