Anaesthesia 2021 doi:10.1111/anae.15560 Original Article Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study COVIDSurg Collaborative* and GlobalSurg Collaborative* NIHR Global Health Research Unit on Global Surgery, Birmingham, UK Summary We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household.The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04– 1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. ................................................................................................................................................................. Correspondence to: J. Simoes Email: jfs945@bham.ac.uk Accepted: 14 July 2021 Keywords: SARS-Cov-2; COVID-19; surgery; pathways; pre-operative isolation *Collaborating authors are listed in online Supporting Information Appendix S1. Twitter: @CovidSurg; @GlobalSurg Introduction range of measures are needed to ensure safe surgery, Several strategies have been explored to mitigate against including: COVID-19-free surgical pathways; patient the risk of peri-operative SARS-CoV-2 infection, given the testing for SARS-CoV-2; and delaying surgery in patients high associated rate of postoperative pulmonary with SARS-CoV-2 infection [2, 3]. These measures will still complications and mortality [1]. It has become clear that a be needed despite the roll-out of vaccination © 2021 Association of Anaesthetists 1 Anaesthesia 2021 COVIDSurg Collaborative and GlobalSurg Collaborative | Isolation and postoperative pulmonary complications programmes, which may take years to achieve globally, be surgery or who had a pre-operative SARS-CoV-2 diagnosis less effective against SARS-CoV-2 variants and not achieve were not included. universal implementation [4, 5]. Pre-operative isolation was defined as limitation of Isolation before elective surgery has been social contacts before surgery during which time patients recommended by several national surgical associations [6– stayed at home, avoided public spaces and transport and 8]. This attempts to reduce the risk of asymptomatic carriers did not receive visitors from outside of their household. undergoing surgery, thereby protecting individual patients Patients who were not required to follow any social and reducing in-hospital transmission to other patients and distancing or isolation measures before surgery were staff. It presents potential problems for patients, including: considered to have not been exposed to pre-operative logistical considerations; reducing patient mobility before isolation. The number of days that each patient was major surgery; and social isolation. It also means that last- required to follow the isolation measures was recorded as minute additions to operating theatre lists are less likely, the duration of isolation. Patients were categorised thereby representing an additional potential burden to according to the duration of pre-operative isolation into surgical recovery plans. three groups: up to 3 days; 4 to 7 days; or ≥ 8 days before These limitations would be acceptable if there was clear their planned surgery. evidence of benefit in regard to reduction of postoperative Multiple variables were collected for each patient: age; complications, both related to SARS-CoV-2 and otherwise. sex; ASA physical status; revised cardiac risk index (RCRI); Demonstrating benefit and optimum duration will support presence of respiratory comorbidities; indication for wider rollout of global best practice in elective surgery. surgery; and grade of surgery. Consistent with previous Demonstrating no benefit will allow units to tailor clinical analyses, age was categorised as < 70 or ≥ 70 y. Country- guidance and consider reducing the burden of isolation. level income was defined according to the World Bank index We aimed to determine the impact of pre-operative classification (updated in 2019) based on gross national isolation on postoperative pulmonary complications after income per capita, which determines three incomegroups: elective surgery. high income; upper-middle income; lower-middle income (including patients from both low- and lower- middle Methods income countries). This was a planned sub-study of an international Pre-operative testing was defined as a reverse prospective cohort study of patients undergoing surgery in transcription-polymerase chain reaction (RT-PCR) or hospitals, regardless of local SARS-CoV-2 infection antigen swab test performed within 3 days before surgery. prevalence or isolation policies during at least one 7-day A patient was considered to have undergone surgery in a study period in October 2020. Full methodology has been COVID-19-free surgical pathway if a completely segregated previously reported [9]. Hospitals providing surgical care pathway was provided (including ward, operating theatre for patients under any surgical specialty were eligible to and critical care areas) or the hospital was not admitting participate. Local and national approvals were obtained patients with SARS-CoV-2 infection. If otherwise, the according to local regulations. In the UK, this study was surgical pathway was recorded as non-segregated. registered as clinical audit or service evaluation at each Community SARS-CoV-2 prevalence was determinedfor participating site. Patient consent was obtained when each patient based on the 14-day case notification rate atthe demanded by local governance requirements,which was time of surgery in each participating country. These rates not required in the UK. The study was registered were extracted from the World Health Organization, prospectively and we adhered to the strengthening of the European Centre for Disease Control, US Centre for Disease reporting of observational studies in epidemiology Control and specific national registries via the Our World in (STROBE) statement for observational studies [10]. Data platform [11]. Hospitals were classified as being in All consecutive patients undergoing elective surgery communities with either a low (< 100 cases per 100,000 for any indication were included. Elective surgery was population) or high (≥ 100 cases per 100,000 population) defined as any procedure routinely performed in an SARS-CoV-2 prevalence. operating theatre by a surgeon during a planned admission. The primary outcome of this study was postoperative A list of excluded procedures (such as central line insertion) pulmonary complications, defined as pneumonia, acute was provided to all collaborators (see online Supporting respiratory distress syndrome or unexpected mechanical Information Table S1). Patients undergoing emergency ventilation within 30 days after surgery. The main secondary outcome was 30-day mortality. Other secondary outcomes 2 © 2021 Association of Anaesthetists COVIDSurg Collaborative and GlobalSurg Collaborative | Isolation and postoperative pulmonary complications Anaesthesia 2021 were postoperative SARS-CoV-2 infection and SARS-CoV-2 from high-income countries and 31,226 (32.4%) patients postoperative pulmonary complications within 30 days for from low- and middle-income countries. There were 74,347 surgery. Postoperative SARS-CoV-2 diagnosis was based on (77.1%) patients who underwent surgery for a benign any one of the following criteria: positive RT-PCR condition and 57,079 (59.2%) who underwent major surgery nasopharyngeal swab; positive rapid antigen test; chest (see online Supporting Information Table S2). Overall, computed tomography (CT) scan showing changes 26,948 (27.9%) patients isolated before surgery, 80,200 consistent with pneumonitis secondary to SARS-CoV-2 (83.1%) underwent surgery in a COVID-19-free pathway and infection; positive immunoglobulin-G or immunoglobulin- 67,612 (70.1%) had a pre-operative SARS-CoV-2 test. M antibody test showing active infection; or clinical Patients who isolated before surgery were older, had diagnosis (in the absence of negative RT-PCR swab results). more respiratory comorbidities and higher ASA physical A SARS-CoV-2 postoperative pulmonary complication was status. Pre-operative isolation was more common in areas defined as a pulmonary complication within 30 days of of high SARS-CoV-2 prevalence and in high-income countries surgery in a patient with a postoperative SARS-CoV-2 (Table 1). Patients who isolated pre-operatively were also infection (see online Supporting Information Appendix S2). more frequently tested for SARS-CoV-2 before surgery and Descriptive results are reported with absolute and underwent surgery in a COVID-19-free surgical pathway proportional frequencies. Chi-square tests were used to more often (see online Supporting Information Figure S1). assess unadjusted differences between groups. The overall rate of postoperative pulmonary compli- Multivariable logistic regression models were performed to cations was reported in 1947 (2.0%) and postoperative test for an independent effect of pre-operative isolation on mortality was reported in 648 (0.7%). Of all the postoperative pulmonary complications and mortality, postoperative pulmonary complications, 227 (11.7%) adjusting for patient, surgical and local setting factors. The occurred in patients with a concomitant postoperative results of the adjusted models were summarised using SARS-CoV-2 infection. Compared with patients who had univariable and multivariable OR (95%CI). The statistical isolated before surgery, those who did not isolate had significance threshold used was p < 0.05. Missing data were similar postoperative pulmonary complication rates (2.1% vs reported in all tables and figures. Statistical analyses were 2.0%), lower mortality (0.4% vs 0.8%) and similar SARS-CoV- performed using R studio V 3.6.1 (RStudio, Boston, USA) and 2 infection rates (0.8% vs 0.8%) (Fig. 1). After adjustment for the packages dplyr, tidyverse, gmodels, finalfit, ggplot2 and measured confounders, isolation was associated with higher forestplot. postoperative pulmonary complication rates (adjusted OR The adjusted model for the primary outcome was 1.20, 95%CI 1.05–1.36, p = 0.005) (Fig. 2) but repeated in key sub-groups to determine the effect of pre- with no significant difference in postoperative mortality operative isolation in patients: with high vs low ASA physical (adjusted OR 0.80, 95%CI 0.62–1.02, p = 0.081) (see online status; in settings where pre-operative testing was or was Supporting Information Table S3). not available; where COVID-19-free surgical pathways were Multiple factors were independently associated with or were not established; and where the community SARS- increased postoperative pulmonary complication rates, CoV-2 prevalence was high or low. A sensitivity analysis was including: age > 70 y; male sex; high ASA physical status; performed to explore the impact of duration of isolation on previous respiratory comorbidities; cancer surgery; and postoperative pulmonary complications, comparing major surgical procedures (Fig. 2). Pre-operative testing patients who were isolated for: up to 3 days; 4 to 7 days; was associated with reduced postoperative pulmonary and ≥ 8 days before surgery. An interaction term was used complication rates (OR 0.81,95%CI 0.73–0.89, p <0.001) in adjusted models to account for the fact that isolation was (online Supporting Information Table S4). likely to be less common in low- and middle-income Isolation was not associated with reduced post- countries where there is a proven higher rate of operative pulmonary complications across any of the pre- postoperative complications and mortality [12]. defined sub-groups (Fig. 3). Pre-operative isolation was associated with higher postoperative pulmonary Results complication rates in: patients with ASA physical status 1–2; A total of 96,454 patients were included from 1634 hospitals those undergoing surgery in a high SARS-CoV-2 prevalence in 114 countries. There were 62,839 (65.1%) patients who area; a COVID-19-free pathway; or those who did not underwent surgery in areas