
==== Front
Ann Surg Oncol
Ann Surg Oncol
Annals of Surgical Oncology
1068-9265
1534-4681
Springer International Publishing Cham

38879673
15594
10.1245/s10434-024-15594-1
Global Health Services Research
Preoperative COVID-19 and Postoperative Mortality in Cancer Surgery: A South Korean Nationwide Study
Ju Jae-Woo MD 12
Yoon Soo-Hyuk MD 1
Oh Tak Kyu MD, PhD 23
http://orcid.org/0000-0002-7134-5044
Lee Ho-Jin MD, PhD hjpainfree@snu.ac.kr

12
1 https://ror.org/01z4nnt86 grid.412484.f 0000 0001 0302 820X Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Republic of Korea
2 https://ror.org/04h9pn542 grid.31501.36 0000 0004 0470 5905 Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
3 https://ror.org/00cb3km46 grid.412480.b 0000 0004 0647 3378 Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
15 6 2024
15 6 2024
2024
31 10 63946404
8 3 2024
28 5 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Background

We evaluated the impact of preoperative COVID-19 on early postoperative mortality in patients undergoing time-sensitive cancer surgery.

Methods

This retrospective, nationwide cohort study included adult patients who underwent various cancer (thyroid, breast, stomach, colorectal, hepatobiliary, genitourinary, lung, and multiple cancer) surgeries under general anesthesia in South Korea in 2022. Patients were grouped according to the duration from the date of COVID-19 confirmation to the date of surgery (0–2 weeks, 3–4 weeks, 5–6 weeks, and ≥7 weeks). Patients without preoperative COVID-19 also were included. Multivariable logistic regression analysis with Firth correction was performed to investigate the association between preoperative COVID-19 and 30-day and 90-day postoperative mortality. The covariates encompassed sociodemographic factors, the type of surgery, and vaccination status in addition to the aforementioned groups.

Results

Of the 99,555 patients analyzed, 30,933 (31.1%) were preoperatively diagnosed with COVID-19. Thirty-day mortality was increased in those who underwent surgery within 0–2 weeks after diagnosis of COVID-19 (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.02–2.12; P = 0.038); beyond 2 weeks, there was no significant increase in mortality. A similar pattern was observed for 90-day mortality. Full vaccination against COVID-19 was associated with reduced 30-day (OR 0.38; 95% CI 0.29–0.50; P < 0.001) and 90-day (OR 0.39; 95% CI 0.33–0.46; P < 0.001) mortality.

Conclusions

Cancer surgery within 2 weeks of COVID-19 diagnosis was associated with increased early postoperative mortality. These findings support current guidelines that recommend postponing elective surgery for at least 2 weeks after the diagnosis of COVID-19.

Supplementary Information

The online version contains supplementary material available at 10.1245/s10434-024-15594-1.

Seoul National UniversityOpen Access funding enabled and organized by Seoul National University.

issue-copyright-statement© Society of Surgical Oncology 2024
==== Body
pmcThe coronavirus disease 2019 (COVID-19) pandemic created unprecedented challenges for global healthcare systems and had a significant impact on perioperative management.1 Therefore, understanding the effects of preoperative COVID-19 on postoperative outcomes has become a major concern associated with perioperative care.2

Early during the pandemic, a multicenter prospective study by the COVIDSurg and GlobalSurg Collaborative highlighted a significant correlation between COVID-19 within 7 weeks before surgery and increased 30-day postoperative mortality.3 This finding was pivotal to determining the proper timing for elective surgeries. However, because of its reduced virulence and the advent of vaccines, the impact of preoperative COVID-19 on postoperative outcomes has evolved. Current guidelines implemented in the United States and the United Kingdom recommend postponing elective surgeries for at least 2 weeks after COVID-19 is diagnosed.4,5 However, the postponement of elective surgery because of COVID-19 can worsen the prognoses of patients with cancer because of the possibility of cancer progression, thus complicating decision-making.6,7 Despite the cancer care guidelines in South Korea during the COVID-19 pandemic advising against delaying surgeries in patients with COVID-19 becaue of the potential risk of cancer progression,8 research regarding the optimal timing of cancer surgery for patients with preoperative COVID-19 to minimize the perioperative mortality risk is still lacking. Although the COVID-19 pandemic has ended, the lingering presence of COVID-19 necessitates continued vigilance. Previous studies on the surgical management of cancer in patients with COVID-19 were limited by their small sample sizes and single institutions.9,10

Therefore, our study utilized recent national health insurance data from South Korea to investigate the short-term postoperative outcomes of patients with a preoperative diagnosis of COVID-19 who underwent cancer surgery. Our study's findings may aid clinicians in determining the optimal timing for cancer surgery for patients who have been diagnosed with COVID-19.

Methods

The Institutional Review Board of Seoul National University Hospital exempted the protocol of this study from review because of its retrospective nature and de-identified data. This study was approved by the Korea Disease Control and Prevention Agency (KDCA) and the National Health Insurance Service (NHIS) (approval number KDCA-NHIS-2023-1-366). This study was conducted in accordance with the guidelines of the Declaration of Helsinki and Strengthening the Reporting of Observational Studies in Epidemiology.11

Data Source

All data were obtained from the K-COV-N cohort database, which was created by merging the NHIS and KDCA databases with de-identified registration numbers. Since 2022, the Korean KDCA and NHIS have offered a database known as the K-COV-N cohort database, which combines the NHIS database with COVID-19-related variables to support research on COVID-19.12 Similar to other NHIS datasets, this database is anonymized and furnished by the National Health Insurance Corporation. Access for researchers is restricted to designated analysis centers.13 The NHIS is a universal mandatory national health insurance system for the Korean population, with an enrollment rate of 97%.14 The NHIS database contains records of all inpatient and outpatient medical services, including diagnoses based on International Classification of Diseases 10th revision (ICD-10) codes, procedures, and prescription codes.15 Additionally, the KDCA database includes detailed information regarding COVID-19 vaccinations in Korea, including the dates of administration and types of vaccinations administered.

Study Participants

We identified adult patients (age 19 years or older) who underwent cancer surgery in South Korea between January 2022 and December 2022. Surgeries of the thyroid, breast, stomach, lung, liver, gallbladder, pancreas, colorectal, uterus, ovary, kidney, prostate, and testis performed because of cancer were included and defined according to the corresponding ICD-10 codes and procedure insurance claim codes listed in the Standard Guide to Statistics of Disease and Procedure published by the Health Insurance Review & Assessment Service in Korea. These codes were used as criteria for generating the surgical healthcare statistics of Korea (Supplemental Table 1).15 Multiple cancer surgeries included those involving two or more cancer surgeries performed simultaneously. To ensure a patient-level analysis, we only analyzed the first surgery performed for each patient during the study period. Patients diagnosed with COVID-19 within 30 days after the index cancer surgery, those who underwent emergency surgery, and those who did not receive general anesthesia (procedure codes L0101, L1211, and L1212) for the index cancer surgery were excluded.Table 1 Baseline characteristics and surgical variables

