Introduction

The novel coronavirus, SARS-CoV-2, as the agent of coronavirus 2019 disease (COVID-19) was first reported in Wuhan, China at the end of December 2019. With rapid spread across the world, COVID-19 was declared a global pandemic in March 2020. The virus enters respiratory cells through angiotensin converting enzyme receptors 2 (ACE-2), and the morbidity and mortality in infected patients are usually due to severe viral pneumonia. Antiviral agents such as favipiravir and remdesivir have been used in treatment, but a specific treatment for COVID-19 is still not widely available¹. During the 1^st few months of the pandemic, all elective operations were cancelled and only urgent cases were operated on. However, as the SARS CoV-2 infection could not be eradicated and continued to spread rapidly, eventually elective surgical operations were re-started. Although most centers checked cases preoperatively for COVID-19 with a nasopharyngeal swab polymerase chain reaction (PCR) test for SARS CoV-2, emergency operations had to be performed even if the patient had a positive PCR test, and some cases developed COVID-19 postoperatively. Pre/post-operative COVID-19 infection has been reported to be related with an increased risk of post-operative complications and mortality²-⁶. However, surgeries for acute abdominal pathologies decreased after the outbreak of the pandemic due to the fear of SARS CoV-2 infection, and in cases with COVID-19, a delayed intervention may result in complications related to an underlying urgent pathology⁷,⁸. To make the decision for surgery in patients infected with SARS-CoV-2, the post-operative risk related to COVID-19 infection must be evaluated carefully and the risk/benefit ratio should be assessed. Therefore, there is a need to investigate the effect of COVID-19 on the course of surgical cases in detail. The aim of this study was to evaluate the effect of COVID-19 infection on the outcomes of surgical patients and the factors associated with post-operative complications and mortality in cases with pre/post-operative SARS CoV-2 infection.

Material and methods

The study group (COVID-19 group) consisted of adult inpatients who underwent a surgical procedure and had SARS-CoV-2 PCR positivity in nasopharyngeal swab before/within 10 days following the surgery in Sultan 2. Abdülhamit Han Training and Research Hospital between March 15, 2020, and May 15, 2021. The control group was formed of patients hospitalized before the pandemic (January 1, 2019, and February 1, 2020), who underwent the same operations and had similar demographic, clinical features, and American Society of Anesthesiologists (ASA) grade but did not have a positive PCR result for SARS-CoV-2 before or within 10 days after the surgery. The study was approved by the Local Ethics Committee (Approval date and number: May 27, 2021, and B.10.1.THK.4.34.H.G.P.0.01/180). Data were extracted from the medical records in respect of demographic information, comorbidities [disseminated cancer, diabetes mellitus (DM), hypertension (HT), congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and acute renal failure (ARF)], systemic sepsis, the need for mechanical ventilation, steroid treatment, smoking status, ASA grade, preoperative functional status, type of surgery (elective/urgent and Group AB/CD) and anesthesia (local/general), laboratory parameters on admission (leukocyte, lymphocyte, eosinophil, and thrombocyte counts, and serum level of CRP and D-dimer), the presence of pneumonia and superinfection, clinical course and outcome (duration of hospitalization and/or ICU follow-up, post-operative complications including thrombolytic, hemorrhagic, pulmonary, cardiac, neurological, and local complications, and mortality). The pre-operative pulmonary functional status data were not available in detail, only pathological findings such as history of chronic pulmonary disease and presence of pneumonic infiltrations on the pre-operative chest X-ray and/or thorax computed tomography (CT) were noted in the medical files. The emergency operations included surgery for acute cholecystitis, gastroduodenal perforated ulcers, acute appendicitis, acute gynecological disorders, trauma, and intracranial hemorrhage. The COVID-19 and control groups were compared in terms of age, sex, smoking status, comorbidities, laboratory parameters, the presence of pneumonia and complications, and 30-day postoperative mortality. The factors associated with complications and mortality were also analyzed.