with high SARS-CoV-2 undergo pre-operative testing (see online Supporting prevalence and 33,615 (34.9%) patients in areas of low Information Tables S5-S12). prevalence. The study included 65,228 (67.6%) patients © 2021 Association of Anaesthetists 3 Anaesthesia 2021 COVIDSurg Collaborative and GlobalSurg Collaborative | Isolation and postoperative pulmonary complications Table 1 Baseline characteristics of patients who isolated and those who did not isolate before surgery. Values are number (proportion). Proportions are expressed as per column total. No isolation Isolation n = 69,436 n = 26,948 p value Age < 70 y 56,593 (81.5%) 20,129 (74.7%) < 0.001 ≥ 70 y 12842 (18.5%) 6819 (25.3%) Missing 1 0 Sex Female 36,609 (52.7%) 14,370 (53.3%) 0.096 Male 32,824 (47.3%) 12,578 (46.7%) Missing 3 0 ASA physical status 1–2 53,452 (77.0%) 20,275 (75.3%) < 0.001 3–5 15,973 (23.0%) 6654 (24.7%) Missing 11 19 Revised cardiac risk index 0 32,045 (46.2%) 12,401 (46.0%) < 0.001 1–2 35,484 (51.1%) 13,950 (51.8%) ≥3 1881 (2.7%) 583 (2.2%) Missing 26 14 Respiratory comorbidities No 63,651 (91.7%) 23,676 (87.9%) < 0.001 Yes 5740 (8.3%) 3250 (12.1%) Missing 45 22 Surgical indication Benign 54,148 (78.0%) 20,143 (74.8%) < 0.001 Cancer 15,287 (22.0%) 6803 (25.2%) Missing 1 2 Surgery grade Minor/intermediate 27,716 (39.9%) 11,611 (43.1%) < 0.001 Major 41,703 (60.1%) 15,336 (56.9%) Missing 17 1 Surgery area Abdominopelvic 34,202 (50.2%) 12,717 (48.2%) < 0.001 Thoracic 3188 (4.7%) 1317 (5.0%) Head and neck 7276 (10.7%) 2727 (10.3%) Limb 9498 (13.9%) 4533 (17.2%) Other 13,930 (20.5%) 5111 (19.4%) Missing 18 1 Anaesthesia Local 6525 (9.4%) 2789 (10.4%) < 0.001 Regional 11,172 (16.1%) 3492 (13.0%) General 51,712 (74.5%) 20,655 (76.7%) Missing 27 12 SARS-CoV-2 community prevalence Low 30,282 (43.6%) 3326 (12.3%) < 0.001 High 39,154 (56.4%) 23,622 (87.7%) (continued) 4 © 2021 Association of Anaesthetists COVIDSurg Collaborative and GlobalSurg Collaborative | Isolation and postoperative pulmonary complications Anaesthesia 2021 Table 1 (continued) No isolation Isolation n = 69,436 n = 26,948 p value Country income High 42,025 (60.5%) 23,166 (86.0%) < 0.001 Upper 13,192 (19.0%) 2979 (11.1%) middle Low/low- 14,219 (20.5%) 803 (3.0%) middle Figure 1 Flowchart of patient inclusion, with postoperative outcomes by isolation group. SARS-CoV-2 associated postoperative pulmonary complications were defined as the presence of postoperative pulmonary complications (PPC) in patients with a postoperative diagnosis of SARS-CoV-2 infection. Missing data for the presented variables: pre-operative isolation n = 70; postoperative pulmonary complications n = 64; postoperative mortality n = 55. Of patients who isolated before surgery, 6971 (26.0%) Discussion isolated for up to 3 days, 10,691 (39.9%) for 4 to 7 days, and Pre-operative isolation was associated with a small but 9164 (34.2%) for ≥ 8 days (see online Supporting Information clinically important increase in postoperative pulmonary Table S13). Patients isolating for longer durations were complications. A sensitivity analysis looking at the duration progressively older and had a greater comorbid burden, of pre-operative isolation found that patients who isolated including respiratory comorbidities. for longer periods had higher rates of postoperative A duration of isolation of up to 3 days before surgery pulmonary complications. Although there was a difference did not show a difference in postoperative pulmonary in mortality rates, the numbers were small and the complication rates compared with no isolation (OR 0.90, difference was not statistically significant following 95%CI 0.70–1.13, p = 0.377). Patients isolating for longer adjustment. There were no clinically relevant differences in durations had higher rates of postoperative pulmonary SARS-CoV-2 positivity or SARS-CoV-2-related postoperative complications when isolating for 4 to 7 days (OR 1.25,95% pulmonary complication rates. We also showed no benefit CI 1.04–1.48, p = 0.015) and for ≥ 8 days (OR 1.31, 95%CI with pre-operative isolation: in areas of different SARS-CoV-2 1.11–1.55, p = 0.001) (Table 2). community prevalence; when pre-operative testing was © 2021 Association of Anaesthetists 5 Anaesthesia 2021 COVIDSurg Collaborative and GlobalSurg Collaborative | Isolation and postoperative pulmonary complications Figure 2 Multivariable logistic regression model exploring the association between pre-operative isolation and postoperative pulmonary complications, adjusting for patient, surgery and surgical setting factors. Number in dataframe = 96,454; number in model = 96,067; missing = 387; AIC = 16,680.6; C-statistic = 0.784. Full model presented in online Supporting Information Table S4, including an interaction term of isolation and country income. Community prevalence of SARS-CoV-2 was defined as the median 14-day cumulative country case notification rate per 100,000 population during October 2020. Country income groups defined as per the World Bank classification. Figure 3 Forest plot of the adjusted odds ratio (95%CI) for the effect of isolation in postoperative pulmonary complications across patient sub-groups for ASA physical status, pre-operative testing, COVID-19-free pathways and community prevalence. Odds ratios are adjusted for the same variables used in the main model, including an interaction term of isolation and country income. 6 © 2021 Association of Anaesthetists COVIDSurg Collaborative and GlobalSurg Collaborative | Isolation and postoperative pulmonary complications Anaesthesia 2021 Table 2 Multivariable logistic regression model exploring the association between pre-operative isolation length and postop- erative pulmonary complications, adjusting for patient, surgery and surgical setting factors. Community incidence of SARS-CoV- 2 was defined as the median 14-day cumulative country case notification rate per 100,000 population during October 2020. Val- ues are number (proportion). No postoperative Postoperative pulmonary pulmonary Univariable OR Multivariable OR complications complication(s) 95%CI p value 95%CI p value Duration of isolation No isolation 67,993 (98.0%) 1386 (2.0%) Reference – Reference – ≤ 3 days 6877 (98.7%) 91 (1.3%) 0.69 (0.54–0.87) 0.002 0.90 (0.70–1.13) 0.377 4–7 days 10,483 (98.1%) 206 (1.9%) 0.99 (0.83–1.17) 0.887 1.25 (1.04–1.48) 0.015 ≥ 8 days 8910 (97.2%) 252 (2.8%) 1.51 (1.29–1.77) < 0.001 1.31 (1.11–1.55) 0.001 Age < 70 y 75,397 (98.3%) 1328 (1.7%) Reference – Reference – ≥ 70 y 19,045 (96.9%) 619 (3.1%) 1.85 (1.67–2.03) < 0.001 1.22 (1.09–1.36) < 0.001 Sex Female 50,218 (98.5%) 783 (1.5%) Reference – Reference – Male 44,222 (97.4%) 1164 (2.6%) 1.69 (1.54–1.85) <0.001 1.53 (1.39–1.68) < 0.001 ASA physical status 1–2 72,837 (98.8%) 884 (1.2%) Reference – Reference – 3–5 21,566 (95.3%) 1063 (4.7%) 4.06 (3.71–4.45) < 0.001 2.33 (2.09–2.60) < 0.001 Revised cardiac risk index 0 44,029 (99.0%) 425 (1.0%) Reference – Reference – 1–2 48,109 (97.3%) 1314 (2.7%) 2.83 (2.54–3.16) < 0.001 1.52 (1.30–1.77) < 0.001 ≥3 2258 (91.7%) 205 (8.3%) 9.41 (7.91–11.15) < 0.001 2.44 (1.95–3.03) < 0.001 Respiratory comorbidities No 85,760 (98.2%) 1560 (1.8%) Reference – Reference – Yes 8609 (95.7%) 384 (4.3%) 2.45 (2.19–2.74) < 0.001 1.67 (1.48–1.89) < 0.001 Surgical indication Benign 73,141 (98.5%) 1151 (1.5%) Reference – Reference – Cancer 21,299 (96.4%) 796 (3.6%) 2.37 (2.17–2.60) < 0.001 1.70 (1.54–1.88) < 0.001 Surgery grade Minor/intermediate 39,019 (99.2%) 306 (0.8%) Reference – Reference – Major 55,409 (97.1%) 1638 (2.9%) 3.77 (3.34–4.27) < 0.001 2.15 (1.88–2.46) < 0.001 Anaesthesia Local 9261 (99.5%) 48 (0.5%) Reference – Reference – Regional 14,524 (99.0%) 154 (1.0%) 2.05 (1.49–2.86) < 0.001 1.68 (1.20–2.40) 0.003 General 70,620 (97.6%) 1745 (2.4%) 4.77 (3.62–6.44) < 0.001 2.49 (1.86–3.43) < 0.001 Surgical area Abdominopelvic 47,310 (98.1%) 921 (1.9%) Reference – Reference – Thoracic 10,196 (98.4%) 168 (1.6%) 0.85 (0.71–1.00) 0.049 1.20 (0.98–1.45) 0.069 Head and neck 13,883 (98.8%) 167 (1.2%) 0.62 (0.52–0.73) < 0.001 1.08 (0.89–1.30) 0.448 Limb 18,909 (98.8%) 226 (1.2%) 0.61 (0.53–0.71) < 0.001 1.04 (0.87–1.24) 0.671 Other 4129 (89.9%) 462 (10.1%) 5.75 (5.11–6.45) < 0.001 2.73 (2.40–3.10) < 0.001 Pre-operative SARS–CoV–2 testing No test 39,375 (97.8%) 871 (2.2%) Reference – Reference – Test 54,957 (98.1%) 1066 (1.9%) 0.88 (0.80–0.96) 0.004 0.82 (0.74–0.91) < 0.001 (continued) © 2021 Association of Anaesthetists 7 Anaesthesia 2021 COVIDSurg Collaborative and GlobalSurg Collaborative | Isolation and postoperative pulmonary complications Table 2 (continued) No postoperative Postoperative pulmonary pulmonary Univariable OR Multivariable OR complications complication(s) 95%CI p value 95%CI p value Surgical pathway Non-segregated 15,830 (97.8%) 354 (2.2%) Reference – Reference – COVID-19-free 78,559 (98.0%) 1587 (2.0%) 0.90 (0.81–1.02) 0.087 0.99 (0.87–1.12) 0.828 SARS-CoV-2 community prevalence Low 32,876 (97.9%) 698 (2.1%) Reference – Reference – High 61,567 (98.0%) 1249 (2.0%) 0.96 (0.87–1.05) 0.341 1.08 (0.95–1.22) 0.235 Country income* High 64,024 (98.2%) 1190 (1.8%) Reference – Reference – Upper middle 15,740 (97.3%) 438 (2.7%) 1.47 (1.29–1.67) < 0.001 1.99 (1.72–2.29) < 0.001 Lower middle/low 14,679 (97.9%) 319 (2.1%) 1.19 (1.04–1.37) 0.010 2.03 (1.71–2.40) < 0.001 Interaction term Isolated ≤ 3 days, LMIC – – 1.71 (0.59–3.91) 0.256 1.54 (0.53–3.57) 0.366 Isolated ≤ 3 days, UMIC – – 0.93 (0.41–1.84) 0.847 0.77 (0.34–1.56) 0.505 Isolated 4–7 days, LMIC – – 0.62 (0.28–1.20) 0.197 0.52 (0.23–1.03) 0.087 Isolated 4–7 days, UMIC – – 0.89 (0.63–1.26) 0.531 0.80 (0.55–1.13) 0.212 Isolated ≥ 8 days, LMIC – – 1.23 (0.43–2.76) 0.660 0.82 (0.28–1.89) 0.682 Isolated ≥ 8 days, UMIC – – 1.28 (0.86–1.86) 0.213 0.82 (0.55–1.21) 0.340 *Country income groups defined as per the World Bank classification. LMIC, low-to-middle income country; UMIC, upper-to-middle income country. implemented; or when COVID-19-free surgical pathways of isolation on 30-day mortality cannot be drawn from our were in place. data. There is a known interaction between mortality, failure Although this study did not directly identify causes for to rescue patients from surgical complications and lower- an association between isolation and increased income surgical settings [12, 21]. Although such an postoperative pulmonary complication rates, it provides an interaction is likely to have contributed to this finding, it was opportunity to generate hypotheses. Isolation is associated beyond the scope of this predefined analysis to explore with decreased physical activity, worse nutritional habits further, especially in the context of small event numbers and and higher levels of anxiety and depression [13–16]. These the likelihood of further unmeasured confounders. effects in already vulnerable patients may have contributed However, benefits of pre-operative isolation are not to an increased risk of pulmonary complications. Further, only for the individual patient but also to other patients and there is increasing evidence demonstrating that staff in hospitals who are at risk from asymptomatic carriers prehabilitation before surgery improves patient recovery of SARS-CoV-2. Although this study included all patients and outcomes [17–19]. It is possible that isolation may have, operated upon during the same week in each specialty and therefore, conversely led to patient deconditioning and hospital, it was not designed to capture cross infection in functional decline [20], adversely influencing patient surgical wards, as only individual level outcomes were outcomes. Although patients who isolated were slightly collected. Social isolation can have a system-wide benefit in more comorbid than those who did not, these findings preventing the admission of patients incubating SARS-CoV- remained present after adjustment. Our evidence suggests 2 that was not captured by our study. Further, a systems risk that removing