	No preoperative COVID-19
(n = 68,622)	Preoperative COVID-19 infection
(by timing of diagnosis before surgery)	
0–2 weeks
(n = 3,489)	3–4 weeks
(n = 2,841)	5–6 weeks
(n = 2,270)	≥7 weeks
(n = 22,333)	
Age, years	
 Mean (SD)	59.7 (13.6)	61.1 (13.9)	58.5 (14.2)	57.8 (14.3)	56.4 (14.3)	
 19–49	16,114 (23.5)	763 (21.9)	812 (28.6)	700 (30.8)	7,630 (34.2)	
 50–69	35,161 (51.2)	1,675 (48.0)	1,334 (47.0)	1,046 (46.1)	10,177 (45.6)	
 ≥ 70	17,347 (25.3)	1,051 (30.1)	695 (24.5)	524 (23.1)	4,526 (20.3)	
Sex	
 Female	43,314 (63.1)	2,152 (61.7)	1,925 (67.8)	1,524 (67.1)	15,781 (70.7)	
 Male	25,308 (36.9)	1,337 (38.3)	916 (32.2)	746 (32.9)	6,552 (29.3)	
Comorbidity	
 Congestive heart failure	8468 (12.3)	538 (15.4)	386 (13.6)	306 (13.5)	2,835 (12.7)	
 Dementia	1,861 (2.7)	143 (4.1)	92 (3.2)	79 (3.5)	687 (3.1)	
 Chronic pulmonary disease	24,146 (35.2)	1,666 (47.8)	1,357 (47.8)	1,046 (46.1)	10,432 (46.7)	
 Rheumatologic disease	3,785 (5.5)	195 (5.6)	163 (5.7)	146 (6.4)	1,342 (6.0)	
 Mild liver disease	32,064 (46.7)	1,929 (55.3)	1,346 (47.4)	1,089 (48.0)	10,654 (47.7)	
 Diabetes with chronic complications	5,060 (7.4)	301 (8.6)	230 (8.1)	169 (7.4)	1,492 (6.7)	
 Hemiplegia or paraplegia	451 (0.7)	29 (0.8)	21 (0.7)	19 (0.8)	169 (0.8)	
 Renal disease	2,746 (4.0)	158 (4.5)	132 (4.6)	99 (4.4)	816 (3.7)	
 Any malignancy, including leukemia and lymphoma	66,553 (97.0)	3,372 (96.6)	2,744 (96.6)	2,205 (97.1)	21,545 (96.5)	
 Moderate or severe liver disease	637 (0.9)	63 (1.8)	29 (1.0)	22 (1.0)	160 (0.7)	
 Metastatic solid tumor	14,009 (20.4)	655 (18.8)	617 (21.7)	459 (20.2)	4,566 (20.4)	
 AIDS/HIV	86 (0.1)	5 (0.1)	5 (0.2)	8 (0.4)	40 (0.2)	
Updated Charlson comorbidity index score	
 Median (IQR)	4 (2–8)	5 (3–8)	5 (3–8)	4 (3–8)	4 (3–8)	
 0–2	17,850 (26.0)	646 (18.5)	603 (21.2)	503 (22.2)	5,021 (22.5)	
 3–4	19,401 (28.3)	983 (28.2)	810 (28.5)	658 (29.0)	6,573 (29.4)	
 ≥ 5	31,371 (45.7)	1,860 (53.3)	1,428 (50.3)	1,109 (48.9)	10,739 (48.1)	
Vaccination	
 Not vaccinated	4,044 (5.9)	229 (6.6)	164 (5.8)	132 (5.8)	1,081 (4.8)	
 Not fully vaccinated	884 (1.3)	29 (0.8)	36 (1.3)	35 (1.5)	270 (1.2)	
 Fully vaccinated	63,694 (92.8)	3,231 (92.6)	2,641 (93.0)	2,103 (92.6)	20,982 (94.0)	
Type of cancer surgery	
 Thyroid	14,171 (20.7)	582 (16.7)	654 (23.0)	623 (27.4)	6,023 (27.0)	
 Breast	17,465 (25.5)	867 (24.8)	780 (27.5)	532 (23.4)	6,398 (28.6)	
 Stomach	8,318 (12.1)	428 (12.3)	293 (10.3)	202 (8.9)	1,970 (8.8)	
 Lung	6,417 (9.4)	297 (8.5)	291 (10.2)	250 (11.0)	2,148 (9.6)	
 Liver	2,545 (3.7)	105 (3.0)	85 (3.0)	74 (3.3)	519 (2.3)	
 Gallbladder	742 (1.1)	52 (1.5)	23 (0.8)	16 (0.7)	221 (1.0)	
 Pancreas	1,258 (1.8)	94 (2.7)	55 (1.9)	48 (2.1)	383 (1.7)	
 Colorectal	11,778 (17.2)	824 (23.6)	435 (15.3)	316 (13.9)	2,665 (11.9)	
 Uterus	1,715 (2.5)	61 (1.7)	72 (2.5)	61 (2.7)	598 (2.7)	
 Ovary	1,576 (2.3)	60 (1.7)	64 (2.3)	68 (3.0)	595 (2.7)	
 Kidney	1,423 (2.1)	51 (1.5)	42 (1.5)	42 (1.9)	400 (1.8)	
 Prostate	659 (1.0)	33 (0.9)	19 (0.7)	14 (0.6)	222 (1.0)	
 Testis	150 (0.2)	6 (0.2)	5 (0.2)	7 (0.3)	85 (0.4)	
 Multiple cancer surgeries	405 (0.6)	29 (0.8)	23 (0.8)	17 (0.7)	106 (0.5)	
Income level at the index procedure	
 1st quartile (lowest)	19,286 (28.1)	989 (28.3)	827 (29.1)	641 (28.2)	6,248 (28.0)	
 2nd quartile	18,566 (27.1)	947 (27.1)	751 (26.4)	638 (28.1)	6,454 (28.9)	
 3rd quartile	15,299 (22.3)	772 (22.1)	624 (22.0)	479 (21.1)	4,793 (21.5)	
 4th quartile (highest)	15,471 (22.5)	781 (22.4)	639 (22.5)	512 (22.6)	4,838 (21.7)	
Area of residence at the index procedure	
 Capital city	13,001 (18.9)	620 (17.8)	600 (21.1)	464 (20.4)	4,768 (21.3)	
 Metropolitan city	17,076 (24.9)	738 (21.2)	725 (25.5)	540 (23.8)	5,748 (25.7)	
 Other areas	38,545 (56.2)	2,131 (61.1)	1,516 (53.4)	1,266 (55.8)	11,817 (52.9)	
Values are expressed as the number (%) unless otherwise indicated

COVID-19 Coronavirus disease 2019; SD standard deviation; IQR interquartile range

Group Classification

The exposure of interest was COVID-19, which was identified using ICD-10 codes (B342, B972, U071, and U072).16,17 The date when COVID-19 was confirmed was established as the initial occurrence of the disease associated with specified codes. We stratified patients into the following four groups according to the interval between the confirmed date of preoperative COVID-19 and the index surgery date for cancer: 0 to 2 weeks, 3 to 4 weeks, 5 to 6 weeks, and 7 or more weeks; furthermore, we included a fifth group of patients without a preoperative diagnosis of COVID-19.3

