The Impact of Instructions for Covering the Mouth and the Nose on Dispatch-Assisted Cardiopulmonary Resuscitation

Introduction: Under the SARS-CoV-2 pandemic, rescuers are recommended to cover their mouth and nose with a facemask or a cloth as well as victim's mouth and nose when performing cardiopulmonary resuscitation (CPR). However, its impact on dispatch-assisted CPR (DACPR) has not been investigated well. Hypothesis: DACPR including the instruction for covering the rescuer's and the victim's mouth and nose can significantly delay the start of the first chest compression. Method(s): We retrospectively analyzed DACPR records of the Nara Wide Area Fire Department, covering population of 853,000/3361km , in Japan. We investigated the key time intervals of 505 DACPR records between May 2020 and March 2021. We also compared the results to that of the same period in 2019 (535 records). Result(s): Dispatchers failed to provide mask instruction in 322 cases (63.8%). The median time interval from the emergency call and the start of CPR instruction was longer in 2020 (197 seconds vs 190 seconds, p=0.641). The time to the first chest compression was also delayed in 2020 (264 seconds vs 246 seconds, p=0.015). Among the cases that dispatchers successfully provided mask instruction (183 cases, 36.2%), median time intervals to the start of instruction and the first chest compression were relatively faster than cases without mask instruction (177 seconds vs 211 seconds and 254 seconds vs 269.5 seconds, respectively). Conclusion(s): Dispatchers failed to provide mask instruction in the majority of CA cases. However, our study results indicate that the impact of mask instruction on DACPR can be minor in terms of immediate CPR provision.

THE RELATIONSHIP BETWEEN CHANGES IN EXERCISE HABITS, PHYSICAL FUNCTION, AND PSYCHOLOGICAL STATUS IN OLDER PATIENTS WITH HYPERTENSION

Objective: Self-restraint from activities due to the COVID-19 pandemic has limited the range of activities and interpersonal relationships for older persons. Moreover, prolonged restraint has been reported to increase the risk of frailty and sarcopenia. Therefore, we examined the effects of changes in exercise habits on physical function and psychological status of older patients with hypertension throughout their self-restraint lifestyle from 2020 to 2022 in the 1-year follow-up study. Design and Methods: Participants were patients with hypertension aged 65 years or older attending outpatient clinics at our institution who could obtain information on exercise habits, history of falls, comprehensive geriatric assessment, and muscle strength. We conducted the same survey in the first year and one year later. The subjects were classified into four groups by combining their exercise habits in the first year with or without one year later. That is Group A: with exercise habits at both times of the survey;Group B: with exercise habits in the first year and without exercise habits one year later;Group C: without exercise habits in the first year and with exercise habits one year later;and Group D: without exercise habits at both times of the survey. Written consent forms were obtained from all participants. Our institutional review board approved the study protocol. Results: The study participants were 183 patients (Group A: 119, Group B: 26, Group C: 17, Group D: 21). The age of the participants was 76.1 ± 5.5 years, 82 (44.8%) were male, and the duration of hypertension was 18.4 ± 11.5 years. Changes in exercise habits were not associated with physical function, history of falls, and comprehensive geriatric assessment at one year. However, when the results were examined separately for men and women, the geriatric depression scale was significantly higher in women in Group B (Dunnett test, p = 0.0094) than in Group A, suggesting that the tendency toward depression had progressed. Group B women also had more falls one year later (chi-square 12.04, p = 0.0072). Conclusions: In a 1-year follow-up study during the COVID-19 pandemic, a relatively high proportion of older patients with hypertension attending our hospital maintained their exercise habits, but 14% of cases lost their exercise habits. Only women showed the development of depression and increased risk of falls when exercise habits were lost. Women were more susceptible to the effects of environmental changes than men in older patients with hypertension.

