Clinical Evaluation of Acute Exacerbation of Interstitial Lung Disease in a Single Tertiary Center: Perspectives before and after the Coronavirus Disease 2019 Pandemic.

Background/Objectives: Acute exacerbation (AE) of interstitial lung disease (ILD) is a major challenge. This study aimed to retrospectively investigate occurrences of AEs in patients with ILDs, including idiopathic pulmonary fibrosis (IPF), non-IPF (iNSIP: idiopathic nonspecific interstitial pneumonia), and connective tissue disease (CTD)-associated ILDs (CTD-ILDs), at a single tertiary center before and after the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to clarify the seasonal and regional trends of AEs of ILDs, assess the roles of viral and bacterial infections, and identify key prognostic factors for patient outcomes. Methods: We conducted a retrospective review of hospitalized adult patients with AEs of ILDs from January 2019 to February 2024. Results: A total of 93 patients were enrolled: IPF (n = 42), iNSIP (n = 37), and CTD-ILDs (n = 14). The median age was 80 years (interquartile range: 74.0-86.0 years), with males comprising 64.5% (n = 60). AEs of ILDs predominantly occurred in winter and were particularly notable after summer 2023, coinciding with the lifting of COVID-19-related travel restrictions in Japan. Patient referrals from different areas (Northern Tama, East and/or Southern Tama, and other Tokyo metropolitan areas) were evenly distributed throughout the study period. Viral infections were detected in only two patients (SARS-CoV-2), and bacterial infections included methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. The Cox regression analysis identified serum lactate dehydrogenase levels ≥350 IU/L and tachypnea (respiratory rate ≥ 30 breaths per min) on admission as prognostic factors for mortality, with a hazard ratio [HR] of 2.783 (95% confidence interval [CI]: 1.480-5.235, p = 0.001) and an HR of 3.332 (95% CI: 1.710-6.492, p < 0.001), respectively. Conclusions: AEs of ILDs predominantly occur in winter, and viral and bacterial infections are infrequently detected. Elevated serum LDH levels and tachypnea are crucial prognostic markers for mortality. This study highlights the seasonal trend in the AE of ILD and emphasizes the importance of specific prognostic indicators in clinical practice.

Serum Derivatives-Reactive Oxygen Metabolite Levels as a Marker of Clinical Conditions in Patients with Bronchial Asthma, COPD, or Asthma-COPD Overlap: A Prospective Study.

Background: Oxidative stress plays an important role in the pathophysiology of bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO), but its relevance has not been fully elucidated. The aim of this study was to measure the levels of oxidative stress and investigate its clinical significance in patients with BA, COPD, or ACO. Methods: We recruited 214 patients between June 2020 and May 2023 (109 patients with BA, 63 with COPD, and 42 with ACO). To assess clinical conditions, we evaluated patient characteristics, results of respiratory function tests and blood tests, and administered several questionnaires. We evaluated oxidative stress using the test for derivatives-reactive oxygen metabolites (d-ROMs) in serum. Results: The d-ROMs levels were significantly higher in patients with COPD or ACO than in patients with BA. There was no difference in serum d-ROMs levels between the COPD and ACO groups. In BA, d-ROMs levels were positively correlated with interleukin (IL)-6, IL-8, serum amyloid A (SAA), and C-reactive protein (CRP) levels; white blood cell (WBC) and neutrophil counts; and St. George's Respiratory Questionnaire (SGRQ) scores, and they were negatively correlated with forced expiratory volume in 1 s (%FEV1) and asthma control test (ACT) score. In COPD, d-ROMs levels were positively correlated with IL-6, SAA, and CRP levels; WBC, neutrophil, and eosinophil counts; and COPD assessment test (CAT) and SGRQ scores, and they were negatively correlated with forced vital capacity (%FVC), %FEV1, and %FEV1/FVC scores. In ACO, d-ROMs levels were positively correlated with IL-6, SAA, tumor necrosis factor alpha (TNF-α), and CRP levels; and CAT and SGRQ scores, and they were negatively correlated with %FVC and %FEV1 scores. Conclusions: Serum d-ROMs levels may serve as a marker reflecting clinical conditions such as systemic inflammation, symptom severity, and airflow limitation in patients with BA, COPD, and ACO.

Association of IL-33 in modeling type-2 airway inflammation and pulmonary emphysema in mice.