Covariates and Outcomes

We also obtained data regarding baseline characteristics, COVID-19 vaccination-related variables, and cancer surgery types (Table 1). Preoperative comorbidities were defined as at least two relevant ICD-10 codes documented within the year before surgery (Supplemental Table 2). These comorbidities included congestive heart failure, dementia, chronic pulmonary disease, rheumatic disease, mild liver disease, diabetes with chronic complications, hemiplegia or paraplegia, renal disease, any malignancy, including leukemia and lymphoma, moderate or severe liver disease, metastatic solid tumors, and acquired immunodeficiency syndrome/human immunodeficiency virus. The updated Charlson comorbidity index (CCI) score was also calculated.18 Regarding the COVID-19 vaccination status, patients were classified as “fully vaccinated” if they received at least one dose of Ad.26.COV2.S or at least two doses of BNT162b2 or mRNA-173 vaccines 14 days or more before the index cancer surgery.19 Patients were considered “not fully vaccinated” if they received only one BNT162b2 or mRNA-173 vaccine 14 days or more before the index cancer surgery. The remaining patients were classified as “not vaccinated.” Based on a previous study that demonstrated the beneficial effect of COVID-19 vaccination on individuals without positive COVID-19 test results, we did not consider the temporal order of vaccination or COVID-19 confirmation.20 Data regarding income level (as quartiles) and area of residence (capital city, metropolitan city, or other area) were also collected. The primary outcome was 30-day postoperative mortality. The secondary outcome was 90-day postoperative mortality. Because the date of death is included in the K-COV-N cohort database that was utilized during this study, there were no missing data regarding these outcomes.Table 2 Postoperative outcomes after elective cancer surgery

	No preoperative COVID-19
(n = 68,622)	Preoperative COVID-19 infection
(by timing of diagnosis before surgery)	
0–2 weeks
(n = 3,489)	3–4 weeks
(n = 2,841)	5–6 weeks
(n = 2,270)	≥7 weeks
(n = 22,333)	
30-day postoperative mortality	326 (0.5)	32 (0.9)	12 (0.4)	14 (0.6)	65 (0.3)	
90-day postoperative mortality	928 (1.4)	97 (2.8)	42 (1.5)	36 (1.6)	220 (1.0)	
Values are expressed as the number (%)

COVID-19 Coronavirus disease 2019

Statistical Analysis

Logistic regression analyses were conducted to compare 30-day postoperative mortality rates across patient groups. To mitigate the bias associated with the low mortality rate presented by our data, we used Firth’s penalized likelihood method, which offers a robust alternative to traditional maximum likelihood logistic regression for analyzing rare events.21 To implement this, we employed the FIRTH option in SAS. Univariable logistic regression analyses of the primary outcome were conducted to examine the study groups and potential confounders, including age (19–49 years, 50–69 years, 70 years or older), male sex, updated CCI score (0–2, 3–4, ≥5), COVID-19 vaccination status (fully vaccinated, not fully vaccinated, or not vaccinated), cancer surgery type, income level (as quartiles), and area of residence. Cancer surgery types were categorized as thyroid, breast, stomach, colorectal, hepatobiliary (liver, gallbladder, pancreas), genitourinary (uterus, ovary, kidney, prostate, testis), lung, and multiple. After the univariable analyses, the association between the primary outcome and study group was adjusted for potential confounders in the multivariable logistic regression analysis without applying a variable selection method. The lack of multicollinearity among the variables was established by assessing the variance inflation factor, which was less than 2 before inclusion in the multivariable model. The results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Logistic regression analyses were repeated in the same manner for the secondary outcome. To confirm our findings, sensitivity analysis was performed by calculating E-value to assess the potential influence of unmeasured confounders on the observed association.22

We performed exploratory, prespecified subgroup analyses to determine whether the impact of preoperative COVID-19 varied according to the prespecified subgroups, including age (19–49 years, 50–69 years, and 70 years or older), sex, updated CCI score (0–2, 3–4, ≥ 5), COVID-19 vaccination status, cancer surgery type, income level, and area of residence. For each subgroup, the same multivariable analysis procedure described above was used but with the inclusion of interaction terms. The likelihood ratio test was used to assess the statistical significance of the interaction. Additionally, during the revision process, we conducted another sensitivity analysis by performing logistic regression analyses by using Firth’s penalized likelihood method on the primary and secondary outcomes in abdominopelvic cancer surgeries, which included surgeries for stomach, liver, gallbladder, pancreas, colorectal, uterus, ovary, kidney, prostate, and testis cancers.

Statistical significance was determined as a two-tailed P-value of <0.05. Continuous variables are presented as means (standard deviations) or medians (interquartile ranges), as appropriate, and categorical variables are presented as counts (percentages). SAS version 9.4 (SAS Institute, Cary, NC) was used for all analyses.

Results

We obtained data from 116,306 adult patients who underwent cancer surgeries covered by the NHIS in South Korea in 2022. After exclusion, the data of 99,555 patients were analyzed (Fig. 1). Among these patients, 30,933 (31.1%) were preoperatively diagnosed with COVID-19. Patient groups were created according to the time between the COVID-19 diagnosis and the index surgery as follows: within 0 to 2 weeks, 3489 (3.5%) patients; within 3 to 4 weeks, 2841 (2.9%) patients; within 5 to 6 weeks, 2270 (2.3%) patients; and within 7 weeks or more, 22,333 (22.4%) patients.Fig. 1 Flowchart of the study. COVID-19 coronavirus disease 2019; NHIS National Health Insurance Service

The 30-day postoperative mortality rate was 0.5% (326/68,622) for patients without preoperative COVID-19 (Table 2). In contrast, the mortality rates of patients with preoperative COVID-19 were 0.9% (32/3489), 0.4% (12/2841), 0.6% (14/2270), and 0.3% (65/22,333) when surgery was performed within 0 to 2 weeks, 3 to 4 weeks, 5 to 6 weeks, and 7 or more weeks after COVID-19 infection, respectively.

Univariate and multivariate logistic regression analyses of the 30-day postoperative mortality rates are presented in Table 3. Patients who underwent surgery within 0 to 2 weeks of the COVID-19 diagnosis had a significantly higher risk of 30-day mortality than those without prior infection (adjusted OR 1.47; 95% CI 1.02–2.12; P = 0.038). No significant associations were observed among patients who underwent surgery beyond 2 weeks after the COVID-19 diagnosis. Factors, such as older age, male sex, higher comorbidity index scores (CCI score ≥5), specific cancer surgery types, and lower income levels, were significantly associated with increased 30-day mortality rates. Being fully vaccinated was also significantly associated with a lower 30-day mortality rate (OR 0.38; 95% CI 0.29–0.50; P < 0.001). The predictive accuracy of this multivariable model, as indicated by the C-statistic, was 0.860 (95% CI 0.838–0.882).Table 3 Univariable and multivariable logistic regression analyses for 30-day postoperative mortality after elective cancer surgery