pre-operative isolation strategies is unlikely of undiagnosed SARS-CoV-2 infection in institutions that to lead to worse postoperative outcomes for patients, but operate COVID-19-free surgical pathways is the risk of institutions should monitor their postoperative pulmonary individual patients affecting these pathways and other complication rates as strategies evolve. patients within them. For example, a COVID-19-free ward Whereas unadjusted mortality rates appeared lower for could become a COVID-19-positive ward if one patient tests patients who isolated, this did not remain significant after positive, thereby undermining the entire pathway. Finally, adjustment. Combined with small numbers, a clear benefit symptomatic screening and pre-operative testing are likely 8 © 2021 Association of Anaesthetists COVIDSurg Collaborative and GlobalSurg Collaborative | Isolation and postoperative pulmonary complications Anaesthesia 2021 to remain key components of elective surgery admissions increased risk in postoperative pulmonary complications. processes to prevent nosocomial infection by SARS-CoV-2 Longer periods of isolation did not reduce the risk of [22]. postoperative pulmonary complications. These findings Our study has limitations. Firstly, postoperative SARS- have implications for the global provision of elective CoV-2 rates were similar in both groups, suggesting that surgery. pre-operative isolation is not effective in reducing nosocomial SARS-CoV-2 infection. However, we did not Acknowledgements include patients who isolated and then tested positive who This trial was registered at clinicaltrials.gov (NCT04509986). may have had their surgery delayed or cancelled. This might Funding was provided by the: National Institute for Health have underestimated the SARS-CoV-2 incidence and Research (NIHR) Global Health Research Unit; Association of postoperative pulmonary complication rates in patientswho Coloproctology of Great Britain and Ireland; Bowel and did not isolate. Secondly, although a definition of pre- Cancer Research; Bowel Disease Research Foundation; operative isolation was stated in the study protocol, slightly Association of Upper Gastrointestinal Surgeons; British different strategies could have been reported as pre- Association of Surgical Oncology; British Gynaecological operative isolation. Patient compliance with isolation Cancer Society; European Society of Coloproctology; recommendations was not measured, which could have Medtronic, NIHR Academy; Sarcoma UK; Urology contributed to the underestimation of the benefits of Foundation; Vascular Society for Great Britain and Ireland; isolation. However, the large numbers and heterogeneous and Yorkshire Cancer Research. The views expressed are sites contribute to a pragmatic study design and those of the authors and not necessarily those of the funding generalisability of our conclusions. Thirdly, although partners. No other competing interests declared. adjustment was performed for all the available variables, there might be residual confounding that affected results. References We addressed this through multiple sensitivity analyses, in 1. COVIDSurg Collaborative. Mortality and pulmonary complications in patients undergoing surgery with which the findings were consistent. 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Going forward, webstspa/wp-content/uploads/2020/05/recomendacoes-de- anestesiologia-obstetrica_final_04052020.pdf (accessed 29/ research to target other causes of postoperative 06/2021). pneumonias is needed, since endemic pathogens may be 9. COVIDSurg Collaborative, GlobalSurg Collaborative. Timing of surgery following SARS-CoV-2 infection: an international the more common organisms. prospective cohort study. Anaesthesia 2021; 76: 748–58. This study demonstrates that patient isolation before 10. Elm EV, Altman DG, Egger M, et al. Strengthening the reporting elective surgery might be associated with a small of observational studies in epidemiology (STROBE) statement: © 2021 Association of Anaesthetists 9 Anaesthesia 2021 COVIDSurg Collaborative and GlobalSurg Collaborative | Isolation and postoperative pulmonary complications guidelines for reporting observational studies. British Medical Supporting Information Journal 2007; 335: 806. 11. Our World in Data. Coronavirus Pandemic (COVID-19). https:// Additional supporting information may be found online via ourworldindata.org/coronavirus (accessed 01/06/2021). the journal website. 12. GlobalSurg Collaborative and National Institute for Health Figure S1. Rates of pre-operative testing, COVID-free Research Global Health Research Unit on Global Surgery. Global variation in postoperative mortality and complications surgical pathways and community incidence by isolation after cancer surgery: a multicentre, prospective cohort study in group. 82 countries. Lancet 2021; 397: 387–97. Table S1. List of excluded procedures. 13. Schuch FB, Bulzing RA, Meyer J, et al. Associations of moderate to vigorous physical activity and sedentary behavior with Table S2. Detailed list of included procedures. depressive and anxiety symptoms in self-isolating people Table S3. Multivariable logistic regression model during the COVID-19 pandemic: A cross-sectional survey in Brazil. Psychiatry Research 2020; 292: 113339. exploring the association between pre-operative isolation 14. Meyer J, McDowell C, Lansing J, et al. Changes in physical and postoperative mortality, adjusting for patient, surgery activity and sedentary behavior in response to COVID-19 and and surgical setting factors. their associations with mental health in 3052 US adults. International Journal of Environmental Research and Public Table S4. Full multivariable logistic regression model Health 2020; 17: 6469. exploring the association between pre-operative isolation 15. Pierce M, McManus S, Hope H, et al. Mental health responses to and postoperative pulmonary complications, in all patients the COVID-19 pandemic: a latent class trajectory analysis using longitudinal UK data. Lancet Psychiatry 2021; 8: 610–9. included in the study. 16. Ammar A, Trabelsi K, Brach M, et al. Effects of home Table S5. Multivariable logistic regression model confinement on mental health and lifestyle behaviours during the COVID-19 outbreak: insights from the ECLB-COVID19 exploring the association between pre-operative isolation multicentre study. Biology of Sport 2020; 38: 9–21. and postoperative pulmonary complications, only for 17. Treanor C, Kyaw T, Donnelly M. An international review and patients with mild comorbidities (ASA physical status 1–2). meta-analysis of prehabilitation compared to usual care for cancer patients. Journal of Cancer Survivorship 2018; 12: 64–73. Table S6. Multivariable logistic regression model 18. Faithfull S, Turner L, Poole K, et al. Prehabilitation for adults exploring the association between pre-operative isolation diagnosed with cancer: a systematic review of long-term and postoperative pulmonary complications, only for physical function, nutrition and patient-reported outcomes. European Journal of Cancer Care 2019; 28: e13023. patients with major comorbidities (ASA physical status 3–5). 19. Kamarajah SK, Brunded J, Weblin J, Tan BHL. Critical appraisal Table S7. Multivariable logistic regression model on the impact of preoperative rehabilitation and outcomes exploring the association between pre-operative isolation after major abdominal and cardiothoracic surgery: a systematic review and meta-analysis. Surgery 2020; 167: 540–9. and postoperative pulmonary complications, only for 20. Silver JK, Sell N, Parangi S, Qadan M. Prehabilitation may patients who were tested pre-operatively. influence surgical morbidity and mortality during and after the covid-19 pandemic. May 2020. https://blogs.bmj.com/bmj/ Table S8. Multivariable logistic regression model 2020/05/21/prehabilitation-may-influence-surgical-morbidity- exploring the association between pre-operative isolation and-mortality-during-and-after-the-covid-19-pandemic and postoperative pulmonary complications, only for (accessed 10/07/2021). 21. GlobalSurg-Collaborative. Mortality of emergency abdominal patients who were not tested pre-operatively. surgery in high-, middle- and low-income countries. British Table S9. Multivariable logistic regression model Journal of Surgery 2016; 103: 971–88. exploring the association between pre-operative isolation 22. El-Boghdadly K, Cook TM, Goodacre T, et al. SARS-CoV-2 infection, COVID-19 and timing of elective surgery: a and postoperative pulmonary complications, only for multidisciplinary consensus statement on behalf of the patients who underwent surgery in a COVID-19-free Association of Anaesthetists, the Centre for Peri-operative Care, the Federation of Surgical Specialty Associations, the pathway. Royal College of Anaesthetists and the Royal College of Table S10. Multivariable logistic regression model Surgeons of England. Anaesthesia 2021; 76: 940–6. exploring the association between pre-operative isolation 23. Mohanan M, Malani A, Krishnan K, et al. Prevalence of SARS- CoV-2 in Karnataka, India. Journal of the American Medical and postoperative pulmonary complications, only for Association 2021; 325: 1001–3. patients who underwent surgery in a non-segregated 24. Mwananyanda L, Gill CJ, MacLeod W, et al. Covid-19 deaths in pathway. Africa: prospective systematic postmortem surveillance study. British Medical Journal 2021; 372: 334. Table S11. Multivariable logistic regression model 25. Verduzco-Gutierrez M, Bean AC, Tenforde AS, et al. How to exploring the association between pre-operative isolation conduct an outpatient telemedicine rehabilitation or prehabilitation visit. Physical Medicine and Rehabilitation 2020; and postoperative pulmonary complications, only for 12: 714–20. patients who underwent surgery in a community with high 26. Sell NM, Silver JK, Rando S, et al. Prehabilitation telemedicine in SARS-CoV-2 prevalence. neoadjuvant surgical oncology patients during the novel COVID-19 coronavirus pandemic. Annals of Surgery 2020; 272: Table S12. Multivariable logistic regression model e81–e83. exploring the association between pre-operative isolation 10 © 2021 Association of Anaesthetists COVIDSurg Collaborative and GlobalSurg Collaborative | Isolation and postoperative pulmonary complications Anaesthesia 2021 and postoperative pulmonary complications, only for Appendix S1. COVIDSurg Collaborative and GlobalSurg patients who underwent surgery in a community with low Collaborative authors (all PubMed indexed co- authors). SARS-CoV-2 prevalence. Appendix S2. Study definitions. Table S13. Baseline characteristics of patients by status and length of pre-operative isolation. © 2021 Association of Anaesthetists 11 Figure S1: Rates of preoperative testing, COVID-free surgical pathways and community prevalence by isolation group. 