Investigating Viral Involvement in Immunocompromised Patients Using Comprehensive Infectious Disease Testing Including FilmArray Respiratory Panel 2.1 on Bronchoscopy: A Retrospective Study.

Introduction Reports are rare on the usefulness of the FilmArray Respiratory Panel 2.1 (FARP) using lower respiratory tract specimens. This retrospective study assessed its use, as part of a comprehensive infectious disease panel, to detect the viral causes of pneumonia using bronchoalveolar lavage samples from immunosuppressed patients. Methods This study included immunocompromised patients who underwent bronchoalveolar lavage or bronchial washing by bronchoscopy between April 1, 2021, and April 30, 2022. The collected samples were submitted for comprehensive testing, including FARP test; reverse transcription polymerase chain reaction (RT-PCR) for cytomegalovirus, varicella-zoster virus DNA, and herpes simplex virus; PCR for Pneumocystis jirovecii DNA; antigen testing for Aspergillus and Cryptococcus neoformans; and loop-mediated isothermal amplification method for Legionella. Results Out of 23 patients, 16 (70%) showed bilateral infiltrative shadows on computed tomography and three (13%) were intubated. The most common causes of immunosuppression were anticancer drug use (n=12, 52%) and hematologic tumors (n=11, 48%). Only two (9%) patients tested positive for severe acute respiratory syndrome coronavirus 2 and adenovirus by FARP. Four patients (17%) tested positive for cytomegalovirus by RT-PCR, but no inclusion bodies were identified cytologically. Nine (39%) patients tested positive for Pneumocystis jirovecii by PCR, but cytology confirmed the organism in only one case. Conclusions Comprehensive infectious disease testing, performed using bronchoalveolar lavage samples collected from lung lesions in immunosuppressed patients, showed low positive detection by FARP. The viruses currently detectable by FARP may be less involved in viral pneumonia diagnosed in immunocompromised patients.

The location of unilateral axillary lymphadenopathy after COVID-19 vaccination compared with that of metastasis from breast cancer without vaccination.

PURPOSE: Unilateral axillary lymphadenopathy is known to occur after coronavirus disease (COVID-19) vaccination. Post-vaccination lymphadenopathy may mimic the metastatic lymph nodes in breast cancer, and it is challenging to distinguish between them. This study investigated whether the localization of axillary lymphadenopathy on magnetic resonance imaging (MRI) could be used to distinguish reactive lymphadenopathy after COVID-19 vaccines from metastatic nodes. MATERIALS AND METHODS: We retrospectively examined preoperative MRI images of 684 axillae in 342 patients who underwent breast cancer surgery from June to October 2021. Lymphadenopathy was defined as cortical thickening or short axis ≥ 5 mm. The axilla was divided into ventral and dorsal parts on the axial plane using a perpendicular line extending from the most anterior margin of the muscle group, including the deltoid, latissimus dorsi, or teres major muscles, relative to a line along the lateral chest wall. We recorded the presence or absence of axillary lymphadenopathy in each area and the number of visible lymph nodes. RESULTS: Of 80 axillae, 41 and 39 were included in the vaccine and metastasis groups, respectively. The median time from the last vaccination to MRI was 19 days in the vaccine group. The number of visible axillary lymph nodes was significantly higher in the vaccine group (median, 15 nodes) than in the metastasis group (7 nodes) (P < 0.001). Dorsal lymphadenopathy was observed in 16 (39.0%) and two (5.1%) axillae in the vaccine and metastasis groups, respectively (P < 0.001). If the presence of both ventral and dorsal lymphadenopathy is considered indicative of vaccine-induced reaction, this finding has a sensitivity of 34.1%, specificity of 97.4%, and positive and negative predictive values of 93.3％ and 58.5%, respectively. CONCLUSION: The presence of deep axillary lymphadenopathy may be an important factor for distinguishing post-vaccination lymphadenopathy from metastasis. The number of axillary lymph nodes may also help.

Progressive pulmonary fibrosis due to diffuse alveolar damage in a COVID-19-infected autopsy case.

We encountered a patient with severe coronavirus disease 2019 (COVID-19)-related pneumonia, who died of progressive respiratory acidosis after 2 months of treatment with mechanical ventilation. The autopsy revealed diffuse alveolar damage (DAD) without any active signs of fungal or bacterial infections, suggesting prolonged and over-activated immune responses against COVID-19 infection. When COVID-19 patients develop acute respiratory distress syndrome, it is essential to remember that the infection can progress to DAD a few months after the disease onset.

Combined treatment with endobronchial Watanabe spigot and N-butyl-2-cyanoacrylate for refractory pneumothorax in COVID-19.

