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Original Article
Timing of surgery following SARS-CoV-2 infection:
an international prospective cohort study
COVIDSurg Collaborative* and GlobalSurg Collaborative*
NIHR Global Health Research Unit on Global Surgery, Birmingham, UK
Summary
Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine
the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This
international, multicentre, prospective cohort study included patients undergoing elective or emergency
surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with
those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative
mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time
from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients
(2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2
infection was 1.5% (95%CI 1.4–1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was
increased in patients having surgery within 0–2 weeks, 3–4 weeks and 5–6 weeks of the diagnosis (odds ratio
(95%CI) 4.1 (3.3–4.8), 3.9 (2.6–5.1) and 3.6 (2.0–5.2), respectively). Surgery performed ≥7 weeks after SARS-
CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9–2.1)). After a
≥7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a
higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2–
8.7) vs. 2.4% (95%CI 1.4–3.4) vs. 1.3% (95%CI 0.6–2.0), respectively). Where possible, surgery should be delayed
for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥7 weeks from diagnosis
may benefit from further delay.
.................................................................................................................................................................
Correspondence to: D. Nepogodiev
Email: dnepogodiev@doctors.org.uk
Accepted: 26 February 2021
Keywords: COVID-19; delay; SARS-CoV-2; surgery; timing
This article is accompanied by an editorial by Wijeysundera and Khadaroo, Anaesthesia 2021; 76: 731–5.
*Collaborating authors are listed in online Supporting Information Appendix S2.
Twitter: @CovidSurg; @GlobalSurg
Introduction
Patients with peri-operative SARS-CoV-2 infection are at
increased risk of death and pulmonary complications
following surgery [1–3]. As the cumulative number of
people who have had SARS-CoV-2 infection rises, it will be
increasingly common for patients needing surgery to have
previously had SARS-CoV-2 infection. High-income
countries that are already implementing vaccination
programmes are likely to experience reductions in new
SARS-CoV-2 case infection rates, but these countries
already have tens of millions of SARS-CoV-2 infection
survivors. Most low- and middle-income countries (LMICs)
are likely to have limited access to SARS-CoV-2 vaccines
until at least 2023 [4, 5]. Thus, pre-operative SARS-CoV-2
infection will remain a challenge for the foreseeable future.
Pre-pandemic studies suggest delaying surgery in
patients who have experienced respiratory infection in the
4 weeks preceding surgery [6–8]. However, there is only
748 ©2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use,
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Anaesthesia 2021, 76, 748–758 doi:10.1111/anae.15458
13652044, 2021, 6, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.15458 by INASP - GHANA, Wiley Online Library on [07/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
limited evidence regarding the optimal timing of surgery
following SARS-CoV-2 infection. A prospective cohort study
including 122 patients having surgical for cancer, found that
surgery ≥4 weeks after a positive SARS-CoV-2 swab result
was associated with a lower risk of postoperative mortality
than earlier surgery [9]. A study in Brazil included 49 patients
whose elective surgery was delayed following the
pre-operative diagnosis of asymptomatic SARS-CoV-2
infection [10]. These patients subsequently underwent
surgery following confirmation of a negative SARS-CoV-2
reverse transcription polymerase chain reaction (RT-PCR)
nasopharyngeal swab result. The postoperative
complication rates were comparable to patients without
SARS-CoV-2 infection. However, the study did not assess the
optimal duration of delay following SARS-CoV-2 diagnosis.
Clinical guidelines support postponing non-emergency
surgery for patients with pre-operative SARS-CoV-2
infection, but specific recommendations are conflicting,
recommending delays ranging from 1 to 12 weeks [11–15].
More granular data are needed urgently to inform
clinical practice, especially regarding the significance of
symptomatic vs. asymptomatic pre-operative SARS-CoV-2
infection. The aim of this study was to determine the optimal
timing of surgery following SARS-CoV-2 infection.
Methods
This was an international, multicentre, prospective cohort
study that included patients undergoing any type of
surgery. The study was registered at each participating
hospital in accordance with local and national regulations.
Informed patient consent was taken if required by local or
national regulations. In the UK, this study was registered as
either a clinical audit or service evaluation at each recruiting
institution. Co-investigators were required to confirm that
applicable local and national approvals were in place
before uploading data to the online database. The study
was compliant with guidelines for the reporting of
observational studies [16]. In the conduct of this study, no
changes were made to usual patient care. Routine,
anonymised data were collected using a secure online
database (REDCap, Vanderbilt University, Nashville, TN,USA).
