Observational Study Open Access
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 16, 2022; 10(29): 10487-10500
Published online Oct 16, 2022. doi: 10.12998/wjcc.v10.i29.10487
Effect of the COVID-19 pandemic on patients with presumed diagnosis of acute appendicitis
Sami Akbulut, Tevfik Tolga Sahin, Cemalettin Koc, Ertugrul Karabulut, Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
Sami Akbulut, Emek Guldogan, Department of Biostatistics and Medical Informatics, Inonu University Faculty of Medicine, Malatya 44280, Turkey
Sami Akbulut, Ali Ozer, Department of Public Health, Inonu University Faculty of Medicine, Malatya 44280, Turkey
Adem Tuncer, Zeki Ogut, Department of Surgery, Inonu University Faculty of Medicine, Malatya 44280, Turkey
Elif Seren Tanriverdi, Department of Medical Microbiology, Inonu University Medical Faculty, Malatya 44280, Turkey
ORCID number: Sami Akbulut (0000-0002-6864-7711); Adem Tuncer (0000-0001-5381-513X); Zeki Ogut (0000-0002-7698-9586); Tevfik Tolga Sahin (0000-0002-9132-6115); Cemalettin Koc (0000-0002-5676-6772); Emek Guldogan (0000-0002-5436-8164); Ertugrul Karabulut (0000-0002-5433-591X); Elif Seren Tanriverdi (0000-0002-0449-0356); Ali Ozer (0000-0002-7144-4915).
Author contributions: Akbulut S, Tuncer A, Ogut Z, Tanriverdi ES, and Koc C collected data; Akbulut S and Ozer A performed statistical analysis; Akbulut S and Sahin TT wrote the manuscript; Akbulut S, Sahin TT, and Yilmaz S contributed to project development and reviewed the final version.
Institutional review board statement: This study was reviewed and approved by the Inonu University institutional review board for non-interventional studies (2021/2293).
Informed consent statement: Verbal and written consents were obtained from all patients who underwent appendectomy.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: There are no additional data available for this study.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sami Akbulut, FACS, MD, PhD, Professor, Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Elazig Yolu 10 Km, Malatya 44280, Turkey. akbulutsami@gmail.com
Received: July 25, 2022
Peer-review started: July 25, 2022
First decision: August 7, 2022
Revised: August 16, 2022
Accepted: September 9, 2022
Article in press: September 9, 2022
Published online: October 16, 2022

Abstract
BACKGROUND

Acute appendicitis (AAp) is the most frequent cause of acute abdominal pain, and appendectomy is the most frequent emergency procedure that is performed worldwide. The coronavirus disease 2019 (COVID-19) pandemic has caused delays in managing diseases requiring emergency approaches such as AAp and trauma.

AIM

To compare the demographic, clinical, and histopathological outcomes of patients with AAp who underwent appendectomy during pre-COVID-19 and COVID-19 periods.

METHODS

The demographic, clinical, biochemical, and histopathological parameters were evaluated and compared in patients who underwent appendectomy with the presumed diagnosis of AAp in the pre-COVID-19 (October 2018-March 2020) and COVID-19 (March 2020-July 2021) periods.

RESULTS

Admissions to our tertiary care hospital for AAp increased 44.8% in the COVID-19 period. Pre-COVID-19 (n = 154) and COVID-19 (n = 223) periods were compared for various parameters, and we found that there were statistically significant differences in terms of variables such as procedures performed on the weekdays or weekends [odds ratio (OR): 1.76; P = 0.018], presence of AAp findings on ultrasonography (OR: 15.4; P < 0.001), confirmation of AAp in the histopathologic analysis (OR: 2.6; P = 0.003), determination of perforation in the appendectomy specimen (OR: 2.2; P = 0.004), the diameter of the appendix (P < 0.001), and hospital stay (P = 0.003). There was no statistically significant difference in terms of interval between the initiation of symptoms and admission to the hospital between the pre-COVID-19 (median: 24 h; interquartile range: 34) and COVID-19 (median: 36 h; interquartile range: 60) periods (P = 0.348). The interval between the initiation of symptoms until the hospital admission was significantly longer in patients with perforated AAp regardless of the COVID-19 or pre-COVID-19 status (P < 0.001).