Coronavirus disease 2019 (COVID-19) causes pneumothorax or mediastinal emphysema in approximately 1% of patients. According to the British Thoracic Society guidelines, the next treatment option for patients with persistent pneumothorax despite chest drainage is pleurodesis or surgery. In fact, there are reports of autologous blood pleurodesis or surgery for the treatment of pneumothorax caused by COVID-19. However, elderly patients or patients in poor general condition may not be able to tolerate surgical invasion. In this report, we present two patients who did not respond to chest drainage or pleurodesis and who were not suitable for surgery because of their poor general condition. These patients were successfully treated with an endobronchial Watanabe spigot and N-butyl-2-cyanoacrylate. This method may be an option for the treatment of refractory pneumothorax in COVID-19.

Visual classification of three computed tomography lung patterns to predict prognosis of COVID-19: a retrospective study.

BACKGROUND: Quantitative evaluation of radiographic images has been developed and suggested for the diagnosis of coronavirus disease 2019 (COVID-19). However, there are limited opportunities to use these image-based diagnostic indices in clinical practice. Our aim in this study was to evaluate the utility of a novel visually-based classification of pulmonary findings from computed tomography (CT) images of COVID-19 patients with the following three patterns defined: peripheral, multifocal, and diffuse findings of pneumonia. We also evaluated the prognostic value of this classification to predict the severity of COVID-19. METHODS: This was a single-center retrospective cohort study of patients hospitalized with COVID-19 between January 1st and September 30th, 2020, who presented with suspicious findings on CT lung images at admission (n = 69). We compared the association between the three predefined patterns (peripheral, multifocal, and diffuse), admission to the intensive care unit, tracheal intubation, and death. We tested quantitative CT analysis as an outcome predictor for COVID-19. Quantitative CT analysis was performed using a semi-automated method (Thoracic Volume Computer-Assisted Reading software, GE Health care, United States). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient clinical data, including demographic and clinical variables at the time of admission. RESULTS: Patients with a diffuse pattern were intubated more frequently and for a longer duration than patients with a peripheral or multifocal pattern. The following clinical variables were significantly different between the diffuse pattern and peripheral and multifocal groups: body temperature (p = 0.04), lymphocyte count (p = 0.01), neutrophil count (p = 0.02), c-reactive protein (p < 0.01), lactate dehydrogenase (p < 0.01), Krebs von den Lungen-6 antigen (p < 0.01), D-dimer (p < 0.01), and steroid (p = 0.01) and favipiravir (p = 0.03) administration. CONCLUSIONS: Our simple visual assessment of CT images can predict the severity of illness, a resulting decrease in respiratory function, and the need for supplemental respiratory ventilation among patients with COVID-19.

Phase II Clinical Trial of Combination Therapy with Favipiravir and Methylprednisolone for COVID-19 with Non-Critical Respiratory Failure.

INTRODUCTION: The administration of systemic corticosteroids is a key strategy for improving COVID-19 outcomes. However, evidence is lacking on combination therapies of antiviral agents and systemic corticosteroids. The objective of this study was to investigate the efficacy and safety of the combination therapy of favipiravir and methylprednisolone in preventing respiratory failure progression in patients with COVID-19 and non-critical respiratory failure. METHODS: We conducted a multicenter, open-label, single-arm phase II study. The patients received favipiravir 3600 mg on the first day, followed by 1600 mg for a total of 10-14 days. Methylprednisolone was administered intravenously at 1 mg/ideal body weight (IBW)/day from days 1 to 5, followed by 0.5 mg/IBW/day from days 6 to 10 if clinically indicated. The primary endpoint was the proportion of patients requiring mechanical ventilation (MV) (including noninvasive positive pressure ventilation) or those who met the criteria for tracheal intubation within 14 days of the study treatment initiation (MVCTI-14). RESULTS: Sixty-nine patients were enrolled and underwent the study treatment. Of them, the MVCTI-14 proportion was 29.2% (90% confidence interval 20.1-39.9, p = 0.200). The proportion of patients who required MV or who died within 30 days was 26.2%, and 30-day mortality was 4.9%. The most significant risk factor for MVCTI-14 was a smoking history (odds ratio 4.1, 95% confidence interval 1.2-14.2). The most common grade 3-4 treatment-related adverse event was hyperglycemia, which was observed in 21.7%. CONCLUSION: The MVCTI-14 proportion did not reach a favorable level in the clinical trial setting with the threshold of 35%. However, the proportion of MV or death within 30 days was 26.6%, which might be close to the findings (28.1%) of the RECOVERY trial, which showed the efficacy of dexamethasone for patients with COVID-19 and non-critical respiratory failure. Further evaluation of this combination therapy is needed. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier jRCTs041200025.

Identification of patients with COVID-19 who are optimal for methylprednisolone pulse therapy.