	Univariable	Multivariable	
Unadjusted OR
(95% CI)	P	Adjusted OR
(95% CI)	P	
Timing of diagnosis of COVID-19 before surgery	
 No preoperative COVID-19	Reference		Reference		
 0–2 weeks	1.97 (1.37–2.82)	< 0.001	1.47 (1.02–2.12)	0.038	
 3–4 weeks	0.92 (0.52–1.63)	0.785	0.90 (0.51–1.59)	0.731	
 5–6 weeks	1.34 (0.79–2.28)	0.272	1.50 (0.88–2.54)	0.134	
 ≥7 weeks	0.62 (0.47–0.80)	< 0.001	0.78 (0.59–1.01)	0.059	
Age, years	
 0–49	Reference		Reference		
 50–69	4.14 (2.48–6.92)	< 0.001	1.73 (1.03–2.92)	0.039	
 ≥ 70	20.13 (12.26–33.05)	< 0.001	5.30 (3.16–8.87)	< 0.001	
 Male (vs. female)	3.75 (3.08–4.57)	< 0.001	1.59 (1.30–1.95)	< 0.001	
Updated Charlson comorbidity index	
 0–3	Reference		Reference		
 4–5	2.01 (1.31–3.10)	0.002	1.27 (0.83–1.96)	0.272	
 ≥ 6	6.37 (4.37–9.27)	< 0.001	2.72 (1.86–3.97)	<0.001	
Fully vaccinated (vs. not vaccinated or not fully vaccinated)	0.43 (0.33–0.56)	< 0.001	0.38 (0.29–0.50)	< 0.001	
Type of cancer surgery	
 Thyroid	Reference		Reference		
 Breast	0.55 (0.22–1.39)	0.207	0.52 (0.21–1.29)	0.156	
 Stomach	11.78 (6.31–22.01)	< 0.001	4.50 (2.36–8.56)	< 0.001	
 Colorectal	25.52 (14.09–46.22)	< 0.001	8.33 (4.51–15.40)	< 0.001	
 Hepatobiliary	22.92 (12.30–42.69)	< 0.001	8.18 (4.31–15.52)	< 0.001	
 Genitourinary	6.11 (3.04–12.26)	< 0.001	3.32 (1.64–6.69)	0.001	
 Lung	10.35 (5.45–19.64)	< 0.001	3.73 (1.93–7.21)	< 0.001	
 Multiple cancer surgeries	18.32 (6.61–50.80)	< 0.001	6.38 (2.28–17.87)	< 0.001	
Income level at the index procedure	
 1st quartile (lowest)	Reference		Reference		
 2nd quartile	0.43 (0.33–0.57)	< 0.001	0.54 (0.41–0.70)	< 0.001	
 3rd quartile	0.71 (0.56–0.91)	0.007	0.78 (0.61–1.00)	0.048	
 4th quartile (highest)	0.70 (0.54–0.89)	0.004	0.64 (0.50–0.82)	< 0.001	
Residence level at the index procedure	
 Capital city	Reference		Reference		
 Metropolitan city	0.92 (0.68–1.25)	0.614	1.01 (0.74–1.36)	0.963	
 Other area	1.28 (1.00–1.65)	0.055	1.11 (0.87–1.43)	0.399	
COVID-19, coronavirus disease 2019; OR, odds ratio; CI, confidence interval

In the sensitivity analysis for the 30-day postoperative mortality, the E-value calculated for the initially observed result where patients who underwent surgery within 0 to 2 weeks of COVID-19 diagnosis had a significantly higher risk compared with those without COVID-19 infection was 1.16. In other words, if there were an unmeasured confounder with an OR greater than 1.16, the risk within the 0 to 2 weeks interval would not be significantly different from that of patients without preoperative COVID-19, suggesting that this finding does not appear to be robust against potential unmeasured confounders. Conversely, to alter the nonsignificant findings to significant ones for patients who underwent surgery 3 to 4 weeks, 5 to 6 weeks, and 7 or more weeks after COVID-19 infection, the E-values required to shift the OR to 1.1 and its lower 95% CI to 1.01 were calculated as 3.37, 2.07, and 2.82, respectively. These findings indicate that nonsignificant findings in patients who underwent surgery more than 2 weeks post-COVID-19 infection are moderately robust against potential unmeasured confounding.

Univariable and multivariable logistic regression analyses of the 90-day postoperative mortality rates are presented in Table 4. The multivariable logistic regression analysis revealed that surgery within 0 to 2 weeks of COVID-19 was significantly associated with an increased 90-day mortality rate compared to that of individuals without COVID-19 (adjusted OR 1.60; 95% CI 1.29–1.99; P < 0.001). Surgeries performed more than 2 weeks after COVID-19 was diagnosed were not significantly associated with the 90-day mortality rate. Being fully vaccinated was correlated with a lower risk of 90-day mortality (OR 0.39; 95% CI 0.33–0.46; P < 0.001). The predictive accuracy of this model, as indicated by the C-statistic, was 0.855 (95% CI 0.842–0.868). For the 90-day postoperative mortality, the E-values for the significance of each group were 1.90 (0–2 weeks), 1.88 (3–4 weeks), 1.67 (5–6 weeks), and 1.91 (7 or more weeks), respectively.Table 4 Univariable and multivariable logistic regression analyses for 90-day postoperative mortality after elective cancer surgery

	Univariable	Multivariable	
Unadjusted OR
(95% CI)	P	Adjusted OR
(95% CI)	P	
Timing of diagnosis of COVID-19 before surgery	
 No preoperative COVID-19	Reference		Reference		
 0–2 weeks	2.10 (1.70–2.59)	<0.001	1.60 (1.29–1.99)	< 0.001	
 3–4 weeks	1.11 (0.81–1.51)	0.521	1.09 (0.79–1.50)	0.594	
 5–6 weeks	1.19 (0.85–1.66)	0.304	1.31 (0.93–1.84)	0.122	
 ≥ 7 weeks	0.73 (0.63–0.84)	< 0.001	0.91 (0.78–1.06)	0.211	
Age, years	
 0–49	Reference		Reference		
 50–69	4.01 (3.02–5.32)	< 0.001	1.61 (1.21–2.16)	0.001	
 ≥ 70	17.54 (13.33–23.08)	< 0.001	4.29 (3.21–5.73)	< 0.001	
 Male (vs. female)	3.47 (3.10–3.89)	< 0.001	1.47 (1.31–1.66)	< 0.001	
Updated Charlson comorbidity index	
 0–3	Reference		Reference		
 4–5	1.68 (1.29–2.19)	< 0.001	1.09 (0.84–1.42)	0.516	
 ≥ 6	6.88 (5.51–8.59)	< 0.001	3.15 (2.52–3.95)	< 0.001	
Fully vaccinated (vs. not vaccinated or not fully vaccinated)	0.44 (0.38–0.51)	< 0.001	0.39 (0.33–0.46)	< 0.001	
Type of cancer surgery	
 Thyroid	Reference		Reference		
 Breast	0.85 (0.49–1.45)	0.546	0.79 (0.46–1.35)	0.384	
 Stomach	16.67 (11.14–24.96)	< 0.001	7.27 (4.79–11.03)	< 0.001	
 Colorectal	33.21 (22.50–49.02)	< 0.001	12.25 (8.19–18.32)	< 0.001	
 Hepatobiliary	27.68 (18.44–41.54)	< 0.001	11.05 (7.27–16.79)	< 0.001	
 Genitourinary	8.21 (5.28–12.76)	< 0.001	4.78 (3.06–7.46)	< 0.001	
 Lung	12.42 (8.19–18.84)	< 0.001	4.95 (3.22–7.60)	< 0.001	
 Multiple cancer surgeries	30.40 (16.97–54.44)	< 0.001	11.86 (6.54–21.50)	< 0.001	
Income level at the index procedure	
 1st quartile (lowest)	Reference		Reference		
 2nd quartile	0.57 (0.49–0.66)	< 0.001	0.70 (0.60–0.82)	< 0.001	
 3rd quartile	0.64 (0.55–0.74)	< 0.001	0.70 (0.60–0.82)	< 0.001	
 4th quartile (highest)	0.82 (0.71–0.94)	0.006	0.77 (0.67–0.90)	0.001	
Residence level at the index procedure	
 Capital city	Reference		Reference		
 Metropolitan city	1.05 (0.89–1.25)	0.571	1.16 (0.97–1.38)	0.098	
 Other area	1.16 (1.00–1.34)	0.050	1.02 (0.88–1.18)	0.840	
COVID-19, coronavirus disease 2019; OR, odds ratio; CI, confidence interval

Exploratory subgroup analyses (Supplemental Tables 3 and 4) revealed that only the cancer surgery type significantly impacted the association between preoperative COVID-19 and 30-day postoperative mortality (P < 0.001). No significant differences were observed in the primary outcome across the other subgroups. The results of the logistic regression analyses on the primary and secondary outcomes of abdominopelvic cancer surgery are provided in Supplemental Tables 5 and 6.