Potential usage of anterior nasal sampling in clinical practice with three rapid antigen tests for SARS-CoV-2

Introduction: Anterior nasal sampling (AN) might be more convenient for patients than NP sampling to diagnose coronavirus disease. This study investigated the feasibility of rapid antigen tests for AN sampling, and the factors affecting the test accuracy. Methods: This single-center prospective study evaluated one qualitative (ESP) and two quantitative (LUMI and LUMI-P) rapid antigen tests using AN and NP swabs. Symptomatic patients aged 20 years or older, who were considered eligible for reverse-transcription quantitative polymerase chain reaction using NP samples within 9 days of onset were recruited. Sensitivity, specificity, and positive and negative concordance rates between AN and NP samples were assessed for the rapid antigen tests. We investigated the characteristics that affected the concordance between AN and NP sampling results. Results: A total of 128 cases were recruited, including 28 positive samples and 96 negative samples. The sensitivity and specificity of AN samples using ESP were 0.81 and 1.00, while those of NP samples were 0.94 and 1.00. The sensitivity of AN and NP samples was 0.91 and 0.97, respectively, and specificity was 1.00, for both LUMI and LUMI-P. The positive concordance rates of AN to NP sampling were 0.87, 0.94, and 0.85 for ESP, LUMI, and LUMI-P, respectively. No factor had a significant effect on the concordance between the sampling methods. Conclusions: ESP, LUMI, and LUMI-P showed practical diagnostic accuracy for AN sampling compared to NP sampling. There was no significant factor affecting the concordance between AN and NP sampling for these rapid antigen tests. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases

Study Protocol for a Randomized Double-blind Placebo-controlled Phase 2 Clinical Trial to Assess Anti-inflammatory Effect of Colchicine(DRC3633)in Mild to Moderately Severe COVID-19 Patients(DRC-06C)

Introduction: Given that coronavirus disease 2019(COVID-19)aggravation is associated with an excessive host immune response, complementary anti-inflammatory treatment is recommended in severe disease. Although dexamethasone is a widely used anti-inflammatory agent in COVID-19 patients with respiratory failure, its use in patients with mild COVID-19 not receiving oxygen could have harmful effects. Colchicine, an anti-inflammatory drug, blocks the upstream immune response by inhibiting NALP3 inflammasome activation. This study aimed to assess the efficacy and safety of low-dose colchicine(DRC 3633)in mild COVID-19. Method(s): This study is a prospective, multicenter, placebo-controlled, double-blind randomized, phase 2 clinical trial patients with moderate COVID-19 admitted at nine hospitals in Japan (jRCT2071200078). The primary endpoint is area under the curve(AUC)for the amount of change of serum hypersensitive C-reactive protein(hs-CRP)from baseline to 1, 2, and 4 weeks after initiating investigational drug. Study participants will be randomly assigned to the colchicine or placebo group at a 1:1 ratio. On day 1, patients in the colchicine group will receive 1 mg of colchicine, followed by 0.5 mg of colchicine after 2 h barring gastrointestinal complications. From day 2 to 28, 0.5 mg of colchicine will be administered once daily. Discussion(s): An appropriate anti-inflammatory strategy is critical to improve the outcome of severe COVID-19 patients. This study will assess the efficacy of low-dose colchicine not only by the AUC of the amount of change in serum hs-CRP from baseline to several time points, but also by evaluating whether the result of the primary endpoint is consistent with other relevant biomarkers and clinical parameters measured as secondary endpoints. Copyright © 2022 the Japanese Society of Clinical Pharmacology and Therapeutics (JSCPT)

Longitudinal SARS-COV-2 anti-spike antibody response in pregnant people with natural infection and variable vaccine uptake

