key: cord-1045091-st1lud1u authors: nan title: Timing of surgery following SARS‐CoV‐2 infection: an international prospective cohort study date: 2021-03-09 journal: Anaesthesia DOI: 10.1111/anae.15458 sha: 30159d9bf84106a7182abb5b521037beccd1fae9 doc_id: 1045091 cord_uid: st1lud1u Peri‐operative SARS‐CoV‐2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS‐CoV‐2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre‐operative SARS‐CoV‐2 infection were compared with those without previous SARS‐CoV‐2 infection. The primary outcome measure was 30‐day postoperative mortality. Logistic regression models were used to calculate adjusted 30‐day mortality rates stratified by time from diagnosis of SARS‐CoV‐2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre‐operative SARS‐CoV‐2 diagnosis. Adjusted 30‐day mortality in patients without SARS‐CoV‐2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre‐operative SARS‐CoV‐2 diagnosis, mortality was increased in patients having surgery within 0–2 weeks, 3–4 weeks and 5–6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3–4.8), 3.9 (2.6–5.1) and 3.6 (2.0–5.2), respectively). Surgery performed ≥ 7 weeks after SARS‐CoV‐2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9–2.1)). After a ≥ 7 week delay in undertaking surgery following SARS‐CoV‐2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2–8.7) vs. 2.4% (95%CI 1.4–3.4) vs. 1.3% (95%CI 0.6–2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS‐CoV‐2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay. Patients with peri-operative SARS-CoV-2 infection are at increased risk of death and pulmonary complications following surgery [1] [2] [3] until at least 2023 [4, 5] . Thus, pre-operative SARS-CoV-2 infection will remain a challenge for the foreseeable future. limited evidence regarding the optimal timing of surgery following SARS-CoV-2 infection. A prospective cohort study including 122 patients having surgical for cancer, found that surgery ≥ 4 weeks after a positive SARS-CoV-2 swab result was associated with a lower risk of postoperative mortality than earlier surgery [9] . A study in Brazil included 49 patients whose elective surgery was delayed following the pre-operative diagnosis of asymptomatic SARS-CoV-2 infection [10] . These patients subsequently underwent surgery following confirmation of a negative SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) nasopharyngeal swab result. The postoperative complication rates were comparable to patients without SARS-CoV-2 infection. However, the study did not assess the optimal duration of delay following SARS-CoV-2 diagnosis. Clinical guidelines support postponing non-emergency surgery for patients with pre-operative SARS-CoV-2 infection, but specific recommendations are conflicting, recommending delays ranging from 1 to 12 weeks [11] [12] [13] [14] [15] . More granular data are needed urgently to inform clinical practice, especially regarding the significance of symptomatic vs. asymptomatic pre-operative SARS-CoV-2 infection. The aim of this study was to determine the optimal timing of surgery following SARS-CoV-2 infection. This was an international, multicentre, prospective cohort study that included patients undergoing any type of surgery. The study was registered at each participating hospital in accordance with local and national regulations. National income was recorded for each participating country, based on the World Bank's classification [17] . To ensure consistent denominators, missing data were included in the descriptive analyses. Imputation for missing data was not planned as, based on previous studies, a < 2% rate of missing data was anticipated [1, 2] . For categorical variables, a chi-squared test was used to test for differences between groups. To adjust time from SARS-CoV-2 diagnosis to surgery for confounding factors, logistic regression models were fitted with variables selected a priori. These were variables that have previously been identified as independent predictors of mortality in patients with peri-operative SARS-CoV-2 infection A total of 140,231 patients were included across 1674 hospitals in 116 countries (see online Supporting Information, Figure S1 ). Patient and surgical characteristics are shown in Table 1 In the adjusted model, there was a significantly higher risk of 30-day mortality in patients with pre-operative SARS-CoV-2 infection diagnosed 0-2 weeks, 3-4 weeks and 5-6 weeks before surgery compared with patients who did not have a pre-operative SARS-CoV-2 infection (Table 2) . However, there was no significant difference in 30-day postoperative mortality rate in those patients diagnosed with SARS-CoV-2 infection ≥ 7 weeks before surgery ( Table 2) . Adjusted 