CONCLUSION

The present study showed that in the COVID-19 period, the ultrasonographic determination rate of AAp, perforation rate of AAp, and duration of hospital stay increased. On the other hand, negative appendectomy rate decreased. There was no statistically significant delay in hospital admissions that would delay the diagnosis of AAp in the COVID-19 period.

Key Words: SARS-CoV-2, COVID-19 pandemic, Acute appendicitis, Perforated appendicitis, Negative appendectomy

Core Tip: The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic as a public health emergency of international concern. Previous studies have shown that the anxiety related with the fear of the COVID-19 pandemic has caused individuals to avoid admission to hospitals even in very urgent conditions. The present study showed that the complicated acute appendicitis rate increased, which has led to prolonged hospital stays during the COVID-19 pandemic. The present study also showed that the negative appendectomy rate decreased during the pandemic.



INTRODUCTION

Coronavirus disease 2019 (COVID-19) emerged as a severe acute viral pneumonia in Wuhan city of Hubei province in China. Soon, investigations showed that a new type of coronavirus caused this condition, and it was genotyped and renamed as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the disease was renamed as COVID-19[1-5]. Soon the disease spread throughout the globe and caused a world-wide catastrophe[2]. On January 30, 2020, the World Health Organization declared the disease as a public health emergency of international concern (in other words a pandemic). In the beginning of the pandemic, there were no effective antiviral treatments or preventive vaccinations, which led to promotion of isolation methods such as social distancing, masking, and staying at home to prevent transmission of the disease between individuals[1]. The first confirmed case of COVID-19 in Turkey was declared on March 11, 2020. Rapidly, the Turkish Ministry of Health established a scientific advisory board, and various guidelines were determined in accord with the recommendations of the World Health Organization for the prevention and management of the COVID-19 pandemic. Cancer surgeries, emergent cases such as appendectomy, viscus perforations, and trauma were allowed provided that necessary precautions were taken in the operating theatre and inpatient wards. It was recommended that any elective procedure shall be postponed if it was for non-life threatening condition[6,7].

In general, acute appendicitis (AAp) is the most frequent cause of acute abdominal pain that requires hospital admissions, and appendectomy is the most frequent emergency procedure that is performed[2,4,8,9]. Appendectomy is the gold standard treatment for AAp; however, nonoperative treatment can be performed in selected cases (non-complicated AAp) and during global crisis such as the COVID-19 pandemic[9-11]. The delay in the diagnosis and management of AAp leads to life threatening conditions such as uncontained perforation, peritonitis, and abscess formation[2,11].

Studies have shown that SARS-CoV-2 infection had a significant impact on the physical and psychological health of individuals. The anxiety related with the fear of contracting the COVID-19 has caused individuals to avoid admission to hospitals even in very emergent conditions[2]. This condition had also an impact on patients with AAp. Patients with AAp had delayed hospital admissions and majority of these patients preferred nonoperative treatments such as antibiotic therapy during the pandemic[2,9,12-16]. Studies have reported that a delay in hospital admissions of patients with AAp have led to increased complication rates[2,17]. There are also contradictory studies that show that hospital admissions did not show significant differences during the COVID-19 pandemic[18-22].

The aim of the present study was to comparatively evaluate the impact of the COVID-19 pandemic with the pre-pandemic period regarding the patients who underwent operations for AAp in terms of negative appendectomy rates and perforation rates. Our secondary aim was to evaluate the impact of the pandemic on the hospital admission rates of the patients with AAp.