Discussion

This study identified a significant association between COVID-19 diagnosed within 2 weeks before surgery and increased 30-day and 90-day mortality rates after elective cancer surgery. This finding corroborates recent guidelines that suggest postponing elective surgery at least 2 weeks after COVID-19 is diagnosed.4,5 Furthermore, preoperative administration of the COVID-19 vaccine was significantly associated with reduced 30-day and 90-day postoperative mortality rates, thereby underscoring the importance of vaccination for patients who require surgery.

Recent studies have suggested shortening the time between elective surgeries and the COVID-19 diagnosis from 7 to 2 weeks.23–25 Additionally, a study performed in the United Kingdom reported a 1.1% postoperative mortality rate for surgeries within 2 weeks of COVID-19 infection, decreasing to 0.3% between 4 and 6 weeks, and aligning with the mortality rate in COVID-19 patients beyond 6 weeks or no preoperative COVID-19 infection.24 However, that study did not adjust for variables that could affect mortality and included various surgeries other than cancer surgeries. A multicenter study performed in France during the Omicron-predominant postvaccine era did not find significant associations between COVID-19 diagnosed within 3 weeks before surgery and increased postoperative respiratory morbidities.23 However, that study included only 4928 patients, and 705 of those patients were diagnosed with COVID-19 within 8 weeks before surgery; therefore, it may have been underpowered to detect the influence of preoperative COVID-19 on postoperative outcomes.23 Despite these limitations, that study emphasized the significance of its findings by considering that delaying time-sensitive surgeries could worsen the postoperative prognosis.23 Our study offers new insights regarding the timing of cancer surgeries after the diagnosis of COVID-19, thereby adding beneficial information to the literature.

The results of our current and previous studies reflect recent changes in the impact of COVID-19 on postoperative outcomes.26 Although our previous study included a variety of surgeries, including cancer surgeries, the 30-day and 90-day postoperative mortality rates among patients without preoperative COVID-19 were similar to those observed during the current study.26 However, our previous study, which focused solely on surgeries conducted in 2021, found that COVID-19 diagnosed up to 8 weeks before surgery was associated with a postoperative mortality rate that was more than double that of patients without preoperative COVID-19 (1.4% vs. 0.4%).26 Furthermore, the adjusted OR for 30-day postoperative mortality observed during our previous study was higher than that observed during our current study (adjusted ORs 0–4 weeks, 4.28 [95% CI 1.81–10.31; P = 0.001]; 4–8 weeks, 3.38 [95% CI 1.54–7.44; P = 0.002]). Because the patients included in this study underwent surgery in 2022, the observed differences were likely attributable to the overall weakened impact of preoperative COVID-19 on surgical patients. According to recent data from the KDCA, compared with the severity and fatality rates of COVID-19 during the pre-delta and delta-dominant periods, those of the Omicron-dominant period, which began in January 2022, significantly decreased.27

Our study found a significant association between elective cancer surgeries conducted within 2 weeks of the COVID-19 diagnosis and increased postoperative mortality; however, no such association was observed for surgeries performed thereafter. This finding suggests the need to delay cancer surgeries for at least 2 weeks for patients with preoperative COVID-19 in agreement with recent guidelines.4,5 Fortunately, this delay falls within the 3-week “safe postponement period” for patients who require cancer surgery, as suggested by a recent study performed in the United States that used the National Cancer Database.28 In addition, the evaluation of robustness using E-values revealed that the nonsignificant association between surgeries performed more than 2 weeks after COVID-19 infection and 30-day postoperative mortality is more robust than the significant association found with surgeries conducted within 2 weeks of a COVID-19 infection. This finding underscores that delaying cancer surgeries for more than 2 weeks because of COVID-19 infection may not be necessary. Therefore, postponing cancer surgery for 2 weeks because of COVID-19 is likely to be an appropriate decision, and there is no justification for further delays.

Our study also found that being fully vaccinated against COVID-19 before surgery reduced early postoperative mortality. A retrospective study conducted in the United States found that the preoperative COVID-19 vaccination status could influence perioperative complications.19 Among a fully vaccinated cohort, COVID-19 diagnosed within 4 weeks before surgery was not significantly associated with increased perioperative complications. However, among the cohort that was not fully vaccinated, COVID-19 diagnosed within 4 weeks before surgery was significantly associated with increased perioperative complications.19 Other retrospective studies performed in the United States showed that being fully vaccinated against COVID-19 decreased perioperative complications and postoperative mortality.20,29 However, our previous study did not show an association between being fully vaccinated and 30-day postoperative mortality,24 possibly because vaccinations were initiated later in South Korea than in other countries and administered to older adults first because they were at higher risk.30 In South Korea, vaccinations became available for all adults on August 26, 2021; therefore, most patients who had received a second preoperative COVID-19 vaccination were likely to be older in our previous study.26 The unadjusted OR for preoperative COVID-19 vaccination in our previous study was associated with an increased risk of 30-day postoperative mortality.26 However, our current findings did not show this increased risk because vaccinations were available for all adults.

This study had a few limitations. First, because of the retrospective design of this study, unmeasured confounders that could affect the primary and secondary outcomes—such as the extent of the surgery, the severity of the patient’s underlying conditions, and the experience of the medical institution—could have influenced the results. As previously mentioned, the robustness of the significant association between COVID-19 infections occurring within 2 weeks preoperatively and an increase in the 30-day mortality, as assessed using the E value, was not substantial. Therefore, our study results should be interpreted cautiously. Second, it focused solely on cancer surgeries performed in South Korea. Because of global variations in cancer treatment outcomes, this limited the generalizability of our findings.31 However, South Korea provides excellent cancer treatment,32 which likely minimized the impact of surgical quality on our study results. Third, the postponement of cancer surgery can be influenced not only by individual medical reasons but also by the healthcare environment and socioeconomic factors.33 We were unable to obtain information regarding the decision-making process in terms of surgical timing for patients with preoperative COVID-19. Fourth, our reliance on national health insurance data restricted our ability to assess the severity of preoperative COVID-19. According to a study that utilized data from the United States National COVID Cohort Collaborative, the severity of COVID-19 could influence the association between the duration of the COVID-19 diagnosis and surgery and the occurrence of major adverse cardiovascular and cerebrovascular events within 30 days postoperatively.25 However, according to the intermediate results of a chronic COVID-19 syndrome study that was recently published by the Korea National Institute of Health, only 0.4% of patients with COVID-19 in South Korea were diagnosed with post-COVID-19 conditions.34 Therefore, the proportion of such patients was very low, leading us to cautiously conclude that this did not significantly impact our study results. Fifth, the long-term postoperative effects of COVID-19 were not assessed, and data beyond 90 days after surgery were lacking. Because COVID-19 is constantly evolving, we included the most recent patient cohort up to December 2022 to observe contemporary trends. During a study that examined the impact of preoperative COVID-19 on mid-term postoperative outcomes, a significant divergence in the prognosis based on the presence of COVID-19 was observed soon after surgery.35 Consequently, the results of our study highlight the risks posed by preoperative COVID-19 to the postoperative prognosis. Sixth, interactions between the cancer surgery type and postoperative mortality were not fully analyzed, because only a few such events occurred. We anticipate a more pronounced association with surgeries with greater severity than with those with lower postoperative mortality rates, such as thyroid surgeries. Finally, resource constraints during the pandemic might have affected the study.36 However, the efficient response of South Korea may have mitigated these effects.37–39