30-day mortality rate in patients who did not have SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). This was increased in patients who had surgery at 0-2 weeks, 3-4 weeks and at 5-6 weeks after SARS-CoV-2 diagnosis (Fig. 1 ). In patients who had surgery ≥ 7 weeks after SARS-CoV-2 diagnosis, the 30-day mortality rate was similar to patients who did not have SARS-CoV-2 infection (Fig. 1 ). Information, Tables S1-S3) and only patients with RT-PCR nasopharyngeal swab-proven SARS-CoV-2 infection (available in online Supporting Information, Tables S4-S5) showed that patients having surgery 0-2 weeks, 3-4 weeks and 5-6 weeks after SARS-CoV-2 diagnosis had significantly higher adjusted 30-day postoperative mortality rates compared with patients who did not have SARS-CoV-2 infection (Fig. 1) . Patients operated ≥ 7 weeks after SARS-CoV-2 infection had a similar mortality as patients without SARS-CoV-2 infection. These findings were also consistent across sub-groups stratified by age, ASA physical status, and grade and urgency of surgery (Fig. 2) . In the analysis restricted to patients who had experienced pre-operative SARS-CoV-2 infection, patients with ongoing COVID-19 symptoms had a higher adjusted 30-day mortality rate than patients whose symptoms had resolved or who had been asymptomatic (Fig. 3) . Following a ≥ 7-week delay between SARS-CoV-2 infection and surgery, patients with ongoing COVID-19 symptoms had a higher mortality rate than patients whose symptoms had resolved or who had been asymptomatic Table S2 ). 754 Figure 3 Adjusted 30-day postoperative mortality rates in patients with pre-operative SARS-CoV-2 infection stratified by COVID-19 symptoms. The time-periods relate to the timing of surgery following the diagnosis of SARS-CoV-2 infection. Full models and results are available in online Supporting Information (Appendix S1, Tables S7-S8). complications is line with previous work [1] [2] [3] . However, this is the first study to provide robust data regarding the optimal timing for surgery following SARS-CoV-2 infection. The greater granularity in this analysis compared with previous studies [9, 10] has enabled ≥ 7 weeks to be determined as the optimal cut-off. Whilst cut-offs beyond 7 weeks were not formally tested, they are unlikely to offer a significant advantage, since adjusted mortality rates for delay intervals ≥ 7 weeks were broadly stable (see online Supporting Information, Appendix S1). Moreover, overall mortality following a delay of ≥ 7 weeks was similar to mortality in patients who did not have pre-operative SARS- There is a backlog of tens of millions of elective operations that were cancelled during the early phase of the Additional supporting information may be found online via the journal website. Appendix S1. Supporting information. Table S1 . Baseline characteristics and outcomes in elective patients. 758 Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: an international, multicenter, comparative cohort study Perioperative SARS-CoV-2 infections increase mortality, pulmonary complications, and thromboembolic events: a Dutch, multicenter, matched-cohort clinical study Economist Intelligence Unit. Coronavirus vaccines: expect delays. Q1 global forecast 2021. 2021 Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment Prediction of postoperative pulmonary complications in a population-based surgical cohort Development and validation of a score to predict postoperative respiratory failure in a multicentre European cohort: a prospective, observational study Prospective external validation of a predictive score for postoperative pulmonary complications Delaying surgery for patients with a previous SARS-CoV-2 infection Early postoperative outcomes among patients with delayed surgeries after preoperative positive test for SARS-CoV-2: a case-control study from a single institution Recomendaciones para la programaci on de cirug ıa en condiciones de seguridad durante la pandemia COVID-19 Gestione della Fase Pre-Operatoria Delaying surgery for patients recovering from COVID-19: a rapid review commissioned by RACS American Society of Anesthesiologists. ASA and APSF Joint Statement on Elective Surgery and Anesthesia for Patients after COVID-19 Infection. 2020 European Association for Endoscopic Surgery and other Interventional Techniques. Preoperative testing and screening for elective surgery during the pandemic COVID-19 to re-start surgery The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies World Bank Country and Lending Groups Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans Mortality due to cancer treatment delay: systematic review and meta-analysis The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study