Effect of COVID-19 on the Treatment of Acute Appendicitis

Background: There has been debate on delaying an appendectomy for acute appendicitis because of the possibility of a severe acute respiratory syndrome coronavirus 2 infection being present and operating immediately due to the high possibility of complications from delaying the surgery. This study aimed to investigate the safety of delaying surgery for acute appendicitis in patients with a conrmed coronavirus disease (COVID-19) status. Methods: Patients admitted for acute appendicitis during the same period in 2019 and 2020 were enrolled in the study. We categorized them into 2 groups: those admitted before the outbreak of the COVID-19 pandemic in 2019 and those admitted after the outbreak in 2020. Clinical variables including demographics, operative and postoperative factors were analyzed. Statistical analyses was performed for the two groups. The primary end point was postoperative complication. Results: A total of 200 consecutive patients (127 from 2019 and 73 from 2020) were included in the study. There was no statistically signicant difference in demographics and laboratory ndings between the groups. In 2020, it took a longer time between a visit and surgery (6.3 vs 14.4 hours, p < 0.001); there was no difference in the type of surgery, appendix pathology, and postoperative complications. Conclusion: Our results demonstrated that, during the COVID-19 pandemic, it is safe to delay a surgery for acute appendicitis until after determining a patient’s COVID-19 status with the possibility of COVID-19 transmission. COVID-19, a COVID-19 polymerase chain reaction (PCR) test using samples collected through nasopharyngeal swab/oropharyngeal (throat) swabs was performed for all hospitalized patients with acute appendicitis, and patients were hospitalized after conrming a negative result. The PCR test took 6-8 hours. If the COVID-19 test result was positive, the patient was transferred to a hospital capable of treating COVID-19. In the case of suspected sepsis due to generalized peritonitis, emergency surgery was performed while wearing personal protective equipment in a negative pressure operating room before the COVID-19 PCR test result was obtained.


Background
Acute appendicitis is one of the most common benign diseases requiring emergency surgical treatment.
When diagnosed with acute appendicitis, if surgery is delayed, perforation of the appendix can occur thereby increasing postoperative complications [1]. It is therefore recommended that surgery be performed as soon as possible after diagnosis [2].
It has been reported that, due to the recent coronavirus disease (COVID-19) pandemic, patients are generally avoiding going to hospital, and patients with acute appendicitis are being admitted to hospital in a more severe condition [3,4]. Snapiri et al. reported that the complication rate in these patients has increased during the pandemic [4].
In these unprecedented times of COVID-19, antibiotics alone might be an option for uncomplicated appendicitis [5]. However, early appendectomy should be performed to achieve a shorter hospital stay than that required in conservative management and to avoid complications after failed conservative management [6].
Recent literature reports that COVID-19 can cause gastrointestinal (GI) symptoms [7]. In addition, fever accompanying acute appendicitis adds a suspicion of COVID-19 infection. Therefore, in our hospital, patients presenting with acute appendicitis have undergone surgery after we obtained the results of their COVID-19 tests because our hospital does not have a unit for treating COVID-19.
However, there have been no reports on the difference in surgical outcomes when surgery was performed with the same protocol as our hospital. Therefore, we aimed to determine changes in the clinical variables of acute appendicitis, its overall effect on surgery, and postoperative complications.

Patient selection
We divided patients into two groups: pre-corona outbreak (May 11 to July 1 in 2019) and corona pandemic period (May 11 to July 1 in 2020) for comparison during the same period. Patients admitted through the emergency room for acute appendicitis during the entire designated period were enrolled in the study. We included cases of acute appendicitis con rmed by radiologists through computer tomography (CT) and ultrasound. Exclusion criteria were as follows: 1) hospitalization to perform interval appendectomy, 2) acute appendicitis during hospitalization due to other diseases, 3) colorectal cancer mistaken for acute appendicitis (cecal cancer or appendix cancer), or 4) pelvic in ammatory disorder or colitis, mistaken for acute appendicitis.

Process
If acute appendicitis is clinically suspected, a preoperative CT or ultrasound for pregnant women is performed to con rm the diagnosis. Prior to the outbreak of COVID-19, emergency surgery was performed when acute appendicitis was con rmed. In the case of a periappendiceal abscess where drainage was possible, broad spectrum antibiotic therapy was administered after percutaneous drainage until the in ammation improved. At the discretion of the attending physician, patients with early appendicitis or uncomplicated appendicitis with a poor general condition were treated with antibiotics only.
Following the pandemic spread of COVID-19, a COVID-19 polymerase chain reaction (PCR) test using samples collected through nasopharyngeal swab/oropharyngeal (throat) swabs was performed for all hospitalized patients with acute appendicitis, and patients were hospitalized after con rming a negative result. The PCR test took 6-8 hours. If the COVID-19 test result was positive, the patient was transferred to a hospital capable of treating COVID-19. In the case of suspected sepsis due to generalized peritonitis, emergency surgery was performed while wearing personal protective equipment in a negative pressure operating room before the COVID-19 PCR test result was obtained.
After surgery, patients were discharged when abdominal pain improved, and oral intake was possible. An outpatient follow-up visit was scheduled to check for wound complications 7-10 days after surgery.

