Asthma is a risk factor for general fatigue of long COVID in Japanese nation-wide cohort study.

BACKGROUND: Multiple prolonged symptoms are observed in patients who recover from an acute COVID-19 infection, which is defined as long COVID. General fatigue is frequently observed in patients with long COVID during acute and post-acute phases. This study aimed to identify the specific risk factors for general fatigue in long COVID. METHODS: Hospitalized patients with COVID-19 aged over 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. RESULTS: Among prolonged symptoms through 1-year follow-ups, general fatigue was the most interfering symptom in daily life. Patients with protracted fatigue at all follow-up periods had lower quality of life scores at the 12-month follow-up. Univariate logistic regression analysis of the presence or absence of general fatigue at the 3-month, 6-month, and 12-month follow-ups identified asthma, younger age, and female sex as risk factors for prolonged fatigue. Multivariable logistic regression analysis revealed that asthma was an independent risk factor for persistent fatigue during the 12-month follow-up period. Longitudinal changes in the symptoms of patients with or without asthma demonstrated that general fatigue, not cough and dyspnea, was significantly prolonged in patients with asthma. CONCLUSIONS: In a Japanese population with long COVID, prolonged general fatigue was closely linked to asthma. A preventive approach against COVID-19 is necessary to avoid sustained fatigue and minimize social and economic losses in patients with asthma.

Cough and sputum in long COVID are associated with severe acute COVID-19: a Japanese cohort study.

BACKGROUND: Multiple prolonged symptoms are observed in patients who recover from acute coronavirus disease 2019 (COVID-19), defined as long COVID. Cough and sputum are presented by patients with long COVID during the acute and post-acute phases. This study aimed to identify specific risk factors for cough and sputum in patients with long COVID. METHODS: Hospitalized patients with COVID-19 aged 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. RESULTS: At the 3-, 6-, and 12-month follow-ups, there were no differences in the incidence rates of wet and dry coughs. In contrast, the proportion of patients presenting sputum without coughing increased over time compared to those with sputum and coughing. Univariate analyses of cough and sputum at all follow-up visits identified intermittent mandatory ventilation (IMV), smoking, and older age as risk factors for prolonged symptoms. At the 12-month follow-up, persistent cough and sputum were associated with the characteristics of severe COVID-19 based on imaging findings, renal and liver dysfunction, pulmonary thromboembolism, and higher serum levels of LDH, KL-6, and HbA1C. The Kaplan-Meier curves showed that the severity of acute COVID-19 infection was correlated with prolonged cough and sputum production. Multivariable logistic regression analysis showed that IMV ventilator management were independent risk factors for prolonged cough and sputum at 12 months. CONCLUSIONS: In a Japanese population with long COVID, prolonged cough and sputum production were closely associated with severe COVID-19. These findings emphasize that a preventive approach including appropriate vaccination and contact precaution and further development of therapeutic drugs for COVID-19 are highly recommended for patients with risk factors for severe infection to avoid persistent respiratory symptoms.

Comprehensive analysis of long COVID in a Japanese nationwide prospective cohort study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly since 2019, and the number of reports regarding long COVID has increased. Although the distribution of long COVID depends on patient characteristics, epidemiological data on Japanese patients are limited. Hence, this study aimed to investigate the distribution of long COVID in Japanese patients. This study is the first nationwide Japanese prospective cohort study on long COVID. METHODS: This multicenter, prospective cohort study enrolled hospitalized COVID-19 patients aged ≥18 years at 26 Japanese medical institutions. In total, 1200 patients were enrolled. Clinical information and patient-reported outcomes were collected from medical records, paper questionnaires, and smartphone applications. RESULTS: We collected data from 1066 cases with both medical records and patient-reported outcomes. The proportion of patients with at least one symptom decreased chronologically from 93.9% (947/1009) during hospitalization to 46.3% (433/935), 40.5% (350/865), and 33.0% (239/724) at 3, 6, and 12 months, respectively. Patients with at least one long COVID symptom showed lower quality of life and scored higher on assessments for depression, anxiety, and fear of COVID-19. Female sex, middle age (41-64 years), oxygen requirement, and critical condition during hospitalization were risk factors for long COVID. CONCLUSIONS: This study elucidated the symptom distribution and risks of long COVID in the Japanese population. This study provides reference data for future studies of long COVID in Japan.

Longitudinal long COVID symptoms in Japanese patients after COVID-19 vaccinations.

We conducted a subgroup analysis of a study on the long-term effects of COVID-19 (long COVID) in Japan to assess the effect of vaccination on long COVID symptoms. We assessed the clinical course of 111 patients with long COVID at the time of vaccination. The follow-up period was one year from the onset of COVID-19 or until the administration of the third vaccine dose. Of the 111 patients, 15 (13.5%) reported improvement, four (3.6%) reported deterioration, and 92 (82.9%) reported no change in their long COVID symptoms after vaccination. The most common long COVID symptoms before vaccination were alopecia, dyspnea, muscle weakness, fatigue, and headache among participants whose symptoms improved. Reduced dyspnea and alopecia were the most frequently reported improvements in symptoms after vaccination. Some symptoms persisted, including sleep disturbance, myalgia, and hypersensitivity. Vaccination did not appear to have a clinically important effect on patients with long COVID symptoms.

