The Impact of the COVID-19 Pandemic on the Incidence, Severity, and Management of Acute Appendicitis: A Single Center Experience in Thailand

Purpose For more than two years since the COVID-19 pandemic, human lives have changed, including the healthcare system. Management of acute appendicitis, the most common emergency surgical disease, has been inevitably affected. This study aimed to assess the effect of the COVID-19 pandemic on the incident rate of complicated appendicitis, management, outcome, and complication of acute appendicitis. Patients and Methods. This study was a retrospective cohort study comparing 574 patients diagnosed with acute appendicitis before the COVID-19 outbreak and 434 patients diagnosed with acute appendicitis during the COVID-19 outbreak. Patient demographic data, type of appendicitis, type of treatment, time to surgery, length of stay, cost, and complications were collected and analyzed. Results During the COVID-19 pandemic, the number of patients diagnosed with acute appendicitis was reduced. CT scan usage for diagnosis was increased compared to pre-COVID-19. Most patients diagnosed with acute appendicitis received operative treatment in both groups. Median time to surgery was significantly longer during the COVID-19 pandemic, 11.93 hours compared to 9.62 hours pre-COVID-19, p-value <0.001 (relative risk 1.5, 95% CI 1.29–1.76, p value 0.041). The incidence of complicated appendicitis was not higher during COVID-19. Compared to pre-COVID-19, ICU admission rate, the use of a mechanical ventilator, length of stay, and cost increased in the univariate analysis but were not statistically significant in the multivariate analyses. Other treatment complications had no statistically significant difference. Conclusion The incidence of complicated appendicitis did not increase during the COVID-19 pandemic. The operation waiting time significantly increased but did not increase the rate of treatment complications in a well-prepared hospital system.


Introduction
Acute appendicitis is both the most common cause of abdominal pain [1] as well as surgical emergency disease worldwide [2], including in Tailand. Te lifetime risk of acute appendicitis is 8.6% in males and 6.7% in females [3]. Te most efective treatment is surgical appendectomy [4], while nonoperative treatment with antibiotics is an alternative method of treatment [5], especially in uncomplicated acute appendicitis. Current data show the safety of nonoperative treatment of acute appendicitis [1]; many high-quality studies and guidelines encourage nonoperative treatment with antibiotics in acute appendicitis with a good outcome, low rate of complication, and decreased length of hospital stay [6] but increased risk of recurrence (39%) in 5 years [1,7].
Since the frst case of COVID-19 was reported [8] and become a pandemic [9], the healthcare system needed to relocate resources and staf in the pandemic era. Some surgical nurses were required to leave the operating room and work in the feld hospital for COVID-19. Intensive care unit (ICU) hospital beds and ventilators were preserved for COVID-19 patients. Staf had to separate into two groups: one work and one stay-at-home, alternating periodically, to minimize face-to-face contact and avoid being a COVID-19 super spreader. Elective surgery was postponed due to closed operating rooms at a maximum of 50% capacity, except for diseases that afect the quality of life such as impending rupture abdominal aorta, critical limb ischemia, or cancer [10][11][12][13]. Te efect of COVID-19 impacted not only elective surgery cases but also emergency cases due to the limit of the emergency operating rooms at daytime and nighttime. Most of the cases needed to delay operations more than normal and needed to wait for the COVID-19 PCR result before going to surgery, except for extremely urgent cases such as trauma or severe peritonitis with unstable vital signs. Acute appendicitis was inevitably afected. To date, most of the literature reported the efect of COVID-19 on acute appendicitis from the beginning of the pandemic, which meant that there was a low sample size and only short-term outcomes were reported but now we have lived with COVID-19 for more than two years, so this study aims to evaluate the efect of COVID-19 on acute appendicitis in a long-term period.

Study Population.
We conducted a retrospective cohort study of adult patients with acute appendicitis who were treated at Tammasat University Hospital between January 31, 2018, and January 30, 2022. Te inclusion criteria were adult patients (age at least 18-year-old) who were diagnosed with acute appendicitis by the International Classifcation of Diseases and Related Health problem 10th Revision (code: K35-37) and were admitted to the ward. Te exclusion criteria were being unable to collect data from medical records or missing medical records, patients denied the treatment and left the hospital, patients with elective appendectomy, and patients with chronic appendicitis. Populations were divided into 2 comparable groups, pre-COVID-19 group, defned as patients in the 2 years before the in-country spreading of COVID-19 (January 31, 2018, until January 30, 2020), and during COVID-19 group, defned as patients in the 2 years after in-country spreading of COVID-19 (January 31, 2020, until January 30, 2022).
Te Human Research Ethics Committee of Tammasat University (Medicine) gave approval and waived informed consent requirements, the Number Certifcate of Approval is 109/2022, and the project Number is MTU-EC-SU-1-067/ 65. Tis study was registered with the Tai Clinical Trials Registry on June 15, 2022, reference number was TCTR20220615001.

