Impact of COVID-19 vaccination on the use of PD-1 inhibitor in treating patients with cancer: a real-world study.

Anti-COVID-19 vaccination may have functional implications for immune checkpoint inhibitor treatment in patients with cancer. This study was undertaken to determine whether the safety or efficacy of anti-PD-1 therapy is reduced in patients with cancer during COVID-19 vaccination. A large multicenter observational study was conducted in 83 Chinese hospitals between January 28, 2021 and September 30, 2021. A total of 3552 patients were screened and 2048 eligible patients with cancer receiving PD-1 inhibitor treatment were recruited. All enrolled patients had received camrelizumab treatment alone or in conjunction with other cancer therapies. Among these, 1518 (74.1%) patients received the BBIBP-CorV vaccine and were defined as the vaccinated subgroup. The remaining 530 (25.9%) patients did not receive anti-COVID-19 vaccination and were defined as the non-vaccinated subgroup. For all participants, Response Evaluation Criteria in Solid Tumor and Common Terminology Criteria for Adverse Events criteria were used to evaluate the efficacy and safety of camrelizumab treatment, respectively. Propensity score match analysis with the optimal pair matching was used to compare these criteria between the vaccinated and non-vaccinated subgroups. A total of 2048 eligible patients with cancer were included (median age 59 years, 27.6% female). Most patients (98.8%) had metastatic cancer of the lung, liver or intestinal tract. Aside from the PD-1 inhibitor treatment, 55.9% of patients received additional cancer therapies. 1518 (74.1%) patients received the BBIBP-CorV vaccine with only mild side effects reported. The remaining patients did not receive COVID-19 vaccination and had a statistically greater percentage of comorbidities. After matching for age, gender, cancer stage/types, comorbidity and performance status, 1060 patients (530 pairs) were selected for propensity score match analysis. This analysis showed no significant differences in overall response rate (25.3% vs 28.9%, p=0.213) and disease control rate (64.6% vs 67.0%, p=0.437) between vaccinated and non-vaccinated subgroups. Immune-related adverse events (irAEs) were reported in both subgroups after camrelizumab treatment. Among vaccinated patients who experienced irAEs, the median interval between the first dose of camrelizumab treatment and the first vaccine shot was ≤16 days. Compared with the non-vaccinated subgroup, irAEs in vaccinated patients were more frequently reported as mild (grade 1 or 2 irAEs; 33.8% vs 19.8%, p<0.001) and these patients were less likely to discontinue the PD-1 inhibitor treatment (4.2% vs 20.4%, p<0.001). Severe irAEs (grade 3 irAE or higher) related to camrelizumab treatment were reported, however no significant differences in the frequency of such events were observed between the vaccinated and non-vaccinated subgroups. The COVID-19 vaccine, BBIBP-CorV, did not increase severe anti-PD-1-related adverse events nor did it reduce the clinical efficacy of camrelizumab in patients with cancer. Thus, we conclude that patients with cancer need not suspend anti-PD-1 treatment during COVID-19 vaccination.

Association of Cigarette Smoking, COPD, and Lung Cancer With Expression of SARS-CoV-2 Entry Genes in Human Airway Epithelial Cells.

SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. In this study, we examined the expression profiles of the three SARS-CoV-2 entry genes in primary human airway epithelial cells isolated from smokers, non-smokers, patients with chronic obstructive pulmonary disease or lung cancer. An exhaustive search of the GEO database was performed to identify eligible data on 1st June 2020. In total, 46 GEO datasets comprising transcriptomic data of 3,053 samples were identified as eligible data for further analysis. All meta-analysis were performed using RStudio. Standardized mean difference was utilized to assess the effect size of a factor on the expression of targeted genes and 95% confidence intervals (CIs) were calculated. This study revealed that (i) cigarette smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; (ii) significant alternations in expression of ACE2, TMPRSS2, and cathepsin L were observed between current smokers and former smokers, but not between former smokers and never smokers; (iii) when compared with healthy controls with identical smoking status, patients with COPD or lung cancer showed negligible changes in expression of ACE2, TMPRSS2, and cathepsin L. Therefore, this study implicates cigarette smoking might contribute to the development of COVID-19 by affecting the expression of SARS-CoV-2 entry genes, while smoking cessation could be effective to reduce the potential risk.