MATERIALS AND METHODS

In Turkey, the first confirmed case of COVID-19 was declared on March 11, 2020. Between March 2020 and July 2021, 223 patients underwent operations on with the presumed diagnosis of AAp at the Department of Surgery, Inonu University Faculty of Medicine, Malatya, Turkey. These patients were included in the COVID-19 group (case group). To evaluate the impact of the COVID-19 pandemic on patients’ behavioral patterns, 154 patients who underwent appendectomy between October 2018 and March 2020 were included in the pre-COVID-19 group (control group).

The study parameters included age (years), gender (female, male), timing of surgery (daytime vs night-time), timing of surgery by working days (weekdays vs weekends), ultrasonographic (US) findings (AAp present or absent), histopathologic findings (AAp present or absent), status of appendiceal perforation (present or absent), type of surgery (open vs laparoscopic), postoperative antibiotic use (yes or no), other histopathological features detected in surgical specimens (neuroendocrine tumor, granulomatous appendicitis, serrated adenoma, cystadenocarcinoma, mucinous adenocarcinoma, fibrous obliteration, hyperplastic polyps, lymphoid hyperplasia, etc.), white blood cell (WBC), neutrophil, lymphocyte, platelets, plateletcrit, red cell distribution width, platelet distribution width, mean corpuscular hemoglobin, mean platelet volume, mean corpuscular volume, C-reactive protein (CRP), total bilirubin, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, white cell neutrophil ratio, white cell lymphocyte ratio, length of appendix (mm), width (diameter) of appendix (mm), duration of hospital stay (days), and pre-admission interval (hour). The city that our institution is situated, Malatya city, has a total population of 806156 people. Our institution has 301 intensive care unit bed and 1368 beds in inpatient wards. Our institution is the largest referral center in the region. Additionally, the state hospital in Malatya became the pandemic center for referral of patients with COVID-19 and for this reason, our hospital became the referral center for all emergency cases.

Diagnostic work-up of the patients in our institution

The diagnosis of AAp was established using the results of a combination of patient symptoms, anamnesis, findings of physical examination, plain abdominal radiography, complete blood cell count, CRP, and urinalysis. In patients with a suspicion of AAp, follow-up visits in the emergency department were performed to re-evaluate the complaints and findings of the physical examination. In our institution, we use the Alvarado scoring system for evaluation of patients with right lower quadrant pain. In summary, patients with a low Alvarado score ranging between 1-4 were discharged because they had a low risk of AAp. Patients with an Alvarado score ranging between 5 to 6 were followed closely. We chose to perform imaging techniques such as US, abdominal computerized tomography (CT), and magnetic resonance imaging in this group of patients. The patients with Alvarado scores ranging between 7 to 10 were considered to have AAp, and emergency operation was planned. The majority of the patients admitted to the emergency department with the complaint of abdominal pain that were considered to have AAp underwent appendectomy. The nonoperative management (NOM) that consists of antibiotic therapy was performed to a limited number of patients, and these patients were excluded from our study[23,24].

During the COVID-19 pandemic, every patient that was admitted to the emergency department with abdominal pain was tested for SARS-CoV-2 by polymerase chain reaction (PCR) test, and chest X-ray was performed for surveillance of the patients. The patients with suspected lung lesions were further evaluated with thorax CT. Some patients were refereed from other centers with all the diagnostic work-up performed including the PCR and thorax CT. These patients had already confirmed diagnoses of AAp, no further tests were performed in our institution, and emergency operation was planned. The patients with high suspicion of COVID-19 infection such as symptoms of pneumonia, fever, or respiratory tract, traveled abroad in the prior 2 wk, or had a history of contact with patients with COVID-19 infection were quarantined after the PCR test and the thorax CT ruled out COVID-19 infection[3,25]. No emergency operation was postponed related to the COVID-19 status of the patients. Precautions were taken in the operating room and the patient wards to protect the staff and other patients. Retrospectively, 35 patients in our COVID-19 cohort had a positive COVID-19 PCR test, and 22 of these patients were infected in a median of 146 d [interquartile range (IQR): 219] following the operation. The remaining 13 patients were infected in median of 162 d (IQR: 146) prior to appendectomy. None of the patients had contracted COVID-19 during the early perioperative period.