Data Collection.
Te electronic medical record and chart review were conducted. Demographic data of patients including age, sex, weight, height, body mass index (BMI), underlying disease, American Association of Anesthesiologist (ASA) score, clinical presentation such as duration of self-report symptom, nausea or vomiting, right lower quadrant pain, fever, diarrhea, rebound tenderness, vital sign, laboratory data such as leukocytosis and neutrophil predominate, along with radiologic data, treatment method, operative time, time to surgery, histopathological data, type of appendicitis, length of stay, cost, and complication were obtained.
Te primary objective was the incidence of complicated appendicitis during the COVID-19 outbreak compared to the pre-COVID-19 outbreak. Te secondary objectives were to compare complication rate, length of hospital stay, time to surgery, and cost.

Statistical Analysis.
All baseline characteristics and demographic data were assessed in both pre-COVID-19 and during COVID-19 period. Mean and standard deviation (SD) with Student t-test analysis were performed in the normal distribution group. Te nonparametric test was performed by Mann-Whitney test and reported in median with interquartile range (iqr) to compare the data between pre-COVID-19 and during COVID-19 period. Te p value <0.05 is considered statistically signifcant. Te equality of distribution (for the data of more than 50 cases) was evaluated by histogram and the Kolmogorov-Smirnov (K-S) test. Multivariate regression analysis was performed to compare primary and secondary outcomes between pre-COVID-19 and during the COVID-19 period. All statistical analyses were performed using a STATA/SE 16.0 for Windows (Stata Corp LP, TX, USA), and p values <0.05 were regarded as indicating statistical signifcance. Te study process and report followed the strengthening of the reporting of observational studies in epidemiology (STROBE) statement on reports of the cohort studies ( Figure 1) [14,15].

Results
One thousand and twenty-fve patients were enrolled in this present study. Two patients refused to stay in the hospital, one in the pre-COVID-19 group and one in the during the COVID-19 group. 15 patients were excluded by exclusion criteria and missing signifcant data. Finally, this study consisted of 574 patients in the pre-COVID-19 group and 434 patients in the during COVID-19 group. Most general demographic data had no statistically signifcant diference between the two groups. However, cases diagnosed as acute appendicitis decreased in the during COVID-19 period contrary to increased airway and chronic kidney disease, which increased to ASA classifcation 2-4 ( Table 1).
In the pre-COVID-19 period, patients presented with right lower quadrant pain, migratory pain, and fever more than during COVID-19 period. Te mean body temperature was 37.29 degrees Celsius in the pre-COVID-19 group and 36.94 degree Celsius in the during COVID-19 group. Pulse rate and respiratory rate were higher in the during COVID-19 group, 92.77 beats/minute, 20.10 beats/minute in the during COVID-19 group, and 89.59 beats/minute and 19.72 beats/minute in the pre-COVID-19 group, respectively. Additionally, neutrophils predominate was higher in the during COVID-19 group (Table 1).
During the COVID-19 pandemic, patients with acute appendicitis were more likely to have a CT scan than pre-COVID-19 pandemic. Te most common CT fnding was fat standing followed by an enlarged appendix, more than 6 millimeters, which was more common during the COVID-19 pandemic than prepandemic. Te most common treatment, surgical appendectomy, did not change but during COVID-19 period, the laparoscopic approach was higher than in pre-COVID-19. Median time to surgery was longer during COVID-19 pandemic at 11.93 hours compared to 9.62 hours in pre-COVID-19, p value <0.001. Operative time was similar in both groups (Table 2).
Gangrenous appendicitis was higher in the pre-COVID-19 group at 14.46% compared to 8.76% in the during COVID-19 group, p value 0.006. Other types of appendicitis normal, simple appendicitis, ruptured appendicitis, appendiceal abscess, and appendiceal phlegmon, were similar. Te most common histopathology was appendicitis in both groups ( Table 2). Table 3 shows the outcome of the treatment. Te complications pneumonia, surgical site infection, abdominal collection, ileus, anastomosis leakage, and acute kidney injury were similar in prepandemic compared to during the pandemic. However, there was a higher intensive care unit admission rate and more ventilators used during COVID-19 compared to pre-COVID-19.
No mortality case was recorded in pre-COVID-19 but one patient died of acute appendicitis during COVID-19. Te death case was an 83-year-old male with underlying diseases of hypertension, heart disease, chronic kidney disease, and benign prostatic hypertrophy. Te diagnosis was ruptured appendicitis. He underwent an open appendectomy, with the time to surgery being 22.78 hours. Postoperative, the patient developed surgical site infection, abdominal collection, upper gastrointestinal bleeding, coagulopathy, atelectasis then dyspnea due to pneumonia with sepsis, ileus, and non-ST-elevated myocardial infarction with volume overload and acute kidney injury. He was resuscitated, had endotracheal tube placement, and was admitted to the ICU ward, but his clinical presentation deteriorated and the patient passed away, with the total LOS being 79 days.
Multivariate analyses of primary and secondary outcomes found no statistically signifcant diference in complicated appendicitis, ventilator use, ICU admission, prolonged LOS, or high cost. However, the during COVID-19 group was associated with a prolonged time to surgery of more than 10 hours with a relative risk of 1.5, 95% CI 1.29-1.76, p value 0.041 (Table 4).

