Prolonged SARS-CoV-2 infection associated with long-term corticosteroid use in a patient with impaired B-cell immunity.

Corticosteroids are widely used to treat severe COVID-19, but in immunocompromised individuals, who are susceptible to persistent infection, long term corticosteroid use may delay viral clearance. We present a case of prolonged SARS-CoV-2 infection in a man with significantly impaired B-cell immunity due to non-Hodgkin lymphoma which had been treated with rituximab. SARS-CoV-2 shedding persisted, despite treatment with remdesivir. Viral sequencing confirmed the persistence of the same viral strain, ruling out the possibility of reinfection. Although SARS-CoV-2 IgG, IgA and IgM remained negative throughout the treatment period, after reduction of the corticosteroid dose, PCR became negative. Long-term corticosteroid treatment, especially in immunocompromised individuals, may result in suppression of cell-mediated immunity and prolonged SARS-CoV-2 infection.

Diagnostic accuracy of direct reverse transcription-polymerase chain reaction using guanidine-based and guanidine-free inactivators for SARS-CoV-2 detection in saliva samples.

This study aimed to evaluate diagnostic accuracy of SARS-CoV-2 RNA detection in saliva samples treated with a guanidine-based or guanidine-free inactivator, using nasopharyngeal swab samples (NPS) as referents. Based on the NPS reverse transcription-polymerase chain reaction (RT-PCR) results, participants were classified as with or without COVID-19. Fifty sets of samples comprising NPS, self-collected raw saliva, and saliva with a guanidine-based, and guanidine-free inactivator were collected from each group. In patients with COVID-19, the sensitivity of direct RT-PCR using raw saliva and saliva treated with a guanidine-based and guanidine-free inactivator was 100.0%, 65.9%, and 82.9%, respectively, with corresponding concordance rates of 94.3% (κ=88.5), 82.8% (κ=64.8), and 92.0% (κ=83.7). Among patients with a PCR Ct value of <30 in the NPS sample, the positive predictive value for the three samples was 100.0%, 80.0%, and 96.0%, respectively. The sensitivity of SARS-CoV-2 RNA detection was lower in inactivated saliva than in raw saliva and lower in samples treated with a guanidine-based than with a guanidine-free inactivator. However, in individuals contributing to infection spread, inactivated saliva showed adequate accuracy regardless of the inactivator used. Inactivators can be added to saliva samples collected for RT-PCR to reduce viral transmission risk while maintaining adequate diagnostic accuracy.

A case of idiopathic multicentric Castleman disease with pulmonary hyalinizing granuloma-like multiple pulmonary nodules.

A 41-year-old man presented with chronic cough and chest pain. Laboratory tests revealed anemia, inflammation, hypoalbuminemia, polyclonal hypergammaglobulinemia, and elevated interleukin-6 levels. Computed tomography revealed diffuse bilateral pulmonary nodules and multicentric lymphadenopathy. Histopathology of the pulmonary nodule resembled pulmonary hyalinizing granuloma (PHG), whereas lymph node histopathology was consistent with idiopathic multicentric Castleman disease (iMCD). The patient was diagnosed with iMCD involving PHG-like pulmonary nodules. Little is known about the association between these two diseases, and the present case provides insights regarding the relationship between PHG and iMCD.

High-flow nasal cannula for severe COVID-19 patients in a Japanese single-center, retrospective, observational study: 1 year of clinical experience.

High-flow nasal cannula (HFNC) can be effective in treating type 1 respiratory failure by reducing the severity of coronavirus disease 2019 (COVID-19). The purpose of this study was to assess the reduction of disease severity and safety of HFNC treatment in patients with severe COVID-19. We retrospectively observed 513 consecutive patients with COVID-19 admitted to our hospital from January 2020 to January 2021. We included patients with severe COVID-19 who received HFNC for their deteriorating respiratory status. HFNC success was defined as improvement in respiratory status after HFNC and transfer to conventional oxygen therapy, while HFNC failure was defined as transfer to non-invasive positive pressure ventilation or ventilator, or death after HFNC. Predictive factors associated with failure to prevent severe disease were identified. Thirty-eight patients received HFNC. Twenty-five (65.8%) patients were classified in the HFNC success group. In the univariate analysis, age, history of chronic kidney disease (CKD), non-respiratory sequential organ failure assessment (SOFA) ≥ 1, oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) before HFNC ≤ 169.2, were significant predictors of HFNC failure. Multivariate analysis revealed that SpO2/FiO2 value before HFNC ≤ 169.2 was an independent predictor of HFNC failure. No apparent nosocomial infection occurred during the study period. Appropriate use of HFNC for acute respiratory failure caused by COVID-19 can reduce the severity of severe disease without causing nosocomial infection. Age, history of CKD, non-respiratory SOFA before HFNC ≤ 1, and SpO2/FiO2 before HFNC ≤ 169.2 were associated with HFNC failure.