Results

The comparisons of the demographic data of the two groups are shown in table 1. The distribution of patients according to age, sex, age groups, ASA grades, minor/major, and elective/urgent surgery was similar in both groups (p > 0.05). The durations of hospitalization and ICU follow-up were longer in the COVID-19 group compared to the control group (16.39 ± 15.6 days vs. 9.37 ± 9.02 days and, 10 ± 10 days vs. 5 ± 9 days, p = 0.003 and p = 0.003, respectively). Urgent operations were performed on 15/38 (39.5%) patients in the COVID-19 group and on 22/76 (28.9%) patients in the control group (p = 0.358). The mortality rate was higher in the COVID-19 group compared to the control group (14/38 (36.8%) vs. 7/76 (9.2%); (p = 0.001). The rate of post-operative superinfection was 12/38 (31.6%) in the COVID-19 group and 16/76 (21.1%) in the control group (p = 0.317). The rate of major surgery was similar in the COVID-19 group [20/38 (52.6%)] and the control group [48/76 (63.2%)], (p = 0.28).

The comparisons of clinical and laboratory features between the two groups are shown in tables 2 and 3. Surgery was performed under general anesthesia in 31/38 (81.6%) cases in the COVID-19 group and in 62/76 (81.6%) cases in the control group (p = 1.000). Post-operative systemic sepsis was diagnosed in 6/38 (15.8%) patients in the COVID-19 group and in 8/76 (10.5) patients in the control group (p = 0.546). Pneumonia was not observed in any of the control group and pneumonia developed in 15/38 cases in the COVID-19 group (p < 0.0001).

The mean lymphocyte and eosinophil counts were significantly lower, and the mean serum CRP level was significantly higher in the COVID-19 group compared to the control group (1.29 ± 0.85 × 10³/ml vs. 1.72 ± 1.03 × 10³/ml, 0.15 ± 0.20 × 10³/ml vs. 0.18 ± 0.20 × 10³/ml, and 99.13 ± 93.72 mg/dl vs. 58.99 ± 79.32 mg/dl, p = 0.024, p = 0.039, p = 0.005, respectively).

Complications developed 2.4-fold more in the COVID-19 group than in the control group; in 20/38 (52.6%) patients in the COVID-19 group and in 24/76 (31.6%) patients in the control group (p = 0.049). Pneumonia developed in 15/38 (39.5%) patients in the COVID-19 group. Pulmonary, cardiac, and local complications were significantly more frequent in the COVID-19 group than in the control group [16/38 (42.1%) vs. 13/76 (17.1%), 13/38 (34.2%) vs. 9/76 (11.8%) and 10/38 (26.3%) vs. 4/76 (5.3%), p = 0.008, p = 0.017, p = 0.002, respectively] (Table 4).

The results of the univariate and multivariate analysis of factors associated with developing complications and mortality are shown in tables 5 and 6. The COVID-19 group patients developed complications more frequently than the control subjects (OR: 2.407 and CI: 1.082-5.356, p = 0.031). Age, serum CRP, and D-dimer were determined to be associated with an increased risk of post-operative complications (OR: 1.054, CI: 1.027-1.083; OR: 1.009, CI: 1.004-1.015; OR: 1.001, CI: 1.000-1.002, p < 0.0001, p < 0.0001, p < 0.0001, respectively). Lymphocyte count was determined to be associated with a decreased risk of developing complications (OR: 0.387, CI: 0.230-0.653; p < 0.0001). Patients with ASA grade 3-4 developed more complications than those with ASA grade 1-2 (OR: 13.2, CI: 4.621-37.709, p < 0.0001). Patients with two or more comorbidities developed significantly more complications compared to patients without comorbidities (OR: 3.24, CI: 1.176-8.929, p = 0.023). Patients who underwent urgent operations developed more complications than those operated on electively (OR: 6.36, CI: 2.687-15.052, p < 0.0001), and patients with pneumonia developed more complications than those without pneumonia (OR: 32.20, CI: 4.049-256.084, p = 0.001). The multivariate analysis revealed that only the D-dimer level was associated with an increased risk of complications (OR: 1.001, CI: 1.000-1.002).

