The coronavirus disease 2019 (COVID-19) pandemic is a significant global concern that has had major implications for the healthcare system. Patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) undergoing elective or emergency surgical procedures have a substantial risk of mortality and peri-operative complications. The present study aimed to describe the characteristics of patients who underwent elective surgery and developed nosocomial SARS-CoV-2 infection post-surgery. Patients who underwent thoracic, upper and lower abdominal or peripheral elective surgery with a polymerase chain reaction diagnosis of COVID-19, at 3-7 days after the surgery, were enrolled in the present retrospective study. Demographics, vaccination status against SARS-CoV-2, Charlson comorbidity index (CCI) and laboratory data were recorded upon admission to the hospital unit. In total, 116 subjects (80 males, 36 females; mean age, 67.31±16.83 years) fulfilling the inclusion criteria were identified. Among the 116 participants, 14 (12.1%) were intubated. From the 116 individuals analyzed, 84 were alive after 30 days (survivors), and 32 had succumbed to the disease (non-survivors). The mortality rate was 27.6% (32/116). The non-survivors had an older age and a higher CCI score. At the evaluation upon admission to the hospital unit, the survivors presented with higher serum albumin levels and a higher number of blood lymphocytes. In addition, the survivors exhibited lower levels of lactate dehydrogenase, aspartate aminotransferase, alkaline phosphatase (ALP) and C-reactive protein (CRP), as well as a higher neutrophil to lymphocyte ratio (NLR) and CRP to albumin ratio (CAR) (P<0.05). The patients that were intubated had higher levels of gamma glutamyl-transferase (GGT), ALP and ferritin, as well as a higher NLR and platelet to lymphocyte ratio upon admission to the hospital unit (P<0.05). According to the Cox proportional hazards multivariate regression analysis, the only independent predictors of mortality and intubation were ALP and GGT upon admission, respectively (P<0.05). On the whole, the findings of the present study suggest that more stringent guidelines are required in order to prevent infection during the post-operative period.
The coronavirus disease 2019 (COVID-19) pandemic is a major global concern that has had significant implications for the healthcare system (
While surgical delays were frequently caused by hospital capacity and infection transmission concerns, there was also ambiguity as regards the peri-operative hazards of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (
It should be noted that COVID-19 infection is linked to significant pulmonary and cardio-circulatory complications, such as respiratory failure, pneumonia, venous thromboembolism, cardiac arrhythmias, or other coagulation issues; thus, a more difficult recovery is anticipated, particularly after the performance of aggressive surgical procedures (
Previous studies have reported that patients with severe SARS-CoV-2 infection who underwent elective surgery had a high risk of post-operative mortality and of developing complications (
However, data on the outcomes of patients undergoing surgery and becoming infected with SARS-CoV-2 during the post-operative period are limited. The present study thus aimed to describe the characteristics of patients who underwent elective surgery and developed nosocomial SARS-CoV-2 infection post-surgery, as well as to identify determinants of mortality and other unfavorable outcomes in these patients.
The present study was a single-center retrospective study of patients with COVID-19 admitted to the Department of Infectious Diseases-COVID-19 Unit of Laiko General Hospital, Athens, Greece between September 21, 2020 and April 15, 2022. The study was conducted in line with the Declaration of Helsinki and was approved by the Institutional Review Board of Laiko General Hospital (protocol no. 765/12-2021). Written informed was obtained from the patients for inclusion in the study.