Study protocol and ethics committee approval

This retrospective case-controlled study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. First, the required official administrative permissions from the Directorate of Surgery were granted (2021/61490). Then, ethical approval was obtained from the Inonu University Institutional Review Board for non-interventional studies (2021/2293). This study was registered in Research Registry, where the protocol and data collections proforma can be accessed (Research Registry UIN: researchregistry7378). Strengthening the reporting of observational studies in epidemiology guidelines were utilized to assess the likelihood of bias and overall quality for this study[26].

Statistical analysis

The statistical analyses were performed using IBM SPSS Statistics v25.0 (Statistical Package for the Social Sciences, Inc, Chicago, IL, United States). The continuous variables were expressed as median, IQR and 95% confidence interval (CI) for median value. The categorical variables were reported as number and percent (%). Kolmogorov-Smirnov were used to assess normality of continuous variable distribution. Non-parametric Mann Whitney U test was used to compare continuous variables. Pearson’s χ2 test was used to compare categorical variables. P ≤ 0.05 was considered statistically significant.

RESULTS
General characteristics of the study population

Three hundred and seventy-seven patients with ages ranging between 17-92 years (median: 36, IQR: 27) were included for analysis in the study. Two hundred and twenty-five (59.7%) of the patients were male, and 152 (40.3%) were female. Among them, 154 patients (40.8%) underwent appendectomy in the pre-COVID-19 pandemic period, and 223 patients (59.2%) underwent appendectomy during the COVID-19 pandemic period. There was a 44.8% increase in the number of patients admitted to our hospital with presumed diagnosis of AAp. Two hundred patients (53.1%) underwent appendectomy during the daytime, and 177 (46.9%) patients underwent appendectomy during the night-time. Two hundred and seventy-four patients (72.7%) underwent appendectomy on the weekdays, and 103 patients (27.3%) underwent appendectomy during the weekends. Two hundred and forty-five patients received laparoscopic appendectomy (65.0%), and 132 patients (35.0%) underwent conventional open appendectomy. In 4 of the 132 patients who underwent open appendectomy, the procedure started with laparoscopy and was converted due to technical difficulties. Histopathological analysis showed that 79 patients (21.0%) had appendiceal perforation, and 42 patients (11.1%) underwent negative appendectomy. Therefore, 335 of the 377 patients (88.9%) included in the study had confirmed AAp with histopathologic analysis.

Comparison of pre-COVID-19 vs COVID-19 groups

The patients in the study were divided into two groups: Pre-COVID-19 (n = 154) and COVID-19 (n = 223). The two groups did not show statistically significant differences in terms of age, timing of the operation (daytime vs night-time) WBC, neutrophil, lymphocyte, or platelet counts, plateletcrit, red cell distribution width, platelet distribution width, mean corpuscular hemoglobin, mean platelet volume, mean corpuscular volume, total bilirubin concentration, CRP, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, platelet-to-neutrophil ratio, white cell lymphocyte ratio, white cell neutrophil ratio, and the length of the appendectomy specimen.