Participating hospitals included consecutive patients
undergoing elective or emergency surgery for any
indication in October 2020. Surgery was defined as any
procedure that is routinely performed in an operating
theatre by a surgeon. A list of excluded procedures was
provided to investigators and is available in online
Supporting Information, Appendix S1. Before commencing
data collection, hospitals defined which surgical specialties
would be participating. Hospitals could choose to collect
data in one or multiple surgical specialties, depending on
local resources. Data could be collected over up to four
blocks of 7 consecutive days (5 October 2020 –1 November
2020).
Patients were classified as having pre-operative SARS-
CoV-2 infection based on any one of the following criteria:
(a) positive RT-PCR nasopharyngeal swab taken before
surgery (even if the result became available after surgery);
(b) positive rapid antigen test performed before surgery; (c)
chest computed tomography (CT) scan performed before
surgery showing changes consistent with pneumonitis
secondary to SARS-CoV-2 infection; (d) positive pre-
operative immunoglobulin G or immunoglobulin M
antibody test; or (e) clinical diagnosis made before surgery
(in the absence of negative RT-PCR swab results). Patients
who were diagnosed with SARS-CoV-2 in the period
between postoperative days 0 and 30 were not studied.
Data were captured on whether patients had experienced
SARS-CoV-2 symptoms, and if so, whether these symptoms
had resolved by the time of surgery. Both respiratory and
non-respiratory symptoms were considered. These were
classified as follows: asymptomatic; symptomatic but
symptoms now resolved; or symptomatic with ongoing
symptoms. Time from the diagnosis of SARS-CoV-2 infection
to day of surgery was collected as a categorical factor and
pre-determined to be analysed in the following categories:
0–2 weeks; 3–4 weeks; 5–6 weeks; and ≥7 weeks.
The primary outcome measure was 30-day
postoperative mortality. Patients were followed-up either in-
person or by telephone, as soon after postoperative day 30
as possible. If it was not possible to complete 30-day follow-
up, in-patient mortality status was recorded. The secondary
outcome measure was the incidence of 30-day
postoperative pulmonary complications. This was a
composite of pneumonia, acute respiratory distress
syndrome (ARDS) and/or unexpected postoperative
ventilation. Full definitions are available in online
Supporting Information, Appendix S1.
The following information was collected for each
patient: age; sex; ASA physical status; revised cardiac risk
index (RCRI); presence of respiratory comorbidities;
indication for surgery; grade of surgery (major/minor); and
surgical urgency (elective/emergency). For data protection
purposes, age was collected as a categorical variable.
Consistent with previous analyses, age was categorised as
<70 years or ≥70 years [1, 2]. American Society of
Anesthesiologists physical status was classified as grades
1–2 or grades 3–5. Patients were recorded as having
respiratory comorbidities if they had a diagnosis of asthma
or chronic obstructive pulmonary disease (COPD).
©2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists. 749
COVIDSurg Collaborative and GlobalSurg Collaborative | Timing of surgery following SARS-CoV-2 infection Anaesthesia 2021, 76, 748–758
13652044, 2021, 6, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.15458 by INASP - GHANA, Wiley Online Library on [07/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Indications for surgery were classified as: benign disease;
cancer; obstetrics; or trauma. Emergency surgery was
defined as surgery on an unplanned admission, and elective
surgery was defined as surgery on a planned admission. The
RCRI calculation and grade of surgery classification are
available in online Supporting Information, Appendix S1.
National income was recorded for each participating
country, based on the World Bank’s classification [17].
To ensure consistent denominators, missing data were
included in the descriptive analyses. Imputation for missing
data was not planned as, based on previous studies, a <2%
rate of missing data was anticipated [1, 2]. For categorical
variables, a chi-squared test was used to test for differences
between groups.
To adjust time from SARS-CoV-2 diagnosis to surgery for
confounding factors, logistic regression models were fitted
with variables selected a priori. These werevariables that have
previously been identified as independent predictors of
mortality in patients with peri-operative SARS-CoV-2 infection
[1] and included: age; sex; ASA physical status; RCRI;
indication for surgery; grade of surgery; urgency of surgery;
presence of respiratory comorbidities; and national income.