The following criteria were required for inclusion in the study: Patients who underwent thoracic, upper and lower abdominal or peripheral elective surgery with a polymerase chain reaction (PCR) diagnosis of COVID-19, at 3-7 days post-surgery, who had been tested negative during the pre-operative evaluation and were admitted to the Department of Infectious Diseases-COVID-19 Unit on the day of COVID-19 diagnosis. Thoracic surgery included esophagectomy. Upper abdominal surgeries included the open repair of an aortic stent leak, the resection of retroperitoneal sarcoma, gastrectomy, splenectomy, hepatectomy, nephrectomy, pancreatectomy and cholopeptic anastomosis. Lower abdominal surgeries included segmental colectomy, the surgical repair of ureteroarterial fistula, cystectomy, hysterectomy, umbilical hernia repair, abdominal wall hernia repair, low anterior resection, abdominoperineal resection and renal transplantation. Peripheral surgeries included orthopedic surgeries, such as the repair of knee, hip and metatarsal fractures, and amputations due to limb gangrene.
The patients were classified into the following categories according to the severity of COVID-19 infection: Asymptomatic, mild/moderate, severe and critical, based on the clinical spectrum of SARS-CoV-2 infection (
Data regarding demographics, vaccination status against SARS-CoV-2 and the Charlson comorbidity index (CCI) were recorded. Hemoglobin (Hb), white blood cells, blood neutrophils, lymphocytes and immature granulocytes, neutrophil to lymphocyte ratio (NLR), platelets (PLTs), platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), serum albumin, CRP to albumin ratio (CAR), serum lactate dehydrogenase (LDH), d-dimer levels, ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl-transferase (GGT) were recorded upon admission to the Department of Infectious Diseases-COVID-19 Unit. Charts were evaluated for the implementation of intubation and all-cause mortality at 30 days.
Continuous variables are presented as the mean (standard deviation). The assessment of the normal distribution of variables was performed with the use the Kolmogorov-Smirnov test. The comparison of normally distributed variables was performed using an independent samples Student's t-test on variables with two groups and not normally distributed variables were examined using an unpaired non-parametric two-tailed Mann-Whitney test. Categorical variables were examined using the Fischer's exact test or the Chi-squared test and are shown as absolute numbers (frequency, percentage). The CCI data were numerically recorded. To identify predictors of event(s) (event=intubation, or mortality at 30 days), statistically significant factors were subsequently examined using Cox proportional hazards multivariate regression analysis. The goodness of fit of the log-likelihood ratio was evaluated. The discriminative ability of variables was evaluated using the area under the receiver operating characteristic curve (ROC). The log-rank (Mantel-Cox) test was used to plot survival curves utilizing significant variables. Kaplan-Meier survival analysis was used to analyze time to event data and to compare two groups of subjects. Participants were censored at 30 days. P-values <0.05 were considered to indicate statistically significant differences. Statistical analysis was conducted using IBM SPSS-Statistics version 26.0 (IBM Corp.).
In total, 116 subjects (80 males, 36 females; mean age, 67.31±16.83 years) fulfilling the inclusion criteria were identified. Among the 116 participants, 14 (12.1%) were intubated. From the 116 individuals examined, 84 were alive after 30 days (survivors), and 32 had succumbed to the disease (non-survivors). The mortality rate was 27.6% (32/116). The Demographics and baseline data of the study population are presented in
The non-survivors had an older age and a higher CCI score. At the evaluation upon admission to the hospital unit, the survivors presented with higher serum albumin levels and a higher number of blood lymphocytes. In addition, the survivors exhibited lower levels of LDH, AST, ALP, CRP, NLR and CAR (P<0.05;
All parameters with significant differences in the univariate analysis were analyzed using the Cox proportional hazards multivariate regression analysis. The outcome was all-cause mortality, and cases were censored at 30 days. The results demonstrated that the only independent predictor of mortality was the ALP levels upon admission (P<0.05;
Cox proportional hazards multivariate regression analysis with intubation as the outcome, identified GGT levels as a significant biomarker for the prediction of intubation (P<0.05;
According to the results of the present study, the mortality rate of patients who underwent elective surgery and were infected with SARS-CoV-2 during the post-operative period was high. In the study by Kader
In their study on the clinical outcomes of patients with COVID-19 following thoracic surgery, Al Masri
Tabourin
Prasad
Of note, association was found between the type of surgery and poor outcomes. It is known that thoracic and abdominal surgery are more frequently related to adverse events and pulmonary complications in particular (
In the present study, liver biomarkers were associated with patient outcomes. It is known that SARS-CoV-2 is a systemic infection that affects numerous organs, including the kidneys, pancreas, liver and heart (
The present study has certain limitations. The present study had a retrospective design, and there no control group was included. Furthermore, it is possible that the negative results obtained in the present study (all-cause mortality) are attributable to other etiologies in addition to severe COVID-19 (thromboembolism, sepsis, or coexisting diseases). In addition, another important limitation is the heterogeneity of the cohort, which underwent lower and upper gastrointestinal surgery or other complex procedures. Finally, the present study did not include patients who underwent other types of surgery, such as neurosurgery or robot-assisted laparoscopy surgery.
