Clinical characteristics of COVID-19 patients infected by the Omicron variants in Macao, China: A cross-sectional study.

Background and Aims: The evolving mutants of SARS-CoV-2 have made the COVID-19 pandemic sustained for over 3 years. In 2022, BA.4 and BA.5 were the Omicron variants dominating the spread globally. Although COVID-19 was no longer a Public Health Emergency of International Concern (PHEIC) as announced by WHO, the SARS-CoV-2 variants remain a challenge to global healthcare under the circumstances of withdrawal and loosening of personal protective behavior in the post-quarantine era. This study aims to acknowledge the clinical characteristics caused by Omicron BA.4/BA.5 in COVID-19 naive people and analyze possible factors affecting disease severities. Methods: In this retrospective study, we report and analyze the clinical features of 1820 COVID-19 patients infected with the BA.4/BA.5 Omicron variants of SARS-CoV-2 during a local outbreak that occurred in Macao SAR, China, from June to July 2022. Results: A total of 83.5% of patients were symptomatic eventually. The most common symptoms were fever, cough, and sore throat. Hypertension, dyslipidemia, and diabetes mellitus were the leading comorbidities. There were significantly more elderly patients (p < 0.001), more patients with comorbidity (p < 0.001) and more patients without vaccination or not completing the series (p < 0.001) in the "Severe to Critical" group. All deceased patients were elderly with at least three comorbidities and were partial to totally dependent in their daily lives. Conclusion: Our data are consistent with a milder disease caused by BA.4/5 Omicron variants in the general population, while patients with old age and comorbidities have developed severe to critical diseases. Complete vaccination series and booster doses are effective strategies to reinforce protection against severe diseases and avoid mortality.

Clinical efficacy and safety of pemetrexed with or without either Bevacizumab or Pembrolizumab in patients with metastatic nonsquamous non-small cell carcinoma.

BACKGROUND: Pemetrexed was approved by United States Food and Drug Administration (US FDA) in combination with platinum for the treatment of advanced nonsquamous non-small cell lung carcinoma (NSCLC) and malignant mesothelioma. Bevacizumab and pembrolizumab can be added to chemotherapy for patients with nonsquamous NSCLC with benefits but there has not been any dedicated head-to-head comparison between pembrolizumab-pemetrexed-platinum (PAC) and bevacizumab-pemetrexed-platinum (BAC) on their efficacy and safety. METHODS: This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong. The study included 451 patients with advanced stage nonsquamous NSCLC that received first-line pemetrexed and platinum with or without bevacizumab or pembrolizumab. Patients who received pemetrexed-platinum (AC) were compared with those who received PAC and BAC. The primary endpoint was the progression-free survival (PFS). RESULTS: The median PFS for patients that received PAC was significantly longer than those who received BAC and AC (9 months vs. 6.8 months vs. 4.8 months, p < 0.05 among all three groups), with OR of 0.578 (95% CI, 0.343-0.976; p = 0.040) and 0.430 (95% CI, 0.273-0.675; p < 0.001) when compared to BAC and AC, respectively. Patients who received PAC also had a higher disease control rate and higher likelihood to receive continuation maintenance therapy than those on AC. There is no statistically significant difference in the grade 3 to 4 toxicity among the three treatment groups. CONCLUSIONS: Although both regimens are superior to pemetrexed-platinum alone, data from this retrospective single center study suggested a better PFS in  advanced stage nonsquamous NSCLC patient treated with first-line pembrolizumab-pemetrexed-platinum than bevacizumab-pemetrexed-platinum without an obvious increase in significant toxicity.

Haematological toxicity of pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung with third-space fluid.

BACKGROUND: Pemetrexed was approved by United States Food and Drug Administration (US FDA) in combination with platinum for the treatment of advanced non-squamous non-small cell lung carcinoma (NSCLC) and malignant mesothelioma. Due to the structural similarity with methotrexate, there has been concern about the accumulation of pemetrexed in third space fluid that may result in increased toxicity. Previous small-scale studies have yet to conclusively prove this association. METHODS: This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong. The study included 329 patients with advanced stage non-squamous NSCLC that received first line pemetrexed and platinum. Patients who had non-evacuated third-space fluid, evacuated third-space fluid and without third-space fluid were compared. The primary endpoint was the occurrence of hematological toxicity. RESULTS: The presence of non-evacuated third-space fluid was shown to be associated with significantly more hematological toxicities, namely grade 3 or above hematological toxicities [Odd ratio (OR) = 2.450, p = 0.002], postponement of chemotherapy (OR = 3.837, p = 0.000) and need for dose adjustment (OR = 2.436, p = 0.022) when compared with those without third-space fluid. For patients with evacuated third-space fluid, these adverse effects were nullified. CONCLUSIONS: Presence of non-evacuated third-space fluid in patients with advanced non-squamous NSCLC predispose patients to significant hematological toxicity when pemetrexed and platinum chemotherapy is used. Evacuation of third-space fluid should be considered before starting pemetrexed and platinum doublet.