Average marginal effects were used to produce adjusted
mortality estimates stratified by time from SARS-CoV-2
diagnosis to surgery. The main modelincluded all patients.
Since delayed surgery is more likely for elective rather
than emergency cases, a sensitivity analysis was performed
including only elective patients. A further sensitivity analysis
was performed including only patients who either had RT-
PCR nasopharyngeal swab-proven pre-operative SARS-
CoV-2 infection or who were not infected. To address
further possible bias, average marginal effects were used to
produce adjusted mortality rates by time from SARS-CoV-2
diagnosis to surgery, stratified by the following pre-selected
variables: age; ASA physical status; urgency of surgery; and
grade of surgery. In order to explore the association of pre-
operative COVID-19 symptoms, a further logistic regression
model was fitted. This included only those patients who had
a pre-operative SARS-CoV-2 diagnosis, since COVID-19
symptom status was not applicable to patients who did not
have pre-operative SARS-CoV-2. These models were fitted
with a primary outcome of 30-day postoperative mortality.
Further models were fitted for the secondary outcome of
the incidence of 30-day postoperative pulmonary
complications. Analyses were completed in Stata, version
15.1 (StataCorp, College Station, TX, USA).
Results
A total of 140,231 patients were included across 1674
hospitals in 116 countries (see online Supporting
Information, Figure S1). Patient and surgical characteristics
are shown in Table 1. Baseline characteristic data for
patients having elective surgery are available in online
Supporting Information (Table S1). In total, 3127 (2.2%)
patients had a pre-operative SARS-CoV-2 diagnosis. The
time from SARS-CoV-2 diagnosis to surgery was 0–2 weeks
in 1138 patients (36.4%), 3–4 weeks in 461 patients
(14.7%), 5–6 weeks in 326 patients (10.4%) and ≥7 weeks
in 1202 patients (38.4%) (Table 1). The majority of patients
were asymptomatic at the time of surgery (either having
Table 1 Baseline characteristics and outcomes for patients undergoing surgery stratified by time from diagnosis of SARS-CoV-2
infection. Values are number (proportion).
No pre-operative
SARS-CoV-2
infection
(n =137,104)
Pre-operative SARS-CoV-2 infection
(by timing of diagnosis prior to surgery)
0–2 weeks
(n =1138)
3–4 weeks
(n =461)
5–6 weeks
(n =326)
≥7 weeks
(n =1202)
Age; years
0–29 31,456 (22.9%) 331 (29.1%) 84 (18.2%) 62 (19.0%) 169 (14.1%)
30–49 37,673 (27.5%) 355 (31.2%) 149 (32.3%) 101 (31.0%) 364 (30.3%)
50–69 41,649 (30.4%) 265 (23.3%) 162 (35.1%) 109 (33.4%) 471 (39.2%)
70–79 17,577 (12.8%) 93 (8.2%) 52 (11.3%) 41 (12.6%) 121 (10.1%)
≥80 8747 (6.4%) 94 (8.3%) 14 (3.0%) 13 (4.0%) 77 (6.4%)
Missing 2 (0%) ––––
Sex
Female 71,375 (52.1%) 610 (53.6%) 220 (47.7%) 177 (54.3%) 634 (52.7%)
Missing 5 (0.0%) ––––
(continued)
750 ©2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.
