Real-World Experience of the Comparative Effectiveness and Safety of Molnupiravir and Nirmatrelvir/Ritonavir in High-Risk Patients with COVID-19 in a Community Setting.

Molnupiravir (MOV) and nirmatrelvir/ritonavir (NMV/r) are efficacious oral antiviral agents for patients with the 2019 coronavirus (COVID-19). However, little is known about their effectiveness in older adults and those at high risk of disease progression. This retrospective single-center observational study assessed and compared the outcomes of COVID-19 treated with MOV and NMV/r in a real-world community setting. We included patients with confirmed COVID-19 combined with one or more risk factors for disease progression from June to October 2022. Of 283 patients, 79.9% received MOV and 20.1% NMV/r. The mean patient age was 71.7 years, 56.5% were men, and 71.7% had received ≥3 doses of vaccine. COVID-19-related hospitalization (2.8% and 3.5%, respectively; p = 0.978) or death (0.4% and 3.5%, respectively; p = 0.104) did not differ significantly between the MOV and NMV/r groups. The incidence of adverse events was 2.7% and 5.3%, and the incidence of treatment discontinuation was 2.7% and 5.3% in the MOV and NMV/r groups, respectively. The real-world effectiveness of MOV and NMV/r was similar among older adults and those at high risk of disease progression. The incidence of hospitalization or death was low.

Effectiveness of monoclonal antibody therapy for COVID-19 patients using a risk scoring system.

INTRODUCTION: Monoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021. METHODS: According to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan. RESULTS: During Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12-0.53) and 0.10 (95% CI: 0.01-0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event. CONCLUSIONS: The administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse.

Clinical utility of the C-reactive protein:albumin ratio in non-small cell lung cancer patients treated with nivolumab.

BACKGROUND: Nivolumab is a second-line chemotherapy for non-small cell lung cancer (NSCLC). This study explored the impact of clinical biomarkers such as neutrophil:lymphocyte ratio (NLR), C-reactive protein:albumin ratio (CAR), and modified Glasgow prognostic score on the efficacy and outcome of nivolumab monotherapy in previously treated NSCLC patients. METHODS: We retrospectively analyzed advanced or postoperative recurrence of NSCLC in 113 patients in two Japanese facilities from January 2015 to December 2019. Optimal cutoff values of NLR and CAR were assessed by the area under the receiver operating characteristic curves predicting death events to conduct regression analysis. Baseline values and values collected eight weeks after nivolumab treatment were measured to investigate time-series changes of these markers. RESULTS: The patients showed median overall survival (OS) and progression-free survival (PFS) of 14.0 months and 2.3 months, respectively, with both being significantly longer in patients with partial response (PR) than in patients with progressive disease (PD). Optimal cutoff levels for NLR and CAR were 5.8 and 0.83, with significant decrease in CAR (P = 0.002) from baseline levels in PR patients and significant increase in PD patients. Baseline CAR ≥0.83 was significantly associated with one-year mortality events and overall survival (OS), and multivariate analysis showed significant association of age ≤70 years, an Eastern Cooperative Oncology Group performance status score of 2 or 3, and a baseline CAR ≥0.83 with inferior OS. CONCLUSIONS: For second-line nivolumab therapy, evaluation of baseline CAR and subsequent changes in CAR may be predictive of therapeutic response to nivolumab and long-term survival in NSCLC patients. KEY POINTS: Significant findings of the study The baseline value of C-reactive protein:albumin ratio was significantly associated with one-year mortality and overall survival in non-small cell lung cancer patients treated with nivolumab. What this study adds Time-series change of C-reactive protein:albumin ratio may be useful for predicting the treatment efficacy in patients treated with nivolumab.

Fatal Primary Human Bocavirus Pneumonia in an Immunocompetent Adult.

A 70-year-old woman was admitted to our hospital for dyspnea and a fever of 2 weeks duration. Chest imaging showed bilateral infiltration, and a rapid diagnostic test for influenza virus, Mycoplasma pneumoniae, Streptococcus pneumoniae, and Legionella spp. was negative. She was intubated and mechanically ventilated and underwent bronchoalveolar lavage. Bronchoalveolar lavage fluid yielded no significant pathogens, and the multiplex polymerase chain reaction test was positive only for human bocavirus. Specific antibodies against significant pathogens were not increased in paired sera, so we diagnosed her with primary human bocavirus pneumonia.

[Successful Treatment of Squamous Cell Lung Cancer without PD-L1 Expression Using Fourth-Line Nivolumab].

A 71-year-old woman was diagnosed with stage ⅢB locally advanced lung squamous cell cancer(cT0N3M0).Programmed death-ligand 1(PD-L1)immunostaining was negative.First -line nedaplatin plus docetaxel and second-line carboplatin plus nab-paclitaxel were followed by sequential thoracic radiation therapy(60 Gy).The patient developed radiation pneumonitis, but her condition improved with corticosteroids.However, chest computed tomography(CT)revealed multiple nodules in both lungs.Third -line carboplatin plus tegafur/gimeracil/oteracil potassium(S-1)was not successful, and fourth- line nivolumab(3mg/kg every 2weeks)was adopted.On day 9 after first administration, she developed fever and radiation recall pneumonitis.Multiple nodules rapidly formed, but they later gradually decreased in number.After 13 courses of nivolumab, the nodules had disappeared completely.Mediastinal lymph nodes decreased in size, but an abdominal lymph node remained enlarged.Nivolumab was continued, and after 24 courses, the abdominal lymph node began to shrink, and the multiple lung metastases continued to disappear.Currently, the best overall response is good partial response to nivolumab.

Allergic bronchopulmonary aspergillosis successfully treated with mepolizumab: Case report and review of the literature.

A 56-year-old woman was referred to our hospital for recurrent asthma of 20 years duration. She was diagnosed as having allergic bronchopulmonary aspergillosis on the basis of clinical symptoms, peripheral blood eosinophilia, elevated total serum immunoglobulin E value, positive results of specific IgE and precipitating antibodies against Aspergillus sp., central bronchiectasis, and mucoid impaction. Systemic corticosteroids and anti-fungal therapy improved her symptoms, but the cessation of these treatments led to frequent exacerbations. Omalizumab improved her asthmatic symptoms to the point that corticosteroids could be stopped; however, radiological findings were not improved, and coexisting eosinophilic sinusitis and otitis media worsened. After her treatment was changed from omalizumab to mepolizumab, not only her asthmatic symptoms but also her sinusitis and otitis media became well controlled, and chest radiological findings improved.