Diagnostic Value of Bronchoscopy for Peripheral Metastatic Lung Tumors.

Although lungs are one of the most frequent sites of metastasis for malignant tumors, little has been reported about the value of bronchoscopy for lung metastases presenting with peripheral pulmonary lesions (PPLs). This retrospective cohort study investigated the diagnostic value of bronchoscopy for peripheral metastatic lung tumors. Consecutive patients who underwent diagnostic bronchoscopy with radial endobronchial ultrasound for PPLs and were finally diagnosed with metastatic lung tumors from April 2012 to March 2019 were included. We analyzed 235 PPLs, with a median size of 18.8 mm. The overall diagnostic yield was 76.6%. In a multivariable analysis, large lesion size (>20.0 mm vs. <20.0 mm: 87.6% vs. 67.7%, p = 0.043, OR = 2.26), inner location (inner 2/3 vs. outer 1/3: 84.8% vs. 69.1%, p = 0.004, OR = 2.79), and visibility on radiography (visible vs. invisible: 83.2% vs. 56.1%, p = 0.015, OR = 3.29) significantly affected the diagnostic yield. Although a positive bronchus sign tended to have a higher yield, no significant difference was observed (81.8% vs. 70.6%, p = 0.063). Only one case of lung abscess was observed, with no serious complications. In conclusion, bronchoscopy is a valuable technique for peripheral metastatic lung tumors, with good diagnostic accuracy and safety.

Clinical outcomes of corticosteroids for COVID-19 patients at the National Center for Global Health and Medicine during the first wave of infections.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, has been a significant concern worldwide since its outbreak in December 2019. Various treatments are being researched and developed, and there are reports that dexamethasone has reduced the mortality rate and improved the clinical course of critically ill patients with COVID-19. In this study, we examined the clinical efficacy of corticosteroid therapy for patients with COVID-19 in our hospital during the first wave of infections. METHODS: We retrospectively reviewed the medical records of patients with COVID-19 who were treated with or without corticosteroid therapy at the National Center for Global Health and Medicine in Japan between February and April 2020. The primary outcome was improvement in the patients' clinical course using a seven-category ordinal scale. We collected data on patient characteristics, treatment, and clinical course, and compared them between two groups: the steroid-using group and the non-steroid-using group. RESULTS: Between February and April 2020, 110 patients were diagnosed with COVID-19. Despite poor conditions during admission into the steroid group, there were no statistical differences in clinical course between both groups, as measured using the scale. There were no statistical differences between the two groups in the number of days to fever resolution or negative polymerase chain reaction results. CONCLUSIONS: There was no difference in the clinical course between both groups. Because of the difference in background, corticosteroids may potentially make the clinical course of severely ill patients similar to that of mildly ill patients.

Impact of inhaled ciclesonide on asymptomatic or mild COVID-19: A randomized trial.