Discussion
Some previous data showed delayed presentation (>72 hours) that was signifcantly higher during COVID-19 than the pre-COVID-19 period, associated with higher complicated appendicitis. [7,16,17] We found no statistical signifcance of longer self-reported symptom period but there was the statistical signifcance of higher ASA classifcation, concomitant with airway and chronic kidney disease, higher pulse rate, respiratory rate, and neutrophil predominate that indicated systemic infammatory response and more severe disease. Te lower number of patients with acute appendicitis in the during COVID-19 group [18][19][20]   Emergency Medicine International the patient being afraid of in-hospital COVID-19 transmission [21,22], so the increased threshold presenting to the hospital, a mild symptom of acute appendicitis may spontaneously regress without treatment or patients may have gone to the drug store and taken oral antibiotics by themselves and then symptoms resolved without the need of hospital treatment [18,[23][24][25] together with the strong government policy of stay-at-home. Te gastrointestinal presenting symptoms of COVID-19 infection mimic the symptoms of acute appendicitis [26][27][28] caused by multisystem infammatory syndrome (MIS), especially in children and adolescents. Abdominal pain, nausea, vomiting, diarrhea, and loss of appetite make the diagnosis of acute appendicitis more difcult and more likely to require preoperative imaging to confrm the diagnosis. Te increased rate of CT scans during the COVID-19 pandemic [20,29] was likely due to the need to confrm the diagnosis and avoid an unnecessary operation.
Te gold standard of acute appendicitis is surgical appendectomy while nonoperative treatment is an alternative method [5]. Nonoperative treatment increased during the COVID-19 pandemic [30,31]; some national surgical guidelines [10,[32][33][34] and literature [23,29,35,36] advocated nonoperative treatment and carefully consider a laparoscopic approach. Te benefts of nonoperative treatment are no anesthetic complications and decreased staf in an operating room, therefore reducing COVID-19 exposure. In normal situations, the preferred appendectomy approach is laparoscopic more than open due to less postoperative pain, lower incidence of surgical site infection, and decreased length of hospital stay [1,33] but, in our institutions, there is limited equipment, nurses, and surgeons skilled in laparoscopic method, as well as fnancial concerns because laparoscopic treatment is not covered by the universal coverage scheme. So, the mainstay of treatment is open appendectomy. At our institute, the increased rate of laparoscopic appendectomy during the pandemic was due to confounder pandemic, we had proper protective equipment and hence no staf member was infected with COVID-19 from any operation.

