Characterizing the impact of SARS-CoV-2 reinfection on surgical outcomes

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The COVID-19 pandemic has changed the delivery of surgical care. Early in the pandemic, an association between SARS-CoV-2 infection and adverse postoperative outcomes prompted the implementation of risk mitigation strategies, including routine asymptomatic COVID-19 testing and the postponement of surgical procedures1–3. In May 2023, the WHO declared an end to the COVID-19 global public health emergency; however, the disease’s implications with regard to perioperative care persist. As novel SARS-CoV-2 variants emerge, understanding the influence of reinfection on postoperative outcomes is an important consideration. Although SARS-CoV-2 reinfection is thought to produce a milder form of COVID-19, it can potentially increase the risk of developing long COVID, which suggests that reinfection is related to persistent physiological changes that can lead to multiorgan or autoimmune symptoms4. The association between COVID-19 severity and surgical outcomes has been previously established5, but the complex immunological and physiological implications of SARS-CoV-2 reinfection warrant further study. This was a retrospective cohort study from January 2020 to June 2023 that used the National COVID Cohort Collaborative (N3C) Data Enclave. The study consisted of adult patients who underwent major inpatient surgery using previously defined criteria5. Patients with COVID-19 were identified by a positive laboratory measurement (PCR or antigen) or a positive COVID-19 diagnosis (ICD-10-CM code U07.1) before surgery. Reinfection was defined as subsequent SARS-CoV-2 positivity occurring more than 90 days after the initial COVID-19 diagnosis. SNOMED codes from the Observational Health Data Science and Informatics ATLAS tool were used to identify elective inpatient procedures, co-morbidities, and complications (Tables S1–S3). Procedures that were excluded were natural orifice or endoscopic, percutaneous, non-open diagnostic, and transplant procedures. The primary outcome of the study was 30-day composite major morbidity or mortality, which included pneumonia, myocardial infarction, pulmonary embolism, respiratory failure, sepsis, and death. Multivariable logistic regression models assessing 30-day major morbidity or mortality were adjusted for age, sex, race and ethnicity, co-morbidities, and relative surgical risk. All analyses were performed within the N3C Data Enclave. Of the 451 287 patients who underwent surgery, 51 989 had a single SARS-CoV-2 infection before surgery and 274 had reinfections (for detailed baseline characteristics, see Table S4). Patients who were reinfected had significantly higher rates of chronic kidney disease, heart failure, depression, gastro-oesophageal reflux disease, and obesity (P < 0.050). Additionally, patients reinfected with SARS-CoV-2 before surgery were younger compared with those with a single infection (aged a median of 56 (interquartile range 43–68) years versus a median of 62 (interquartile range 50–71) years respectively; P < 0.001). Rates of composite major morbidity or mortality varied significantly across groups (11% in patients without a history of COVID-19, 13% in patients with a single infection, and 9.1% in patients with reinfection; P < 0.001). Adjusted analysis found that patients with a single SARS-CoV-2 infection demonstrated higher odds of 30-day major morbidity or mortality (1.13 (1.10–1.16)) and that patients with reinfection did not experience an elevated risk of postoperative major morbidity or mortality (0.68 (0.43–1.03)) compared with patients without a history of COVID-19 (Fig. 1). Multivariable logistic regression assessing the relationship between single infection and reinfection with composite 30-day major morbidity or mortality, adjusted for age, sex, race and ethnicity, co-morbidities, and relative surgical risk Relative surgical risk is omitted from the forest plot to maintain the scale. The adjusted ORs for medium-risk and high-risk surgeries were 