50.0% 79.3% (n=34643) (n=21349) 81.0% 88.9% (n=56226) (n=23945) 56.4% 87.7% (n=39154) (n=23622) Plot displays proportion of patients being tested preoperatively, undergoing surgery in a COIVD-free surgical pathway and in a high SARS-CoV-2 prevalence areas, by isolation group. Missing data for the presented variables: preoperative isolation n=70, preoperative testing n=121, surgical pathway (COVID-free versus non-segregated) n=60. Community prevalence of SARS-CoV-2 was defined as the median 14-day cumulative country case notification rate per 100,000 population during October 2020. Table S1: List of excluded procedures Specialty Excluded procedures Abdominal surgery Ascitic drain (drainage of peritoneal cavity) Endoscopic ultrasound Laparoscopic ultrasound Breast surgery Breast biopsy Cardiac surgery Insertion of cardiac pacemaker Percutaneous coronary intervention Transluminal balloon angioplasty of coronary artery Colorectal surgery Colonoscopy (diagnostic or therapeutic) Flexible sigmoidoscopy (diagnostic or therapeutic) Proctoscopy (diagnostic or therapeutic) Dental procedures Implantation of tooth Insertion of dental prosthesis Orthodontic operations Restoration of tooth Extraction of tooth Gynaecology Cervical biopsy Colposcopy (diagnostic or therapeutic) Obstetrics Any vaginal delivery (normal delivery, breech delivery, forceps delivery, vacuum delivery) Surgical termination of pregnancy Ophthalmology Removal of foreign body from cornea Orthopaedics Bone biopsy Injection in to joint Muscle biopsy Otolaryngology Laryngoscopy (diagnostic or therapeutic) Nasendoscopy (diagnostic) Packing of cavity of nose Thoracic surgery Bronchoscopy (diagnostic) Insertion of chest drain Upper gastrointestinal surgery Endoscopic retrograde cholangiopancreatography (diagnostic or therpaeutic) Liver biopsy Oesophago-gastro-duodenoscopy (diagnostic or therapeutic) Urology Bladder biopsy Extracorporeal shock-wave lithotripsy Flexible cystoscopy (diagnostic) Percutaneous nephrostomy Vascular surgery Endovenous laser treatment for varicose veins Insertion or removal of dialysis catheter injection into varicose vein of leg Transluminal (endovascular) procedures on arteries (diagnostic or therapeutic), including with open cut down to the artery Transluminal (endovascular) procedures on veins (diagnostic or therapeutic) Insertion or removal of Hickmann line Other Insertion of central venous catheter/ line Insertion of chest drain Lumbar (spinal) puncture Percutaneous tracheostomy Skin biopsy (including shave biopsy of skin) Therapeutic epidural injection Vacuum dressing Table S2: Detailed list of included procedures ANATOMICAL AREA - surgical procedure Number of patients (%) BRAIN & SKULL - any other procedures not listed 191 (0.2) BRAIN & SKULL - brain - any operation on the meninges 107 (0.1) BRAIN & SKULL - brain - any operation on ventricles of brain 73 (0.1) BRAIN & SKULL - brain - biopsy of lesion of tissue of brain 125 (0.1) BRAIN & SKULL - brain - clipping of intracranial aneurysm 29 (0.0) BRAIN & SKULL - brain - deep brain stimulation 93 (0.1) BRAIN & SKULL - brain - drainage of lesion of tissue of brain 44 (0.0) BRAIN & SKULL - brain - excision of tissue of brain 473 (0.5) BRAIN & SKULL - brain - intracranial pressure 21 (0.0) BRAIN & SKULL - insertion of ventriculoperitoneal shunt 178 (0.2) BRAIN & SKULL - skull - craniectomy 37 (0.0) BRAIN & SKULL - skull - craniotomy 311 (0.3) BRAIN & SKULL - skull - drainage of extradural space 7 (0.0) BRAIN & SKULL - skull - drainage of subdural space (subdural haemorrhage; SDH) 31 (0.0) BRAIN & SKULL - skull - repair of cranium 99 (0.1) BRAIN & SKULL - skull - repair of dura 15 (0.0) BREAST - .any other procedures not listed 189 (0.2) BREAST - augmentation or reduction 241 (0.3) BREAST - axilla - axillary clearance (lymphadenectomy) 163 (0.2) BREAST - axilla - sential node biopsy 123 (0.1) BREAST - immediate reconstruction - implant/ LD/ DIEP 265 (0.3) BREAST - incision and drainage of breast abscess 40 (0.0) BREAST - lumpectomy/ wide local excision +/- wire 2005 (2.1) BREAST - mastectomy 1917 (2.0) BREAST - oncoplasty/ mammoplasty 341 (0.4) COLON & RECTUM - .any other procedures not listed 237 (0.2) COLON & RECTUM - abdominoperineal resection (APR; APE) 283 (0.3) COLON & RECTUM - anterior resection (LAR) 821 (0.9) COLON & RECTUM - any operation for prolapse of rectum 145 (0.2) COLON & RECTUM - completion proctectomy 70 (0.1) COLON & RECTUM - formation of colostomy (stoma) 283 (0.3) COLON & RECTUM - left hemicolectomy (excision of left hemicolon) 396 (0.4) COLON & RECTUM - panproctocolectomy (total excision of colon and rectum) 57 (0.1) COLON & RECTUM - parastomal hernia repair 28 (0.0) COLON & RECTUM - proctology - any other proctology (pilonidal sinus; fistula-in-ano) 1941 (2.0) COLON & RECTUM - proctology - excision of lesion of anus 308 (0.3) COLON & RECTUM - proctology - haemorrhoidopexy (hemorrhoidopexy) 121 (0.1) COLON & RECTUM - proctology- haemorrhoidectomy (haemorrhoidectomy; excision of haemorrhoid) 771 (0.8) COLON & RECTUM - refashioning or resiting of colostomy (stoma) 64 (0.1) COLON & RECTUM - reversal of colostomy (colostomy closure; stoma) 490 (0.5) COLON & RECTUM - right hemicolectomy (excision of right hemicolon) 1052 (1.1) COLON & RECTUM - sigmoid colectomy (Hartmanns procedure; excision of sigmoid colon) 466 (0.5) COLON & RECTUM - subtotal colectomy 108 (0.1) COLON & RECTUM - surgery for anorectal malformations (pull- through; posterior sagital anorectoplasty; Hirschsprung's disease) 52 (0.1) COLON & RECTUM - total colectomy (total excision of colon) 90 (0.1) COLON & RECTUM - transanal endoscopic microsurgery (TEMS) 115 (0.1) COLON & RECTUM - transanal total mesorectal excision (taTME) 54 (0.1) COLON & RECTUM - transverse colectomy (excision of transverse colon) 49 (0.1) DENTAL - .any other dental procedure not separately listed (note non-surgical extraction of teeth excluded) 51 (0.1) DENTAL - any procedure on gingiva (gum) 17 (0.0) DENTAL - excision of dental lesion of jaw 68 (0.1) DENTAL - orthodontic procedures (tooth; teeth) 45 (0.0) DENTAL - restoration of tooth (teeth) 27 (0.0) DENTAL - surgical tooth extraction 143 (0.1) EMERGENCY SURGERY - abdominal packing 5 (0.0) EMERGENCY SURGERY - any other procedures not listed 7 (0.0) EMERGENCY SURGERY - drainage of haematoma 13 (0.0) EMERGENCY SURGERY - neck wound exploration 3 (0.0) EMERGENCY SURGERY - peri-anal/ pilonidal abscess drainage (incision and drainage; I&D) 188 (0.2) EMERGENCY SURGERY - superficial abscess drainage - non-anorectal (incision and drainage; I&D) 129 (0.1) EMERGENCY SURGERY - trauma laparotomy 13 (0.0) EMERGENCY SURGERY - wound exploration & washout (debridement) 140 (0.1) ENDOCRINE - adrenals - .any other procedures not listed 8 (0.0) ENDOCRINE - adrenals - adrenalectomy (excision of adrenal gland) 159 (0.2) ENDOCRINE - parathyroid - .any other procedures not listed 7 (0.0) ENDOCRINE - parathyroid - parathyroidectomy (excision of parathyroid gland) 369 (0.4) ENDOCRINE - pituitary - excision of pituitary gland 32 (0.0) ENDOCRINE - thymus - excision of thymus gland 33 (0.0) ENDOCRINE - thyroid - .any other procedures not listed 97 (0.1) ENDOCRINE - thyroid - thyroidectomy (excision of thyroid gland) 2039 (2.1) EYES - .any other procedure not separately listed 669 (0.7) EYES - corneal surgery 17 (0.0) EYES - correction of deformity of eyelid 177 (0.2) EYES - excision of lesion of eyelid 123 (0.1) EYES - extracapsular cataract extraction 24 (0.0) EYES - glaucoma surgery 18 (0.0) EYES - operations on iris 21 (0.0) EYES - operations on retina 206 (0.2) EYES - operations on vitreous body 351 (0.4) EYES - phacoemulsification (cataract surgery) 2666 (2.8) EYES - pterygium surgery 44 (0.0) EYES - stabismus surgery 71 (0.1) FEMALE REPRODUCTIVE ORGANS - abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) 147 (0.2) FEMALE REPRODUCTIVE ORGANS - ablation or excision of intra-abdominal endometriosis 193 (0.2) FEMALE REPRODUCTIVE ORGANS - any other operation not listed 232 (0.2) FEMALE REPRODUCTIVE ORGANS - dilatation and curettage 127 (0.1) FEMALE REPRODUCTIVE ORGANS - evacuation of retained products of pregnancy 187 (0.2) FEMALE REPRODUCTIVE ORGANS - fallopian tubes - female sterilisation 144 (0.1) FEMALE REPRODUCTIVE ORGANS - fallopian tubes - salpingectomy (excision of fallopian tube; ectopic) 153 (0.2) FEMALE REPRODUCTIVE ORGANS - hysteroscopy + insertion / removal of contraceptive implant 49 (0.1) FEMALE REPRODUCTIVE ORGANS - hysteroscopy + intervention 193 (0.2) FEMALE REPRODUCTIVE ORGANS - hysteroscopy + polypectomy / biopsy 203 (0.2) FEMALE REPRODUCTIVE ORGANS - laparoscopic procedures for ovarian cysts other than oophorectomy 393 (0.4) FEMALE REPRODUCTIVE ORGANS - oophorectomy - unilateral/ bilateral (excision of ovary/ ovaries) 170 (0.2) FEMALE REPRODUCTIVE ORGANS - open procedures for ovarian cysts other than oophorectomy 11 (0.0) FEMALE REPRODUCTIVE ORGANS - ovarian cystectomy 75 (0.1) FEMALE REPRODUCTIVE ORGANS - ovarian detorsion 1 (0.0) FEMALE REPRODUCTIVE ORGANS - ovaries - other 19 (0.0) FEMALE REPRODUCTIVE ORGANS - perineum - any procedures on female perineum 88 (0.1) FEMALE REPRODUCTIVE ORGANS - salpingo-oophorectomy - unilateral/ bilateral (excision of ovary/ ovaries and fallopian tubes) 349 (0.4) FEMALE REPRODUCTIVE ORGANS - uterus - abdominal hysterectomy (excision of uterus) 1777 (1.8) FEMALE REPRODUCTIVE ORGANS - uterus - any other procedures not listed 162 (0.2) FEMALE REPRODUCTIVE ORGANS - uterus - excision of uterus (trachelectomy; cervicectomy) 302 (0.3) FEMALE REPRODUCTIVE ORGANS - uterus - partial excision of uterus (including myomectomy) 419 (0.4) FEMALE REPRODUCTIVE ORGANS - uterus - repair of uterus 180 (0.2) FEMALE REPRODUCTIVE ORGANS - uterus - vaginal hysterectomy (excision of uterus) 391 (0.4) FEMALE REPRODUCTIVE ORGANS - vagina - .any other procedures not listed 254 (0.3) FEMALE REPRODUCTIVE ORGANS - vagina - excision of vagina 29 (0.0) FEMALE REPRODUCTIVE ORGANS - vagina - repair of vaginal prolapse 233 (0.2) FEMALE REPRODUCTIVE ORGANS - vulva - excision of vulva 136 (0.1) GALLBLADDER & BILIARY TREE - .any other procedure not separately listed 103 (0.1) GALLBLADDER & BILIARY TREE - bilio-intestinal diversion 85 (0.1) GALLBLADDER & BILIARY TREE - cholecystectomy 6069 (6.3) GENERAL SURGERY - appendicectomy (appendectomy; excision of appendix) 259 (0.3) GENERAL SURGERY - diagnostic laparoscopy +/- washout or drainage 506 (0.5) GENERAL SURGERY - diagnostic laparotomy +/- washout or drainage 235 (0.2) GENERAL SURGERY - laparoscopic adhesiolysis 75 (0.1) GENERAL SURGERY - laparotomy + adhesiolysis 90 (0.1) HEAD & NECK - any other procedures not listed 285 (0.3) HEAD & NECK - ear - attachment of hearing prosthesis 41 (0.0) HEAD & NECK - ear - drainage of middle ear 101 (0.1) HEAD & NECK - ear - exenteration of mastoid air cells 92 (0.1) HEAD & NECK - ear - other procedures on mastoid 84 (0.1) HEAD & NECK - ear - procedures on the external auditory canal 49 (0.1) HEAD & NECK - ear - procedures on cochlear 99 (0.1) HEAD & NECK - ear - procedures on inner ear 23 (0.0) HEAD & NECK - ear - procedures on middle ear 222 (0.2) HEAD & NECK - ear - procedures on the external ear 150 (0.2) HEAD & NECK - ear - repair of eardrum 139 (0.1) HEAD & NECK - excision of adenoids 217 (0.2) HEAD & NECK - larynx - .any MAJOR procedures not separately listed 111 (0.1) HEAD & NECK - larynx - .any MINOR procedures not separately listed 371 (0.4) HEAD & NECK - larynx - excision of larynx (laryngectomy) 89 (0.1) HEAD & NECK - lip - any procedures on the lips 79 (0.1) HEAD & NECK - mandible - any other procedure 252 (0.3) HEAD & NECK - mandible - orthognathic surgery (jaw) 92 (0.1) HEAD & NECK - mandible - reduction and/or fixation of mandible 72 (0.1) HEAD & NECK - maxilla - partial excision of bone of face 139 (0.1) HEAD & NECK - microlaryngoscopy 23 (0.0) HEAD & NECK - mouth - any other procedures on the mouth 134 (0.1) HEAD & NECK - mouth - any procedures on the palate 92 (0.1) HEAD & NECK - mouth - drainage extra-oral abscess 10 (0.0) HEAD & NECK - mouth - drainage intra-oral abscess 12 (0.0) HEAD & NECK - mouth - orofacial cleft surgery 125 (0.1) HEAD & NECK - mouth - reconstruction of mouth 40 (0.0) HEAD & NECK - mouth - removal of lesion of mouth 151 (0.2) HEAD & NECK - nasendoscopy + intervention 21 (0.0) HEAD & NECK - neck - radical neck dissection 98 (0.1) HEAD & NECK - neck - selective neck dissection 261 (0.3) HEAD & NECK - neck - thyroglossal duct cyst surgery 12 (0.0) HEAD & NECK - nose - any other procedure on nose 577 (0.6) HEAD & NECK - nose - closed reduction nasal fracture 29 (0.0) HEAD & NECK - nose - endoscopic sinus surgery 243 (0.3) HEAD & NECK - nose - operations on septum of nose 682 (0.7) HEAD & NECK - nose - other endoscopic surgery 40 (0.0) HEAD & NECK - nose - surgical arrest of bleeding from internal nose 7 (0.0) HEAD & NECK - orbit - exploration +/- repair 83 (0.1) HEAD & NECK - pharynx - any procedures other than excision 98 (0.1) HEAD & NECK - pharynx - excision of pharynx (pharyngectomy) 29 (0.0) HEAD & NECK - repair fractured zygoma 46 (0.0) HEAD & NECK - repair soft tissue of head and neck 40 (0.0) HEAD & NECK - salivary gland/ duct - any other procedure on the salivary gland or duct 46 (0.0) HEAD & NECK - salivary gland/ duct - excision of parotid gland 256 (0.3) HEAD & NECK - salivary gland/ duct - excision of submandibular/sublingual gland 77 (0.1) HEAD & NECK - skin - excisional of lesion of skin of head or neck 282 (0.3) HEAD & NECK - submental mandibulectomy 29 (0.0) HEAD & NECK - surgical tracheostomy (note: percutaneous tracheostomy excluded) 106 (0.1) HEAD & NECK - tongue - .any other procedures on the tongue 71 (0.1) HEAD & NECK - tongue - partial glossectomy 131 (0.1) HEAD & NECK - tongue - tongue tie division (lingual frenectomy) 33 (0.0) HEAD & NECK - tonsils - operation on tonsils ther than tonsillectomy 38 (0.0) HEAD & NECK - tonsils - tonsillectomy (excision of tonsil) 739 (0.8) HEART (CARDIAC) - any other procedures not listed 278 (0.3) HEART (CARDIAC) - aortic root/ascending aorta surgery 37 (0.0) HEART (CARDIAC) - aortic valve surgery (AVR; valvular) 582 (0.6) HEART (CARDIAC) - atrial septal defect repair (ASD) 41 (0.0) HEART (CARDIAC) - coronary artery bypass graft (CABG) 812 (0.8) HEART (CARDIAC) - heart transplant 2 (0.0) HEART (CARDIAC) - insertion of pacemaker 15 (0.0) HEART (CARDIAC) - mitral valve surgery (valvular) 319 (0.3) HEART (CARDIAC) - surgery on any other valve than aortic/mitral valves (valvular) 61 (0.1) HEART (CARDIAC) - ventricular septal defect repair (VSD) 45 (0.0) HERNIA - abdominal wall reconstruction (component separation) 269 (0.3) HERNIA - any hernia repair not separately listed (herniorrhaphy; hernioplasty) 366 (0.4) HERNIA - femoral hernia repair (herniorrhaphy; hernioplasty) 97 (0.1) HERNIA - incisional hernia repair (herniorrhaphy; hernioplasty) 910 (0.9) HERNIA - inguinal hernia repair (herniorrhaphy; hernioplasty) 4565 (4.7) HERNIA - umbilical hernia repair (herniorrhaphy; hernioplasty) 1197 (1.2) HERNIA - ventral / Spigelian / epigastric hernia repair (herniorrhaphy; hernioplasty) 102 (0.1) KIDNEY - any other procedures not listed 84 (0.1) KIDNEY - nephrectomy (excision of kidney) 751 (0.8) KIDNEY - percutaneous nephrolithotomy (PCNL; stone; calculus) 271 (0.3) KIDNEY - pyeloplasty 110 (0.1) KIDNEY - transplantation of kidney 128 (0.1) LIMB - any operation on bursa (joint) 44 (0.0) LIMB - any operation on ligament 102 (0.1) LIMB - any operation on nerve 64 (0.1) LIMB - any operation on tendon 254 (0.3) LIMB - excision of ganglion 118 (0.1) LIMB - lower limb 207 (0.2) LIMB - lower limb - .any other procedure repair not separately listed (keywords: orthopaedics) 624 (0.6) LIMB - lower limb - ACL repair 28 (0.0) LIMB - lower limb - amputation of foot 50 (0.1) LIMB - lower limb - amputation of leg 143 (0.1) LIMB - lower limb - amputation of toe 102 (0.1) LIMB - lower limb - ankle replacement 35 (0.0) LIMB - lower limb - any other operation on toe 290 (0.3) LIMB - lower limb - arthroscopy of joint other than knee - diagnostic (keywords: orthopaedic; orthopedic) 46 (0.0) LIMB - lower limb - arthroscopy of joint other than knee - therapeutic (keywords: orthopaedic; orthopedic) 159 (0.2) LIMB - lower limb - arthroscopy of knee - diagnostic (keywords: orthopaedic; orthopedic) 92 (0.1) LIMB - lower limb - arthroscopy of knee - therapeutic (keywords: orthopaedic; orthopedic) 783 (0.8) LIMB - lower limb - bone lengthening 30 (0.0) LIMB - lower limb - closed reduction of dislocation of joint 22 (0.0) LIMB - lower limb - closed reduction, wire fixation 37 (0.0) LIMB - lower limb - debridement and irrigation of joint 72 (0.1) LIMB - lower limb - debridement of diabetic foot 50 (0.1) LIMB - lower limb - fasciotomy 12 (0.0) LIMB - lower limb - joint fusion 129 (0.1) LIMB - lower limb - knee replacement (keywords: orthopaedic; orthopedic) 1510 (1.6) LIMB - lower limb - manipulation under anaesthetic (any fracture) (MUA) 12 (0.0) LIMB - lower limb - open reduction, wire fixation (k-wire; wire) 154 (0.2) LIMB - lower limb - osteotomy and fixation (scarf osteotomy) 189 (0.2) LIMB - lower limb - reconstruction of wound (including skin graft, local, regional or free flap) 209 (0.2) LIMB - lower limb - removal of implant 590 (0.6) LIMB - lower limb - revascularisation of lower limb 46 (0.0) LIMB - lower limb - revision of total hip replacement 176 (0.2) LIMB - lower limb - total hip replacement 1159 (1.2) LIMB - lower limb - wound debridement 235 (0.2) LIMB - Lower limb fracture - cannulated screws for proximal femoral fracture 34 (0.0) LIMB - lower limb fracture - closed reduction and external fixation 53 (0.1) LIMB - lower limb fracture - closed reduction and internal fixation 133 (0.1) LIMB - lower limb fracture - closed reduction of fracture, no fixation 13 (0.0) LIMB - lower limb fracture - dynamic hip screw (DHS) 64 (0.1) LIMB - lower limb fracture - FEMUR - open reduction and intramedullary fixation 264 (0.3) LIMB - lower limb fracture - FOOT - open reduction and intramedullary fixation 3 (0.0) LIMB - lower limb fracture - open reduction, no fixation 22 (0.0) LIMB - lower limb fracture - partial hip replacement (hemiarthroplasty) 90 (0.1) LIMB - lower limb fracture - TIBIA - open reduction and intramedullary fixation 235 (0.2) LIMB - muscle - any other procedure on muscle 39 (0.0) LIMB - muscle - muscle excision 46 (0.0) LIMB - upper limb - amputation of hand 16 (0.0) LIMB - upper limb - .any other procedure repair not separately listed 397 (0.4) LIMB - upper limb - amputation of arm 17 (0.0) LIMB - upper limb - amputation of finger 55 (0.1) LIMB - upper limb - arthroscopy of joint other than knee - diagnostic 46 (0.0) LIMB - upper limb - arthroscopy of joint other than knee - therapeutic 392 (0.4) LIMB - upper limb - carpal tunnel release 517 (0.5) LIMB - upper limb - closed reduction of dislocation of joint 9 (0.0) LIMB - upper limb - closed reduction, wire fixation (k-wire; wire) 112 (0.1) LIMB - upper limb - cubital / carapal tunnel release 21 (0.0) LIMB - upper limb - debridement and irrigation of joint 36 (0.0) LIMB - upper limb - Dupuytren's disease / trigger finger surgery 86 (0.1) LIMB - upper limb - elbow replacement 22 (0.0) LIMB - upper limb - fasciotomy 63 (0.1) LIMB - upper limb - injection into joint 26 (0.0) LIMB - upper limb - joint fusion 53 (0.1) LIMB - upper limb - manipulation of hand fracture 62 (0.1) LIMB - upper limb - manipulation under anaesthetic (any fracture) (MUA) 5 (0.0) LIMB - upper limb - nail bed surgery 16 (0.0) LIMB - upper limb - open reduction, wire fixation (k-wire; wire) 242 (0.3) LIMB - upper limb - osteotomy and fixation 97 (0.1) LIMB - upper limb - percutaneous pinning of hand fracture 27 (0.0) LIMB - upper limb - removal of implant 360 (0.4) LIMB - upper limb - repair of ligament 144 (0.1) LIMB - upper limb - repair of nerve 53 (0.1) LIMB - upper limb - repair of tendon 174 (0.2) LIMB - upper limb - revascularisation or replantation of amputated part 9 (0.0) LIMB - upper limb - shoulder replacement 170 (0.2) LIMB - upper limb - trapeziectomy 32 (0.0) LIMB - upper limb - washout and closure of wound 69 (0.1) LIMB - upper limb - washout of joint 12 (0.0) LIMB - upper limb fracture - closed reduction and external fixation 29 (0.0) LIMB - upper limb fracture - closed reduction and internal fixation 145 (0.2) LIMB - upper limb fracture - closed reduction of fracture, no fixation 16 (0.0) LIMB - upper limb fracture - open reduction and intramedullary fixation 376 (0.4) LIMB - upper limb fracture - open reduction, no fixation 29 (0.0) LIVER - anatomical liver resection (hepatic resection) 265 (0.3) LIVER - any other procedures not listed 144 (0.1) LIVER - non-anatomical liver resection (hepatic resection) 228 (0.2) LIVER - partial hepatectomy 207 (0.2) LIVER - transplantation of liver 52 (0.1) LOWER LIMB - joint aspiration 7 (0.0) LUNG & AIRWAYS - anatomical/non-anatomical lung resection (excision of a lung lobe) 966 (1.0) LUNG & AIRWAYS - any other procedures not listed 338 (0.4) LUNG & AIRWAYS - bronchoscopy, therapeutic 77 (0.1) LUNG & AIRWAYS - chest exploration for trauma 27 (0.0) LUNG & AIRWAYS - mediastinal mass resection 80 (0.1) LUNG & AIRWAYS - mediastinoscopy 81 (0.1) LUNG & AIRWAYS - operations on bronchus 14 (0.0) LUNG & AIRWAYS - pneumonectomy (excision of whole lung) 34 (0.0) LUNG & AIRWAYS - radical surgery for pleural mesothelioma 5 (0.0) LUNG & AIRWAYS - resection of chest wall tumour +/- lung resection 115 (0.1) LUNG & AIRWAYS - transplantation of lung 11 (0.0) MALE REPRODUCTIVE ORGANS - any operation on epididymis 25 (0.0) MALE REPRODUCTIVE ORGANS - any operation on varicocoele 114 (0.1) MALE REPRODUCTIVE ORGANS - any other procedures not listed 82 (0.1) MALE REPRODUCTIVE ORGANS - any procedure on scrotum 71 (0.1) MALE REPRODUCTIVE ORGANS - circumcision 403 (0.4) MALE REPRODUCTIVE ORGANS - male sterilisation 50 (0.1) MALE REPRODUCTIVE ORGANS - penis - any operation on penis 325 (0.3) MALE REPRODUCTIVE ORGANS - penis - any operations on the penis 162 (0.2) MALE REPRODUCTIVE ORGANS - penis - hypospadia repair 159 (0.2) MALE REPRODUCTIVE ORGANS - prostate - prostatectomy 657 (0.7) MALE REPRODUCTIVE ORGANS - prostate biopsy 47 (0.0) MALE REPRODUCTIVE ORGANS - scrotal / testicular exploration 3 (0.0) MALE REPRODUCTIVE ORGANS - spermatic cord - any operation on spermatic cord 18 (0.0) MALE REPRODUCTIVE ORGANS - testis - any procedure other than orchidectomy 112 (0.1) MALE REPRODUCTIVE ORGANS - testis - hydrocele surgery 126 (0.1) MALE REPRODUCTIVE ORGANS - testis - orchidectomy (excision of testis) 188 (0.2) MALE REPRODUCTIVE ORGANS - testis - orchiopexy 374 (0.4) OBSTETRICS - any other procedures not listed 54 (0.1) OBSTETRICS - Caesarean section 3121 (3.2) OBSTETRICS - evacuation of contents of uterus / manual removal of placenta (MROP) 133 (0.1) OBSTETRICS - repair of obstetric laceration (3rd/4th degree) 5 (0.0) OESOPHAGUS & STOMACH - Heller myotomy 49 (0.1) OESOPHAGUS & STOMACH - nissens fundoplication (anti-reflux surgery) 273 (0.3) OESOPHAGUS & STOMACH - oesophagus - any other procedure 101 (0.1) OESOPHAGUS & STOMACH - oesophagus - oesophagectomy 172 (0.2) OESOPHAGUS & STOMACH - oesophagus - oesophagogastrectomy (excision of oesophagus and stomach) 52 (0.1) OESOPHAGUS & STOMACH - revision of antireflux operation 19 (0.0) OESOPHAGUS & STOMACH - stomach - any other procedure 86 (0.1) OESOPHAGUS & STOMACH - stomach - feeding gastrostomy 155 (0.2) OESOPHAGUS & STOMACH - stomach - gastrectomy (excision of stomach) 566 (0.6) OESOPHAGUS & STOMACH - stomach - gastric band insertion (obesity surgery) 59 (0.1) OESOPHAGUS & STOMACH - stomach - gastric bypass, roux en y / single anastomosis gastric bypass (obesity surgery) 570 (0.6) OESOPHAGUS & STOMACH - stomach - pyloroplasty 18 (0.0) OESOPHAGUS & STOMACH - stomach - repair of perforated peptic ulcer (gastric) 5 (0.0) OESOPHAGUS & STOMACH - stomach - sleeve gastrectomy (obesity surgery) 762 (0.8) OTHER - block dissection of lymph nodes 136 (0.1) OTHER - Excision of lipoma 534 (0.6) OTHER - excision of rib 1 (0.0) OTHER - Extraction of foreign body 84 (0.1) OTHER - hyperthermic intraperitoneal chemotherapy (HIPEC) 82 (0.1) OTHER - lymph node biopsy 416 (0.4) OTHER - multiorgan resection (sarcoma; including pelvic exenteration) 149 (0.2) OTHER - Operation on Germ cell tumour 3 (0.0) OTHER - repair of diaphragmatic hernia 117 (0.1) OTHER - skin - suture of skin of head or neck 35 (0.0) OTHER - skin - suture of skin other than head or neck 60 (0.1) PANCREAS - any other procedure not separately listed 53 (0.1) PANCREAS - distal pancreatectomy (excision of pancreas) 162 (0.2) PANCREAS - pancreaticoduodenectomy (Whipple) 441 (0.5) PANCREAS - total pancreatectomy (excision of pancreas) 40 (0.0) PLASTICS - abdominoplasty 117 (0.1) PLASTICS - any other procedure not separately listed 269 (0.3) PLASTICS - burns - debridement, excision or dressing 153 (0.2) PLASTICS - burns - reconstruction 81 (0.1) PLASTICS - free flap 23 (0.0) PLASTICS - liposuction 77 (0.1) PLASTICS - local flap 27 (0.0) PLASTICS - paediatric - any operation 106 (0.1) PLASTICS - regional lymphadenectomy for skin cancer 43 (0.0) PLASTICS - sentinel lymph node biopsy for skin cancer 70 (0.1) PLASTICS - Skin - excision of benign skin lesion 898 (0.9) PLASTICS - Skin - excision of malignant skin cancer 654 (0.7) PLASTICS - Skin - excision of malignant skin cancer and reconstruction (any type) 318 (0.3) PLASTICS - Skin - excision of scar 143 (0.1) PLASTICS - skin - excision of sebaceous cyst 34 (0.0) PLASTICS - skin graft 69 (0.1) SARCOMA - Excision of lesion of extremity (major) 58 (0.1) SARCOMA - Excision of lesion of extremity (minor/intermediate) 96 (0.1) SARCOMA - Excision of lesion of posterior peritoneum 84 (0.1) SMALL BOWEL - .any other procedure not separately listed 60 (0.1) SMALL BOWEL - feeding jejunostomy 69 (0.1) SMALL BOWEL - formation of ileostomy (stoma) 83 (0.1) SMALL BOWEL - ileocaecal resection (excision of ileum) 123 (0.1) SMALL BOWEL - refashioning or resiting of ileostomy (stoma) 38 (0.0) SMALL BOWEL - repair of perforated duodenal ulcer (PUD) 3 (0.0) SMALL BOWEL - reversal of ileostomy (ileostomy closure; stoma) 590 (0.6) SMALL BOWEL - small bowel bypass (including gastrojejunostomy) 105 (0.1) SMALL BOWEL - small bowel resection 184 (0.2) SPINE & NERVOUS SYSTEM - any operation on cranial nerves 50 (0.1) SPINE & NERVOUS SYSTEM - any operation on peripheral nerve 100 (0.1) SPINE & NERVOUS SYSTEM - any operation on spinal cord 318 (0.3) SPINE & NERVOUS SYSTEM - any operation on sympathetic nerve 38 (0.0) SPINE & NERVOUS SYSTEM - any other operation on vertebrae 903 (0.9) SPINE & NERVOUS SYSTEM - decompression or excision of intervebral disc 1087 (1.1) SPINE & NERVOUS SYSTEM - laminectomy 2 (0.0) SPLEEN - .any other procedure not separately listed 6 (0.0) SPLEEN - splenectomy 100 (0.1) URINARY TRACT - bladder - .any other procedure not separately listed 456 (0.5) URINARY TRACT - bladder - cystectomy (excision of urinary bladder) 210 (0.2) URINARY TRACT - bladder - transurethral resection of bladder tumour (TURBT) 1074 (1.1) URINARY TRACT - bladder - transurethral resection of the prostate (TURP) 718 (0.7) URINARY TRACT - female incontinence surgery 136 (0.1) URINARY TRACT - flexible cystoscopy + intervention 154 (0.2) URINARY TRACT - lithotripsy 89 (0.1) URINARY TRACT - rigid cystoscopy 105 (0.1) URINARY TRACT - ureter - replantation of ureter 72 (0.1) URINARY TRACT - ureter - uretectomy (excision of ureter) 24 (0.0) URINARY TRACT - ureter - ureteric stent insertion 683 (0.7) URINARY TRACT - ureteroscopy (therapeutic) 703 (0.7) URINARY TRACT - urethra - any procedure 521 (0.5) VASCULAR - .any other procedure not separately listed (artery; vein) 306 (0.3) VASCULAR - bypass of femoral artery 140 (0.1) VASCULAR - bypass of iliac artery 24 (0.0) VASCULAR - carotid endarterectomy 204 (0.2) VASCULAR - embolectomy / thrombectomy 39 (0.0) VASCULAR - femoral artery endarterectomy 83 (0.1) VASCULAR - formation of arterio-venous fistula 336 (0.3) VASCULAR - lower limb - amputation of foot 18 (0.0) VASCULAR - lower limb - amputation of leg 49 (0.1) VASCULAR - lower limb - amputation of toe 46 (0.0) VASCULAR - lower limb - any other operation on toe 14 (0.0) VASCULAR - lower limb - fasciotomy 2 (0.0) VASCULAR - repair of abdominal aorta aneurysm (AAA) 174 (0.2) VASCULAR - repair of femoral artery aneurysm 10 (0.0) VASCULAR - repair of iliac artery aneurysm 16 (0.0) VASCULAR - varicose vein - ligation and stripping 448 (0.5) Table S3: Multivariate logistic regression model exploring the association between preoperative isolation and postoperative mortality, adjusting for patient, surgery and surgical setting factors. Alive Dead OR (univariable) OR (multivariable) No Isolation 68859 (99.2%) 530 (0.8%) - - Isolation Preop Isolation 26822 (99.6%) 118 (0.4%) 0.70 (0.55-0.89, p=0.004) 0.80 (0.62-1.02, p=0.081) <70 years 76350 (99.5%) 383 (0.5%) - - Age ≥70 years 19400 (98.7%) 265 (1.3%) 2.72 (2.32-3.19, p<0.001) 1.69 (1.42-2.02, p<0.001) Female 50734 (99.5%) 270 (0.5%) - - Sex Male 45014 (99.2%) 378 (0.8%) 1.58 (1.35-1.85, p<0.001) 1.31 (1.11-1.54, p=0.001) ASA physical Grades 1-2 73521 (99.7%) 208 (0.3%) - - status Grades 3-5 22190 (98.1%) 440 (1.9%) 7.01 (5.95-8.29, p<0.001) 4.60 (3.79-5.59, p<0.001) Revised Cardiac 0 44349 (99.7%) 112 (0.3%) - - Risk Index 1-2 48982 (99.1%) 443 (0.9%) 3.58 (2.92-4.43, p<0.001) 2.28 (1.76-2.97, p<0.001) ≥3 2370 (96.2%) 93 (3.8%) 15.54 (11.75-20.50, p<0.001) 4.57 (3.23-6.45, p<0.001) No 86786 (99.4%) 541 (0.6%) - - Respiratory comorbidities Yes 8889 (98.8%) 106 (1.2%) 1.91 (1.54-2.35, p<0.001) 1.19 (0.96-1.48, p=0.111) Benign 73981 (99.6%) 321 (0.4%) - - Surgical indication Cancer 21767 (98.5%) 327 (1.5%) 3.46 (2.97-4.04, p<0.001) 2.50 (2.10-2.96, p<0.001) Minor/Intermediate 39202 (99.7%) 127 (0.3%) - - Surgery grade Major 56531 (99.1%) 521 (0.9%) 2.84 (2.35-3.47, p<0.001) 1.57 (1.27-1.95, p<0.001) Local 9280 (99.7%) 31 (0.3%) - - Anaesthesia Regional 14629 (99.7%) 49 (0.3%) 1.00 (0.64-1.59, p=0.991) 0.91 (0.57-1.48, p=0.699) General 71803 (99.2%) 568 (0.8%) 2.37 (1.68-3.47, p<0.001) 1.62 (1.11-2.46, p=0.016) Abdominopelvic 47908 (99.3%) 323 (0.7%) - - Surgery Thoracic 10308 (99.5%) 57 (0.5%) 0.82 (0.61-1.08, p=0.169) 1.43 (1.04-1.95, p=0.024) area Head & Neck 13987 (99.5%) 68 (0.5%) 0.72 (0.55-0.93, p=0.015) 1.70 (1.25-2.29, p=0.001) Limb 19043 (99.5%) 95 (0.5%) 0.74 (0.59-0.93, p=0.010) 1.34 (1.01-1.75, p=0.037) Other 4486 (97.7%) 105 (2.3%) 3.47 (2.77-4.32, p<0.001) 1.52 (1.19-1.93, p=0.001) Preoperative No test 39916 (99.2%) 338 (0.8%) - - Testing Test 55715 (99.4%) 309 (0.6%) 0.65 (0.56-0.76, p<0.001) 0.75 (0.63-0.89, p=0.001) Non-Segregated 16057 (99.2%) 131 (0.8%) - - Surgical Pathway COVID-free 79634 (99.4%) 517 (0.6%) 0.80 (0.66-0.97, p=0.020) 0.88 (0.72-1.08, p=0.199) SARS-CoV-2 Low 33310 (99.2%) 269 (0.8%) - - community prevalence High 62441 (99.4%) 379 (0.6%) 0.75 (0.64-0.88, p<0.001) 1.19 (0.97-1.47, p=0.100) High income 64893 (99.5%) 326 (0.5%) - - Country income Upper middle income 16013 (99.0%) 164 (1.0%) 1.98 (1.60-2.43, p<0.001) 3.12 (2.48-3.92, p<0.001) Lower middle / Low income 14845 (98.9%) 158 (1.1%) 1.90 (1.54-2.33, p<0.001) 4.88 (3.74-6.38, p<0.001) Interaction term Isolation*LMIC - - 1.35 (0.59-2.71, p=0.435) 0.86 (0.37-1.76, p=0.710) Isolation*UMIC - - 0.82 (0.47-1.38, p=0.477) 0.57 (0.32-0.97, p=0.046) Number in dataframe = 96454, Number in model = 96075, Missing = 379, AIC = 6610, C-statistic = 0.852. ASA=American Society of Anaesthesiologists classification. Community prevalence of SARS-CoV-2 was defined as the median 14-day cumulative country case notification rate per 100,000 population during October 2020. Country income groups defined as per the WHO World Bank classification. Table S4: Full multivariate logistic regression model exploring the association between preoperative isolation and postoperative pulmonary complications, in all patients included in the study. No PPC PPC OR (univariable) OR (multivariable) No Isolation 67993 (98.0%) 1386 (2.0%) - - Isolation Preop Isolation 26387 (97.9%) 554 (2.1%) 1.08 (0.96-1.22, p=0.197) 1.20 (1.05-1.36, p=0.005) <70 years 75397 (98.3%) 1328 (1.7%) - - Age ≥70 years 19045 (96.9%) 619 (3.1%) 1.85 (1.67-2.03, p<0.001) 1.22 (1.09-1.36, p<0.001) Female 50218 (98.5%) 783 (1.5%) - - Sex Male 44222 (97.4%) 1164 (2.6%) 1.69 (1.54-1.85, p<0.001) 1.52 (1.38-1.68, p<0.001) ASA physical Grades 1-2 72837 (98.8%) 884 (1.2%) - - status Grades 3-5 21566 (95.3%) 1063 (4.7%) 4.06 (3.71-4.45, p<0.001) 2.32 (2.09-2.59, p<0.001) Revised Cardiac 0 44029 (99.0%) 425 (1.0%) - - Risk Index 1-2 48109 (97.3%) 1314 (2.7%) 2.83 (2.54-3.16, p<0.001) 1.51 (1.30-1.76, p<0.001) ≥3 2258 (91.7%) 205 (8.3%) 9.41 (7.91-11.15, p<0.001) 2.43 (1.95-3.02, p<0.001) No 85760 (98.2%) 1560 (1.8%) - - Respiratory comorbidities Yes 8609 (95.7%) 384 (4.3%) 2.45 (2.19-2.74, p<0.001) 1.69 (1.49-1.90, p<0.001) Benign 73141 (98.5%) 1151 (1.5%) - - Surgical indication Cancer 21299 (96.4%) 796 (3.6%) 2.37 (2.17-2.60, p<0.001) 1.71 (1.55-1.89, p<0.001) Minor/Intermediate 39019 (99.2%) 306 (0.8%) - - Surgery grade Major 55409 (97.1%) 1638 (2.9%) 3.77 (3.34-4.27, p<0.001) 2.15 (1.88-2.46, p<0.001) Local 9261 (99.5%) 48 (0.5%) - - Anaesthesia Regional 14524 (99.0%) 154 (1.0%) 2.05 (1.49-2.86, p<0.001) 1.70 (1.21-2.42, p=0.003) General 70620 (97.6%) 1745 (2.4%) 4.77 (3.62-6.44, p<0.001) 2.52 (1.88-3.47, p<0.001) Abdominopelvic 47310 (98.1%) 921 (1.9%) - - Surgery Thoracic 10196 (98.4%) 168 (1.6%) 0.85 (0.71-1.00, p=0.049) 1.19 (0.98-1.45, p=0.075) area Head & Neck 13883 (98.8%) 167 (1.2%) 0.62 (0.52-0.73, p<0.001) 1.08 (0.89-1.31, p=0.413) Limb 18909 (98.8%) 226 (1.2%) 0.61 (0.53-0.71, p<0.001) 1.05 (0.87-1.25, p=0.621) Other 4129 (89.9%) 462 (10.1%) 5.75 (5.11-6.45, p<0.001) 2.79 (2.45-3.16, p<0.001) Preoperative No test 39375 (97.8%) 871 (2.2%) - - Testing Test 54957 (98.1%) 1066 (1.9%) 0.88 (0.80-0.96, p=0.004) 0.81 (0.73-0.89, p<0.001) Non-Segregated 15830 (97.8%) 354 (2.2%) - - Surgical Pathway COVID-free 78559 (98.0%) 1587 (2.0%) 0.90 (0.81-1.02, p=0.087) 0.99 (0.87-1.12, p=0.842) SARS-CoV-2 Low 32876 (97.9%) 698 (2.1%) - - community prevalence High 61567 (98.0%) 1249 (2.0%) 0.96 (0.87-1.05, p=0.341) 1.08 (0.96-1.22, p=0.224) High income 64024 (98.2%) 1190 (1.8%) - - Country income Upper middle income 15740 (97.3%) 438 (2.7%) 1.47 (1.29-1.67, p<0.001) 1.99 (1.72-2.29, p<0.001) Lower middle / Low inco 14679 (97.9%) 319 (2.1%) 1.19 (1.04-1.37, p=0.010) 2.02 (1.71-2.39, p<0.001) me Interaction term Isolation*LMIC - - 0.99 (0.58-1.57, p=0.955) 0.75 (0.44-1.21, p=0.271) Isolation*UMIC - - 1.11 (0.85-1.44, p=0.424) 0.83 (0.63-1.09, p=0.179) Number in dataframe = 96454, Number in model = 96067, Missing = 387, AIC = 16680.6, C-statistic = 0.784. ASA=American Society of Anaesthesiologists physical status classification. Table S5: Multivariate logistic regression model exploring the association between preoperative isolation and postoperative pulmonary complications, only for patients with mild comorbidities (ASA physical status 1-2). No PPC PPC OR (univariable) OR (multivariable) No Isolation 52770 (98.8%) 630 (1.2%) - - Isolation Preop Isolation 20023 (98.8%) 247 (1.2%) 1.25 (1.03-1.52, p=0.022) 1.36 (1.11-1.66, p=0.003) <70 years 62564 (98.9%) 704 (1.1%) - - Age ≥70 years 10273 (98.3%) 180 (1.7%) 1.56 (1.32-1.83, p<0.001) 1.48 (1.23-1.76, p<0.001) Female 40166 (99.0%) 414 (1.0%) - - Sex Male 32669 (98.6%) 470 (1.4%) 1.40 (1.22-1.59, p<0.001) 1.55 (1.35-1.78, p<0.001) Revised Cardiac 0 38830 (99.2%) 312 (0.8%) - - Risk Index 1-2 33729 (98.4%) 554 (1.6%) 2.04 (1.78-2.35, p<0.001) 1.16 (0.93-1.45, p=0.196) ≥3 259 (93.8%) 17 (6.2%) 8.17 (4.76-13.11, p<0.001) 2.89 (1.61-4.92, p<0.001) No 68256 (98.8%) 801 (1.2%) - - Respiratory comorbidities Yes 4545 (98.2%) 81 (1.8%) 1.52 (1.20-1.90, p<0.001) 1.45 (1.13-1.83, p=0.002) Benign 58470 (99.1%) 521 (0.9%) - - Surgical indication Cancer 14367 (97.5%) 363 (2.5%) 2.84 (2.48-3.24, p<0.001) 2.07 (1.78-2.41, p<0.001) Minor/Intermediate 32447 (99.5%) 157 (0.5%) - - Surgery grade Major 40377 (98.2%) 726 (1.8%) 3.72 (3.13-4.43, p<0.001) 2.55 (2.12-3.09, p<0.001) Local 7371 (99.7%) 21 (0.3%) - - Anaesthesia Regional 12217 (99.1%) 112 (0.9%) 3.22 (2.06-5.27, p<0.001) 2.05 (1.27-3.49, p=0.005) General 53219 (98.6%) 751 (1.4%) 4.95 (3.30-7.90, p<0.001) 2.50 (1.61-4.11, p<0.001) Abdominopelvic 37282 (98.7%) 487 (1.3%) - - Surgery Thoracic 8375 (99.0%) 87 (1.0%) 0.80 (0.63-0.99, p=0.050) 0.92 (0.68-1.23, p=0.570) area Head & Neck 10901 (99.3%) 79 (0.7%) 0.55 (0.43-0.70, p<0.001) 0.83 (0.62-1.10, p=0.197) Limb 14853 (99.2%) 120 (0.8%) 0.62 (0.50-0.75, p<0.001) 0.86 (0.65-1.13, p=0.283) Other 1412 (92.8%) 110 (7.2%) 5.96 (4.80-7.35, p<0.001) 3.70 (2.94-4.61, p<0.001) Preoperative No test 31863 (98.6%) 460 (1.4%) - - Testing Test 40894 (99.0%) 417 (1.0%) 