The advantages of the present study however, are the relatively large number of patients who underwent surgery, as well as the fact that the participants were patients who underwent several different types of surgery. Other additional strong points of the study are the reliable follow-up and the availability of 30-day data.
In conclusion, in the present retrospective study, mortality occurred in 27.6% of the patients who underwent elective surgery and who were infected with SARS-CoV-2 during the post-operative period. The predictors of mortality and intubation were ALP and GGT levels, respectively. Survival did not differ among patients who underwent different types of surgery. Given that the pandemic crisis is ongoing, closer post-operative follow-up periods for COVID-19-related manifestations, and stricter guidelines in order to prevent infection in the post-operative period are required. Larger studies on mortality and risk factors for poor outcomes of patients undergoing surgery and who are infected with SARS-CoV-2 during the post-operative period are also warranted.
Not applicable.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
KT, GF and VEG conceptualized the study. VEG, DB, PMV, GK, IE, SP and CVP advised on patient care and medical treatment, were involved in data analysis and wrote and prepared the draft of the manuscript. NM, KT, DAS, PP, GF and NVS analyzed the data and provided critical revisions. VEG and NVS confirm the authenticity of all the data. All authors contributed to manuscript revision and have read and approved the final version of the manuscript.
The present study was conducted in line with the Declaration of Helsinki and was approved by the Institutional Review Board of Laiko General Hospital (protocol no. 765/12-2021). Written informed was obtained from the patients for inclusion in the study. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Not applicable.
DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests.
Receiver operating characteristic curve for ALP predicting the mortality rate of patients who underwent elective surgery and were infected with COVID-19 post-operatively. AUC, 0.702 (P<0.05). ALP, alkaline phosphatase; AUC, area under the curve.
Kaplan-Meier survival curve. A significantly worse survival was observed for patients with ALP levels >122.5 U/l (P<0.05). ALP, alkaline phosphatase.
Receiver operating characteristic curve for GGT predicting intubation in patients who underwent elective surgery and were infected with COVID-19 post-operatively. AUC, 0.742. GGT, gamma glutamyl-transferase; AUC, area under the curve.
Demographics and baseline characteristics of the study population.
Parameter | No. of patients | Value |
---|---|---|
Age, years; mean (SD) | 116 | 67.31 (16.83) |
Sex, n (%) | ||
Female | 36 | 31 |
Male | 80 | 69 |
Mortality, n (%) | ||
No | 84 | 72.4 |
Yes | 32 | 27.6 |
Intubation, n (%) | ||
No | 102 | 87.9 |
Yes | 14 | 12.1 |
Type of surgery, n (%) | ||
Thoracic | 10 | 8.6 |
Upper abdominal | 32 | 27.6 |
Lower abdominal | 35 | 30.2 |
Peripheral | 39 | 33.6 |
Disease severity, n (%) | ||
Asymptomatic | 26 | 22.4 |
Mild/moderate | 30 | 25.9 |
Severe | 27 | 23.3 |
Critical | 33 | 28.3 |
Vaccination status, n (%) | ||
Unvaccinated | 72 | 62.1 |
Fully vaccinated | 44 | 37.9 |
SD, standard deviation.