Background. Natural SARS-CoV-2 infection results in anti-nucleocapsid (N) and anti-spike (S) antibody (Ab) development. Anti-S Ab response (conferred by infection and/or vaccination) is more closely associated with protection. We evaluated anti-N/S Ab responses in vaccinated (> 1 dose) and unvaccinated pregnant people with prior SAR-CoV-2 infection. Methods. During January 2021-March 2022, we enrolled participants with SARS-CoV-2 infection identified in pregnancy (26 via anti-N IgG+;52 via prior RT-PCR+). Baseline, 1, 2, 3, 6, and 12 months, and delivery samples were tested for anti-N (index >= 1.4 positive) and anti-S (>= 50 AU/mL positive) IgG Ab by Abbott Architect. Kaplan-Meier methods were used to measure Ab response duration. Results. Among 78 participants, 62 (79%) enrolled in pregnancy (median 27 weeks gestation), and 16 (21%) at delivery/postpartum (median 2 weeks);34 (44%) had received >=1 vaccine prior to initial Ab testing. At baseline, 59 (75%) participants had concordant anti-N/S positive results (median anti-N index 3.58 [IQR 2.01-5.82], median anti-S 5529 AU/ml [IQR 687-25000]). Anti-S IgG was higher (25000 vs 774, p< 0.001) among participants receiving >=1 vaccine vs no vaccine, while anti-N IgG indices were similar. Among 59 participants with initial anti-N IgG+ results, median time to anti-N IgG negative results was 31 weeks after first RT-PCR+ (median 17 weeks after first anti-N IgG+ result). Only 1 (unvaccinated) participant had an anti-S IgG negative result by 22 weeks after first RT-PCR+ result. Among 30 participants with delivery samples (median 16 weeks after RT-PCR+, 12 weeks after baseline anti-N IgG+ samples), 15 (52%) remained anti-N IgG+;29 (97%) remained anti-S IgG+. Anti-S IgG was higher (25000 vs 826 AU/ml, p< 0.001) among participants receiving >= 1 vaccine vs. no vaccine prior to delivery. Conclusion. Among pregnant persons with prior SARS-CoV-2 infection, duration of anti-S IgG response was longer than anti-N IgG irrespective of vaccine status;vaccination during pregnancy was associated with higher anti-S levels at baseline and delivery. While anti-S IgG were detectable for >= 6 months, longer term follow-up is needed to assess durability of hybrid immunity vs. infection alone and has implications for maternal and infant protection.

Safety and efficacy of atezolizumab (Atezo) + bevacizumab (Bev) in Japanese patients (pts) with unresectable hepatocellular carcinoma (uHCC): A prospective, multicenter, observational study (ELIXIR) - A preliminary analysis

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

LONGITUDINAL SARS-CoV-2 ANTIBODY RESPONSE in PREGNANCY and TRANSPLACENTAL TRANSFER

Background: Longitudinal assessment of SARS-CoV-2 antibody (Ab) response during pregnancy after infection and transplacental transfer may inform durability of maternally derived Ab for mothers and infants. Methods: Between October 2020-September 2021, pregnant people testing SARS-CoV-2 IgG positive by Abbott Architect chemiluminescent immunoassay (CMIA) for anti-nucleocapsid (N) antibody (semi-quantitative index ≥1.4 considered IgG+) during pregnancy or delivery in a seroprevalence study, or identified with RT-PCR+ results via medical records, were invited to enroll in a longitudinal evaluation of maternal Ab responses and transplacental transfer. Maternal blood collected at 1, 2, 3, and 6 months after enrollment and maternal and cord blood collected at delivery were tested with the same assay. Results: Among 40 participants testing IgG+ for anti-N, 31 (78%) had a prior RT-PCR+ result. Median age was 32 years (IQR 29-35);27 (68%) enrolled during pregnancy at median 18 weeks gestation (IQR 13-33), while 13 (33%) enrolled at delivery or early postpartum. Median Abbott index was 3.06 (IQR 1.96-5.74) at first IgG+ result obtained at a median of 9 weeks (IQR 4-16) after RT-PCR+ result, for those with a known RT-PCR. Among 23 participants with ≥2 samples, 50% had IgG results below positivity threshold at median 17 weeks (IQR 12-28) after first IgG+ result (Figure). Seventeen mother-infant pairs had delivery samples collected at median 66 days (IQR 60-71 days) from maternal RT-PCR+ result. Six (35%) maternal samples remained IgG+ (median Abbott index 2.97 [IQR 2.35-7.01]) at delivery (gestational age 30-40 weeks) with all 6 paired cord sera testing IgG+ (median Abbott index 4.30 [IQR 2.93-7.22]). Median placental transfer ratio of maternally derived IgG Abs based on a positive Abbott index was 1.13 (95%CI 0.98-1.30) among mothers with samples remaining IgG+ at delivery. Conclusion: Within 4 months after first IgG+ result primarily in second trimester, about half of pregnant persons had SARS-CoV-2 IgG anti-N Ab levels below the Abbott CMIA positive threshold. Among evaluable mother-infant pairs, two-thirds of mothers no longer tested anti-N IgG+ at delivery. Transplacental transfer of maternal antibodies was confirmed in all infants born to mothers with samples remaining IgG+ at delivery. Durability of maternal SARS-CoV-2 Ab response and transplacental transfer following infection has implications for maternal and neonatal susceptibility to SARS-CoV-2 infection.