The aim of this study was to determine the efficacy and safety of ciclesonide in the treatment of novel coronavirus disease 2019 (COVID-19) as gauged by pneumonia progression. This multi-center, open-label randomized trial was conducted with patients recruited from 22 hospitals across Japan. Participants were patients admitted with mild or asymptomatic COVID-19 without signs of pneumonia on chest X-rays. Asymptomatic participants were diagnosed after identification through contact tracing. Trial participants were randomized to either the ciclesonide or control arm. Participants in the treatment arm were administered 400 µg of ciclesonide three times a day over seven consecutive days. The primary endpoint was exacerbated pneumonia within seven days. Secondary outcomes were changes in clinical findings, laboratory findings, and changes over time in the amount of the viral genome. In the treatment group, 16 patients (39.0%) were classified as having exacerbated pneumonia compared to 9 (18.8%) in the control group. The risk ratio (RR) was 2.08 (95% confidence interval (CI): 1.15-3.75), indicating a worsening of pneumonia in the ciclesonide group. Significant differences were noted in participants with a fever on admission (RR: 2.62, 90% CI: 1.17-5.85, 95% CI: 1.00-6.82) and individuals 60 years of age or older (RR: 8.80, 90% CI: 1.76-44.06, 95% CI: 1.29-59.99). The current results indicated that ciclesonide exacerbates signs of pneumonia on images in individuals with mild or asymptomatic symptoms of COVID-19 without worsening clinical symptoms.

Utility of the antigen test for coronavirus disease 2019: Factors influencing the prediction of the possibility of disease transmission.

OBJECTIVES: Rapid antigen testing (RAT) for coronavirus disease 2019 (COVID-19) has lower sensitivity but high accuracy during the early stage when compared to reverse transcription quantitative polymerase chain reaction (RT-qPCR). The aim of this study was to investigate the concordance between RAT and RT-qPCR results, and their prediction of disease transmission. METHODS: This single-center retrospective observational study of inpatients with COVID-19 was conducted from March 6 to June 14, 2020. Nasopharyngeal swabs were used to perform RAT and RT-qPCR. The primary endpoint was concordance between RAT and RT-qPCR results. The secondary endpoints were the factors causing disagreement in the results and the estimated transmissibility in RT-qPCR-positive patients with mild symptoms. RESULTS: Overall, 229 samples in viral transport medium (VTM) were obtained from 105 patients. The positive and negative concordance rates for VTM were 41% vs 99% (κ = 0.37) and 72% vs 100% (κ = 0.50) for samples collected on disease days 2-9. An increased body temperature (odds ratio 0.54) and absence of drugs with potential antiviral effect (odds ratio 0.48) yielded conflicting results. RAT was associated with the ability to end isolation (OR 0.11, 95% confidence interval 0.20-0.61). CONCLUSIONS: RAT and RT-qPCR results were highly consistent for samples collected at the appropriate time and could be useful for inferring the possibility of transmissibility.

A Kidney Transplant Patient Who Died of COVID-19-associated Severe Acute Respiratory Distress Syndrome.

We herein report a 67-year-old kidney transplant patient who died of COVID-19. He was treated with hydroxychloroquine and azithromycin and received mechanical ventilation that temporarily improved his respiratory status. Despite our efforts, however, he later developed respiratory failure and died 43 days after the disease onset. The autopsy revealed prominent organization of alveoli and alveolar ducts, with a massive accumulation of macrophages in the lungs. A few severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-positive cells were detected in the lung, suggesting delayed virus clearance owing to his long-term immunosuppressed state, leading to constant lung damage and ultimately respiratory failure.

Diagnostic accuracy of nasopharyngeal swab, nasal swab and saliva swab samples for the detection of SARS-CoV-2 using RT-PCR.

BACKGROUND: The current gold standard in coronavirus disease (COVID-19) diagnostics is the real-time reverse transcription-polymerase chain reaction (RT-PCR) assay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasopharyngeal swab (NPS) samples. Alternatively, nasal swab (NS) or saliva swab (SS) specimens are used, although available data on test accuracy are limited. We examined the diagnostic accuracy of NPS/NS/SS samples for this purpose. METHODS: Ten patients were included after being tested positive for SARS-CoV-2 RT-PCR in NPS samples according to the National Institute of Infectious Disease guidelines. In comparison with this conventional diagnostic method, NPS/NS/SS samples were tested using the cobas 6800 systems RT-PCR device. To investigate the usefulness of the cobas method and the difference among sample types, the agreement and sensitivity were calculated. Five to six samples were collected over a total period of 5-6 d from each patient. RESULTS: Fifty-seven sets of NPS/NS/SS samples were collected, of which 40 tested positive for COVID-19 by the conventional method. Overall, the concordance rates using the conventional method were 86.0%/70.2%/54.4% for NPS/NS/SS samples (cobas); however, for samples collected up to and including on Day 9 after disease onset (22 negative and one positive specimens), the corresponding rates were 95.7%/87.0%/65.2%. The overall sensitivity estimates were 100.0%/67.5%/37.5% for NPS/NS/SS samples (cobas). For samples up to 9 d after onset, the corresponding values were 100.0%/86.4%/63.6%. CONCLUSIONS: NS samples are more reliable than SS samples and can be an alternative to NPS samples. They can be a useful diagnostic method in the future.

