Effectiveness of neutralizing antibody cocktail in hemodialysis patients: a case series of 20 patients treated with or without REGN-COV2.

The number of patients with SARS-CoV-2 infection continues to increase, and it has become a global pandemic. Although there is an urgent need to establish an effective treatment, the medication available for dialysis patients has been limited. An antibody cocktail containing two SARS-CoV-2-neutrarizing antibodies, REGN-COV2 has been granted special approval for COVID-19 in Japan, since July 2021, and this intravenous preparation can be used for dialysis patients. At our hospital, we had 22 hemodialysis patients with COVID-19, and five of them were treated with REGN-COV2. On admission, four of the five patients had moderate disease (pneumonia but O2 inhalation) and one patient had mild disease (not having pneumonia). The mean duration of hospitalization treated with REGN-COV2 was 10.2 ± 2.86 days (mean ± SD), which was less than half, compared to patients untreated of similar severity on admission (22.12 ± 15.5). The time to fever resolution was average 7 days, and no cases progressed to severe illness or death. Among these patients, no obvious adverse reactions were shown. Although more studies with a larger number of patients could be needed for a rigorous evaluation of the effect, our result suggests that REGN-COV2 may be safe and having the possibilities in preventing severe disease in hemodialysis patients. Given the difficulty in securing inpatient beds tend to be in short supply, the strategy combined with neutralizing antibody could be beneficial for end-stage kidney disease (ESKD) patients with hemodialysis who are at high risk of severe disease.

Efficacy and Safety of Weekly Ultraviolet Germicidal Irradiation for the Reuse of N95 Filtering Respirators.

Background During the ongoing coronavirus disease (COVID-19) pandemic, N95 filtering facepiece respirators (N95 respirators) are in short supply in many countries. Considering this, the Centers for Disease Control and Prevention suggested reusing N95 respirators and recommended the use of ultraviolet germicidal irradiation (UVGI) for sterilizing the respirators. However, only a few reports have described UVGI protocols for sterilizing the N95 respirators for reuse. Therefore, in this study, we aimed to develop and evaluate a novel method for the reuse of N95 respirators after sterilization by UVGI. Methods Before conducting the study, the function of N95 respirators after multiple UVGI with a total dose of up to 10 J (1 J/cm2 or more per dose) was assessed by measuring the particle collection efficiency and ventilation resistance. The participants used N95 respirators during work if they passed the fit test. After use, the respirators were sterilized using UVGI (1 J/cm2) and stored in a breathable paper bag for a week. The procedure was repeated up to three times after confirming the successful results of the fit tests. Results The particle collection efficiency without UVGI was 96.7%, while those after one, five, and 10 cycles of UGVI were 96.8%, 97.2%, and 97.2%, respectively. Ventilation resistance without UVGI was 42 Pa, and 43 Pa, 42 Pa, and 41 Pa after one, five, and 10 cycles of UVGI, respectively, which satisfied the Japanese national certification standard DS2. All 43 participants passed the fit test before the first reuse, and 39 participants (90.7%) completed the entire study protocol. The results of this study showed that N95 respirators could be used safely after repeated UVGI treatment. Conclusions This study developed a novel method for reusing the N95 respirators. A few cycles of UV radiation N95 masks retain their functionalities and can be reused with proper UVGI.

Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy. METHODS: COVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions. RESULTS: A total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher. CONCLUSIONS: The results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered. TRIAL REGISTRATION: Clinicaltrials.jp number: JapicCTI-205238.

Reusing N95 Respirators at Weekly Intervals During the COVID-19 Pandemic.