SARS-CoV-2 Seroprevalence and Antibody Response among Pregnant People in Seattle, WA

Background. Antenatal care is a unique opportunity to assess SARS-CoV-2 seroprevalence and antibody response in pregnant people, including those with previously unknown infection. Methods. Pregnant people were screened for SARS-CoV-2 IgG during antenatal care or delivery in Seattle, Washington with Abbott Architect chemiluminescent immunoassay which provides quantitative index (positive ≥1.4). Participants with IgG+ results or identified with RT-PCR+ results via medical records were invited to enroll in a longitudinal evaluation of antibody responses. We report preliminary results of an ongoing seroprevalence and longitudinal study with planned 18-month follow-up. Results. Between September 9, 2020-May 7, 2021, we screened 1304 pregnant people;62 (4.8%) tested SARS-CoV-2 IgG+, including 28 (45%) with known prior SARS-CoV-2 infection. Among participants testing IgG+, median age was 32 years (interquartile range [IQR] 26-35) and median gestational age was 21 weeks (IQR 12-38) at screening;median IgG index was 3.2 (IQR 2.1-4.9, range 1.4-9.9), including 3.9 (IQR 2.3-5.8) among those with vs. 2.7 (IQR 1.9-4.2) among those without prior RT-PCR+ results (p=0.05 by Wilcoxon rank-sum). Of 30 longitudinal study participants enrolled, 24 tested IgG+ at baseline (75% with prior RT-PCR+ result) and 6 tested IgG- on enrollment but were identified as previously RT-PCR+ via medical records;24/30 (80%) reported previous symptoms. Of 24 participants testing IgG+ at baseline, 14 (58%) had first follow-up IgG results at median of 66 days (IQR 42-104) since initial testing, with median IgG index of 2.0 (IQR 1.0-3.8). 9/14 (64%) participants with repeat IgG testing remained IgG+ at first follow-up (≤280 days after first RT-PCR+ result for those with and ≥104 days after first IgG detection for those without prior RT-PCR+ results), while 5/14 (26%) had a negative Abbott IgG test at a median of 81 days (IQR 75-112) since initial testing. Conclusion. Nearly half of pregnant people testing SARS-CoV-2 IgG+ reported no known prior SARS-CoV-2 diagnosis or symptoms. SARS-CoV-2 IgG antibody response and durability in pregnancy has implications for maternal and neonatal protection and susceptibility and highlights potential benefits of vaccination in this population.

Positive Ratio of Polymerase Chain Reaction (PCR) and Validity of Pre-Screening Criteria at an Outpatient Screening Center during the Early Phase of the COVID-19 Epidemic in Japan

Despite the increase in COVID-19 cases globally, the number of cases in Japan has been relatively low, and an explosive surge in the prevalence has not occurred. In March 2020, the Ministry of Health, Labour and Welfare (MHLW) in Japan recommended the original criteria for polymerase chain reaction (PCR) testing, although there was a lack of evidence for appropriate targets for COVID-19 testing. This study aimed to evaluate the COVID-19 positive ratio and pre-screening criteria in Tokyo immediately after the insurance-covered SARS-CoV-2 PCR testing became available in Japan. We subjected 277 individuals with mild symptoms in metropolitan Tokyo (positive: 9.0%) from March 9 to 29, 2020, to SARS-CoV-2 PCR testing. The results revealed that 25 (9.0%) of them were PCR-positive. The sensitivity and specificity of the MHLW criteria were 100% and 10.7%, respectively. When the criteria excluded nonspecific symptoms, fatigue, and dyspnea, the sensitivity slightly decreased to 92%, and the specificity increased to 22.2%. The specificity was highest when the fever criterion was >= 37.5 degrees C for >= 4 days, and exposure/travel history, including age and underlying comorbidities, was considered. Our findings suggest that the MHLW criteria, including the symptoms and exposure/travel history, may be useful for COVID-19 pre-screening.