The diagnosis of COVID-19 infection was determined to increase the risk of mortality (OR: 5.75, CI: 2.075-15.934, p = 0.001). Age and serum CRP level were associated with an increased risk of mortality (OR: 1.063, CI: 1.024-1.104; OR: 1.011, CI: 1.005-1.016, p = 0.001, p < 0.0001, respectively). Lymphocyte count and eosinophil count were found to be associated with a decreased risk of mortality (OR: 0.139, CI: 0.047-0.412; OR: 0.005, CI:0.001-0.011, p < 0.0001, p = 0.001 respectively). The mortality risk was seen to be significantly higher in patients with two or more comorbidities compared to patients without comorbidities (OR: 12, CI: 1.498-96.149, p = 0.019). Patients who underwent urgent operations had an increased risk of mortality compared to those operated on electively (OR: 23.368, CI: 6.229-87.663, p < 0.0001), and patients with pneumonia were at greater risk of mortality than patients without pneumonia (OR: 184, CI: 21.021-1610.6, p < 0.0001). The multivariate analysis revealed that only emergent surgery and having pneumonia were risk factors for increased post-operative mortality (OR: 9.431, CI: 1.469-60.542, and OR: 15.27, CI: 2.06-113.095, respectively).

Discussion

In the study, patients with and without pre/post-operative COVID-19 infection were compared postoperatively. The durations of hospitalization and ICU follow-up were longer in the COVID-19 group and the mortality rate of 36.8% was significantly higher compared to the control group (9.2%). In a previous study, the 30-day post-operative mortality rate was reported as 23.8%, which was mostly due to pulmonary complications⁴. Several studies have reported increased morbidity and mortality rates among surgical patients pre/postoperatively infected with SARS CoV-2²-⁶. In contrast, Seretis et al. evaluated general surgery patients operated for emergency abdominal pathologies and reported a 5% overall postoperative respiratory complication rate, and 3% infection rate for COVID-19; neither the stay in ICU and need for mechanical ventilation nor the postoperative mortality rate were determined to be increased related to COVID-19 infection. It was concluded that if indicated, emergency surgery should not be delayed because of fear of COVID-19-related morbidity or mortality risks. However, that study included cases operated on during the first 3 months of the pandemic so the data were from a low number of patients⁹.

In the current study, the risk of developing postoperative complications was seen to be increased 2.4-fold more in the COVID-19 group than in the control group. Local, pulmonary and cardiac complications were more frequent in the COVID-19 group. In a multicenter study, the rate of pulmonary complications was 57.9 % which was comparable with the results of previous studies⁴. The rate of pulmonary complications in the current study was 42.1%, which was compatible with the results of the above-mentioned cohort. Prasad et al. investigated the risk of postoperative complications in patients who had a negative PCR test before surgery but developed COVID-19 postoperatively and the complication rate ratio for the COVID [-/+] group vs. COVID [−/−] was reported to be 8.4 (CI: 4.9-14.4) for pulmonary complications, 3.0 (CI: 2.2-4.1) for major complications, and 2.6 (CI: 1.9-3.4) for any complication³. In contrast, a study that compared the clinical outcomes of patients infected with SARS CoV-2 pre and postoperatively who underwent emergency surgery reported that patients with a concomitant diagnosis of COVID-19 preoperatively had a lower mortality rate (14.3% vs. 33.3%), lower ARDS rate (28.5% vs. 50.0%), lower rates of preoperative invasive ventilation (14.3% vs. 50.0%) and postoperative invasive ventilation (28.5% vs. 100.0%), and a shorter duration of invasive ventilation compared to patients with severe postoperative COVID-19¹⁰. In the current study, there was no further analysis of the morbidity and mortality rates of patients with pre/postoperative COVID-19. However, this issue may be a subject for further studies.