We developed pulmonary emphysema and a type 2 airway inflammation overlap mouse model. The bronchoalveolar lavage (BAL) interleukin 13 (IL-13), IL-4, and IL-5 levels in the overlap model were higher than in the pulmonary emphysema model and lower than in the type 2 airway inflammation model, but IL-33 level in the lung was higher than in other models. IL-33 and interferon-γ (IFNγ) in lungs may control the severity of a type 2 airway inflammation in lung.

Impact of Cough Severity on the Diagnostic Yield of Endobronchial Ultrasonography Transbronchial Biopsy with Guide Sheath: A Retrospective Observational Study.

Bronchoscopy is an invasive procedure, and patient coughing during examination has been reported to cause patient distress. This study aimed to clarify the relationship between cough severity and diagnostic yield of endobronchial ultrasonography with guide sheath transbronchial biopsy (EBUS-GS-TBB). Data of patients who underwent bronchoscopy at Kyorin University Hospital between April 2019 and March 2022 were retrospectively evaluated. Bronchoscopists assessed the cough severity upon completion of the procedure using a four-point cough scale. Cough severity was included as a predictive factor along with those reportedly involved in bronchoscopic diagnosis, and their impact on diagnostic yield was evaluated. Predictors of cough severity were also examined. A total of 275 patients were enrolled in this study. In the multivariate analysis, the diagnostic group (n = 213) had significantly more 'within' radial endobronchial ultrasound findings (odds ratio [OR] 5.900, p < 0.001), a lower cough score (cough score per point; OR 0.455, p < 0.001), and fewer bronchial generations to target lesion(s) (OR 0.686, p < 0.001) than the non-diagnostic group (n = 62). The predictive factors for severe cough include the absence of virtual bronchoscopic navigation (VBN) and prolonged examination time. Decreased cough severity was a positive predictive factor for successful EBUS-GS-TBB, which may be controlled using VBN and awareness of the procedural duration.

Predictive factors of the presence of pulmonary embolism in patients with interstitial lung disease: Observational study.

In patients with interstitial lung disease (ILD), the risk of pulmonary embolism (PE) is increased; however, distinguishing between PE and ILD exacerbation can be difficult. Therefore, this study investigated the usefulness of the Wells criteria and revised Geneva score and predictive factors for diagnosing PE in ILD patients with worsening respiratory symptoms. We retrospectively collected the data of 65 patients with ILD who underwent computed tomography pulmonary angiography at Fukujuji Hospital and Kyorin University Faculty of Medicine from January 2018 to March 2023, including 18 patients in the PE group and 47 patients in the non-PE group, and the data were compared between the 2 groups. The Wells score (P = .165) and revised Geneva score (P = .140) were not useful for distinguishing between the PE and non-PE groups. Patients in the PE group showed higher D-dimer, total protein (TP), and globulin levels than those in the non-PE group (D-dimer median 24.5 µg/mL [range 3.0-79.3] vs 9.3 µg/mL [range 0.5-80.8], P = .016; TP median 7.2 g/dL [range 5.1-8.7] vs 6.4 g/dL [range 5.0-8.2], P = .002; globulin median 3.8 g/dL [range 2.6-5.5] vs 3.2 g/dL [range 3.0-5.3], P = .041). Using cutoff values of TP ≥ 7.0 g/dL and D-dimer ≥ 11.8 µg/mL, the odds ratios for predicting PE were 10.5 and 4.90, respectively. This study demonstrates that high TP and D-dimer levels are useful indicators for predicting PE in ILD patients with worsening respiratory symptoms, while the Wells score and revised Geneva score are not reliable in diagnosing PE.

Listeria monocytogenes bacteremia developed during treatment of COVID-19.

Listeria monocytogenes is an important pathogen in older patients and immunosuppressed patients, often causing bacteremia. Complications resulting from infections other than COVID-19 must also be considered during COVID-19 treatment.

A Real-World Prognosis in Idiopathic Pulmonary Fibrosis: A Special Reference to the Role of Antifibrotic Agents for the Elderly.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia, and its prevalence increases with age. In the era of pre-antifibrotic agents, the median survival time of Japanese patients with IPF is 35 months, with a 5-year survival rate in western countries ranging from 20% to 40%. The prevalence of IPF is highest in elderly patients aged ≥75 years; however, the efficacy and safety of long-term use of pirfenidone and/or nintedanib are not fully understood. OBJECTIVE: This study aimed to determine the efficacy and safety of the sole use of antifibrotic agents (pirfenidone or nintendanib) for IPF in the elderly. METHOD: We retrospectively reviewed patients with IPF who were diagnosed and treated with either pirfenidone or nintedanib in our hospital between 2008 and 2019. We excluded patients with the subsequent use of both antifibrotic agents. We examined the survival probability and frequency of acute exacerbation, with focus on long-term use (≥1 year), elderly patients (≥75 years of age), and disease severity. RESULTS: We identified 91 patients with IPF (male to female ratio: 63 to 28, age 42 to 90 years). The numbers of patients with disease severity classified by JRS (I/II/III/IV) and GAP stage (I/II/III) were (38/6/17/20) and (39/36/6), respectively. The survival probabilities were comparable between the elderly (n = 46) and non-elderly groups (n = 45, p = 0.877). After the initiation of antifibrotic agents, the cumulative incidence ratio of acute exacerbation of IPF was significantly lower in the early stage (GAP stage I, n = 20) than in the progressive stage of disease (GAP stages II and III, n = 20, p = 0.028). A similar trend was noted in the JRS disease severity classification (I, II vs. III, IV) (n = 27 vs. n = 13, p = 0.072). In the long-term treatment (≥1 year) group (n = 40), the survival probabilities at 2 and 5 years after treatment initiation were 89.0% and 52.4%, respectively, which did not reach the median survival rate. CONCLUSIONS: Even in elderly patients (≥75 years of age), antifibrotic agents demonstrated positive effects on survival probability and the frequency of acute exacerbation. These positive effects would be improved for earlier JRS/GAP stages or long-term use.

Characteristics of pleural effusion with a high adenosine deaminase level: a case-control study.

BACKGROUND: Increased pleural fluid adenosine deaminase (ADA) is useful for diagnosing tuberculous pleurisy (TB), but high ADA levels are associated with other diseases. In this study, we compare various disease characteristics in patients with high-ADA pleural effusion. METHODS: We retrospectively collected data for 456 patients with pleural fluid ADA levels of ≥ 40 U/L from January 2012 to October 2021. Cases were classified as TB (n = 203), pleural infection (n = 112), malignant pleural effusion (n = 63), nontuberculous mycobacteria (n = 22), malignant lymphoma (ML) (n = 18), autoimmune diseases (n = 11), and other diseases (n = 27), and data were compared among those diseases. Predictive factors were identified by comparing data for a target disease to those for all other diseases. A diagnostic flowchart for TB was developed based on those factors. RESULTS: The most frequent disease was TB, though 60.0% of patients were diagnosed with other diseases. Median ADA levels in patients with TB were 83.1 U/L (interquartile range [IQR] 67.2-104.1), higher than those of patients with pleural infection (median 60.9 [IQR 45.3-108.0], p = 0.004), malignant pleural effusion (median 54.1 [IQR 44.8-66.7], p < 0.001), or autoimmune diseases (median 48.5 [IQR 45.9-58.2], p = 0.008), with no significant difference from NTM (p = 1.000) or ML (p = 1.000). Pleural fluid lactate dehydrogenase (LDH) levels of < 825 IU/L were beneficial for the diagnosis of TB. Neutrophil predominance or cell degeneration, white blood cell count of ≥ 9200/µL or C-reactive protein levels of ≥ 12 mg/dL helped in diagnosing pleural infection. Pleural fluid amylase levels of ≥ 75 U/L and a pleural fluid ADA/total protein (TP) ratio of < 14 helped in diagnosing malignant pleural effusion. High serum LDH and high serum/pleural fluid eosinophils helped in diagnosing ML and autoimmune diseases, respectively. The flowchart was comprised of the following three factors: pleural fluid LDH < 825 IU/L, pleural fluid ADA/TP of < 14, and neutrophil predominance or cell degeneration, which were decided by a decision tree. The diagnostic accuracy rate, sensitivity, and specificity for the diagnosis of TB were 80.9%, 78.8%, and 82.6%, respectively. CONCLUSION: Cases involving high pleural fluid ADA levels should be investigated using several factors to distinguish TB from other diseases.

Molecular Evolution of the Pseudomonas aeruginosa DNA Gyrase gyrA Gene.