0.71 (0.62-0.81, p<0.001) 0.76 (0.65-0.88, p<0.001) Non-Segregated 10762 (98.8%) 127 (1.2%) - - Surgical Pathway COVID-free 62024 (98.8%) 751 (1.2%) 1.03 (0.85-1.25, p=0.790) 0.94 (0.78-1.14, p=0.524) SARS-CoV-2 Low 27299 (98.5%) 402 (1.5%) - - community prevalence High 45538 (99.0%) 482 (1.0%) 0.72 (0.63-0.82, p<0.001) 1.02 (0.86-1.22, p=0.818) High income 46231 (99.1%) 425 (0.9%) - - Country income Upper middle income 13374 (98.3%) 235 (1.7%) 1.90 (1.56-2.30, p<0.001) 1.88 (1.53-2.31, p<0.001) Lower middle / Low inco 13232 (98.3%) 224 (1.7%) 1.98 (1.64-2.38, p<0.001) 2.24 (1.78-2.81, p<0.001) me Interaction term Isolation*LMIC - - 1.03 (0.55-1.77, p=0.930) 0.75 (0.40-1.31, p=0.336) Isolation*UMIC - - 1.13 (0.78-1.62, p=0.513) 0.93 (0.64-1.34, p=0.686) Number in dataframe = 73778, Number in model = 73495, Missing = 283, AIC = 8736.9, C-statistic = 0.754. ASA=American Society of Anaesthesiologists physical status classification. Table S6: Multivariate logistic regression model exploring the association between preoperative isolation and postoperative pulmonary complications, only for patients with major comorbidities (ASA physical status 3-5). No PPC PPC OR (univariable) OR (multivariable) No Isolation 15212 (95.3%) 756 (4.7%) - - Isolation Preop Isolation 6345 (95.4%) 307 (4.6%) 1.11 (0.96-1.30, p=0.166) 1.12 (0.95-1.31, p=0.174) <70 years 12798 (95.4%) 624 (4.6%) - - Age ≥70 years 8767 (95.2%) 439 (4.8%) 1.03 (0.91-1.16, p=0.676) 1.08 (0.94-1.23, p=0.261) Female 10030 (96.5%) 369 (3.5%) - - Sex Male 11535 (94.3%) 694 (5.7%) 1.64 (1.44-1.86, p<0.001) 1.52 (1.33-1.74, p<0.001) Revised Cardiac 0 5188 (97.9%) 113 (2.1%) - - Risk Index 1-2 14374 (95.0%) 760 (5.0%) 2.43 (2.00-2.98, p<0.001) 1.73 (1.37-2.19, p<0.001) ≥3 1999 (91.4%) 188 (8.6%) 4.32 (3.41-5.50, p<0.001) 2.65 (2.01-3.51, p<0.001) No 17489 (95.8%) 759 (4.2%) - - Respiratory comorbidities Yes 4062 (93.1%) 303 (6.9%) 1.72 (1.50-1.97, p<0.001) 1.77 (1.54-2.04, p<0.001) Benign 14643 (95.9%) 630 (4.1%) - - Surgical indication Cancer 6923 (94.1%) 433 (5.9%) 1.45 (1.28-1.65, p<0.001) 1.39 (1.21-1.59, p<0.001) Minor/Intermediate 6548 (97.8%) 149 (2.2%) - - Surgery grade Major 15016 (94.3%) 912 (5.7%) 2.67 (2.25-3.19, p<0.001) 1.68 (1.39-2.04, p<0.001) Local 1886 (98.6%) 27 (1.4%) - - Anaesthesia Regional 2307 (98.2%) 42 (1.8%) 1.27 (0.79-2.09, p=0.333) 1.13 (0.68-1.90, p=0.633) General 17367 (94.6%) 994 (5.4%) 4.00 (2.78-6.02, p<0.001) 2.68 (1.81-4.12, p<0.001) Abdominopelvic 10022 (95.8%) 434 (4.2%) - - Surgery Thoracic 1797 (95.7%) 81 (4.3%) 1.04 (0.81-1.32, p=0.746) 1.35 (1.04-1.75, p=0.024) area Head & Neck 2981 (97.1%) 88 (2.9%) 0.68 (0.54-0.86, p=0.001) 1.25 (0.96-1.62, p=0.085) Limb 4048 (97.4%) 106 (2.6%) 0.60 (0.49-0.75, p<0.001) 1.07 (0.84-1.36, p=0.572) Other 2716 (88.5%) 352 (11.5%) 2.99 (2.58-3.47, p<0.001) 2.46 (2.10-2.88, p<0.001) Preoperative No test 7497 (94.8%) 411 (5.2%) - - Testing Test 14056 (95.6%) 649 (4.4%) 0.84 (0.74-0.96, p=0.008) 0.86 (0.75-1.00, p=0.043) Non-Segregated 5040 (95.7%) 227 (4.3%) - - Surgical Pathway COVID-free 16523 (95.2%) 836 (4.8%) 1.12 (0.97-1.31, p=0.129) 1.07 (0.91-1.25, p=0.436) SARS-CoV-2 Low 5564 (94.9%) 296 (5.1%) - - community prevalence High 16002 (95.4%) 767 (4.6%) 0.90 (0.79-1.04, p=0.137) 1.15 (0.97-1.37, p=0.106) High income 17754 (95.9%) 765 (4.1%) - - Country income Upper middle income 2365 (92.1%) 203 (7.9%) 2.12 (1.76-2.54, p<0.001) 2.24 (1.83-2.73, p<0.001) Lower middle / Low inco 1447 (93.8%) 95 (6.2%) 1.66 (1.31-2.08, p<0.001) 1.77 (1.34-2.31, p<0.001) me Interaction term Isolation*LMIC - - 0.41 (0.12-1.02, p=0.089) 0.54 (0.16-1.35, p=0.240) Isolation*UMIC - - 0.78 (0.52-1.15, p=0.223) 0.65 (0.43-0.97, p=0.037) Number in dataframe = 22636, Number in model = 22572, Missing = 64, AIC = 7900.4, C-statistic = 0.72. ASA=American Society of Anaesthesiologists physical status classification. Table S7: Multivariate logistic regression model exploring the association between preoperative isolation and postoperative pulmonary complications, only for patients who were tested pre-operatively. No PPC PPC OR (univariable) OR (multivariable) No Isolation 33986 (98.1%) 668 (1.9%) - - Isolation Preop Isolation 20944 (98.1%) 398 (1.9%) 0.98 (0.85-1.13, p=0.759) 1.14 (0.98-1.33, p=0.080) <70 years 43028 (98.4%) 689 (1.6%) - - Age ≥70 years 11929 (96.9%) 377 (3.1%) 1.97 (1.74-2.24, p<0.001) 1.25 (1.08-1.44, p=0.002) Female 29053 (98.7%) 383 (1.3%) - - Sex Male 25902 (97.4%) 683 (2.6%) 2.00 (1.76-2.27, p<0.001) 1.79 (1.57-2.04, p<0.001) ASA physical Grades 1-2 40894 (99.0%) 417 (1.05) - - status Grades 3-5 14056 (95.6%) 649 (4.4%) 4.53 (4.00-5.13, p<0.001) 2.41 (2.08-2.79, p<0.001) Revised Cardiac 0 25013 (99.2%) 204 (0.8%) - - Risk Index 1-2 28488 (97.5%) 743 (2.5%) 3.20 (2.74-3.75, p<0.001) 1.61 (1.29-2.00, p<0.001) ≥3 1450 (92.4%) 119 (7.6%) 10.06 (7.96-12.67, p<0.001) 2.35 (1.74-3.17, p<0.001) Respiratory No 49367 (98.3%) 850 (1.7%) - - comorbidities Yes 5568 (96.3%) 216 (3.7%) 2.25 (1.93-2.62, p<0.001) 1.55 (1.32-1.82, p<0.001) Surgical indication Benign 41922 (98.6%) 606 (1.4%) - - Cancer 13033 (96.6%) 460 (3.4%) 2.44 (2.16-2.76, p<0.001) 1.73 (1.51-1.98, p<0.001) Minor/Intermediate 22127 (99.3%) 145 (0.7%) - - Surgery grade Major 32828 (97.3%) 921 (2.7%) 4.28 (3.60-5.12, p<0.001) 2.34 (1.94-2.83, p<0.001) Local 4485 (99.5%) 21 (0.5%) - - Anaesthesia Regional 7627 (99.2%) 59 (0.8%) 1.65 (1.02-2.78, p=0.049) 1.47 (0.89-2.53, p=0.145) General 42824 (97.7%) 986 (2.3%) 4.92 (3.28-7.83, p<0.001) 2.55 (1.66-4.13, p<0.001) Abdominopelvic 27655 (98.3%) 480 (1.7%) - - Surgery Thoracic 6170 (98.7%) 82 (1.3%) 0.77 (0.60-0.96, p=0.027) 1.22 (0.92-1.59, p=0.161) area Head & Neck 8201 (98.9%) 92 (1.1%) 0.65 (0.51-0.80, p<0.001) 1.30 (0.99-1.68, p=0.053) Limb 10110 (98.9%) 113 (1.1%) 0.64 (0.52-0.79, p<0.001) 1.13 (0.88-1.45, p=0.328) Other 2819 (90.4%) 299 (9.6%) 6.11 (5.26-7.09, p<0.001) 2.84 (2.41-3.34, p<0.001) Non-Segregated 8501 (97.6%) 211 (2.4%) - - Surgical Pathway COVID-free 46444 (98.2%) 855 (1.8%) 0.74 (0.64-0.87, p<0.001) 0.92 (0.78-1.09, p=0.315) SARS-CoV-2 Low 11559 (97.9%) 249 (2.1%) - - community prevalence High 43398 (98.2%) 817 (1.8%) 0.87 (0.76-1.01, p=0.065) 0.98 (0.82-1.18, p=0.836) High income 44833 (98.3%) 796 (1.7%) - - Country income Upper middle income 6054 (97.1%) 181 (2.9%) 1.57 (1.28-1.91, p<0.001) 2.28 (1.82-2.84, p<0.001) Lower middle / Low in come 4070 (97.9%) 89 (2.1%) 1.22 (0.95-1.54, p=0.111) 1.74 (1.29-2.33, p<0.001) Interaction term Isolation*LMIC - - 1.04 (0.51-1.92, p=0.905) 0.92 (0.45-1.71, p=0.798) Isolation*UMIC - - 1.25 (0.88-1.76, p=0.209) 0.89 (0.62-1.27, p=0.528) Number in dataframe = 56049, Number in model = 55932, Missing = 117, AIC = 9187.3, C-statistic = 0.806. ASA=American Society of Anaesthesiologists physical status classification. Table S8: Multivariate logistic regression model exploring the association between preoperative isolation and postoperative pulmonary complications, only for patients who were not tested pre-operatively. No PPC PPC OR (univariable) OR (multivariable) No Isolation 33951 (97.9%) 716 (2.1%) - - Isolation Preop Isolation 5417 (97.2%) 154 (2.8%) 1.58 (1.26-1.96, p<0.001) 1.44 (1.14-1.81, p=0.002) <70 years 32280 (98.1%) 634 (1.9%) - - Age ≥70 years 7094 (96.8%) 237 (3.2%) 1.70 (1.46-1.98, p<0.001) 1.19 (1.00-1.41, p=0.051) Female 21101 (98.2%) 395 (1.8%) - - Sex Male 18273 (97.5%) 476 (2.5%) 1.39 (1.22-1.59, p<0.001) 1.26 (1.10-1.46, p=0.001) ASA physical Grades 1-2 31863 (98.6%) 460 (1.4%) - - status Grades 3-5 7497 (94.8%) 411 (5.2%) 3.80 (3.32-4.35, p<0.001) 2.23 (1.89-2.62, p<0.001) 0 18969 (98.9%) 218 (1.1%) - - Revised Cardiac Risk Index 1-2 19575 (97.2%) 564 (2.8%) 2.51 (2.15-2.94, p<0.001) 1.43 (1.15-1.77, p=0.001) ≥3 807 (90.4%) 86 (9.6%) 9.27 (7.12-11.97, p<0.001) 2.61 (1.88-3.61, p<0.001) Respiratory No 36309 (98.1%) 701 (1.9%) - - comorbidities Yes 3031 (94.8%) 167 (5.2%) 2.85 (2.39-3.38, p<0.001) 1.89 (1.56-2.28, p<0.001) Benign 31137 (98.3%) 537 (1.7%) - - Surgical indication Cancer 8238 (96.1%) 334 (3.9%) 2.35 (2.04-2.70, p<0.001) 1.69 (1.45-1.97, p<0.001) Minor/Intermediate 16851 (99.1%) 159 (0.9%) - - Surgery grade Major 22511 (96.9%) 709 (3.1%) 3.34 (2.82-3.98, p<0.001) 1.95 (1.61-2.36, p<0.001) Local 4772 (99.5%) 26 (0.5%) - - Anaesthesia Regional 6876 (98.7%) 92 (1.3%) 2.46 (1.61-3.88, p<0.001) 1.92 (1.22-3.12, p=0.006) General 27710 (97.4%) 753 (2.6%) 4.99 (3.44-7.57, p<0.001) 2.53 (1.70-3.94, p<0.001) Abdominopelvic 19596 (97.8%) 434 (2.2%) - - Thoracic 4003 (97.9%) 86 (2.1%) 0.97 (0.76-1.22, p=0.799) 1.22 (0.92-1.60, p=0.161) Surgery area Head & Neck 5670 (98.7%) 74 (1.3%) 0.59 (0.46-0.75, p<0.001) 0.92 (0.69-1.21, p=0.545) Limb 8787 (98.7%) 113 (1.3%) 0.58 (0.47-0.71, p<0.001) 0.97 (0.75-1.25, p=0.822) Other 1305 (89.0%) 161 (11.0%) 5.57 (4.60-6.72, p<0.001) 2.68 (2.17-3.29, p<0.001) Non-Segregated 7302 (98.1%) 143 (1.9%) - - Surgical Pathway COVID-free 32052 (97.8%) 728 (2.2%) 1.16 (0.97-1.40, p=0.109) 1.11 (0.92-1.34, p=0.291) SARS-CoV-2 Low 21291 (97.9%) 449 (2.1%) - - community prevalence High 18084 (97.7%) 422 (2.3%) 1.11 (0.97-1.27, p=0.140) 1.18 (1.00-1.39, p=0.049) High income 19121 (98.0%) 390 (2.0%) - - Country income Upper middle income 9662 (97.5%) 251 (2.5%) 1.41 (1.17-1.68, p<0.001) 1.79 (1.48-2.17, p<0.001) Lower middle / Low income 10592 (97.9%) 230 (2.1%) 1.18 (0.99-1.41, p=0.067) 2.13 (1.72-2.63, p<0.001) Interaction term Isolation*LMIC - - 0.72 (0.30-1.49, p=0.424) 0.56 (0.23-1.18, p=0.163) Isolation*UMIC - - 0.70 (0.45-1.06, p=0.103) 0.57 (0.36-0.88, p=0.013) Number in dataframe = 40284, Number in model = 40135, Missing = 149, AIC = 7493.1, C-statistic = 0.759. ASA=American Society of Anaesthesiologists physical status classification. Table S9: Multivariate logistic regression model exploring the association between preoperative isolation and postoperative pulmonary complications, only for patients who underwent surgery in a COVID-free pathway. No PPC PPC OR (univariable) OR (multivariable) No Isolation 55091 (98.1%) 1087 (1.9%) - - Isolation Preop Isolation 23440 (97.9%) 499 (2.1%) 1.19 (1.05-1.36, p=0.008) 1.23 (1.07-1.42, p=0.003) <70 years 62669 (98.3%) 1083 (1.7%) - - Age ≥70 years 15889 (96.9%) 504 (3.1%) 1.84 (1.65-2.04, p<0.001) 1.21 (1.07-1.36, p=0.002) Female 41764 (98.5%) 629 (1.5%) - - Sex Male 36794 (97.5%) 958 (2.5%) 1.73 (1.56-1.91, p<0.001) 1.55 (1.40-1.73, p<0.001) ASA physical Grades 1-2 62024 (98.8%) 751 (1.2%) - - status Grades 3-5 16523 (95.2%) 836 (4.8%) 4.18 (3.78-4.62, p<0.001) 2.25 (2.00-2.54, p<0.001) 0 36300 (99.1%) 339 (0.9%) - - Revised Cardiac Risk Index 1-2 40595 (97.4%) 1085 (2.6%) 2.86 (2.53-3.24, p<0.001) 1.45 (1.22-1.73, p<0.001) ≥3 1639 (91.1%) 160 (8.9%) 10.45 (8.59-12.67, p<0.001) 2.51 (1.95-3.21, p<0.001) Respiratory No 71482 (98.3%) 1266 (1.7%) - - comorbidities Yes 7028 (95.7%) 318 (4.3%) 2.55 (2.25-2.89, p<0.001) 1.76 (1.54-2.01, p<0.001) Benign 60358 (98.5%) 912 (1.5%) - - Surgical indication Cancer 18198 (96.4%) 675 (3.6%) 2.45 (2.22-2.71, p<0.001) 1.75 (1.56-1.95, p<0.001) Minor/Intermediate 33094 (99.3%) 239 (0.7%) - - Surgery grade Major 45450 (97.1%) 1345 (2.9%) 4.10 (3.58-4.72, p<0.001) 2.34 (2.02-2.74, p<0.001) Local 8011 (99.5%) 43 (0.5%) - - Anaesthesia Regional 12222 (98.9%) 130 (1.1%) 1.98 (1.41-2.83, p<0.001) 1.42 (0.99-2.08, p=0.060) General 58300 (97.6%) 1414 (2.4%) 4.52 (3.38-6.22, p<0.001) 2.00 (1.46-2.81, p<0.001) Abdominopelvic 39933 (98.2%) 749 (1.8%) - - Thoracic 8521 (98.4%) 137 (1.6%) 0.86 (0.71-1.03, p=0.100) 1.19 (0.95-1.47, p=0.122) Surgery area Head & Neck 11281 (98.8%) 136 (1.2%) 0.64 (0.53-0.77, p<0.001) 1.12 (0.90-1.38, p=0.304) Limb 15629 (98.9%) 169 (1.1%) 0.58 (0.49-0.68, p<0.001) 0.98 (0.80-1.20, p=0.837) Other 3179 (89.0%) 393 (11.0%) 6.59 (5.80-7.48, p<0.001) 3.10 (2.70-3.56, p<0.001) Preoperative No test 32052 (97.8%) 728 (2.2%) - - Testing Test 46444 (98.2%) 855 (1.8%) 0.81 (0.73-0.90, p<0.001) 0.78 (0.70-0.87, p<0.001) SARS-CoV-2 Low 28704 (97.9%) 628 (2.1%) - - community