Enpatoran in COVID-19 pneumonia: Safety and efficacy results from a phase II randomized trial.

Enpatoran is a selective inhibitor of toll-like receptors 7 and 8 (TLR7/8) that potentially targets pro-inflammatory pathways induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A phase II study conducted in Brazil, the Philippines, and the USA during the early pandemic phase assessed the safety and efficacy of enpatoran in patients hospitalized with COVID-19 pneumonia (NCT04448756). A total of 149 patients, who scored 4 on the World Health Organization's (WHO) 9-point ordinal severity scale, were randomized 1:1:1 and received enpatoran 50 mg (n = 54) or 100 mg (n = 46), or placebo (n = 49) twice daily (b.i.d.) for 14 days plus standard of care. The primary objectives were safety and time to recovery (WHO 9-point scale ≤3). Clinical deterioration (WHO 9-point scale ≥ 5) was a key secondary objective. Treatment-emergent adverse events (TEAEs) were comparable across groups (56.5%-63.0%). Treatment-related TEAEs were numerically higher with enpatoran 50 mg (14.8%) than 100 mg (10.9%) or placebo (8.2%). Serious TEAEs were numerically lower with enpatoran (50 mg 9.3%, 100 mg 2.2%) than placebo (18.4%). The primary efficacy objective was not met; median time to recovery was 3.4-3.9 days across groups, with placebo-treated patients recovering on average faster than anticipated. Clinical deterioration event-free rates up to Day 7 were 90.6%, 95.6%, and 81.6% with enpatoran 50 mg, 100 mg, and placebo, respectively. Enpatoran was well tolerated by patients acutely ill and hospitalized with COVID-19 pneumonia. Positive signals in some secondary end points suggested potential beneficial effects, supporting further evaluation of enpatoran in patients with hyperinflammation due to infection or autoimmunity.

Impact of Molnupiravir Treatment on Patient-Reported COVID-19 Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Molnupiravir is an orally administered antiviral authorized for COVID-19 treatment in adults at high risk of progression to severe disease. Here, we report secondary and post hoc analyses of participants' self-reported symptoms in the MOVe-OUT trial, which evaluated molnupiravir initiated within 5 days of symptom onset in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID-19. METHODS: Eligible participants completed a 15-item symptom diary daily from day 1 (randomization) through day 29, rating symptom severity as "none," "mild," "moderate," or "severe"; loss of smell and loss of taste were rated as "yes" or "no." Time to sustained symptom resolution/improvement was defined as the number of days from randomization to the first of 3 consecutive days of reduced severity, without subsequent relapse. Time to symptom progression was defined as the number of days from randomization to the first of 2 consecutive days of worsening severity. The Kaplan-Meier method was used to estimate event rates at various time points. The Cox proportional hazards model was used to estimate the hazard ratio between molnupiravir and placebo. RESULTS: For most targeted COVID-19 symptoms, sustained resolution/improvement was more likely, and progression was less likely, in the molnupiravir versus placebo group through day 29. When evaluating 5 distinctive symptoms of COVID-19, molnupiravir participants had a shorter median time to first resolution (18 vs 20 d) and first alleviation (13 vs 15 d) of symptoms compared with placebo. CONCLUSIONS: Molnupiravir treatment in at-risk, unvaccinated patients resulted in improved clinical outcomes for most participant-reported COVID-19 symptoms compared with placebo. Clinical Trials Registration. ClinicalTrials.gov: NCT04575597.

Erasmus Syndrome: A Case Report and Literature Review.

BACKGROUND Erasmus syndrome is a rare disease entity characterized by the development of systemic sclerosis (SSc) in a background of silica exposure or silicosis. CASE REPORT We report the case of a 40-year-old Filipino man who previously worked in a silica grind mill for 10 years and eventually developed Erasmus syndrome. The patient initially presented with chronic back pain in 2018 associated with findings of pulmonary tuberculosis on chest X-ray, with notable improvement after 6 months of anti-tuberculosis treatment. However, his back pain recurred in 2021; this time with arthralgia, Raynaud's phenomenon, thickening of both hands, skin hypopigmentation on the chest, back, and forehead, and exertional dyspnea. Physical examination revealed salt-and-pepper dermopathy and skin tightening over the back, chest, and extremities. Mobility of his hands was limited, associated with sclerodactyly and digital pitting. Antinuclear antibody-immunofluorescence and anti-scleroderma-70 antibodies were strongly positive, confirming the diagnosis of SSc. Chest computed tomography illustrated multiple subcentimeter nodules and enlarged mediastinal lymph nodes with eggshell calcifications, consistent with silicosis. Spirometry with body plethysmography was normal but diffusing capacity for carbon monoxide was severely reduced. Histopathology of the skin showed markedly thickened collagen bundles in the dermis. CONCLUSIONS Chronic silica exposure is a risk factor for the development of silicosis. The clinical course of patients with silicosis may be complicated by SSc. Maintaining a high index of suspicion is key to the diagnosis of Erasmus syndrome. The present report emphasizes the importance of preventive measures and surveillance among those with occupational exposure to silica. To our knowledge, this is the first documented case of Erasmus syndrome in the Philippines.

