Case report: Understanding the impact of persistent tissue-localization of SARS-CoV-2 on immune response activity via spatial transcriptomic analysis of two cancer patients with COVID-19 co-morbidity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient. Using spatial whole-transcriptomic analysis, we demonstrated spatial profiles consistent with a lymphocyte-associated SARS-CoV-2 response (based on two public COVID-19 gene sets) in the tumors and adjacent normal tissues, despite intra-tumor heterogeneity. The use of RNAscope and multiplex immunohistochemistry revealed that the spatial localization of B cells was significantly associated with lymphocyte-associated SARS-CoV-2 responses within the spatial transcriptomic (ST) niches showing the highest levels of virus. Furthermore, single-cell RNA sequencing data obtained from previous (CRC) or new (HCC) ex vivo stimulation experiments showed that patient-specific SARS-CoV-2 memory B cells were the main contributors to this positive association. Finally, we evaluated the spatial associations between SARS-CoV-2-induced immunological effects and immunotherapy-related anti-tumor immune responses. Immuno-predictive scores (IMPRES) revealed consistent positive spatial correlations between T cells/cytotoxic lymphocytes and the predicted immune checkpoint blockade (ICB) response, particularly in the HCC tissues. However, the positive spatial correlation between B cells and IMPRES score was restricted to the high-virus ST niche. In addition, tumor immune dysfunction and exclusion (TIDE) analysis revealed marked T cell dysfunction and inflammation, alongside low T cell exclusion and M2 tumor-associated macrophage infiltration. Our results provide in situ evidence of SARS-CoV-2-generated persistent immunological memory, which could not only provide tissue protection against reinfection but may also modulate the tumor microenvironment, favoring ICB responsiveness. As the number of cancer patients with COVID-19 comorbidity continues to rise, improved understanding of the long-term immune response induced by SARS-CoV-2 and its impact on cancer treatment is much needed.

Did the COVID-19 lockdown result in a delay of colorectal cancer presentation and outcomes? A single centre review.

PURPOSE: The COVID-19 pandemic and resultant lockdown measures potentially delay management of non-communicable, life-limiting diseases like colorectal cancer (CRC) through avoidance of healthcare facilities by the public and diversion of resources within healthcare systems. This study aims to evaluate the impact of Singapore's "Circuit Breaker (CB)" lockdown measures on CRC disease presentation and short-term surgical outcomes, while comparing Singapore's approach against other countries which employed similar lockdown measures. METHODS: Patients whose initial diagnosis of CRC was made within the 6-month pre-CB (6/10/19-6/4/20) ("pre-CB group") and post-CB (7/4/20-7/10/20) ("post-CB group") period were enrolled retrospectively. The groups were compared based on severity of disease on presentation and short-term operative outcomes. RESULTS: In total, 105 patients diagnosed with CRC were enrolled in this study. When comparing pre-CB and post-CB groups, there was no significant difference in stage of CRC on presentation (p = 0.850). There was also no increase in need for emergent operations (p = 0.367). For patients who had undergone an operation, postoperative morbidity was not significantly higher in the post-CB group (p = 0.201). Both groups of patients had similar length of stay in the hospital (p = 0.438). CONCLUSION: Unlike similar high-income countries, Singapore did not see later stage disease on presentation and poorer operative outcomes after lockdown measures. Possible reasons include lesser healthcare avoidance behaviours amongst Singaporeans, and adequate preparation of resources and contingency plans formed by hospitals after previous pandemics.