Univariate analysis (outcome, mortality).
Parameter | Outcome | No. of patients | Mean | SD | P-value |
---|---|---|---|---|---|
Age, years | Recovery | 84 | 64.95 | 17.97 | 0.03 |
Mortality | 32 | 73.50 | 11.48 | ||
CCI | Recovery | 80 | 4.30 | 2.61 | 0.01 |
Mortality | 36 | 5.94 | 2.37 | ||
Hb (g/dl) | Recovery | 80 | 10.40 | 1.63 | 0.97 |
Mortality | 36 | 10.44 | 1.63 | ||
WBCs (K/µl) | Recovery | 84 | 8.99 | 4.26 | 0.20 |
Mortality | 32 | 10.16 | 4.82 | ||
IGs (109/l) | Recovery | 84 | 0.17 | 0.24 | 0.80 |
Mortality | 32 | 0.18 | 0.19 | ||
Lymphocytes (K/µl) | Recovery | 84 | 1.10 | 0.58 | 0.04 |
Mortality | 32 | 0.86 | 0.57 | ||
Neutrophils (K/µl) | Recovery | 84 | 7.08 | 3.97 | 0.06 |
Mortality | 32 | 8.75 | 4.56 | ||
PLTs (K/µl) | Recovery | 84 | 396.52 | 420.25 | 0.10 |
Mortality | 30 | 269.60 | 111.01 | ||
Fibrinogen (mg/dl) | Recovery | 64 | 561.00 | 160.48 | 0.10 |
Mortality | 30 | 499.13 | 184.99 | ||
Albumin (g/l) | Recovery | 82 | 32.55 | 5.00 | 0.01 |
Mortality | 32 | 28.00 | 5.82 | ||
GGT (U/l) | Recovery | 82 | 135.76 | 194.38 | 0.26 |
Mortality | 32 | 182.00 | 203.80 | ||
LDH (U/l) | Recovery | 84 | 266.26 | 105.29 | 0.01 |
Mortality | 32 | 397.75 | 287.10 | ||
ALT (U/l) | Recovery | 84 | 36.76 | 31.76 | 0.21 |
Mortality | 30 | 81.20 | 191.30 | ||
d-Dimers (µg/ml) | Recovery | 56 | 3.32 | 2.74 | 0.92 |
Mortality | 30 | 3.80 | 3.29 | ||
Creatinine (mg/dl) | Recovery | 80 | 1.14 | 0.80 | 0.54 |
Mortality | 36 | 1.42 | 1.41 | ||
AST (U/l) | Recovery | 80 | 35.48 | 27.46 | 0.03 |
Mortality | 36 | 150.44 | 284.95 | ||
ALP (U/l) | Recovery | 80 | 118.02 | 90.68 | 0.005 |
Mortality | 36 | 181.77 | 149.97 | ||
Ferritin (ng/ml) | Recovery | 66 | 733.74 | 559.13 | 0.06 |
Mortality | 32 | 1367.28 | 1917.45 | ||
CRP (mg/l) | Recovery | 78 | 74.74 | 58.34 | 0.003 |
Mortality | 36 | 131.87 | 110.36 | ||
NLR | Recovery | 80 | 10.16 | 17.31 | 0.01 |
Mortality | 36 | 14.56 | 11.43 | ||
PLR | Recovery | 80 | 517.53 | 872.83 | 0.33 |
Mortality | 34 | 439.11 | 287.33 | ||
CAR | Recovery | 76 | 2.40 | 2.03 | 0.004 |
Mortality | 36 | 5.44 | 5.58 | ||
Sex | 0.61 | ||||
Female | Recovery | 26 | |||
Mortality | 10 | ||||
Male | Recovery | 54 | |||
Mortality | 26 | ||||
Type of surgery | 0.15 | ||||
Thoracic | Recovery | 6 | |||
Mortality | 4 | ||||
Upper abdominal | Recovery | 22 | |||
Mortality | 8 | ||||
Lower abdominal | Recovery | 30 | |||
Mortality | 10 | ||||
Peripheral | Recovery | 22 | |||
Mortality | 14 | ||||
Vaccination status | 0.15 | ||||
Unvaccinated | Recovery | 46 | |||
Mortality | 26 | ||||
Fully vaccinated | Recovery | 34 | |||
Mortality | 10 |
SD, standard deviation; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CCI, Charlson comorbidity index; CRP, C-reactive protein; CAR, CRP to albumin ratio; GGT, gamma glutamyl-transferase; Hb, hemoglobin; IGs, immature granulocytes; LDH, lactate dehydrogenase; NLR, neutrophil to lymphocyte ratio platelets; PLTs, platelets; PLR, platelet to lymphocyte ratio; WBCs, white blood cells.