Anaesthesia 2021, 76, 748–758 COVIDSurgCollaborative and GlobalSurg Collaborative | Timing of surgery following SARS-CoV-2 infection
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Table 1 (continued)
No pre-operative
SARS-CoV-2
infection
(n =137,104)
Pre-operative SARS-CoV-2 infection
(by timing of diagnosis prior to surgery)
0–2 weeks
(n =1138)
3–4 weeks
(n =461)
5–6 weeks
(n =326)
≥7 weeks
(n =1202)
ASA physical status
1–2 103,503 (75.5%) 779 (68.5%) 316 (68.5%) 227 (69.6%) 805 (67.0%)
3–5 33,553 (24.5%) 359 (31.5%) 145 (31.5%) 99 (30.4%) 397 (33.0%)
Missing 48 (0.0%) ––––
Revised cardiac risk index
0 61,379 (44.8%) 433 (38.0%) 176 (38.2%) 123 (37.7%) 446 (37.1%)
1 60,722 (44.3%) 512 (45.0%) 211 (45.8%) 145 (44.5%) 564 (46.9%)
2 11,116 (8.1%) 134 (11.8%) 50 (10.8%) 41 (12.6%) 129 (10.7%)
≥3 3818 (2.8%) 59 (5.2%) 24 (5.2%) 17 (5.2%) 62 (5.2%)
Missing 69 (0.1%) –––1 (0.1%)
Respiratory comorbidities
Yes 12,190 (8.9%) 114 (10.0%) 45 (9.8%) 31 (9.5%) 123 (10.2%)
Missing 111 (0.1%) ––––
Indication for surgery
Benign 86,764 (63.3%) 629 (55.3%) 273 (59.2%) 208 (63.8%) 822 (68.4%)
Cancer 23,612 (17.2%) 100 (8.8%) 117 (25.4%) 73 (22.4%) 234 (19.5%)
Trauma 17,048 (12.4%) 193 (17.0%) 48 (10.4%) 27 (8.3%) 96 (8.0%)
Obstetrics 9673 (7.1%) 216 (19.0%) 23 (5.0%) 18 (5.5%) 50 (4.2%)
Missing 7 (0.0%) ––––
Grade of surgery
Minor 55,301 (40.3%) 400 (35.1%) 131 (28.4%) 122 (37.4%) 462 (38.4%)
Major 81,771 (59.6%) 738 (64.9%) 330 (71.6%) 204 (62.6%) 739 (61.5%)
Missing 32 (0.0%) –––1 (0.1%)
Urgency of surgery
Elective 95,680 (69.8%) 338 (29.7%) 300 (65.1%) 232 (71.2%) 892 (74.2%)
Emergency 41,413 (30.2%) 800 (70.3%) 161 (34.9%) 94 (28.8%) 310 (25.8%)
Missing 11 (0.0%) ––––
COVID-19 symptoms
Asymptomatic –731 (64.2%) 203 (44.0%) 133 (40.8%) 317 (26.4%)
Symptomatic –resolved –124 (10.9%) 193 (41.9%) 163 (50.0%) 820 (68.2%)
Symptomatic –ongoing –277 (24.3%) 65 (14.1%) 28 (8.6%) 56 (4.7%)
Missing –6 (0.5%) - 2 (0.6%) 9 (0.7%)
Country income
High 90,024 (65.7%) 461 (40.5%) 159 (34.5%) 135 (41.4%) 696 (57.9%)
Low/middle 47,080 (34.3%) 677 (59.5%) 302 (65.5%) 191 (58.6%) 506 (42.1%)
30-day postoperative mortality
Yes 1973 (1.4%) 104 (9.1%) 32 (6.9%) 18 (5.5%) 24 (2.0%)
Missing 92 (0.1%) 0 (0.0%) ––2 (0.2%)
30-day postoperative pulmonary complications
Yes 3654 (2.7%) 149 (13.1%) 60 (13.0%) 33 (10.1%) 42 (3.5%)
Missing 105 (0.1%) –––3 (0.2%)
ASA, American Society of Anaesthesiologists.
©2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists. 751
COVIDSurg Collaborative and GlobalSurg Collaborative | Timing of surgery following SARS-CoV-2 infection Anaesthesia 2021, 76, 748–758
13652044, 2021, 6, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.15458 by INASP - GHANA, Wiley Online Library on [07/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
never had symptoms or symptoms having resolved)
(Table 1).
Compared with patients who did not have SARS-CoV-2
infection, patients with pre-operative SARS-CoV-2 infection
were more likely to be ASA physical status 3–5 (24.5% vs.
32.0%; p <0.001), to undergo major surgery (59.6% vs.
64.2%; p <0.001) and to undergo emergency surgery
(30.2% vs. 43.7%; p <0.001). However, there was lower
proportion of patients aged ≥70 years in the cohort with
SARS-CoV-2 infection (16.1% vs. 19.2%; p <0.001).
The overall 30-day postoperative mortality rate was
1.5% (2151/140,231). When stratified by time from
Table 2 Unadjusted and adjusted model for 30-day postoperative mortality in all patients. Values are odds ratio (OR) (95%CI).