Although our results support delaying cancer surgeries for at least 2 weeks after COVID-19 is diagnosed, they did not conclusively establish the safety of conducting surgeries beyond 2 weeks after infection. Factors, such as the severity of COVID-19 and related symptoms, should be considered. However, delaying cancer surgeries for at least 2 weeks for patients with COVID-19 is a reasonable strategy to mitigate the risk of worsened prognoses caused by infection. Importantly, this timeframe is unlikely to negatively affect cancer surgery outcomes, thus making it a feasible and practical approach.

Supplementary Information

Below is the link to the electronic supplementary material.Supplementary file1 (DOCX 46 kb)

This study used the databases of the KDCA (Republic of Korea) and NHIS (Republic of Korea) for policy and academic research. The research number of this study is KDCA-NHIS-2023-1-366. The authors thank the Division of Statistics in the Medical Research Collaborating Centre at Seoul National University Hospital for their assistance with the statistical analyses.

Funding

Open Access funding enabled and organized by Seoul National University. The authors have no sources of funding to declare.

DISCLOSURE

The authors declare no competing interests.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Greenland JR Michelow MD Wang L London MJ COVID-19 Infection: implications for perioperative and critical care physicians Anesthesiology. 2020 132 1346 1361 10.1097/ALN.0000000000003303 32195698
Greenland JR, Michelow MD, Wang L, London MJ. COVID-19 Infection: implications for perioperative and critical care physicians. Anesthesiology. 2020;132:1346–61.32195698
2. COVIDSurg Collaborative. Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Lancet. 2020;396:27–38.
3. COVIDSurg Collaborative, GlobalSurg Collaborative. Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study. Anaesthesia. 2021;76:748–58.
4. El-Boghdadly K Cook TM Goodacre T Kua J Denmark S Mercer N Moonesinghe SR Summerton DJ Timing of elective surgery and risk assessment after SARS-CoV-2 infection: 2023 update Anaesthesia. 2023 78 1147 1152 37337416
El-Boghdadly K, Cook TM, Goodacre T, Kua J, Denmark S, Mercer N, Moonesinghe SR, Summerton DJ. Timing of elective surgery and risk assessment after SARS-CoV-2 infection: 2023 update. Anaesthesia. 2023;78:1147–52.37337416
5. American Society of Anesthesiologists, Anesthesia Patient Safety Foundatoin: ASA and APSF joint statement on elective surgery/procedures and anesthesia for patients after COVID-19 infection. https://www.asahq.org/about-asa/newsroom/news-releases/2022/02/asa-and-apsf-joint-statement-on-elective-surgery-procedures-and-anesthesia-for-patients-after-covid-19-infection. Accessed 3 Jan 2024.
6. Whittaker TM Abdelrazek MEG Fitzpatrick AJ Froud JLJ Kelly JR Williamson JS Williams GL Delay to elective colorectal cancer surgery and implications for survival: a systematic review and meta-analysis Colorectal Dis. 2021 23 1699 1711 10.1111/codi.15625 33714235
Whittaker TM, Abdelrazek MEG, Fitzpatrick AJ, Froud JLJ, Kelly JR, Williamson JS, Williams GL. Delay to elective colorectal cancer surgery and implications for survival: a systematic review and meta-analysis. Colorectal Dis. 2021;23:1699–711.33714235
7. Hanna TP King WD Thibodeau S Jalink M Paulin GA Harvey-Jones E O'Sullivan DE Booth CM Sullivan R Aggarwal A Mortality due to cancer treatment delay: systematic review and meta-analysis BMJ. 2020 371 m4087 10.1136/bmj.m4087 33148535
Hanna TP, King WD, Thibodeau S, Jalink M, Paulin GA, Harvey-Jones E, O’Sullivan DE, Booth CM, Sullivan R, Aggarwal A. Mortality due to cancer treatment delay: systematic review and meta-analysis. BMJ. 2020;371:m4087.33148535
8. Lee JB Jung M Kim JH Kim BH Kim Y Kim YS Kim BC Kim J Moon SH Park KU Park M Park HJ Sim SH Yoon HM Lee SJ Lee E Chun JY Chung YK Jung SY Chung J Lee ES Chung HC Yun T Rha SY Guidelines for cancer care during the COVID-19 pandemic in South Korea Cancer Res Treat. 2021 53 323 329 10.4143/crt.2020.1256 33721486
Lee JB, Jung M, Kim JH, Kim BH, Kim Y, Kim YS, Kim BC, Kim J, Moon SH, Park KU, Park M, Park HJ, Sim SH, Yoon HM, Lee SJ, Lee E, Chun JY, Chung YK, Jung SY, Chung J, Lee ES, Chung HC, Yun T, Rha SY. Guidelines for cancer care during the COVID-19 pandemic in South Korea. Cancer Res Treat. 2021;53:323–9.33721486
9. Pandrowala S Ramraj D Shankar R Chopra S Das A Mishra A Pandey D Impact of preoperative COVID infection on the outcomes of planned curative-intent cancer surgeries in the second wave of the pandemic from a tertiary care center in India J Surg Oncol. 2022 125 107 112 10.1002/jso.26697 34569620
Pandrowala S, Ramraj D, Shankar R, Chopra S, Das A, Mishra A, Pandey D. Impact of preoperative COVID infection on the outcomes of planned curative-intent cancer surgeries in the second wave of the pandemic from a tertiary care center in India. J Surg Oncol. 2022;125:107–12.34569620
10. Wang Y Ma J Wu Y Zhang S Li X Xia Y Yan Z Liu J Shen F Zhang X Outcomes of liver cancer patients undergoing elective surgery after recovering from mild SARS-CoV-2 Omicron infection: a retrospective cohort study Cancers (Basel). 2023 15 4254 10.3390/cancers15174254 37686530
Wang Y, Ma J, Wu Y, Zhang S, Li X, Xia Y, Yan Z, Liu J, Shen F, Zhang X. Outcomes of liver cancer patients undergoing elective surgery after recovering from mild SARS-CoV-2 Omicron infection: a retrospective cohort study. Cancers (Basel). 2023;15:4254.37686530
11. von Elm E Altman DG Egger M Pocock SJ Gøtzsche PC Vandenbroucke JP The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies Ann Intern Med. 2007 147 573 577 10.7326/0003-4819-147-8-200710160-00010 17938396
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147:573–7.17938396
12. Huh K Kang M Kim YE Choi Y An SJ Seong J Go MJ Kang JM Jung J Risk of severe COVID-19 and protective effectiveness of vaccination among solid organ transplant recipients J Infect Dis 2023 10.1093/infdis/jiad501
Huh K, Kang M, Kim YE, Choi Y, An SJ, Seong J, Go MJ, Kang JM, Jung J. Risk of severe COVID-19 and protective effectiveness of vaccination among solid organ transplant recipients. J Infect Dis. 2023. 10.1093/infdis/jiad501.