prevalence High 49855 (98.1%) 959 (1.9%) 0.88 (0.79-0.97, p=0.013) 1.02 (0.90-1.16, p=0.756) High income 52443 (98.3%) 934 (1.7%) - - Country income Upper middle income 14169 (97.4%) 383 (2.6%) 1.55 (1.34-1.79, p<0.001) 1.91 (1.64-2.23, p<0.001) Lower middle / Low income 11947 (97.8%) 270 (2.2%) 1.36 (1.17-1.58, p<0.001) 1.93 (1.61-2.31, p<0.001) Interaction term Isolation*LMIC - - 0.79 (0.44-1.32, p=0.398) 0.69 (0.38-1.16, p=0.190) Isolation*UMIC - - 1.05 (0.80-1.38, p=0.706) 0.84 (0.63-1.11, p=0.225) Number in dataframe = 80200, Number in model = 79941, Missing = 259, AIC = 13550.6, C-statistic = 0.79. ASA=American Society of Anaesthesiologists physical status classification. Table S10: Multivariate logistic regression model exploring the association between preoperative isolation and postoperative pulmonary complications, only for patients who underwent surgery in a non-segregated pathway. No PPC PPC OR (univariable) OR (multivariable) No Isolation 12873 (97.7%) 299 (2.3%) - - Isolation Preop Isolation 2942 (98.2%) 55 (1.8%) 0.75 (0.54-1.02, p=0.080) 0.99 (0.71-1.37, p=0.962) <70 years 12680 (98.1%) 240 (1.9%) - - Age ≥70 years 3150 (96.5%) 114 (3.5%) 1.91 (1.52-2.39, p<0.001) 1.25 (0.98-1.60, p=0.074) Female 8420 (98.2%) 151 (1.8%) - - Sex Male 7409 (97.3%) 203 (2.7%) 1.53 (1.24-1.89, p<0.001) 1.38 (1.11-1.72, p=0.004) ASA physical Grades 1-2 10762 (98.8%) 127 (1.2%) - - status Grades 3-5 5040 (95.7%) 227 (4.3%) 3.82 (3.07-4.77, p<0.001) 2.61 (2.00-3.42, p<0.001) 0 7701 (98.9%) 83 (1.1%) - - Revised Cardiac Risk Index 1-2 7489 (97.1%) 226 (2.9%) 2.80 (2.18-3.63, p<0.001) 1.73 (1.24-2.42, p=0.001) ≥3 618 (93.2%) 45 (6.8%) 6.76 (4.62-9.75, p<0.001) 2.49 (1.54-3.98, p<0.001) Respiratory No 14229 (98.0%) 289 (2.0%) - - comorbidities Yes 1576 (96.0%) 65 (4.0%) 2.03 (1.53-2.65, p<0.001) 1.43 (1.06-1.89, p=0.016) Benign 12734 (98.2%) 233 (1.8%) - - Surgical indication Cancer 3096 (96.2%) 121 (3.8%) 2.14 (1.70-2.66, p<0.001) 1.52 (1.19-1.93, p=0.001) Minor/Intermediate 5900 (98.9%) 66 (1.1%) - - Surgery grade Major 9930 (97.2%) 288 (2.8%) 2.59 (1.99-3.42, p<0.001) 1.55 (1.17-2.07, p=0.003) Local 1247 (99.7%) 4 (0.3%) - - Anaesthesia Regional 2284 (99.1%) 21 (0.9%) 2.87 (1.09-9.84, p=0.054) 3.64 (1.35-12.71, p=0.021) General 12289 (97.4%) 329 (2.6%) 8.35 (3.56-27.03, p<0.001) 6.94 (2.90-22.74, p<0.001) Abdominopelvic 7334 (97.8%) 167 (2.2%) - - Thoracic 1674 (98.2%) 31 (1.8%) 0.81 (0.54-1.18, p=0.295) 1.17 (0.74-1.78, p=0.488) Surgery area Head & Neck 2597 (98.9%) 30 (1.1%) 0.51 (0.34-0.74, p=0.001) 0.89 (0.57-1.35, p=0.584) Limb 3275 (98.3%) 57 (1.7%) 0.76 (0.56-1.03, p=0.083) 1.21 (0.84-1.73, p=0.293) Other 950 (93.2%) 69 (6.8%) 3.19 (2.38-4.24, p<0.001) 1.63 (1.18-2.25, p=0.003) Preoperative No test 7302 (98.1%) 143 (1.9%) - - Testing Test 8501 (97.6%) 211 (2.4%) 1.27 (1.02-1.57, p=0.030) 1.00 (0.78-1.27, p=0.976) SARS-CoV-2 Low 4156 (98.3%) 70 (1.7%) - - community prevalence High 11674 (97.6%) 284 (2.4%) 1.44 (1.12-1.89, p=0.006) 1.75 (1.16-2.73, p=0.010) High income 11565 (97.8%) 256 (2.2%) - - Country income Upper middle income 1548 (96.9%) 49 (3.1%) 1.39 (0.99-1.92, p=0.049) 2.57 (1.76-3.69, p<0.001) Lower middle / Low income 2717 (98.2%) 49 (1.8%) 0.74 (0.53-1.01, p=0.069) 3.29 (1.94-5.62, p<0.001) Interaction term Isolation*LMIC - - 2.90 (0.67-8.60, p=0.090) 1.28 (0.29-3.96, p=0.703) Isolation*UMIC - - 1.00 (0.33-2.48, p=0.999) 0.78 (0.25-1.98, p=0.634) Number in dataframe = 16194, Number in model = 16126, Missing = 68, AIC = 3120.6, C-statistic = 0.766..ASA=American Society of Anaesthesiologists physical status classification. Table S11: Multivariate logistic regression model exploring the association between preoperative isolation and postoperative pulmonary complications, only for patients who underwent surgery in a community with high SARS-CoV-2 prevalence. No PPC PPC OR (univariable) OR (multivariable) No Isolation 38361 (98.0%) 773 (2.0%) - - Isolation Preop Isolation 23149 (98.0%) 470 (2.0%) 1.05 (0.92-1.19, p=0.482) 1.23 (1.08-1.41, p=0.002) <70 years 47044 (98.4%) 769 (1.6%) - - Age ≥70 years 14523 (96.8%) 480 (3.2%) 2.02 (1.80-2.27, p<0.001) 1.26 (1.11-1.43, p<0.001) Female 32844 (98.5%) 493 (1.55) - - Sex Male 28722 (97.4%) 756 (2.6%) 1.75 (1.56-1.97, p<0.001) 1.57 (1.39-1.77, p<0.001) ASA physical Grades 1-2 45538 (99.0%) 482 (1.0%) - - status Grades 3-5 16002 (95.4%) 767 (4.6%) 4.53 (4.04-5.08, p<0.001) 2.42 (2.11-2.78, p<0.001) 0 28286 (99.2%) 241 (0.8%) - - Revised Cardiac 1-2 31583 (97.4%) 853 (2.6%) 3.17 (2.75-3.67, p<0.001) 1.51 (1.24-1.84, p<0.001) Risk Index ≥3 1666 (91.5%) 155 (8.5%) 10.92 (8.86-13.43, p<0.001) 2.54 (1.94-3.31, p<0.001) Respiratory No 55077 (98.2%) 994 (1.8%) - - comorbidities Yes 6438 (96.2%) 254 (3.8%) 2.19 (1.90-2.51, p<0.001) 1.46 (1.26-1.69, p<0.001) Surgical Benign 47161 (98.5%) 705 (1.5%) - - indication Cancer 14406 (96.4%) 544 (3.6%) 2.53 (2.25-2.83, p<0.001) 1.70 (1.51-1.93, p<0.001) Minor/Intermediate 26126 (99.3%) 191 (0.7%) - - Surgery grade Major 35435 (97.1%) 1058 (2.9%) 4.08 (3.51-4.78, p<0.001) 2.17 (1.84-2.58, p<0.001) Local 6384 (99.6%) 28 (0.4%) - - Anaesthesia Regional 8575 (99.1%) 74 (0.9%) 1.97 (1.29-3.09, p=0.002) 1.70 (1.08-2.76, p=0.025) General 46582 (97.6%) 1147 (2.4%) 5.61 (3.94-8.37, p<0.001) 3.03 (2.06-4.63, p<0.001) Abdominopelvic 30330 (98.1%) 589 (1.9%) - - Thoracic 6555 (98.5%) 97 (1.5%) 0.76 (0.61-0.94, p=0.014) 1.14 (0.88-1.45, p=0.317) Surgery area Head & Neck 9516 (98.9%) 105 (1.1%) 0.57 (0.46-0.70, p<0.001) 1.04 (0.82-1.33, p=0.729) Limb 12223 (98.9%) 134 (1.1%) 0.56 (0.47-0.68, p<0.001) 1.02 (0.81-1.27, p=0.886) Other 2937 (90.1%) 324 (9.9%) 5.68 (4.93-6.53, p<0.001) 2.71 (2.33-3.16, p<0.001) Preoperative No test 18084 (97.7%) 422 (2.3%) - - Testing Test 43398 (98.2%) 817 (1.8%) 0.81 (0.72-0.91, p<0.001) 0.73 (0.64-0.84, p<0.001) SARS-CoV-2 Low 11674 (97.6%) 284 (2.4%) - - community prevalence High 49855 (98.1%) 959 (1.9%) 0.79 (0.69-0.91, p=0.001) 0.96 (0.83-1.11, p=0.546) High income 52041 (98.1%) 1004 (1.9%) - - Country income Upper middle income 8908 (97.6%) 220 (2.4%) 1.26 (1.06-1.50, p=0.009) 1.78 (1.46-2.15, p<0.001) Lower middle / Low inco 618 (96.1%) 25 (3.9%) 2.09 (1.31-3.14, p=0.001) 2.54 (1.57-3.92, p<0.001) me Interaction term Isolation*LMIC - - 1.17 (0.27-3.52, p=0.806) 0.89 (0.20-2.77, p=0.861) Isolation*UMIC - - 0.99 (0.69-1.39, p=0.936) 0.64 (0.44-0.92, p=0.017) Number in dataframe = 62839, Number in model = 62603, Missing = 236, AIC = 10608, C-statistic = 0.801. ASA=American Society of Anaesthesiologists physical status classification. Table S12: Multivariate logistic regression model exploring the association between preoperative isolation and postoperative pulmonary complications, only for patients who underwent surgery in a community with low SARS-CoV-2 prevalence. No PPC PPC OR (univariable) OR (multivariable) No Isolation 29632 (98.0%) 613 (2.0%) - - Isolation Preop Isolation 3238 (97.5%) 84 (2.5%) 1.01 (0.64-1.52, p=0.975) 0.88 (0.55-1.35, p=0.582) <70 years 28353 (98.1%) 559 (1.9%) - - Age ≥70 years 4522 (97.0%) 139 (3.0%) 1.56 (1.29-1.88, p<0.001) 1.09 (0.88-1.35, p=0.399) Female 17374 (98.4%) 290 (1.6%) - - Sex Male 15500 (97.4%) 408 (2.6%) 1.58 (1.36-1.84, p<0.001) 1.44 (1.23-1.69, p<0.001) ASA physical Grades 1-2 27299 (98.5%) 402 (1.5%) - - status Grades 3-5 5564 (94.9%) 296 (5.1%) 3.61 (3.10-4.21, p<0.001) 2.17 (1.80-2.60, p<0.001) 0 15743 (98.8%) 184 (1.2%) - - Revised Cardiac Risk Index 1-2 16526 (97.3%) 461 (2.7%) 2.39 (2.01-2.84, p<0.001) 1.52 (1.19-1.94, p=0.001) ≥3 592 (92.2%) 50 (7.8%) 7.23 (5.18-9.90, p<0.001) 2.11 (1.40-3.13, p<0.001) Respiratory No 30683 (98.2%) 566 (1.8%) - - comorbidities Yes 2171 (94.4%) 130 (5.6%) 3.25 (2.66-3.93, p<0.001) 2.36 (1.90-2.91, p<0.001) Benign 25980 (98.3%) 446 (1.7%) - - Surgical indication Cancer 6893 (96.5%) 252 (3.5%) 2.13 (1.82-2.49, p<0.001) 1.67 (1.40-1.99, p<0.001) Minor/Intermediate 12893 (99.1%) 115 (0.9%) - - Surgery grade Major 19974 (97.2%) 580 (2.8%) 3.26 (2.67-4.00, p<0.001) 2.11 (1.70-2.65, p<0.001) Local 2877 (99.3%) 20 (0.7%) - - Anaesthesia Regional 5949 (98.7%) 80 (1.3%) 1.93 (1.21-3.25, p=0.009) 1.54 (0.93-2.65, p=0.107) General 24038 (97.6%) 598 (2.4%) 3.58 (2.35-5.79, p<0.001) 1.80 (1.15-2.99, p=0.015) Abdominopelvic 16980 (98.1%) 332 (1.9%) - - Thoracic 3641 (98.1%) 71 (1.9%) 1.00 (0.76-1.28, p=0.984) 1.31 (0.95-1.78, p=0.092) Surgery area Head & Neck 4367 (98.6%) 62 (1.4%) 0.73 (0.55-0.95, p=0.022) 1.19 (0.87-1.62, p=0.267) Limb 6686 (98.6%) 92 (1.4%) 0.70 (0.55-0.88, p=0.003) 1.10 (0.82-1.47, p=0.524) Other 1192 (89.6%) 138 (10.4%) 5.92 (4.80-7.27, p<0.001) 2.98 (2.36-3.75, p<0.001) Preoperative No test 21291 (97.9%) 449 (2.1%) - - Testing Test 11559 (97.9%) 249 (2.1%) 1.02 (0.87-1.19, p=0.790) 0.88 (0.74-1.03, p=0.122) SARS-CoV-2 Low 4156 (98.3%) 70 (1.7%) - - community prevalence High 28704 (97.9%) 628 (2.1%) 1.30 (1.02-1.68, p=0.040) 1.14 (0.89-1.48, p=0.322) High income 11983 (98.5%) 186 (1.5%) - - Country income Upper middle income 6832 (96.9%) 218 (3.1%) 1.91 (1.54-2.37, p<0.001) 2.30 (1.83-2.89, p<0.001) Lower middle / Low income 14061 (98.0%) 294 (2.0%) 1.34 (1.11-1.64, p=0.003) 2.10 (1.70-2.59, p<0.001) Interaction term Isolation*LMIC - - 0.99 (0.49-1.94, p=0.983) 0.95 (0.47-1.89, p=0.893) Isolation*UMIC - - 1.54 (0.90-2.69, p=0.121) 1.66 (0.95-2.94, p=0.078) Number in dataframe = 33615, Number in model = 33464, Missing = 151, AIC = 6062.4, C-statistic = 0.758. ASA=American Society of Anaesthesiologists physical status classification. Table S13: Baseline characteristics of patients by status and length of preoperative isolation. Isolated Isolated Isolated No Isolation 8 days p-value** (n=69436) (n=6971) (n=10691) (n=9164) <70 years 56593 (81.5%) 5361 (76.9%) 7988 (74.7%) 6698 (73.1%) <0.001 Age ≥70 years 12842 (18.5%) 1610 (23.1%) 2703 (25.3%) 2466 (26.9%) Missing (n) 1 0 0 0 Female 36609 (52.7%) 3749 (53.8%) 5720 (53.5%) 4849 (52.9%) 0.206 Sex Male 32824 (47.3%) 3222 (46.2%) 4971 (46.5%) 4315 (47.1%) Missing (n) 3 0 0 0 Grades 1-2 53452 (77.0%) 5276 (75.7%) 8248 (77.2%) 6659 (72.7%) <0.001 ASA physical status Grades 3-5 15973 (23.0%) 1691 (24.3%) 2433 (22.8%) 2501 (27.3%) Missing (n) 11 4 10 4 0 32045 (46.2%) 3327 (47.7%) 5051 (47.3%) 3950 (43.1%) <0.001 Revised Cardiac Risk Index 1-2 35484 (51.1%) 3518 (50.5%) 5433 (50.9%) 4951 (54.0%) ≥3 1881 (2.7%) 125 (1.8%) 196 (1.8%) 262 (2.9%) Missing (n) 26 1 11 1 No 63651 (91.7%) 6295 (90.3%) 9371 (87.8%) 7903 (86.3%) <0.001 Respiratory comorbidities Yes 5740 (8.3%) 673 (9.7%) 1305 (12.2%) 1258 (13.7%) Missing (n) 45 3 15 3 Benign 54148 (78.0%) 5519 (79.2%) 8062 (75.4%) 6478 (70.7%) <0.001 Surgical indication Cancer 15287 (22.0%) 1450 (20.8%) 2629 (24.65%) 2686 (29.3%) Missing (n) 1 2 0 0 Minor/Intermediate 27716 (39.9%) 3115 (44.7%) 5201 (48.6%) 3245 (35.4%) <0.001 Surgery grade Major 41703 (60.1%) 3855 (55.3%) 5490 (51.4%) 5919 (64.6%) Missing (n) 17 1 0 0 Abdomen & pelvis 35115 (50.6%) 3661 (52.5%) 5099 (47.7%) 4314 (47.1%) <0.001 Thoracic 3264 (4.7%) 199 (2.9%) 347 (3.2%) 779 (8.5%) Surgery area Head & Neck 7525 (10.8%) 826 (11.9%) 1101 (10.3%) 911 (9.9%) Limb 9509 (13.7%) 964 (13.8%) 1930 (18.1%) 1597 (17.4%) Other 14005 (20.2%) 1320 (18.9%) 2214 (20.7%) 1563 (17.1%) Missing (n) 18 1 0 0 Local 6525 (9.4%) 855 (12.3%) 1316 (12.3%) 610 (6.7%) <0.001 Anaesthesia Regional 11172 (16.1%) 1130 (16.2%) 1198 (11.2%) 1157 (12.6%) General 51712 (74.5%) 4983 (71.5%) 8173 (76.5%) 7395 (80.7%) Missing (n) 27 3 4 2 SARS-CoV-2 community Low 30282 (43.6%) 847 (12.2)% 1080 (10.1%) 1395 (15.2%) <0.001 prevalence High 39154 (56.4%) 6124 (87.8%) 9611 (89.9%) 7769 (84.8%) High income 42025 (60.5%) 6294 (90.3%) 9350 (87.5%) 7401 (80.8%) <0.001 Country income Upper-middle income 13192 (19.0%) 477 (6.8%) 1144 (10.7%) 1358 (14.8%) Low / Low-Middle 14219 (20.5%) 200 (2.9%) 197 (1.8%) 405 (4.4%) Income Percentages expressed of column total. ASA=American Society of Anaesthesiologists classification. ** p-value for Chi-square test