Unadjusted Adjusted
OR (95%CI) p value OR (95%CI) p value
Age; years
0–69 Reference –Reference –
≥70 3.12 (2.86–3.40) <0.001 1.72 (1.56–1.90) <0.001
Sex
Female Reference –Reference –
Male 1.41 (1.29–1.53) <0.001 1.09 (0.99–1.19) 0.068
ASA physical status
1–2 Reference –Reference –
3–5 8.96 (8.13–9.87) <0.001 5.32 (4.75–5.96) <0.001
Revised cardiac risk index
0 Reference –Reference –
1 2.33 (2.07–2.61) <0.001 1.43 (1.26–1.63) <0.001
2 6.50 (5.69–7.42) <0.001 1.82 (1.56–2.13) <0.001
≥3 12.81 (11.02–14.89) <0.001 2.78 (2.32–3.32) <0.001
Respiratory comorbidities
No Reference –Reference –
Yes 1.71 (1.51–1.94) <0.001 1.02 (0.89–1.16) 0.767
Indication for surgery
Benign Reference –Reference –
Cancer 1.62 (1.46–1.80) <0.001 1.98 (1.76–2.23) <0.001
Trauma 1.60 (1.43–1.80) <0.001 0.91 (0.79–1.04) 0.173
Obstetrics 0.27 (0.19–0.37) <0.001 0.23 (0.16–0.33) <0.001
Grade of surgery
Minor Reference –Reference –
Major 3.25 (2.90–3.63) <0.001 2.37 (2.11–2.67) <0.001
Urgency of surgery
Elective Reference –Reference –
Emergency 5.60 (5.10–6.15) <0.001 6.48 (5.83–7.21) <0.001
Country income
High Reference –Reference –
Low/middle 1.76 (1.61–1.92) <0.001 2.96 (2.69–3.26) <0.001
Pre-operative SARS-CoV-2 by timing of pre-operative diagnosis
No diagnosis Reference –Reference –
0–2 weeks 6.88 (5.60–8.46) <0.001 3.22 (2.55–4.07) <0.001
3–4 weeks 5.11 (3.56–7.33) <0.001 3.03 (2.03–4.52) <0.001
5–6 weeks 4.00 (2.48–6.45) <0.001 2.78 (1.64–4.71) <0.001
≥7 weeks 1.40 (0.93–2.10) 0.107 1.02 (0.66–1.56) 0.940
ASA, American Society of Anesthesiologists.
752 ©2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.
Anaesthesia 2021, 76, 748–758 COVIDSurgCollaborative and GlobalSurg Collaborative | Timing of surgery following SARS-CoV-2 infection
13652044, 2021, 6, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.15458 by INASP - GHANA, Wiley Online Library on [07/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SARS-CoV-2 diagnosis to surgery, 30-day postoperative
mortality rates were as follows: 9.1% (104/1138) 0–2 weeks;
6.9% (32/461) 3–4 weeks; 5.5% (18/326) 5–6 weeks; and
2.0% (24/1202) at ≥7 weeks. The 30-day mortality rate in
patients who did not have a pre-operative SARS-CoV-2
infection was 1.4% (1973/137,104).
In the adjusted model, there was a significantly higher
risk of 30-day mortality in patients with pre-operative SARS-
CoV-2 infection diagnosed 0–2weeks, 3–4weeks and 5–
6 weeks before surgery compared with patients who did not
have a pre-operative SARS-CoV-2 infection (Table 2).
However, there was no significant difference in 30-day
postoperative mortality rate in those patients diagnosed with
SARS-CoV-2 infection ≥7 weeks before surger y (Table 2).
Adjusted 30-day mortality rate in patients who did
not have SARS-CoV-2 infection was 1.5% (95%CI 1.4–
1.5). This was increased in patients who had surgery at
0–2 weeks, 3–4 weeks and at 5–6 weeks after SARS-CoV-
2 diagnosis (Fig. 1). In patients who had surgery
≥7 weeks after SARS-CoV-2 diagnosis, the 30-day
mortality rate was similar to patients who did not have
SARS-CoV-2 infection (Fig. 1).
Sensitivity analyses including only patients having
elective surgery (available in online Supporting
Information, Tables S1–S3) and only patients with RT-PCR
nasopharyngeal swab-proven SARS-CoV-2 infection
(available in online Supporting Information, Tables S4–S5)
showed that patients having surgery 0–2 weeks, 3–4 weeks
and 5–6 weeks after SARS-CoV-2 diagnosis had
significantly higher adjusted 30-day postoperative
mortality rates compared with patients who did not have
SARS-CoV-2 infection (Fig. 1). Patients operated ≥7 weeks
after SARS-CoV-2 infection had a similar mortality as
patients without SARS-CoV-2 infection. These findings were
also consistent across sub-groups stratified by age, ASA
physical status, and grade and urgency of surgery (Fig. 2).