Univariate analysis (outcome, intubation).
Parameter | Outcome | No. of patients | Mean | SD | P-value |
---|---|---|---|---|---|
Age, years | Non-intubated | 102 | 67.16 | 17.34 | 0.79 |
Intubated | 14 | 68.43 | 12.97 | ||
CCI | Non-intubated | 102 | 4.73 | 2.61 | 0.57 |
Intubated | 14 | 5.43 | 2.92 | ||
Hb (g/dl) | Non-intubated | 102 | 10.43 | 1.62 | 0.83 |
Intubated | 14 | 10.31 | 1.70 | ||
WBCS (K/µl) | Non-intubated | 102 | 9.33 | 4.41 | 0.91 |
Intubated | 14 | 9.19 | 4.78 | ||
IGs (109/l) | Non-intubated | 102 | 0.17 | 0.24 | 0.75 |
Intubated | 14 | 0.15 | 0.14 | ||
Lymphocytes (K/µl) | Non-intubated | 102 | 1.07 | 0.58 | 0.07 |
Intubated | 14 | 0.78 | 0.54 | ||
Neutrophils (K/µl) | Non-intubated | 102 | 7.48 | 4.18 | 0.69 |
Intubated | 14 | 8.00 | 4.37 | ||
PLTs (K/µl) | Non-intubated | 100 | 369.34 | 392.23 | 0.63 |
Intubated | 14 | 318.71 | 91.4 | ||
Fibrinogen (mg/dl) | Non-intubated | 80 | 541.37 | 173.04 | 0.98 |
Intubated | 14 | 540.57 | 158.73 | ||
Albumin (g/l) | Non-intubated | 100 | 31.64 | 5.45 | 0.06 |
Intubated | 14 | 28.65 | 6.20 | ||
GGT (U/l) | Non-intubated | 102 | 130.04 | 179.00 | 0.04 |
Intubated | 12 | 307.67 | 273.40 | ||
LDH (U/l) | Non-intubated | 102 | 300.14 | 190.32 | 0.70 |
Intubated | 14 | 320.00 | 127.92 | ||
ALT (U/l) | Non-intubated | 100 | 51.56 | 108.86 | 0.39 |
Intubated | 14 | 26.28 | 24.13 | ||
d-Dimers (µg/ml) | Non-intubated | 72 | 3.53 | 3.14 | 0.40 |
Intubated | 14 | 3.24 | 1.54 | ||
Creatinine (mg/dl) | Non-intubated | 102 | 1.21 | 1.05 | 0.48 |
Intubated | 14 | 1.34 | 0.89 | ||
AST (U/l) | Non-intubated | 102 | 70.80 | 174.49 | 0.90 |
Intubated | 14 | 73.71 | 108.91 | ||
ALP (U/l) | Non-intubated | 102 | 134.27 | 119.99 | 0.015 |
Intubated | 14 | 163.57 | 74.89 | ||
Ferritin (ng/ml) | Non-intubated | 84 | 770.47 | 655.04 | 0.015 |
Intubated | 14 | 1961.42 | 2635.74 | ||
CRP (mg/l) | Non-intubated | 100 | 89.84 | 80.17 | 0.46 |
Intubated | 14 | 113.80 | 98.18 | ||
NLR | Non-intubated | 102 | 11.00 | 16.30 | 0.02 |
Intubated | 14 | 15.36 | 11.36 | ||
PLR | Non-intubated | 100 | 482.76 | 791.23 | 0.008 |
Intubated | 14 | 575.44 | 273.55 | ||
CAR | Non-intubated | 98 | 3.21 | 3.62 | 0.47 |
Intubated | 14 | 4.53 | 5.04 | ||
Sex | 0.90 | ||||
Female | Non-intubated | 32 | |||