BACKGROUND: Corticosteroids have been reported to reduce the mortality rates in patients with coronavirus disease 2019 (COVID-19). Additionally, the role of high-dose methylprednisolone pulse therapy in reducing mortality in critically ill patients has also been documented. The purpose of this study is to identify patients with COVID-19 who are suitable for methylprednisolone pulse therapy. METHODS: This was a retrospective study that included patients with COVID-19 receiving methylprednisolone pulse therapy (≥250 mg/day for 3 days) with subsequent tapering doses at our hospital between June 2020 and January 2021. We examined the differences in background clinical factors between the surviving group and the deceased group. RESULTS: Out of 156 patients who received steroid therapy, 17 received methylprednisolone pulse therapy. Ten patients recovered (surviving group) and seven patients died (deceased group). The median age of the surviving and deceased groups was 64.5 years (range, 57-85) and 79 years (73-90), respectively, with a significant difference (p=0.004). Five of the deceased patients (71%) had developed serious complications associated with the cause of death, including pneumothorax, pneumomediastinum, COVID-19-associated pulmonary aspergillosis, cytomegalovirus infection, and bacteremia. On the other hand, out of the 10 survivors, only one elderly person had cytomegalovirus infection and the rest recovered without complications. CONCLUSION: Administration of methylprednisolone pulse therapy with subsequent tapering may be an effective treatment in patients with COVID-19 up to the age of early 70s; however, severe complications may be seen in elderly patients.

Steroid resistance and rebound phenomena in patients with COVID-19.

BACKGROUND: In patients with coronavirus disease (COVID-19) pneumonia, corticosteroids reduce progression to respiratory failure and death. Some patients, however, remain unresponsive to this treatment, or experience a rebound after termination. METHODS: This retrospective cohort study included COVID-19 patients treated with systemic corticosteroids in a Japanese hospital between June 1, 2020, and January 17, 2021. Patients were categorized into three groups: success, rebound, and refractory, and clinical characteristics and outcomes were compared. RESULTS: A total of 319 COVID-19 patients were admitted to our hospital and 113 patients met inclusion criteria. The success group had 83 patients (73.5%), the rebound group had nine patients (8.0%), and the refractory group had 21 patients (18.6%). Compared with the success group, the rebound group received corticosteroids earlier, for a shorter duration, and stopped them sooner. The median time from symptom onset to rebound was 12 days. There was no rebound after 20 days. Compared with the success group, the hazard ratio for the number of days from corticosteroid onset to an improvement of two points on a seven-point ordinal scale was 0.29 (95% confidence interval [CI], 0.14-0.60, P < .001) for the rebound group versus 0.13 (95% CI, 0.07-0.25, P < .001) for the refractory group. CONCLUSIONS: COVID-19 patients treated with corticosteroids were classified into three response groups: success, rebound, and refractory, between which recovery time and prognosis differed. It was found that corticosteroid administration may prevent rebound phenomena if administered at least two weeks from symptom onset.

Ultrasonic humidifier lung as a mimic of COVID-19.

Chest computed tomography (CT) has been used to complement coronavirus disease 2019 (COVID-19) diagnosis due to its high sensitivity. However, owing to the low specificity of CT findings, differential diagnosis is essential. The typical CT findings of COVID-19 include ground-glass opacifications and consolidations with predominant distribution in bilateral, peripheral, and subpleural parts of the lung. These imaging findings are non-specific and may resemble other lung conditions, including ultrasonic humidifier lung, which is a condition that develops on inhaling aerosols generated by ultrasonic humidifiers. We present two patients with initial symptoms similar to COVID-19. CT examination revealed centrilobular nodules and consolidations with upper lobe-predominant distribution, although atypical for COVID-19, but key findings for ultrasonic humidifier lung. Therefore, ultrasonic humidifier lung could be a differential diagnosis for COVID-19 in dry environments. Characteristic CT findings and a history of ultrasonic humidifier use are critical to the final diagnosis.

High-dose, short-term corticosteroids for ARDS caused by COVID-19: a case series.

We report a case series of seven mechanically ventilated patients with acute respiratory distress syndrome (ARDS) caused by coronavirus disease (COVID-19) who received early treatment with high-dose, short-term systemic corticosteroids to prevent cytokine overproduction. Of the seven patients, four were male and median age was 69 years. They were intubated within seven days after admission when their respiratory status rapidly worsened. At that time, we administered 1000 or 500 mg/day for three days of methylprednisolone intravenously, followed by 1 mg/kg and tapered off. The median duration for the total administration of corticosteroids was 13 days. This high-dose, short-term corticosteroid therapy enabled extubation of the patients within seven days. Many questions on the clinical management of COVID-19 remain unanswered, and data on corticosteroid therapy as a choice of treatment are mixed. We present the clinical course of our cases, review the previous evidence, and discuss management.