In the analysis restricted to patients who had
experienced pre-operative SARS-CoV-2 infection, patients
with ongoing COVID-19 symptoms had a higher
adjusted 30-day mortality rate than patients whose
Figure 1 Overall adjusted 30-day postoperative mortality from main analysis and sensitivity analyses for patients having
elective surgery and those patients with a reverse transcription polymerase chain reaction (RT-PCR) nasopharyngeal swab
positive result for SARS-CoV-2. ‘No pre-operative SARS-CoV-2’refers to patients without a diagnosis of SARS-CoV-2 infection.
The time-periods relate to the timing of surgery following the diagnosis of SARS-CoV-2 infection. Sensitivity analysis for RT-PCR
nasopharyngeal swab proven SARS-CoV-2 includes patients who either had RT-PCR nasopharyngeal swab proven SARS-CoV-2
or did not have a SARS-CoV-2 diagnosis; patients with a SARS-CoV-2 diagnosis which was not supported by a RT-PCR
nasopharyngeal swab were not analysed. Full models and results are available in online Supporting Information (Appendix S1,
Tables S3–S4 (elective patients), Tables S5–S6 (swab-proven SARS-CoV-2 infection)).
©2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists. 753
COVIDSurg Collaborative and GlobalSurg Collaborative | Timing of surgery following SARS-CoV-2 infection Anaesthesia 2021, 76, 748–758
13652044, 2021, 6, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.15458 by INASP - GHANA, Wiley Online Library on [07/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
symptoms had resolved or who had been asymptomatic
(Fig. 3). Following a ≥7-week delay between SARS-CoV-2
infection and surgery, patients with ongoing COVID-19
symptoms had a higher mortality rate than patients whose
symptoms had resolved or who had been asymptomatic
(Fig. 3).
Overall, 2.8% (3938/140,231) of patients developed a
postoperative pulmonary complication within 30 days,
including 1.7% (2387/140,231) who developed pneumonia,
0.8% (1100/140,231) who developed ARDS, and 0.8%
(1137/140,231) who had an unexpected requirement for
mechanical ventilation. In both the overall analysis and the
sensitivity analysis for elective surgery, patients who had
surgery 0–2 weeks, 3–4 weeks and 5–6 weeks after SARS-
CoV-2 diagnosis had significantly higher adjusted 30-day
postoperative pulmonary complication rates compared
with patients who did not have SARS-CoV-2 infection.
However, patients who had surgery ≥7 weeks after
SARS-CoV-2 infection had similar rates of postoperative
pulmonary complications as patients without SARS-CoV-2
infection (Fig. 4). Among patients operated ≥7 following
SARS-CoV-2 diagnosis, those with ongoing COVID-19
symptoms were at greatest risk of 30-day postoperative
pulmonary complications (Fig. 5).
Discussion
This study found that patients operated within 6 weeks of
SARS-CoV-2 diagnosis were at an increased risk of 30-day
postoperative mortality and 30-day postoperative
pulmonary complications. These risks decreased to
baseline in patients who underwent surgery ≥7 weeks after
SARS-CoV-2 diagnosis. These findings were consistent
across both low-risk (age <70 years, ASA physical status
1–2, minor surgery) and high-risk (age ≥70 years, ASA
physical status 3–5, major surgery) sub-groups. Therefore,
surgery should be delayed for at least 7 weeks following
SARS-CoV-2 infection to reduce the risk of postoperative
mortality and pulmonary complications. In addition, we have
shown that patients who are still symptomatic ≥7 weeks after
SARS-CoV-2 infection and undergo surgery also have an
increased mortality rate. As such, these patients may benefit
from a further delay until their symptoms resolve.
Our findings that pre-operative SARS-CoV-2 infection
increases the risk of postoperative mortality and pulmonary
Figure 2 Adjusted 30-day postoperative mortality rates from main analysis, stratified by pre-defined sub-groups. ‘No pre-
operative SARS-CoV-2’refers to patients without a diagnosis of SARS-CoV-2 infection. The time-periods relate to the timing of
surgery following the diagnosis of SARS-CoV-2 infection. Full models and results are available in online Supporting Information
(Appendix S1, Table S2).