13. National Health Insurance Data Sharing Service. https://nhiss.nhis.or.kr/bd/ab/bdaba032eng.do Accessed 7 April 2024.
14. Cheol Seong S Kim YY Khang YH Heon Park J Kang HJ Lee H Do CH Song JS Hyon Bang J Ha S Lee EJ Ae Shin S Data resource profile: the National Health Information Database of the National Health Insurance Service in South Korea Int J Epidemiol. 2017 46 799 800 27794523
Cheol Seong S, Kim YY, Khang YH, Heon Park J, Kang HJ, Lee H, Do CH, Song JS, Hyon Bang J, Ha S, Lee EJ, Ae Shin S. Data resource profile: the National Health Information Database of the National Health Insurance Service in South Korea. Int J Epidemiol. 2017;46:799–800.27794523
15. Health Insurance Review & Assessment Service. Standard Guide to Statistics of Disease and Procedure. https://opendata.hira.or.kr/co.apndFile.dir/download.do?fileNm=illnessBehavior.pdf. Accessed 15 Dec 2022.
16. Kim SY Kim JH Kim M Wee JH Jung Y Min C Yoo DM Sim S Choi HG The associations of previous influenza/upper respiratory infection with COVID-19 susceptibility/morbidity/mortality: a nationwide cohort study in South Korea Sci Rep. 2021 11 21568 10.1038/s41598-021-00428-x 34732751
Kim SY, Kim JH, Kim M, Wee JH, Jung Y, Min C, Yoo DM, Sim S, Choi HG. The associations of previous influenza/upper respiratory infection with COVID-19 susceptibility/morbidity/mortality: a nationwide cohort study in South Korea. Sci Rep. 2021;11:21568.34732751
17. Choi Y Kang M Shin DH Jung J Choi SJ Kim NH Moon SM Song KH Kim ES Jung J Kim HB Antibiotic prescription in patients with coronavirus disease 2019: analysis of National Health Insurance System Data in the Republic of Korea J Korean Med Sci. 2023 38 e189 10.3346/jkms.2023.38.e189 37365725
Choi Y, Kang M, Shin DH, Jung J, Choi SJ, Kim NH, Moon SM, Song KH, Kim ES, Jung J, Kim HB. Antibiotic prescription in patients with coronavirus disease 2019: analysis of National Health Insurance System Data in the Republic of Korea. J Korean Med Sci. 2023;38:e189.37365725
18. Quan H Li B Couris CM Fushimi K Graham P Hider P Januel JM Sundararajan V Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries Am J Epidemiol. 2011 173 676 682 10.1093/aje/kwq433 21330339
Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, Januel JM, Sundararajan V. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173:676–82.21330339
19. Le ST Kipnis P Cohn B Liu VX COVID-19 vaccination and the timing of surgery following COVID-19 infection Ann Surg. 2022 276 e265 e272 10.1097/SLA.0000000000005597 35837898
Le ST, Kipnis P, Cohn B, Liu VX. COVID-19 vaccination and the timing of surgery following COVID-19 infection. Ann Surg. 2022;276:e265–72.35837898
20. Prasad NK Lake R Englum BR Turner DJ Siddiqui T Mayorga-Carlin M Sorkin JD Lal BK COVID-19 vaccination associated with reduced postoperative SARS-CoV-2 infection and morbidity Ann Surg. 2022 275 31 36 10.1097/SLA.0000000000005176 34417362
Prasad NK, Lake R, Englum BR, Turner DJ, Siddiqui T, Mayorga-Carlin M, Sorkin JD, Lal BK. COVID-19 vaccination associated with reduced postoperative SARS-CoV-2 infection and morbidity. Ann Surg. 2022;275:31–6.34417362
21. Wang Xuefeng Firth logistic regression for rare variant association tests Front Genet. 2014 5 187 10.3389/fgene.2014.00187 24995013
Wang Xuefeng. Firth logistic regression for rare variant association tests. Front Genet. 2014;5:187.24995013
22. VanderWeele TJ Ding P Sensitivity analysis in observational research: introducing the E-value Ann Intern Med. 2017 167 268 274 10.7326/M16-2607 28693043
VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med. 2017;167:268–74.28693043
23. Garnier M Constantin JM Cinotti R Daoui C Margetis D Destruhaut G Cirenei C Noll E Quesnel C Lecinq A Lasocki S Charbonneau H Abrard S Quemeneur C Pastene B Lapidus N Leone M Association of preoperative COVID-19 and postoperative respiratory morbidity during the Omicron epidemic wave: the DROMIS-22 multicentre prospective observational cohort study EClinicalMedicine. 2023 58 101881 10.1016/j.eclinm.2023.101881 36873425
Garnier M, Constantin JM, Cinotti R, Daoui C, Margetis D, Destruhaut G, Cirenei C, Noll E, Quesnel C, Lecinq A, Lasocki S, Charbonneau H, Abrard S, Quemeneur C, Pastene B, Lapidus N, Leone M. Association of preoperative COVID-19 and postoperative respiratory morbidity during the Omicron epidemic wave: the DROMIS-22 multicentre prospective observational cohort study. EClinicalMedicine. 2023;58:101881.36873425
24. McInerney CD Kotzé A Bacon S Cutting JE Fisher L Goldacre B Johnson OA Kua J McGuckin D Mehrkar A OpenSAFELY Collaborative, Moonesinghe SR Postoperative mortality and complications in patients with and without pre-operative SARS-CoV-2 infection: a service evaluation of 24 million linked records using OpenSAFELY Anaesthesia. 2023 78 692 700 10.1111/anae.16001 36958018
McInerney CD, Kotzé A, Bacon S, Cutting JE, Fisher L, Goldacre B, Johnson OA, Kua J, McGuckin D, Mehrkar A, OpenSAFELY Collaborative, Moonesinghe SR. Postoperative mortality and complications in patients with and without pre-operative SARS-CoV-2 infection: a service evaluation of 24 million linked records using OpenSAFELY. Anaesthesia. 2023;78:692–700.36958018
25. SenthilKumar G Verhagen NB Sheriff SA Yang X Figueroa Castro CE Szabo A Taylor BW Wainaina N Lauer K Gould JC Kothari AN N3C Consortium Preoperative SARS-CoV-2 infection increases risk of early postoperative cardiovascular complications following noncardiac surgery Am J Physiol Heart Circ Physiol. 2023 324 H721 H731 10.1152/ajpheart.00097.2023 36930659
SenthilKumar G, Verhagen NB, Sheriff SA, Yang X, Figueroa Castro CE, Szabo A, Taylor BW, Wainaina N, Lauer K, Gould JC, Kothari AN, N3C Consortium. Preoperative SARS-CoV-2 infection increases risk of early postoperative cardiovascular complications following noncardiac surgery. Am J Physiol Heart Circ Physiol. 2023;324:H721–31.36930659
26. Ju JW Kim T Yoon SH Kim WH Lee HJ The impact of preoperative coronavirus disease 19 infection on early postoperative mortality during the vaccination era: a nationwide retrospective cohort study Korean J Anesthesiol. 2024 10.4097/kja.23761 38273737