Intubated | 4 | ||||
Male | Non-intubated | 70 | |||
Intubated | 10 | ||||
Type of surgery | 0.46 | ||||
Thoracic | Non-intubated | 8 | |||
Intubated | 2 | ||||
Upper abdominal | Non-intubated | 28 | |||
Intubated | 2 | ||||
Lower abdominal | Non-intubated | 30 | |||
Intubated | 8 | ||||
Peripheral | Non-intubated | 34 | |||
Intubated | 2 | ||||
Vaccination status | 0.13 | ||||
Unvaccinated | Non-intubated | 46 | |||
Intubated | 26 | ||||
Fully vaccinated | Non-intubated | 34 | |||
Intubated | 10 |
SD, standard deviation; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CCI, Charlson comorbidity index; CRP, C-reactive protein; CAR, CRP to albumin ratio; GGT, gamma glutamyl-transferase; Hb, hemoglobin; IGs, immature granulocytes; LDH, lactate dehydrogenase; NLR, neutrophil to lymphocyte ratio platelets; PLTs, platelets; PLR, platelet to lymphocyte ratio; WBCs, white blood cells.
Cox regression multivariable analysis (outcome, mortality).
95% CI for Exp(B) | ||||
---|---|---|---|---|
Parameter | P-value | Exp(B) | Lower | Upper |
Age (years) | 0.275 | 1.018 | 0.986 | 1.051 |
CCI | 0.972 | 0.997 | 0.837 | 1.187 |
Lymphocytes (K/µl) | 0.052 | 0.384 | 0.146 | 1.010 |
AST (U/l) | 0.494 | 1.001 | 0.998 | 1.004 |
ALP (U/l) | 1.003 | 1.000 | 1.007 | |
LDH (U/l) | 0.926 | 1.000 | 0.997 | 1.003 |
CRP (mg/l) | 0.631 | 0.995 | 0.976 | 1.015 |
ALB (g/l) | 0.413 | 0.955 | 0.855 | 1.067 |
NLR | 0.565 | 0.991 | 0.963 | 1.021 |
CAR | 0.555 | 0.131 | 0.751 | 1.703 |
Values in bold font indicate a statistically significant difference (P<0.05). ALP, alkaline phosphatase; ALB, albumin; AST, aspartate aminotransferase; CCI, Charlson comorbidity index; CRP, C-reactive protein; CAR, CRP to albumin ratio; LDH, lactate dehydrogenase; NLR, neutrophil to lymphocyte ratio.
Cox regression multivariable analysis (outcome, intubation).
95% CI for Exp(B) | ||||
---|---|---|---|---|
Parameter | P-value | Exp(B) | Lower | Upper |
NLR | 0.209 | 1.060 | 0.968 | 1.162 |
PLR | 0.278 | 0.999 | 0.997 | 1.001 |
GGT (U/l) | 0.015 | 1.006 | 1.001 | 1.012 |
Ferritin (ng/ml) | 0.736 | 1.000 | 0.990 | 0.999 |
ALP (U/l) | 0.294 | 0.994 | 0.982 | 1.005 |
ALP, alkaline phosphatase; GGT, gamma glutamyl-transferase; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio.