Introduction: The COVID-19 pandemic has significantly influenced surgical practices, with SARS-CoV-2 variants presenting unique pathologic profiles and potential impacts on perioperative outcomes. This study explores associations between Alpha, Delta, and Omicron variants of SARS-CoV-2 and surgical outcomes.

Methods: We conducted a retrospective analysis using the National COVID Cohort Collaborative database, which included patients who underwent selected major inpatient surgeries within eight weeks post-SARS-CoV-2 infection from January 2020 to April 2023. The viral variant was determined by the predominant strain at the time of the patient's infection. Multivariable logistic regression models explored the association between viral variants, COVID-19 severity, and 30-d major morbidity or mortality.

Results: The study included 10,617 surgical patients with preoperative COVID-19, infected by the Alpha (4456), Delta (1539), and Omicron (4622) variants. Patients infected with Omicron had the highest vaccination rates, most mild disease, and lowest 30-d morbidity and mortality rates. Multivariable logistic regression demonstrated that Omicron was linked to a reduced likelihood of adverse outcomes compared to Alpha, while Delta showed odds comparable to Alpha. Inclusion of COVID-19 severity in the model rendered the odds of major morbidity or mortality equal across all three variants.

Conclusions: Our study examines the associations between the clinical and pathological characteristics of SARS-CoV-2 variants and surgical outcomes. As novel SARS-CoV-2 variants emerge, this research supports COVID-19-related surgical policy that assesses the severity of disease to estimate surgical outcomes.