754 ©2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.
Anaesthesia 2021, 76, 748–758 COVIDSurgCollaborative and GlobalSurg Collaborative | Timing of surgery following SARS-CoV-2 infection
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Figure 3 Adjusted 30-day postoperative mortality rates in patients with pre-operative SARS-CoV-2 infection stratified by
COVID-19 symptoms. The time-periods relate to the timing of surgery following the diagnosis of SARS-CoV-2 infection. Full
models and results are available in online Supporting Information (Appendix S1, Tables S7–S8).
Figure 4 Overall adjusted 30-day postoperative pulmonary complications (PPC) rate from main analysis and sensitivity analysis
for patients having elective surgery. ‘No pre-operative SARS-CoV-2’refers to patients without a diagnosis of SARS-CoV-2
infection. The time-periods relate to the timing of surgery following the diagnosis of SARS-CoV-2 infection. Full models and
results are shown in online Supporting Information (Appendix S1, Tables S9–S10).
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complications is line with previous work [1–3]. However, this
is the first study to provide robust data regarding the
optimal timing for surgery following SARS-CoV-2 infection.
The greater granularity in this analysis compared with
previous studies [9, 10] has enabled ≥7 weeks to be
determined as the optimal cut-off. Whilst cut-offs beyond
7 weeks were not formally tested, they are unlikely to offer a
significant advantage, since adjusted mortality rates for
delay intervals ≥7 weeks were broadly stable (see online
Supporting Information, Appendix S1). Moreover, overall
mortality following a delay of ≥7 weeks was similar to
mortality in patients who did not have pre-operative SARS-
CoV-2 infection.
There is a backlog of tens of millions of elective
operations that were cancelled during the early phase of the
COVID-19 pandemic [18]. This study offers evidence to
support the safe restarting of surgery in the context of a
rapidly increasing number of people who have survived
SARS-CoV-2. This study’sfindings should support informed
shared decision-making by anaesthetists, surgeons and
patients. Decisions should be tailored for each patient, since
the possible advantages of delaying surgery for at least
7 weeks following SARS-CoV-2 diagnosis must be balanced
against the potential risks of delay. For some urgent surgical
procedures, such as resection of advanced tumours [19, 20],
surgeons and patients may decide that the risks of delay are
not justified.
This study has some limitations. Firstly, ascertainment of
SARS-CoV-2 status was based on routine pre-operative
tests. Therefore, it is possible that some patients who had
previously experienced SARS-CoV-2 infection may have
been misclassified as never having been infected. This
Figure 5 Adjusted 30-day postoperative pulmonary complications (PPC) rate in patients with pre-operative SARS-CoV-2
infection stratified by COVID-19 symptoms. The time-periods relate to the timing of surgery following the diagnosis of SARS-
CoV-2 infection. Full model and results are available in online Supporting Information (Appendix S1, Tables S13–S14).
756 ©2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.
Anaesthesia 2021, 76, 748–758 COVIDSurgCollaborative and GlobalSurg Collaborative | Timing of surgery following SARS-CoV-2 infection
13652044, 2021, 6, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.15458 by INASP - GHANA, Wiley Online Library on [07/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
could be particularly likely for patients with asymptomatic
infection who may be less likely to get tested. However, it is
re-assuring that a high proportion of patients in this cohort
were recorded as having had asymptomatic infection,
suggesting that many such cases were detected. Secondly,
this study was based on time from SARS-CoV-2 diagnosis to
surgery, but it is possible that diagnosis was delayed in
some patients, underestimating the true delay from when
patients were infected to the date of surgery. This was
addressed by a sensitivity analysis restricting SARS-CoV-2
diagnosis to those patients who had positive RT-PCR
nasopharyngeal swab results, since swab-based diagnosis
is likely to give the best approximation of date of infection.
The results of this sensitivity analysis were consistent with
the main analyses. Thirdly, it was not possible to conduct
procedure-specific analyses, although exploration of results
stratified by grade (minor vs. major) and urgency of surgery
(elective vs. urgency) demonstrates that the overall findings
were consistent across these groups. Finally, whilst both
subgroup analyses by age, ASA physical status, urgency
and grade of surgery, and sensitivity analyses for elective
surgery were all consistent with the main analysis, there is a
possibility of residual bias.