Evaluation of droplet and aerosol dispersion under high flow nasal cannula with or without surgical mask

Rationale: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), transmit by droplet and aerosol particles. Droplets and aerosol generation during the oxygen delivery methods such as high flow oxygen therapy (HFNC) and noninvasive positive pressure ventilation (NPPV) during COVID-19 respiratory care, may poses a risk of increasing transmission to healthcare workers. We aimed to evaluate droplet and aerosol dispersion associated with oxygen delivery modes, and further to verify the effect of surgical mask (SM) on preventing particle dispersion.Methods: Two experiments were performed at the laboratory of Shin Nippon Air Technologies, Japan, to visualize (Experiment 1) and to quantify (Experiment 2) dispersing particles. Three (Experiment 1) and five (Experiment 2) healthy Japanese male volunteers aged 30-40s and non-smokers, were recruited. For visualization study (Experiment 1), dispersing particles (>5μm) were recorded by ultra-high sensitive video camera 'eye scope'. For quantification study (Experiment 2), two types of micro-particle detection panel 'Type S' which counts particles > 0.5μm or >5μm were used under air-controlled room with down-flow of 0.3m/sec to avoid contamination of dusts and to drop aerosols on Type S panel. Five patterns of oxygen delivery modalities (No device, 5L/min of nasal cannula, 30L/min or 60L/min of HFNC, 10L/min of oxygen mask, and NPPV) with and without SM, while three breathing patterns (rest breathing, speaking, and coughing) were recorded. The differences in continuous numbers between corresponding two groups were analyzed by ratio paired t-test. A P-value <0.05 was considered as statistically significant.Results: Droplets were able to visualize at further than 50cm while speaking, and further than 1m while coughing. Without SM, droplets were more visible with nasal cannula compared to HFNC. SM effectively reduced droplets under each oxygen delivery modes, and they are hard to visualize even in speaking or coughing. In NPPV mode, floating droplets were visible while coughing. Droplets and aerosols were counted 10-times more while coughing compared to speaking. SM significantly reduced both of droplets and aerosol dispersion while speaking or coughing regardless of oxygen delivery mode. Reduction rate of dispersion under HFNC was higher compared to nasal cannula. 60L/min of HFNC did not increase droplets or aerosol dispersion by counts or by distance compared to 30L/min of HFNC. SM effectively reduced over 90% of droplets and over 95% of aerosols during HFNC mode.Conclusions: SM over HFNC mode may be used safely in appropriate infection control setting and recommended for acute hypoxemic respiratory failure in COVID-19 patients.

Nightlife clusters of coronavirus disease in Tokyo between March and April 2020.

We analysed associations between exposure to nightlife businesses and severe acute respiratory syndrome coronavirus 2 PCR test results at a tertiary hospital in Tokyo between March and April 2020. A nightlife group was defined as those who had worked at or visited the businesses. We included 1517 individuals; 196 (12.9%) were categorised as the nightlife group. After propensity score matching, the proportion of positive PCR tests in the nightlife group was significantly higher than that in the non-nightlife group (nightlife, 63.8%; non-nightlife, 23.0%; P < 0.001). An inclusive approach to mitigate risks related to the businesses needs to be identified.

Quantitative proteomic analysis of the tizoxanide effect in vero cells.

Nitazoxanide (NTZ) is effective against helminths and numerous microorganisms, including bacteria and viruses. In vivo, NTZ is metabolized into Tizoxanide (TIZ), which is the active circulating metabolite. With the emergence of SARS-Cov-2 as a Pandemic agent, NTZ became one of the molecules already approved for human use to engage clinical trials, due to results in vitro showing that NTZ was highly effective against the SARS-Cov-2, agent of COVID-19. There are currently several ongoing clinical trials mainly in the USA and Brazil involving NTZ due not only to the in vitro results, but also for its long-known safety. Here, we study the response of Vero cells to TIZ treatment and unveil possible mechanisms for its antimicrobial effect, using a label-free proteomic approach (LC/MS/MS) analysis to compare the proteomic profile between untreated- and TIZ-treated cells. Fifteen differentially expressed proteins were observed related to various biological processes, including translation, intracellular trafficking, RNA processing and modification, and signal transduction. The broad antimicrobial range of TIZ points towards its overall effect in lowering cell metabolism and RNA processing and modification. The decreased levels of FASN, HNRNPH and HNRNPK with the treatment appear to be important for antiviral activity.