Association between delayed surgery and survival in early-stage cervical cancer in mainland China: Implications during the coronavirus pandemic (preprint)

Objective: The COVID-19 pandemic has had a significant impact on oncogynecologic patients worldwide, particularly with respect to delayed diagnosis and treatment. During the COVID-19 pandemic, few studies have examined the impact of delayed surgery on survival in early-stage cervical cancer patients. The purpose of this study was to determine the effect of delayed surgical time on survival in patients with early cervical cancer. Design A retrospective cohort study. Setting A single general hospital in Shaanxi, Northwest China. Population A total of 1207women with early cervical cancer were recruited between April 2013 and December 2018 in Mainland China and followed up until 29 Feb 2022. Methods This retrospective cohort study was conducted in a comprehensive tertiary hospital in Shaanxi, Xi’an, China. We used a Cox proportional hazard model with delay time in weeks as a categorical variable to analyse the effect of surgical delay time on survival. Main Outcome Measures The 5-year overall and disease-free survival were used as the primary outcome measures. Results A total of 800 participants were included in the final cohort. In the multivariate Cox regression analysis (median follow-up, 58 months), patients in the long delay time group had DFS (5-year rates, 91.5% versus 90.9%, HR 0.99, 95% CI 0.62~1.59, P=0.98) and OS (5-year rates of 92.9% versus 90.8%, HR 0.68, 95% CI 0.42~1.10, P=0.11) similar to those in the short delay time group. Conclusions Our findings indicate that a 12-week delay in surgery is not associated with long-term survival in women with early-stage cervical cancer.

The SARS-CoV-2 transcriptome and the dynamics of the S gene furin cleavage site in primary human airway epithelia (preprint)

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the devastating ongoing coronavirus disease-2019 (COVID-19) pandemic which poses a great threat to global public health. The spike (S) polypeptide of SARS-CoV-2 consists of the S1 and S2 subunits and is processed by cellular proteases at the S1/S2 boundary. The inclusion of the 4 amino acids (PRRA) at the S1/S2 boundary forms a furin cleavage site (FCS), 682RRAR{downarrow}S686, distinguishing SARS-CoV-2 from its closest relative, the SARS-CoV. Various deletions surrounding the FCS have been identified in patients. When SARS-CoV-2 propagated in Vero cells, the virus acquired various deletions surrounding the FCS. In the present study, we studied the viral transcriptome in SARS-CoV-2 infected primary human airway epithelia (HAE) cultured at an air-liquid interface (ALI) with an emphasis on the viral genome stability at the S1/S2 boundary using RNA-seq. While we found overall the viral transcriptome is similar to that generated from infected Vero cells, we identified a high percentage of mutated viral genome and transcripts in HAE-ALI. Two highly frequent deletions were found at the S1/S2 boundary of the S gene: one is a deletion of 12 amino acids, 678TNSPRRAR{downarrow}SVAS689, which contains the FCS, another is a deletion of 5 amino acids, 675QTQTN679, which is two amino acids upstream of the FCS. Further studies on the dynamics of the FCS deletions in apically released virions revealed that the selective pressure for the FCS maintains the S gene stability in HAE-ALI but with exceptions, in which the FCS deletions are remained at a high rate. Thus, our study presents evidence for the role of unique properties of human airway epithelia in the dynamics of the FCS region during infection of human airways, which is donor-dependent.