There are limited data in literature about the postoperative complications and mortality rates in Turkey. In a previous study which evaluated 26 patients who underwent cancer surgery, 4 of whom were diagnosed with COVID-19 infection, the post-operative complication rate was reported to be 2/26 and mortality was 1/26¹¹. Only 1/4 COVID-19 patients developed surgery-related post-operative complications and the other complications and mortality were reported to be unrelated with COVID-19. However, as the number of COVID-19 patients was quite low in that study, the current study findings cannot be compared with these results.

It has been reported that coincidentally asymptomatic COVID-19 patients who undergo surgery may develop severe complications and the preoperative chest X-ray evaluation is not sufficient to detect asymptomatic patients with SARS CoV-2 infection, and therefore all surgical cases should be tested for COVID-19 before surgery¹². This may also help to prevent postoperative COVID-19 in surgical patients. The monitoring of patients for symptoms of COVID-19 after surgery is also important. Lei et al. reported that all patients who developed COVID-19 postoperatively developed pneumonia and the most frequent symptoms were fever, fatigue, and dry cough⁶.

The analyses of the current study showed that age, PCR positivity, increased serum CRP and D-dimer levels, ASA grade 3-4, having 2 or more comorbidities, emergency operations, and COVID-19 pneumonia were associated with an increased risk of complications, while the lymphocyte count was associated with a decreased risk of developing postoperative complications. The mortality risk was determined to be 5.75-fold greater in the COVID-19 group than in the control group. Similarly, age, PCR positivity, increased serum CRP level, having 2 or more comorbidities, emergency operations, and COVID-19 pneumonia were associated with increased mortality while the lymphocyte count and eosinophil count were associated with survival. In a multicenter study including a total of 1128 surgical patients, 294 of whom were detected as COVID-19 (+) preoperatively, the 30-day mortality rate was 38% and increased risk for mortality was associated with male sex, age > 70 years, ASA grade 3-5, operation for malignancy, emergency, and major surgery⁴. Rasslan et al. reported that of patients with COVID-19-positivity who were operated on for abdominal emergencies, the postoperative morbidity and mortality rates were high in patients with respiratory compromise¹³. In the current study, pneumonia was also a risk factor for complications and mortality but no effects were detected of sex, malignancy, and major surgery. This may have been due to the small sample size of this study.

The current study results showed that the mean level of serum CRP was higher in the COVID-19 group and the mean lymphocyte and eosinophil counts were significantly lower compared to the control group. The mean serum D-dimer level was also increased in the COVID-19 group but the difference was not statistically significant. These laboratory findings are frequently observed in COVID-19 patients and in addition to older age and comorbidities these laboratory parameters have been reported to be associated with poor COVID-19 prognosis in several studies¹⁴-¹⁷. Therefore, it can be assumed that the factors associated with poor clinical course and outcome in SARS CoV-2 infection may also be associated with the development of post-operative complications and mortality.

There were some limitations to this study, primarily that the sample size was small as it was a single center study. There is need for multicenter studies to support these results. A second limitation was that the surgery performed was not evaluated in detail such as surgery for malignant / benign disease, or abdominal surgery, neurosurgery, and orthopedic surgery. Third, the effect of obesity could not be evaluated because of the lack of body mass index data in most of the patients. Finally, again because of the relatively low number of patients, it was not possible to evaluate if there was any difference among the COVID-19 patients according to the time of SARS CoV-2 infection – pre- or post-operative PCR positivity - in terms of morbidity and mortality.

Conclusion

From the results of this study, it was concluded that age, emergency surgery, higher ASA grade, 2 or more comorbidities and SARS CoV-2 infection, D-dimer, and pneumonia were associated with an increased risk of postoperative complications and mortality. A detailed risk evaluation should be performed in surgical patients concerning these prognostic factors to assess the postoperative risk, especially in patients infected with COVID-19. Delaying operations in appropriate surgical patients with COVID-19 may also help to decrease morbidity and mortality rates.