Cost-effectiveness of bronchial thermoplasty for severe asthmatic patients in Japan.

Bronchial thermoplasty (BT) is an interventional endoscopic treatment for severe bronchial asthma. Some studies have shown the clinical efficacy of this intervention, but its cost-effectiveness is unclear. The aim of this study was to evaluate the cost-effectiveness of BT. We collected data from the medical records of 16 Japanese patients who were treated with BT between February 2015 and April 2017, and compared asthma-related medical expenses between the year preceding and the year following BT. Four patients were Global Initiative for Asthma (GINA) treatment step 4, and 12 were step 5. In 8 patients who had a successful response to BT, the annual asthma-related medical expenses decreased because of a reduction in hospitalization and emergency outpatient visits due to asthma attacks, and termination of the use of biologics. Most patients in the non-responder group had increased asthma-related medical costs postoperatively. The main reason for the increase in medical costs was the add-on treatment of biologics. BT was cost-effective in the responder group. If its effects continue for more than 10 years, BT will be a cost-effective treatment. Medical costs will be reduced if those who respond to BT can be identified prior to commencement of treatment.

Pembrolizumab-induced pancytopenia in a patient with squamous cell lung cancer.

Immune checkpoint inhibitors (ICIs) are reportedly effective against many kinds of neoplasm, but may be responsible for several kinds of immune-related adverse events (irAEs). Among these irAEs, the incidence of myelosuppression due to ICIs is relatively low. Corticosteroids are needed to control most cases of myelosuppression. Here, we report an 88-year-old woman with squamous cell lung cancer who was administered pembrolizumab. After five cycles of pembrolizumab, she developed severe pancytopenia. The pancytopenia improved under observation without steroid administration after cessation of pembrolizumab. During recovery from this irAE, the patient also maintained long-term antitumor efficacy. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: There are several kinds of immune-related adverse events. We encountered a case of pembrolizumab-induced pancytopenia with squamous cell lung cancer. WHAT THIS STUDY ADDS: Corticosteroids are needed to control most cases of myelosuppression induced by ICIs, but pancytopenia induced by pembrolizumab in our case improved without steroids.

Can the Number of Radiofrequency Activations Predict Serious Adverse Events after Bronchial Thermoplasty? A Retrospective Case-Control Study.

INTRODUCTION: Bronchial thermoplasty (BT) is a bronchoscopic procedure that involves the delivery of thermal radiofrequency energy to the bronchial wall for treating severe asthma. It has been suggested that too many radiofrequency activations could induce serious adverse events (SAEs) at an early stage. We aimed to examine the number of radiofrequency activations at each session and early lung function changes from baseline to determine whether these are related to SAEs. METHODS: We retrospectively investigated 13 consecutive patients who underwent three sessions each of BT for severe asthma from February 2015 to January 2016. Lung function tests were performed on the day before and after each BT procedure. Since we compared the number of activations and lung function changes from baseline after each session, a total of 39 sessions were reviewed. The relationship between the number of radiofrequency activations and each lung function change from baseline was also examined by linear regression analysis. RESULTS: A total of 10 SAEs (4 of pneumonia, 3 of atelectasis, 2 of bronchial asthma exacerbation and 1 of hemoptysis) were observed following the 39 BT sessions. When we compared sessions with and without SAEs, there were no differences in the number of activations (mean ± SD, 71.5 ± 28.6 times in sessions with SAEs; 66.5 ± 25.1 times in sessions without SAEs; p = 0.772) and lung function changes (mean changes in FVC/%FVC/FEV1/%FEV1/%PEF from baseline; - 0.49 l/- 14.2%/- 0.36 l/- 11.7%/- 9.6% in sessions with SAEs; - 0.43 l/- 13.3%/- 0.34 l/- 12.1%/- 9.4% in sessions without SAEs; p > 0.05 for all the above). Increase in the number of activations correlated with decreased FEV1 (R2 = 0.17, p = 0.0088) and %FEV1 (R2 = 0.11, p = 0.0357). CONCLUSIONS: Increase in the number of radiofrequency activations during BT is related to a decrease in FEV1 and %FEV1 from baseline. The number of radiofrequency activations, however, is not associated with SAEs after BT.