Objectives A surge in the demand for N95 filtering facepiece respirators (N95 respirators) due to the worldwide spread of coronavirus disease 2019 (COVID-19) has resulted in a global shortage of N95 respirators. This study was performed to evaluate the clinical validation of reusing N95 respirators following stringent fit test protocols. Methods After passing the first fit test, we prospectively enrolled healthcare workers who used N95 respirators for two hours per shift (duckbill-shaped HPR-R/HPR-S, dome-shaped Hi-Luck 350, and three-panel flat-fold respirators 9211) in settings such as bronchoscopy or respiratory specimen sampling. These procedures were repeated for up to three weeks, with the fit test performed every week. At each timing of the fit test, we used a fit-testing system for quantitatively evaluating particle leakage. Results A total of 41 participants were enrolled, including 24 doctors and 17 nurses, of whom 25 were women. The pass rate of successful reuse over three observational weeks using four fit tests was 85.4%, which was comparable among the three types of N95 respirators. Six (14.6%) participants failed the fit test, while no participants dropped out of protocol due to either N95 respirator damage or contamination. Among the six dropped out participants, four reused the duckbill-shaped type and two reused the three-panel flat-fold type. All participants using the cup-shaped type mask successfully completed the protocol. However, the passing rate of this study was not statistically different among the three types of N95 respirators. Conclusion This study shows that N95 respirators can be safely reused for a short period irrespective of their type, as quantitatively assessed by fit tests.

[round-table discussion : How to confront COVID-19]

Saratani: The epidemic of the novel coronavirus infection (COVID-19) drew attention to the number of hospital beds and physicians, and terms such as "PCR test," "cluster," and "incubation period" became widely known and were bandied about by the general public. In addition, the number of papers related to COVID-19 rapidly increased in real time, and we felt that information was being shared all over the world. We would like to invite doctors who are dealing with COVID-19 at different institutions to talk about COVID-19, which is having such a great impact.

Keeping PPE barriers in COVID-19 wards while doing proper auscultation.

The emerging COVID-19 pandemic poses many difficulties to medical professionals. One of them is the need to use personal protective equipment (PPE) in order to protect themselves and their families, while not compromising their care. Physical examination is one of the cornerstones of medical assessment but parts of it are nearly impossible to do while wearing protective equipment. In this brief report we demonstrate a novel wireless stethoscope and its use for treating suspected and proven COVID-19 patients, as a representative to other infectious diseases.

Evidence of the Sequential Changes of Lung Sounds in COVID-19 Pneumonia Using a Novel Wireless Stethoscope with the Telemedicine System.

A 60-year-old woman was admitted to our hospital due to coronavirus disease 2019 (COVID-19) pneumonia with a chief complaint of persistent low-grade fever and dry cough for two weeks. Thoracic computed tomography demonstrated a crazy paving pattern in the bilateral lower lobes. In a COVID-19 ward, we used a novel wireless stethoscope with a telemedicine system and successfully recorded and shared the lung sounds in real-time between the red and green zones. The fine crackles at the posterior right lower lung fields changed from mid-to-late (day 1) to late inspiratory crackles (day 3), which disappeared at day 5 along with an improvement in both the clinical symptoms and thoracic CT findings.

Detailed Molecular Interactions of Favipiravir with SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza Virus Polymerases In Silico.

Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp). As a result, no interactions between favipiravir ribofuranosyl-5'-triphosphate (F-RTP), the active form of favipiravir, and the active sites of RdRps (PB1 proteins) from influenza A (H1N1)pdm09 virus were found, yet the agent bound to the tunnel of the replication genome of PB1 protein leading to the inhibition of replicated RNA passage. In contrast, F-RTP bound to the active sites of coronavirus RdRp in the presence of the agent and RdRp. Further, the agent bound to the replicated RNA terminus in the presence of agent, magnesium ions, nucleotide triphosphate, and RdRp proteins. These results suggest that favipiravir exhibits distinct mechanisms of action against influenza virus and various coronaviruses.

[Two Cases of COVID-19 Pneumonia�E�One Case from the Cruise ship, Diamond Princess, and the Other, A Case of Community Transmission]

We encountered two female patients with COVID-19  Eone transferred from the cruise ship, Diamond Princess, docked in the Yokohama port, and the other with community transmission of the infection. The former patient had asymptomatic pneumonia, which subsided spontaneously. The latter patient suffered from severe rapidly worsening pneumonia which necessitated mechanical ventilation and extracorporeal membrane oxygenation, but eventually showed complete resolution of the disease. Although the lung involvement in those two cases at their first evaluation seemed to be equal, they exhibited very different clinical courses  Eone showing self-limiting asymptomatic pneumonia and the other showing severe progressive pneumonia.