Ju JW, Kim T, Yoon SH, Kim WH, Lee HJ. The impact of preoperative coronavirus disease 19 infection on early postoperative mortality during the vaccination era: a nationwide retrospective cohort study. Korean J Anesthesiol. 2024. 10.4097/kja.23761.38273737
27. Choi S Park C Park H Jung YH Hwang M-J Son T Severity of COVID-19 associated with SARS-CoV-2 variants circulating in the Republic of Korea Public Heal Wkly Rep. 2022 15 2873 2895 10.56786/PHWR.2022.15.47.2873
Choi S, Park C, Park H, Jung YH, Hwang M-J, Son T. Severity of COVID-19 associated with SARS-CoV-2 variants circulating in the Republic of Korea. Public Heal Wkly Rep. 2022;15:2873–95.
28. Turaga KK Girotra S Are We harming cancer patients by delaying their cancer surgery during the COVID-19 Pandemic? Ann Surg. 2023 278 e960 e965 10.1097/SLA.0000000000003967 32487802
Turaga KK, Girotra S. Are We harming cancer patients by delaying their cancer surgery during the COVID-19 Pandemic? Ann Surg. 2023;278:e960–5.32487802
29. Prasad NK Englum BR Mayorga-Carlin M Turner DJ Sahoo S Sorkin JD Lal BK Partial COVID-19 vaccination associated with reduction in postoperative mortality and SARS-CoV-2 infection Am J Surg. 2022 224 1097 1102 10.1016/j.amjsurg.2022.03.038 35465949
Prasad NK, Englum BR, Mayorga-Carlin M, Turner DJ, Sahoo S, Sorkin JD, Lal BK. Partial COVID-19 vaccination associated with reduction in postoperative mortality and SARS-CoV-2 infection. Am J Surg. 2022;224:1097–102.35465949
30. Nham E Song JY Noh JY Cheong HJ Kim WJ COVID-19 vaccination in Korea: past, present, and the way forward J Korean Med Sci. 2022 37 e351 10.3346/jkms.2022.37.e351 36472087
Nham E, Song JY, Noh JY, Cheong HJ, Kim WJ. COVID-19 vaccination in Korea: past, present, and the way forward. J Korean Med Sci. 2022;37:e351.36472087
31. GlobalSurg Collaborative and National Institute for Health Research Global Health Research Unit on Global Surgery. Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries. Lancet. 2021;397:387–97.
32. Allemani C Matsuda T Di Carlo V Harewood R Matz M Nikšić M Bonaventure A Valkov M Johnson CJ Estève J Ogunbiyi OJ Azevedo E Silva G Chen WQ Eser S Engholm G Stiller CA Monnereau A Woods RR Visser O Lim GH Aitken J Weir HK Coleman MP Global surveillance of trends in cancer survival 2000–2014 (CONCORD-3): analysis of individual records for 37,513,025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries Lancet 2018 391 1023 1075 10.1016/S0140-6736(17)33326-3 29395269
Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, Bonaventure A, Valkov M, Johnson CJ, Estève J, Ogunbiyi OJ, Azevedo E, Silva G, Chen WQ, Eser S, Engholm G, Stiller CA, Monnereau A, Woods RR, Visser O, Lim GH, Aitken J, Weir HK, Coleman MP. Global surveillance of trends in cancer survival 2000–2014 (CONCORD-3): analysis of individual records for 37,513,025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391:1023–75.29395269
33. Llanos AAM Ashrafi A Ghosh N Tsui J Lin Y Fong AJ Ganesan S Heckman CJ Evaluation of inequities in cancer treatment delay or discontinuation following SARS-CoV-2 infection JAMA Netw Open. 2023 6 e2251165 10.1001/jamanetworkopen.2022.51165 36637818
Llanos AAM, Ashrafi A, Ghosh N, Tsui J, Lin Y, Fong AJ, Ganesan S, Heckman CJ. Evaluation of inequities in cancer treatment delay or discontinuation following SARS-CoV-2 infection. JAMA Netw Open. 2023;6:e2251165.36637818
34. Korea Disease Control and Prevention Agency. Intermediate results of a study on chronic COVID-19 syndrome using big data. https://www.kdca.go.kr/filepath/boardDownload.es?bid=0015&list_no=722896&seq=2. Accessed 3 Jan 2024.
35. Prasad NK Mayorga-Carlin M Sahoo S Englum BR Turner DJ Siddiqui T Lake R Sorkin JD Lal BK Mid-term surgery outcomes in patients with COVID-19: results from a nationwide analysis Ann Surg. 2023 277 920 928 10.1097/SLA.0000000000005515 35762608
Prasad NK, Mayorga-Carlin M, Sahoo S, Englum BR, Turner DJ, Siddiqui T, Lake R, Sorkin JD, Lal BK. Mid-term surgery outcomes in patients with COVID-19: results from a nationwide analysis. Ann Surg. 2023;277:920–8.35762608
36. Sud A Jones ME Broggio J Loveday C Torr B Garrett A Nicol DL Jhanji S Boyce SA Gronthoud F Ward P Handy JM Yousaf N Larkin J Suh YE Scott S Pharoah PDP Swanton C Abbosh C Williams M Lyratzopoulos G Houlston R Turnbull C Collateral damage: the impact on outcomes from cancer surgery of the COVID-19 pandemic Ann Oncol. 2020 31 1065 1074 10.1016/j.annonc.2020.05.009 32442581
Sud A, Jones ME, Broggio J, Loveday C, Torr B, Garrett A, Nicol DL, Jhanji S, Boyce SA, Gronthoud F, Ward P, Handy JM, Yousaf N, Larkin J, Suh YE, Scott S, Pharoah PDP, Swanton C, Abbosh C, Williams M, Lyratzopoulos G, Houlston R, Turnbull C. Collateral damage: the impact on outcomes from cancer surgery of the COVID-19 pandemic. Ann Oncol. 2020;31:1065–74.32442581
37. Oh J Lee JK Schwarz D Ratcliffe HL Markuns JF Hirschhorn LR National response to COVID-19 in the Republic of Korea and lessons learned for other countries Heal Syst Reform. 2020 6 e1753464 10.1080/23288604.2020.1753464
Oh J, Lee JK, Schwarz D, Ratcliffe HL, Markuns JF, Hirschhorn LR. National response to COVID-19 in the Republic of Korea and lessons learned for other countries. Heal Syst Reform. 2020;6:e1753464.
38. Han C Changes in mortality rate of the general population during the COVID-19 pandemic: an interrupted time series study in Korea Int J Epidemiol. 2022 51 1396 1407 10.1093/ije/dyac083 35462402
Han C. Changes in mortality rate of the general population during the COVID-19 pandemic: an interrupted time series study in Korea. Int J Epidemiol. 2022;51:1396–407.35462402
39. Yoo KJ Lee Y Lee S Friebel R Shin SA Lee T Bishai D The road to recovery: impact of COVID-19 on healthcare utilization in South Korea in 2016–2022 using an interrupted time-series analysis Lancet Reg Health West Pac. 2023 41 100904 37780633
Yoo KJ, Lee Y, Lee S, Friebel R, Shin SA, Lee T, Bishai D. The road to recovery: impact of COVID-19 on healthcare utilization in South Korea in 2016–2022 using an interrupted time-series analysis. Lancet Reg Health West Pac. 2023;41:100904.37780633