Variables
Clinical variables before surgery (sex, age, white blood cell [WBC], C-reactive protein [CRP], segment neutrophil count), factors related to surgery (operation name, appendix pathology, duration of operation), postoperative clinical ndings (duration of hospital stay, postoperative complications) were investigated.
The appendix pathology was divided into the following categories: hyperemic, suppurative, gangrenous, and perforated.

Statistical analysis
In order to compare the continuous variables between the two groups, a Mann-Whitney U test was performed for variables showing non-normal distribution, and a Student's t-test was performed for variables showing a normal distribution. A Kolmogorov-Smirnov test was used to assess the assumption of a normal distribution. For categorical variables, the Chi-square test, Fisher's exact test, and linear-bylinear association were performed where appropriate. We used an SPSS version 21.0 for Windows (IBM Corp, Armonk, NY, USA) for analysis. A p-value of < 0.05 was considered statistically signi cant

Results
The number of patients diagnosed with acute appendicitis was 134 in 2019 and 82 in 2020. After applying the inclusion and exclusion criteria, 127 patients in 2019 and 73 in 2020 were included in the analysis (Fig. 1). There were no patients who were diagnosed with COVID-19.
The demographics and clinical characteristics of the two groups are shown in Table 1. The median ages for 2019 and 2020 were 37 and 41 years old, respectively and there were more males than females in both groups. The duration of the symptoms before the visit to the hospital was 20 hours in 2020, about 7 hours longer than in 2019, but there was no statistically signi cant difference (p = 0.086). Additionally, there was no signi cant difference in laboratory ndings (Table 1).
At the discretion of the attending physician, there were 5 and 2 patients who used only antibiotics and 2 and 1 patients who inserted the drainage tube into the periappendiceal abscess in 2019 and 2020, respectively, as shown in Fig. 1.
In the analysis of the surgery and postoperative factors of patients who underwent surgery, it took a longer time from admission to surgery (6.3 vs 14.4 hours, p < 0.001) in 2020 than in 2019. There was no signi cant difference in the type of surgery, appendix pathology, or postoperative complications (Table 2).
Re-admission occurred in 1 case of conservative management for ileus and 2 cases of percutaneous drainage and laparoscopic exploration for intraabdominal abscess formation, in 2019 (total: 3 cases (2.5%)). In 2020, there was 1 case (1.4%) of antibiotic therapy for intraabdominal abscess formation.

Discussion
This study showed that following the outbreak of COVID-19, there was no increase in postoperative complications although there was a delay in the time from the diagnosis of acute appendicitis to surgery. Although the number of patients was relatively decreased within this period, there was no signi cant difference in clinical variables including demographics and clinical data. This proved that it is safe to wait for about 14 hours to perform a surgery after the con rmation of results of the COVID-19 PCR test.
Romero et al. reported that after the outbreak of COVID-19, not only did the number of patients with acute appendicitis decline, but also the patients who visited were in a more severe condition [3]. Snapiri et al.
reported that the incidence of complications increased in pediatric patients due to late presentation to hospital, because their parents feared that they would contract COVID-19 at the hospital [4]. However, unlike these reports, the severity of in ammation such as WBC count and CRP level and the appendix pathology after surgery was similar between the two groups in our study. Accordingly, the delay in surgery did not increase the frequency of complications.
Apart from cases of perforated appendicitis with generalized peritonitis, our hospital performed surgeries after con rming the COVID-19 PCR test result, which delayed the time from admission to surgery by about 6-8 hours compared to before the pandemic. A previous study has already reported that the incidence of complications does not increase if surgery is performed within 24 hours of presentation at hospital [8]. Most patients at our hospital underwent surgery within 24 hours after visiting the hospital; accordingly, our ndings are consistent with presented in the literature.
Appendicitis is often accompanied by fever; it is therefore di cult to rule out a COVID-19 infection. In addition, some COVID-19 patients are asymptomatic [9] and the symptoms of COVID-19 itself include GI symptoms [7]. Therefore, the COVID-19 test has been routinely performed before admission and surgery in our hospital after the outbreak of the pandemic. Some patients may be treated with antibiotics only in the case of uncomplicated appendicitis following the outbreak of COVID-19 [5]. However, due to the possibility of treatment failure with antibiotic treatment alone, the treatment of choice for appendicitis is surgery. Therefore, the results of our research have great signi cance in that they demonstrate that it is safe to wait to perform surgery until after the COVID-19 PCR test result has been obtained.
The limitations of our study are that it is a retrospective, single-institutional study and is likely to have an information and selection bias. Therefore, it is necessary to conduct a multicenter study with our protocol using the same COVID-19 test that provides the results within 6-8 hours.
In conclusion, it is safe to delay performing surgery for acute appendicitis until the COVID-19 test results have been obtained, provided that the delay is not more than 8 hours.