Clinically simplified screening methods to evaluate maximum standard uptake value from F-18-FDG-PET/CT in patients with non-small-cell lung cancer.

Maximum standard uptake value (SUVmax) of F-18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) is reportedly useful for evaluating regional lymph nodes (RLNs) of non-small-cell lung cancer (NSCLC) to predict malignancy. However, it is difficult for clinicians to measure SUVmax (mSUVmax) as calculated by a workstation.We assessed the utility of simplified SUVmax (sSUVmax) in screening RLNs for pathologic malignancy. The highest color was visually defined in the region of interest. The resulting color can be quantified using the color bar, and interpreted as sSUVmax. Patients in respiratory medicine and surgery who underwent both contrast-enhanced CT and FDG-PET/CT within 3 months before radical lobectomy were evaluated retrospectively. The correlation was examined by regression analysis and receiver operating characteristic (ROC) curve analyses.Participants comprised 69 patients with NSCLC treated between May 2009 and April 2016. Medical group comprised 22 patients from respiratory medicine. The prediction model could be written as a linear relationship (mSUVmax = 1.019 × sSUVmax; R = 0.930). A total of 316 RLNs resected by surgery in total cohort were pathologically determined. From ROC curves, area under curve for sSUVmax was 0.72 (95% confidence interval, 0.61-0.83; P < .0002). The cutoff sSUVmax was 2.42 (sensitivity, 52%; specificity, 88%; accuracy, 85%).The sSUVmax allows quantification of colors from FDG-PET/CT and shows a close correlation to mSUVmax. This value may have potential in screening for RLNs, and thoracic clinicians can readily determine the value. These findings may facilitate better planning of therapeutic strategy in the real world.

Clinico-microbiological analysis of 121 patients with pulmonary Mycobacteroides abscessus complex disease in Japan - An NTM-JRC study with RIT.

RATIONALE: No comprehensive analysis has previously been performed to evaluate the clinical aspects of and microbiological evidence associated with Mycobacteroides abscessus complex (MABC) infection in a region, such as Japan, with a low MABC incidence. OBJECTIVES: This study aimed to clarify the clinicopathological characteristics of MABC, which included clinical relatedness to erm(41) sequevar, phenotype (as colony morphology and minimum inhibitory concentration), and genotype. METHODS: A total of 121 MABC patients (68 with M. abscessus subsp. abscessus and 53 with M. abscessus subsp. massiliense) were recruited into this retrospective clinical-biological study from tertiary hospitals in Japan between 2004 and 2014. RESULTS: Approximately 30% of MABC patients had a history of previous nontuberculous mycobacterium (NTM) disease. Furthermore, 24.8% of the patients had another concomitant NTM infection after they were diagnosed with MABC. Fewer than 10% of the patients in the M. abscessus group had T28C in erm(41). While we observed a higher conversion rate for M. massiliense than for M. abscessus (72.4% and 34.8%, respectively, p = 0.002), recurrence remained relatively common for M. massiliense (31.0%). In the M. abscessus patients, the MIC of clarithromycin (CLR) was significantly lower on day 3 in patients with a better treatment response than in refractory patients (The median MIC; 0.75 µg/ml v.s 2.0 µg/ml, p = 0.03). There was no significant relation between clinical manifestations and variable number of tandem repeat genotypes. CONCLUSIONS: Because the history and simultaneous isolation of other NTM in MABC infection are relatively common, these information should be carefully translated into clinical actions. The evaluation of early CLR resistance in M. abscessus and the erm(41) functions should be important to improve the treatment strategy.