In conclusion, we performed an international, multicentre,
prospective cohort study of 140,231 patients undergoing
surgery in 116 countries, in order to determine the optimal
timing of surgery after SARS-CoV-2 infection. We found that
risks of postoperative morbidity and mortality are greatest if
patients are operated within 6 weeks of diagnosis of SARS-
CoV-2 infection. Our results suggest that, where possible,
surgery should be delayed for at least 7 weeks following
SARS-CoV-2 infection. Patients with ongoing symptoms at
≥7 weeks from diagnosis may benefitfromfurtherdelay.
Acknowledgements
Trial registration at clinicaltrials.gov (NCT04509986). The
authors would like to thank the RCS Covid Research Group
for their support. Funding was provided by: the National
Institute for Health Research (NIHR) Global Health Research
Unit; Association of Coloproctology of Great Britain and
Ireland; Bowel and Cancer Research; Bowel Disease
Research Foundation; Association of Upper Gastrointestinal
Surgeons; British Association of Surgical Oncology; British
Gynaecological Cancer Society; European Society of
Coloproctology; Medtronic; NIHR Academy; Sarcoma UK;
the Urology Foundation; Vascular Society for Great Britain
and Ireland; and Yorkshire Cancer Research. The views
expressed are those of the authors and not necessarily those
of the funding partners. No other competing interests.
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Supporting Information
Additional supporting information may be found online via
the journal website.
Appendix S1. Supporting information.
Table S1. Baseline characteristics and outcomes in
elective patients.
Table S2. Unadjusted and adjusted 30-day
postoperative mortality (95%CI) in key sub-groups from
main analysis.
Table S3. Sensitivity analysis for elective patients with
unadjusted and adjusted models for 30-day postoperative
mortality.
Table S4. Sensitivity analysis for elective patients with
unadjusted and adjusted 30-day postoperative mortality
(95%CI) in key sub-groups.
Table S5. Sensitivity analysis for RT-PCR nasopharyngeal
swab proven SARS-CoV-2 infection, with unadjusted and
adjusted models for 30-day postoperative mortality.
Table S6. Sensitivity analysis for RT-PCR
nasopharyngeal swab proven SARS-CoV-2 infection with
unadjusted and adjusted 30-day postoperative mortality in
key sub-groups.
Table S7. Unadjusted and adjusted models for 30-day
postoperative mortality in patients with pre-operative SARS-
CoV-2 infection.
Table S8. Unadjusted and adjusted 30-day
postoperative mortality in patients with pre-operative SARS-
CoV-2 infection in key sub-groups.
Table S9. Unadjusted and adjusted model for 30-day
postoperative pulmonary complications in all patients.
Table S10. Unadjusted and adjusted 30-day
postoperative pulmonary complications in key sub-groups
from main analysis.
Table S11. Sensitivity analysis for elective patients with
unadjusted and adjusted model for 30-day postoperative
pulmonary complications.
Table S12. Sensitivity analysis for elective patients with
unadjusted and adjusted 30-day postoperative pulmonary
complications in key sub-groups.
Table S13. Unadjusted and adjusted models for 30-
day postoperative pulmonary complications in patients with
pre-operative SARS-CoV-2 infection.
Table S14. Unadjusted and adjusted 30-day
postoperative pulmonary complications in patients with
pre-operative SARS-CoV-2 infection in key sub-groups.
Table S15. List of excluded procedures.
Table S16. 30-day postoperative mortality and
postoperative pulmonary complication rates stratified by
timing of surgery after SARS-CoV-2 diagnosis.
Table S17. 30-day postoperative mortality and
postoperative pulmonary complication rates in patients
operated ≥3 weeks after SARS-CoV-2 diagnosis, stratified by
results of most recentrepeat RT-PCR nasopharyngeal swab.
Figure S1. Study flowchart.
Figure S2. Adjusted 30-day postoperative mortality
rates from sensitivity analysis for elective patients, stratified
by pre-defined sub-groups.
Appendix S2. COVIDSurg Collaborative and
GlobalSurg Collaborative authors (all PubMed indexed co-
authors).
758 ©2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.
Anaesthesia 2021, 76, 748–758 COVIDSurgCollaborative and GlobalSurg Collaborative | Timing of surgery following SARS-CoV-2 infection
13652044, 2021, 6, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.15458 by INASP - GHANA, Wiley Online Library on [07/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License