Pulmonary Function and Chest Computed Tomography (CT) Scan Findings After Antifibrotic Treatment for COVID-19-Related Pulmonary Fibrosis.

BACKGROUND Physicians worldwide have been reporting many cases of COVID-19-induced pulmonary fibrosis. We report the case of a 51-year-old Filipino asthmatic woman who developed post-COVID-19 pulmonary fibrosis subsequently treated with Nintedanib. CASE REPORT The patient presented with a 4-day history of flu-like symptoms in September 2020 and was eventually diagnosed with severe COVID-19 pneumonia. Despite receiving Dexamethasone, Tocilizumab, Remdesivir, and multiple antibiotics, there was increasing oxygen requirement, necessitating ICU admission and high-flow nasal cannula (HFNC). An additional course of hydrocortisone was given due to asthma exacerbation, gradually liberating her from the HFNC. A chest CT scan showed extensive parenchymal changes, for which she received methylprednisolone and physical rehabilitation with persistence of respiratory symptoms. After 40 days of hospitalization, she was sent home on oxygen support and Nintedanib. The patient initially had severe dyspnea (Borg Scale 7) with 6-minute walk distance (6MWD) of 295 meters. Pulmonary function showed moderately severe restrictive lung defect at 52% predicted total lung capacity (TLC) and severely reduced DLCO (28% predicted). Chest CT scoring indicated severe lung involvement. One month after Nintedanib treatment, her Borg Scale improved to 4. Her 6MWD, TLC, and DLCO increased to 434 meters, 64% predicted, and 36% predicted, respectively. A chest CT scan showed regressing fibrosis. After 6 months of treatment, her pulmonary function normalized. DLCO remained moderately reduced (59% predicted) but her 6MWD (457 meters) and CT scan results continued to improve. CONCLUSIONS Nintedanib, along with other interventions, may have potentially improved pulmonary function and CT scan findings in a COVID-19 survivor with pulmonary fibrosis 6 months after treatment.

Prevalence of anxiety and depression among Filipino patients with chronic obstructive pulmonary disease: A multi-center study

BACKGROUND: One under-explored area in chronic obstructive pulmonary disease (COPD) patients is anxiety and/or depression, which may have negative impact in the patients' condition. This is possibly the first study to possibly assess the burden of anxiety and depression in COPD patients in the Philippines. STUDY DESIGN: This is a prospective descriptive survey in three tertiary care hospitals in Manila, Philippines. PARTICIPANTS: A total of 204 patients were enrolled in the study with the following inclusion criteria: Filipino patients who are aged more than or equal to 40 years with a diagnosis of COPD (documented post-bronchodilator FEV1/FVC ratio less than 0.7) by a physician seen at the outpatient clinics of three tertiary care hospitals with no primary diagnosis of asthma, no previous lung volume reduction surgery, lung transplantation or pneumonectomy and at least finished Grade 2 education. Exclusion criteria include pregnant patients and patients previously diagnosed to have an anxiety, depression, or on any anti-depressant medications. METHODS: Descriptive statistics was obtained with frequency and percentages of the demographic and physiologic variables in the study by tabulation and graph. The prevalence of anxiety and depression was determined by calculating the percentage of each patient with a score of 8 or higher on the Hospital Anxiety and Depression Scale (HADS) with validated Tagalog version, respectively. RESULTS: The prevalence of anxiety in Filipino COPD patients is 47.55%. The prevalence of depression in Filipino COPD patients is 31.37%. CONCLUSION: The prevalence of depression in Filipino COPD patients is comparable to the prevalence of depression from other general medical conditions nationwide according to the study of Batar (31.37% vs. 31%). Anxiety is slightly more prevalent in COPD from other general medical conditions (47.55% vs. 36%). A study on the risk factors of anxiety and depression among Filipino COPD patients is recommended.