Safety and efficacy of 5-aminolevulinic acid phosphate/iron in mild-to-moderate coronavirus disease 2019: A randomized exploratory phase II trial.

BACKGROUND: 5-aminolevulinic acid (5-ALA), a natural amino acid that is marketed alongside sodium ferrous citrate (SFC) as a functional food, blocks severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proliferation in vitro and exerts anti-inflammatory effects. In this phase II open-label, prospective, parallel-group, randomized trial, we aimed to evaluate the safety and efficacy of 5-ALA in patients with mild-to-moderate coronavirus disease 2019. METHODS: This trial was conducted in patients receiving 5-ALA/SFC (250/145 mg) orally thrice daily for 7 days, followed by 5-ALA/SFC (150/87 mg) orally thrice daily for 7 days. The primary endpoints were changes in SARS-CoV-2 viral load, clinical symptom scores, and 5-ALA/SFC safety (adverse events [AE] and changes in laboratory values and vital signs). RESULTS: A total of 50 patients were enrolled from 8 institutions in Japan. The change in SARS-CoV-2 viral load from baseline was not significantly different between the 5-ALA/SFC (n = 24) and control (n = 26) groups. The duration to improvement was shorter in the 5-ALA/SFC group than in the control group, although the difference was not significant. The 5-ALA/SFC group exhibited faster improvement rates in "taste abnormality," "cough," "lethargy," and "no appetite" than the control group. Eight AEs were observed in the 5-ALA/SFC group, with 22.7% of patients experiencing gastrointestinal symptoms (decreased appetite, constipation, and vomiting). AEs occurred with 750/435 mg/day in 25.0% of patients in the first phase and with 450/261 mg/day of 5-ALA/SFC in 6.3% of patients in the second phase. CONCLUSION: 5-ALA/SFC improved some symptoms but did not influence the SARS-CoV-2 viral load or clinical symptom scores over 14 days. The safety of 5-ALA/SFC in this study was acceptable. Further evaluation using a larger sample size or modified method is warranted.

Case of organising pneumonia in HIV infection.

A man in his 50s presented to his doctor with a fever, sore throat, cough, dysgeusia and dyspnoea of several days' duration. Tests for HIV antigen, HIV antibody and HIV PCR were positive. He was referred to our hospital for initiation of antiretroviral therapy and bronchoscopy to clarify the cause of an abnormal lung shadow on chest CT. He was diagnosed with organising pneumonia, with concurrent HIV infection. His pulmonary lesions were remitted spontaneously, and he was administered a fixed-dose combination of tenofovir (50 mg), emtricitabine (200 mg) and bictegravir (25 mg) for HIV. This is a rare report of organising pneumonia with HIV infection. Physicians need to consider organising pneumonia when lung opacity is observed in a patient with HIV infection.

Severe Anemia Due to Cold Agglutinin Syndrome in a COVID-19 Patient with IgM Monoclonal Gammopathy of Undetermined Significance Successfully Treated with Corticosteroids.

Secondary cold agglutinin syndrome (CAS) is autoimmune hemolytic anemia secondary to infections and lymphoid disorder. We here report the first Asian case of CAS secondary to novel coronavirus disease 2019 (COVID-19). A 72-year-old Japanese woman presented with a 2-week history of dyspnea and cough, and laboratory data revealed severe hemolytic anemia with a hemoglobin level of 4.7 g/dL. She was diagnosed with COVID-19, CAS, and monoclonal gammopathy of undetermined significance (MGUS). The anemia responded to corticosteroids administered for COVID-19 and required maintenance therapy. Although corticosteroids are not a standard therapy for CAS, they might be effective for CAS secondary to COVID-19 complicated with MGUS.

Analysis of bronchoalveolar lavage samples collected from 30 patients with drug-induced pneumonitis.

BACKGROUND: Drug-induced pneumonitis is a disease encountered by pulmonologists in the clinical setting. The diagnosis generally considers the patient's clinical course and the results of peripheral blood tests, radiological examinations, and often bronchoscopic examinations. However, few studies have reported the association between radiological patterns such as ground-glass opacity (GGO) or consolidation, and bronchoalveolar lavage fluid (BALF) cell fractions. This study aimed to clarify this association. METHODS: Patients with a Naranjo's score of probable or definite were enrolled, and all 30 patients were categorized under probable. Data such as patient background, blood examination results, radiological findings, and BALF cell fractions were retrospectively collected. The association between BALF cell fractions and other factors such as chest computed tomography (CT) findings was evaluated. RESULTS: The most common radiological finding in patients with lymphocyte-dominant BALF was GGO, with only one patient exhibiting consolidation. However, patients with eosinophil-dominant BALF were more likely to have consolidation; only three cases showed crazy paving and one showed GGO. In addition, patients with a GGO-dominant pattern on CT had an increased lymphocyte fraction of 41.0%; those with a consolidation-dominant pattern showed a relatively high eosinophil fraction of 5.2%; and those with a crazy paving pattern showed elevated eosinophil and neutrophil fractions of 19.1% and 9.9%, respectively. CONCLUSIONS: In this study, a remarkable difference in radiological findings was observed among different BALF patterns.

Diagnostic performance of serum interferon gamma, matrix metalloproteinases, and periostin measurements for pulmonary tuberculosis in Japanese patients with pneumonia.

Serum markers that differentiate between tuberculous and non-tuberculous pneumonia would be clinically useful. However, few serum markers have been investigated for their association with either disease. In this study, serum levels of interferon gamma (IFN-γ), matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9, respectively), and periostin were compared between 40 pulmonary tuberculosis (PTB) and 28 non-tuberculous pneumonia (non-PTB) patients. Diagnostic performance was assessed by analysis of receiver-operating characteristic (ROC) curves and classification trees. Serum IFN-γ and MMP-1 levels were significantly higher and serum MMP-9 levels significantly lower in PTB than in non-PTB patients (p < 0.001, p = 0.002, p < 0.001, respectively). No significant difference was observed in serum periostin levels between groups. ROC curve analysis could not determine the appropriate cut-off value with high sensitivity and specificity; therefore, a classification tree method was applied. This method identified patients with limited infiltration into three groups with statistical significance (p = 0.01), and those with MMP-1 levels < 0.01 ng/mL and periostin levels ≥ 118.8 ng/mL included only non-PTB patients (95% confidence interval 0.0-41.0). Patients with extensive infiltration were also divided into three groups with statistical significance (p < 0.001), and those with MMP-9 levels < 3.009 ng/mL included only PTB patients (95% confidence interval 76.8-100.0). In conclusion, the novel classification tree developed using MMP-1, MMP-9, and periostin data distinguished PTB from non-PTB patients. Further studies are needed to validate our cut-off values and the overall clinical usefulness of these markers.