4.24 (95% c.i. 4.11 to 4.37) and 8.61 (95% c.i. 8.30 to 8.92) respectively (reference = low-risk surgeries). This study demonstrates that SARS-CoV-2 reinfection before surgery is not an independent risk factor for 30-day postoperative adverse outcomes. Whilst patients with reinfection had a notably higher burden of co-morbid health conditions, reinfection was not independently associated with an elevated risk of postoperative major morbidity or mortality. Moreover, these findings suggest that prior exposure to the virus may mitigate disease severity and, as a result, reduce the surgical risk associated with SARS-CoV-2 infection. This study is limited by reduced COVID-19 testing over time, which may lead to underestimation of reinfection rates within the data set. As the perioperative community cares for an increasing number of patients reinfected with SARS-CoV-2, these results support ongoing evaluation of the severity of COVID-19 to accurately assess a patient’s preoperative risk. National COVID Cohort Collaborative (N3C) Consortium Adam B. Wilcox; Adam M. Lee; Alexis Graves; Alfred (Jerrod) Anzalone; Amin Manna; Amit Saha; Amy Olex; Andrea Zhou; Andrew E. Williams; Andrew Southerland; Andrew T. Girvin; Anita Walden; Anjali A. Sharathkumar; Benjamin Amor; Benjamin Bates; Brian Hendricks; Brijesh Patel; Caleb Alexander; Carolyn Bramante; Cavin Ward-Caviness; Charisse Madlock-Brown; Christine Suver; Christopher Chute; Christopher Dillon; Chunlei Wu; Clare Schmitt; Cliff Takemoto; Dan Housman; Davera Gabriel; David A. Eichmann; Diego Mazzotti; Don Brown; Eilis Boudreau; Elaine Hill; Elizabeth Zampino; Emily Carlson Marti; Emily R. Pfaff; Evan French; Farrukh M Koraishy; Federico Mariona; Fred Prior; George Sokos; Greg Martin; Harold Lehmann; Heidi Spratt; Hemalkumar Mehta; Hongfang Liu; Hythem Sidky; J.W. Awori Hayanga; Jami Pincavitch; Jaylyn Clark; Jeremy Richard Harper; Jessica Islam; Jin Ge; Joel Gagnier; Joel H. Saltz; Joel Saltz; Johanna Loomba; John Buse; Jomol Mathew; Joni L. Rutter; Julie A. McMurry; Justin Guinney; Justin Starren; Karen Crowley; Katie Rebecca Bradwell; Kellie M. Walters; Ken Wilkins; Kenneth R. Gersing; Kenrick Dwain Cato; Kimberly Murray; Kristin Kostka; Lavance Northington; Lee Allan Pyles; Leonie Misquitta; Lesley Cottrell; Lili Portilla; Mariam Deacy; Mark M. Bissell; Marshall Clark; Mary Emmett; Mary Morrison Saltz; Matvey B. Palchuk; Melissa A. Haendel; Meredith Adams; Meredith Temple-O'Connor; Michael G. Kurilla; Michele Morris; Nabeel Qureshi; Nasia Safdar; Nicole Garbarini; Noha Sharafeldin; Ofer Sadan; Patricia A. Francis; Penny Wung Burgoon; Peter Robinson; Philip R. O. Payne; Rafael Fuentes; Randeep Jawa; Rebecca Erwin-Cohen; Rena Patel; Richard A. Moffitt; Richard L. Zhu; Rishi Kamaleswaran; Robert Hurley; Robert T. Miller; Saiju Pyarajan; Sam G. Michael; Samuel Bozzette; Sandeep Mallipattu; Satyanarayana Vedula; Scott Chapman; Shawn T. O'Neil; Soko Setoguchi; Stephanie S. Hong; Steve Johnson; Tellen D. Bennett; Tiffany Callahan; Umit Topaloglu; Usman Sheikh; Valery Gordon; Vignesh Subbian; Warren A. Kibbe; Wenndy Hernandez; Will Beasley; Will Cooper; William Hillegass; Xiaohan Tanner Zhang. The authors have no funding to declare. The analyses described in this publication were conducted under the Data Use Request (DUR) RP-A39709 and Institutional Review Board (IRB)#PRO00042159 with data or tools accessed through the National Center for Advancing Translational Science (NCATS) N3C Data Enclave covid.cd2h.org/enclave and supported by CD2H—The National COVID Cohort Collaborative (N3C) IDeA CTR Collaboration 3U24TR002306-04S2 NCATS U24 TR002306. This research was possible because of the patients whose information is included within the data from participating organizations (covid.cd2h.org/dtas) and the organizations and scientists (covid.cd2h.org/duas) who have contributed to the ongoing development of this community resource (https://doi.org/10.1093/jamia/ocaa196). Details regarding N3C contributions are available at covid.cd

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