How Can Dupilumab Cause Eosinophilic Pneumonia?

Reports of eosinophilic pneumonia (EP) as a side effect of dupilumab administration are limited in previous studies. Herein, we report two cases in which EP developed subsequent to the administration of dupilumab for eosinophilic chronic rhinosinusitis (ECRS). Case 1: A 55-year-old woman presented with ECRS, eosinophilic otitis media, and bronchial asthma, and was treated with dupilumab for ECRS. Five weeks later, fever and dyspnea developed, and infiltration shadows were observed in her lungs. The peripheral blood eosinophil count (PBEC) was 3848/µL (26%), bronchoalveolar lavage fluid showed eosinophilic infiltration, and EP was subsequently diagnosed. Her condition improved following prednisolone treatment. Case 2: A 59-year-old man presented with fatigue and dyspnea after receiving dupilumab for ECRS. He had infiltrative shadows throughout his left lung field, and his PBEC was 4850/µL (26.5%). Prednisolone was initiated, and his condition improved. EP developed in both patients during the period of elevated PBEC after dupilumab administration, and dupilumab was suspected to be the causative agent in their EP. Hence, EP should be considered as a differential diagnosis when fever and dyspnea appear following dupilumab administration.

Remarkable Differences in Calcification between the Primary Tumor and Metastatic Lymph Nodes in a Patient with ALK-Positive Non-Small-Cell Lung Cancer.

Calcified bilateral mediastinal lymph nodes are not common in malignant tumors. A 51-year-old woman presented to our hospital with a 20 mm nodule in the lower left lobe of the lung and extensive calcification in the bilateral mediastinal lymph nodes. Computed tomography indicated no calcification of the primary lesion. Immunohistochemical staining and fluorescent in situ hybridization detected an anaplastic lymphoma kinase (ALK) fusion. Treatment with alectinib, an ALK inhibitor, led to a significant reduction in tumor size and calcification in the lymph nodes. This case shows that different degrees of calcification can be associated with malignant tumors and may be reversible in some cases.

The effect of statins for asthma. A systematic review and meta-analysis.

OBJECTIVE: To assess the effects of statins on asthma by systematically reviewing and conducting a meta-analysis on all clinical studies, including randomized controlled trials (RCTs) and observational studies, that examined the effects of statins on asthma. METHODS: PubMed, EMBASE databases, and Cochrane reviews were searched to identify RCTs and observational studies, conducted through June 16, 2020, that assessed the effect of statins as a treatment for asthma. A meta-analysis was conducted using the following main outcomes: asthma control test (ACT), asthma control questionnaire (ACQ), pre- and post-bronchodilator forced expiratory volume in one second (FEV1), peak flow (PEF), and asthma exacerbation (asthma-related emergency department (ED) visits and hospitalization). RESULTS: Our search revealed 11 RCTs and 8 observational studies that met the inclusion criteria. A meta-analysis demonstrated that statin treatment significantly improved ACT scores (mean difference: 1.61, P < 0.001) and ACQ scores (mean difference: -0.38, P < 0.001) compared to a placebo. Furthermore, statin treatment significantly reduced asthma-related ED visits (hazard ratio [HR], 95% confidence interval [CI], 0.83 [0.75-0.92], P < 0.001, number needed to treat [NNT], 5.9). However, statin treatment did not improve pulmonary function (FEV1 and PEF). CONCLUSION: Our results suggest that statins have the potential to improve asthma control and reduce asthma exacerbation without any improvement in pulmonary function.Supplemental data for this article can be accessed at publisher's website.

Analysis of clinical outcomes in elderly patients with impaired swallowing function.

Japan is the world's leading aging society, and increasing medical expenses for elderly people is an urgent issue. Since aspiration pneumonia in elderly people with impaired swallowing function is a huge problem in Japan, their expected long-term clinical course should be clarified. Accordingly, we collected data from 991 elderly (≥75 years old) patients whose swallowing function was evaluated by Kitasato Institute Hospital's speech therapists (January 1, 2010 to December 31, 2017). We analyzed the relationship between swallowing function and the subjects' long-term prognosis. To clarify the prognostic factors of patients with dysphagia, we obtained their clinical information (age, gender, activities of daily living, nutritional status, availability of alternative feeding pathways such as percutaneous endoscopic gastrostomy, and cognitive function). We confirmed 372 death cases and stratified the cases into three groups using Fujishima's swallowing ability grade, which is used to predict elderly people's real-world life expectancy. Results showed the median survival days were 331 and 952 days in Groups I (Grades 1-3, n = 308) and II (Grades 4-6, n = 153), respectively, whereas the median survival days for Group III (Grades 7-10, n = 530) could not be calculated. We conducted a multivariate analysis using the Cox proportional hazards model with Group I, which revealed that initial grade and percutaneous endoscopic gastrostomy were significant prognostic factors for the subjects' long-term survival. Nevertheless, further discussion is necessary, particularly to determine advanced care planning regarding indications for alternative feeding pathways in elderly patients with severe dysphagia, since percutaneous endoscopic gastrostomy could significantly prolong their survival.