DNA gyrase plays important roles in genome replication in various bacteria, including Pseudomonasaeruginosa. The gyrA gene encodes the gyrase subunit A protein (GyrA). Mutations in GyrA are associated with resistance to quinolone-based antibiotics. We performed a detailed molecular evolutionary analyses of the gyrA gene and associated resistance to the quinolone drug, ciprofloxacin, using bioinformatics techniques. We produced an evolutionary phylogenetic tree using the Bayesian Markov Chain Monte Carlo (MCMC) method. This tree indicated that a common ancestor of the gene was present over 760 years ago, and the offspring formed multiple clusters. Quinolone drug-resistance-associated amino-acid substitutions in GyrA, including T83I and D87N, emerged after the drug was used clinically. These substitutions appeared to be positive selection sites. The molecular affinity between ciprofloxacin and the GyrA protein containing T83I and/or D87N decreased significantly compared to that between the drug and GyrA protein, with no substitutions. The rate of evolution of the gene before quinolone drugs were first used in the clinic, in 1962, was significantly lower than that after the drug was used. These results suggest that the gyrA gene evolved to permit the bacterium to overcome quinolone treatment.

Pulmonary Involvement in Microscopic Polyangiitis: Computed Tomography Findings in 55 Patients With Analysis of Risk Factors for Recurrence.

Background and objective Pulmonary involvement is seen in up to 30% of microscopic polyangiitis (MPA) patients. Pulmonary radiological findings for MPA have been scarcely reported to date. This study was conducted to evaluate computed tomography (CT) and clinical findings at the time of MPA diagnosis as predictors for systemic or lung recurrence. Methods We retrospectively reviewed the medical records and radiological data of 55 MPA patients with pulmonary involvement who were admitted to our hospital between April 2008 and December 2016. Results Aside from pulmonary lesions, lesions were found in the kidneys (52.7%), skin (7.3 %), and peripheral nerves (3.6%). Biopsies were performed for 29.1% of the patients, with an overall diagnostic accuracy of 78.9%. Parenchymal opacities (74.5%, mainly ground-glass opacities and reticular shadowing) were more commonly seen than airway abnormalities were (40.0%, mainly bronchiectasis). Systemic recurrence in the first year after diagnosis was found in 10.9% of the patients, and it mainly involved the kidneys or lungs. A serum WBC count ≥ 10,900/µL was a risk factor for predicting systemic recurrence within the first year after diagnosis according to the Cox regression analysis (HR 11.1, 95%CI: 1.3-95.9, p=0.028). Lung recurrence within five years after the diagnosis was observed in 9.1% of the patients. The incidences of reticular shadowing and honeycombing in thoracic CT at diagnosis were significantly higher in recurrence-positive patients than in recurrence-negative patients, but these differences could not be used to predict lung recurrence. Conclusions Ground glass opacities, reticular shadowing, and bronchiectasis are prominent thoracic CT findings for MPA. There are no radiological patterns capable of predicting recurrence. However, a serum WBC count ≥ 10,900/µL at diagnosis might be a predictive factor for systemic recurrence within the year.

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.

Detailed Analyses of Molecular Interactions between Favipiravir and RNA Viruses In Silico.

There are currently no antiviral agents for human metapneumovirus (HMPV), respiratory syncytial virus (RSV), mumps virus (MuV), or measles virus (MeV). Favipiravir has been developed as an anti-influenza agent, and this agent may be effective against these viruses in vitro. However, the molecular mechanisms through which the agent affects virus replication remain to be fully elucidated. Thus, to clarify the detailed molecular interactions between favipiravir and the RNA-dependent RNA polymerase (RdRp) of HMPV, RSV, MuV, MeV, and influenza virus, we performed in silico studies using authentic bioinformatics technologies. As a result, we found that the active form of favipiravir (favipiravir ribofuranosyl-5'-triphosphate [F-RTP]) can bind to the RdRp active sites of HMPV, RSV, MuV, and MeV. The aspartic acid residue of RdRp active sites was involved in the interaction. Moreover, F-RTP was incorporated into the growing viral RNA chain in the presence of nucleotide triphosphate and magnesium ions. The results suggested that favipiravir shows two distinct mechanisms in various viruses: RdRp active site inhibition and/or genome replication inhibition.

Diagnostic method for malignant pleural effusion distinguishing malignant mesothelioma from lung cancer using pleural carcinoembryonic antigen and hyaluronic acid levels.