Emergency Medicine International
Te time to surgery was signifcantly longer during the COVID-19 pandemic due to limited operating rooms and staf because the hospital policy divided staf into two groups that do not contact each other so as to limit infection if one team member became infected with COVID-19. Some operative nurses also had to leave the operating room and had a new workload to take care of COVID-19 patients. Te hospital policy announced that every patient who was to undergo surgery needed to have a COVID-19 PCR test. Te waiting time for the test results prolonged the time for surgery. Except for patients with emergency conditions that could not wait for test results, all staf had to do the operation in a negative pressure room and be dressed in a proper personal protective equipment suit. Tere was no signifcantly longer operative time during the pandemic. Tis was similar to previous literature regarding acute care surgery including acute appendicitis from Krutsri et al. [37] which found that the waiting time for surgery was signifcantly longer in the pandemic period compared to the previous year. Operative time and morbidity and mortality had no signifcant diference.
Nonoperative management with intravenous antibiotics was higher in the COVID-19 group with no increase in complication rate [29,38,39]. Te cause of increased nonoperative treatment is likely due to the risk of perioperative morbidity-mortality in surgical patients with concomitant COVID-19 infection [40]. Te PCR for the COVID-19 test result of one of the patients in the during COVID-19 group was positive, which resulted in a change of treatment plan. First, the patient was diagnosed with acute appendicitis by clinical presentation and laboratory test and it was planned to set the operating room for an open appendectomy after the report of PCR for COVID-19 test was expected to be not detected. Unfortunately, the result was detected so the surgeon decided to work up imaging by CT scan and found that the patient had an appendiceal phlegmon, so the plan of treatment changed to intravenous antibiotics alone and follow-up by clinical examination. Te patient improved every day and had successful conservative treatment and was discharged from the hospital after completing isolation. Our case was similar to a case report of successful conservative management of acute appendicitis in a coronavirus disease 2019 patient from the USA [41].
Although some studies have shown higher complicated appendicitis during the COVID-19 outbreak [2,16,18,21,42,43] along with a higher complication rate [2,7,35] of statistical signifcance, our study showed no statistically signifcant complicated appendicitis or complication rate during the COVID-19 outbreak. Even with signifcantly longer waiting times for surgery, a wellprepared healthcare system managed to maintain a standard of care during the pandemic. Similar fndings from Antakia et al. [44] showed a signifcant increase in the radiological evaluation and an increase in nonoperative management during COVID-19 period in the United Kingdom but no signifcant diference in the length of hospital stays or mortality. Studies from Ganesh et al. [45] and Pringle et al. [46] also showed a signifcant increase in imaging investigations during the COVID-19 pandemic but no signifcant diference in the outcome of treatment of acute appendicitis. Zhou and Cen [42] reported on the outcome of acute appendicitis in Jiaxing, China, and reported a higher proportion of perforated appendicitis but no long-term postoperative complication was found during the pandemic. In the study from Turanli and Kiziltan [47], there was no clear increased rate of perforated appendicitis during the pandemic period (Table 5).
In univariate analysis, it was found that LOS, ICU admission, and ventilator use statistically signifcantly increased, possibly due to increased concomitant disease (ASA 2-4). Te cost was signifcantly higher, which may have been caused by the expense of routine preoperative PCR COVID testing and increased LOS.
Our advice is that a preoperative CT scan is important to decrease the negative appendectomy rate and is highly recommended for patients with concomitant COVID-19 infection to avoid unnecessary operations. Te waiting time for COVID-19 results is an adaptable problem for delayed time to surgery and is associated with complicated appendicitis. Tere should be a hospital policy and limited maximum laboratory time for testing PCR to minimize the time to surgery and provide the best outcome. We encourage patients not to hesitate and be quick to seek medical attention at a hospital if they have unusual abdominal pain because of the delayed presentation associated with higher complications.
Te Covid-19 pandemic has had a negative impact on patients with acute appendicitis by increasing the time to surgery. However, complicated appendicitis, including gangrenous, rupture appendicitis, appendiceal abscess, and phlegmon, was not signifcantly higher during the COVID period when compared with the pre-COVID period. ICU admission, ventilator use, LOS, and cost were statistically signifcant in univariate analysis but not statistically signifcant in multivariate analyses.
At present, some countries have announced COVID-19 as an endemic, not pandemic anymore and some countries plan to do the same, so we have to adapt to a new normal

Conclusions
Te COVID-19 pandemic has had no signifcant efect on complicated appendicitis but signifcantly delayed the time to surgery. However, it did not increase any complications of acute appendicitis under a well-prepared hospital system.

Data Availability
Te data used to support the fndings of this study are included within the article.

Conflicts of Interest
Te authors declare that they have no conficts of interest.