Quality
Oladunni Olanubi, BSc, MSc
PhD Student
Ottawa Hospital Research Institute (OHRI), United States
Taylor Dion, BSc
MSc Student
Ottawa Hospital Research Institute (OHRI), United States
Rafeah Alam, BSc, MSc, PhD
Research Associate
Ottawa Hospital Research Institute (OHRI), United States
Christiano Tanese de Souza, DVM
Research technician
Ottawa Hospital Research Institute (OHRI), United States
Richard Hu, BSc, MSc, MD
Surgical Resident
Ottawa Hospital Research Institute (OHRI)
Ottawa, Ontario, United States
Angela Crawley, BSc, MSc, PhD
Associate Professor
Ottawa Hospital Research Institute (OHRI), United States
Rebecca C. Auer, MD, MSc, FRCSC, FACS (she/her/hers)
Director of Cancer Research
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada
Rebecca C. Auer, MD, MSc, FRCSC, FACS (she/her/hers)
Director of Cancer Research
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada
Infection with COVID-19 within 30 days after surgery is associated with an increased risk of major complications, despite preoperative vaccination. In murine models, cancer antigen-specific T cells are highly dysfunctional following surgery, leading to cancer recurrence. The effect of surgery on antigen-specific T cell and B cell function has not been well studied in humans. The widespread vaccination against COVID-19 and the availability of immunological assays to measure SARS-CoV2 specific immune responses presents and ideal opportunity to evaluate the effect of surgery on the adaptive cellular and humoral immune system.
Methods:
Patients undergoing major abdominal surgery for malignancy, who had received at least 2 doses of the Pfizer BNT vaccine were included. Blood was collected at baseline (POD0) and then on postoperative day (POD) 1, 3 and 28. Peripheral Blood Mononuclear Cells (PBMC) were isolated immediately and cryopreserved for flow cytometry and functional assays, including T and B cell ELISpot for measurement of IFNγ and IgG3 respectively, in response to the RBD domain of the SARS-CoV2 spike (S) protein. Flow cytometry was used to characterize the cell surface phenotype of CD8+ T cells and intracellular IFNγ and TNFα. Serum was collected for quantification of antibody titres against the S-protein. Statistical comparisons were conducted on SAS® using the paired t-test and Wilcoxon Rank test for parametric and non-parametric data respectively.
Results:
A total of 30 patients were included in the study. Surgical stress resulted in a significant reduction in the proportion of CD3+ T cells that secreted IFNγ in response to the SARS-CoV2 spike protein on POD1 by ELISpot (90.9±56.8 spots) as compared to POD0 (181.3±72.2, p< 0.0001), which persisted on POD3 (128.5±49.2, p< 0.01), but recovered by POD28 (163.2±51.9, p=0.1). This was associated with a significant decrease in intracellular TNFα expression (p=0.01) and an increase in cell surface expression of PD-1 (p=0.03), but no change in the expression of exhaustion markers, TIM-3 or TIGIT, nor of T-bet. Surgery also significantly impaired the production of IgG antibody by CD19+ memory B cells upon stimulation with the SARS-CoV2 spike protein on POD1 (49.1±47.9 vs. 105.7±67.7 spots on POD0, p< 0.0001). There was no measurable decrease in the IgG, IgM or IgA serum antibody titers against the S-protein on POD1.
Conclusions:
Surgery results in measurable suppression of antigen-specific T and B cell responses to COVID-19, with implications for both postoperative infections and cancer recurrence.