ABSTRACT: Malignant mesothelioma (MM) is difficult to diagnose because of the lack of parenchymal opacities, often revealing minimal or absent pleural thickening. Furthermore, pleural effusion has diverse differential diagnoses, including malignancies, infections, as well as collagen vascular and other benign diseases. In general practice, lung cancer (LC) is the most common malignancy causing pleural effusion; therefore, a simple method using pleural diagnostic markers to differentiate between LC and mesothelioma is crucial.We retrospectively reviewed the data of 530 adult patients diagnosed with pleural effusion between January 2010 and December 2020 in an outpatient or inpatient setting. Patients with pathologically diagnosed MM or LC with cytologically positive (class IV or V) pleural effusion were analyzed, and the characteristics of these 2 diseases were compared.During the study period, 27 patients diagnosed with MM and 100 patients diagnosed with LC were enrolled. Receiver operating characteristic curve analysis demonstrated that pleural carcinoembryonic antigen (CEA) and hyaluronic acid (HA) could discriminate MM from LC with an area under the curve of 0.925 (95% confidence interval [CI]: 0.879-0.972, P < .001) and 0.815 (95% CI: 0.686-0.943, P < .001), respectively. To diagnose MM, the accuracy of pleural HA >30,000 ng/mL revealed a sensitivity of 75.0%, specificity of 72.6%, and odds ratio of 7.94 (95% CI: 2.5-25.2, P = .001); pleural CEA <6.0 ng/mL revealed a sensitivity of 95.2%, specificity of 84.9%, smaller negative likelihood ratio of 0.06, and odds ratio of 112.5% (95% CI: 14.4-878.1, P < .001). Multiple logistic regression analysis revealed that these 2 parameters could discriminate MM from LC, with a hazard ratio of 23.6 (95% CI: 2.437-228.1, P = .006) and 252.3 (95% Cl: 16.4-3888.1, P < .001), respectively, and their combination had a high specificity of 98.3%.Pleural CEA (≥6.0 ng/mL) can rule out MM with a high degree of certainty, and the positive results for combination of pleural CEA <6.0 ng/mL and HA >30,000 ng/mL can confirm MM with high specificity, prior to cytological or pathological examinations.

Chronic pulmonary aspergillosis in a patient with hyper-IgE syndrome.

Hyperimmunoglobulin E (IgE) syndrome (HIES) is a rare disease with an unclear prognosis. We report a case of HIES comorbid with chronic pulmonary aspergillosis (CPA). A 19-year-old male was referred to our department with a medical history of bacterial pneumonia and skin infection. Laboratory data showed an elevated eosinophil count and serum IgE level. Chest computed tomography (CT) showed a pneumatocele and bronchiectasis. On the basis of the clinical and laboratory findings and genetic mutation analysis, we diagnosed him as having HIES. Fourteen months later, he complained of blood-tinged sputum and haemoptysis. Chest CT showed pneumatocele wall thickening, fungus ball and consolidation. Serum Aspergillus precipitating antibody and serum galactomannan Aspergillus antigen were positive, and Aspergillus fumigatus was detected in the sputum. We diagnosed CPA and treated him using antifungal agents and bronchial artery embolization. CPA is a complication that requires attention in patients with HIES.

Prospective nationwide multicentre cohort study of the clinical significance of autoimmune features in idiopathic interstitial pneumonias.

BACKGROUND: Some patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported conflicting results of its prognosis. Therefore, this study was conducted to prospectively evaluate the clinical significance of autoimmune features in patients with IIP. METHODS: This nationwide multicentre study prospectively enrolled consecutive patients with IIP. At the diagnosis, we systematically evaluated 63 features suggestive of connective tissue diseases using a checklist including symptoms/signs and autoantibodies, which contained most items of the IPAF criteria and followed up with the patients. Clinical phenotypes were included in a cluster analysis. RESULTS: In 376 patients with IIP enrolled, 70 patients (18.6%) met the IPAF criteria. The proportion of patients with IPAF was significantly lower in idiopathic pulmonary fibrosis (IPF) than in non-IPF (6.0% vs 24.3%, respectively). During a median observation period of 35 months, patients with IPAF more frequently developed systemic autoimmune diseases and had less frequent acute exacerbation of IIPs than patients with non-IPAF. IPAF diagnosis was significantly associated with better survival and was an independent positive prognostic factor in total and patients with non-IPF. Cluster analysis by similarity of clinical phenotypes identified a cluster in which there was a higher number of women, and patients had more autoimmune features and a better prognosis than other clusters. INTERPRETATION: These observations suggest that some patients with IIP show autoimmune features with distinct characteristics and favourable prognosis. However, we were not able to determine the appropriate therapies for these patients.

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.