On the other hand, the groups were statistically different in terms of surgery being performed on the weekends vs weekdays (P = 0.018), detection of AAp on US (P < 0.001), histopathologic confirmation of AAp (P = 0.003), presence of perforation in the surgical specimen (P = 0.004), diameter of the appendiceal surgical specimen (P < 0.001), and duration of hospital stay (P = 0.003). Evaluation of our results show that during the COVID-19 pandemic, appendectomy was 1.76 times more frequent during the weekends, the diagnostic rate (AAp) of US was 15.4 times higher, negative appendectomy rate was reduced by 2.6 fold, and the perforation rate was increased by 2.2 fold. The duration of the hospital stay following appendectomy in the pre-COVID-19 and COVID-19 groups were 1 d to 11 d (mean ± SD: 2.2 ± 1.5) and 1 d to 17 d (mean ± SD: 3.3 ± 3.2), respectively. The sensitivity, pulse pressure variation and accuracy of US during the COVID-19 pandemic period were 97%, 93%, and 90%, respectively. The sensitivity, pulse pressure variation, and accuracy in the pre-COVID-19 period were 77%, 83%, and 68%, respectively. The results of the univariate analysis of the patients are presented in Tables 1 and 2.

Table 1 Comparison of pre-coronavirus disease 2019 era and coronavirus disease 2019 groups in terms of categorical variables.
Parameters
Pre-COVID-19, n = 154
COVID-19, n = 223
OR (95 %CI)
P value
SexNS0.140
Male85 (55.2)140 (62.8)
Female69 (44.8)83 (37.2)
Surgery timeNS0.160
Daytime75 (48.7)125 (56.1)
Nighttime79 (51.3)98 (43.9)
Surgery time1.8 (1.1-2.9)0.018
Weekdays122 (79.2)152 (68.2)
Weekend32 (20.8)71 (31.8)
US findings, n = 34315.4 (4.6-52.6)< 0.001
AAp (+)120 (80.5)191 (98.5)
AAp (-)29 (19.5)3 (1.5)
Histopathological findings2.6 (1.4-5.1)0.003
AAp (+)128 (83.1)207 (92.8)
AAp (-)26 (16.9)16 (7.2)
Appendiceal perforation2.2 (1.3-3.9)0.004
Yes21 (13.6)58 (26.0)
No133 (86.4)165 (74.0)
Type of surgery1.5 (1.0-2.4)0.046
Open appendectomy63 (40.9)69 (30.9)
Lap appendectomy91 (59.1)154 (69.1)
Postoperative antibiotics useNS0.596
Yes14 (9.1)24 (10.8)
No140 (90.9)199 (89.2)
Histopathological features
AAp (+)105145
AAp (+), granulomatous01
AAp (+), diverticulitis01
AAp (+), hyperplastic polyps01
AAp (+), serrated adenoma01
AAp (+), perforated2156
AAp (+), perforated (NET)01
AAp (+), perforated101
AAp (+), LAMN20
AAp (-), cystic adenocarcinoma10
AAp (-), mucinous adenocarcinoma01
AAp (-), fibrous obliteration84
AAp (-), lymphoid hyperplasia156
AAp (-), LAMN01
AAp (-), NET01
AAp (-), diverticulosis01
AAp (-), appendix vermiform22
Table 2 Comparison of pre-coronavirus disease 2019 era and coronavirus disease 2019 groups in terms of continuous variables.
ParametersPre-COVID-19, n = 154
COVID-19, n = 223
P value
Median (IQR)
95%CI
Median (IQR)
95%CI
Age35 (22) 30-3836 (28)33-390.347
WBC12.5 (6.3)11.7-13.112.7 (5.9)11.9-13.40.798
Neutrophil9.7 (5.7)8.7-10.79.5 (5.9)8.9-10.30.659
Lymphocyte1.8 (1.3)1.5-2.01.7 (1.1)1.50-1.800.500
PLT238 (94)224-256242 (108)231-2540.682
PCT0.24 (0.1)0.20-0.300.25 (0.1)0.24-0.260.545
RDW13 (1.6)12.8-13.213 (1.4)12.9-13.20.746
PDW11.5 (2.5)11.1-12.011.5 (2.5)11.2-11.90.795
MCH28.7 (3.1)28.2-29.029 (2.8)28.7-29.20.376
MPV10.2 (1.3)10.0-10.410.2 (1.3)10.1-10.30.601
MCV84 (5.5)83.5-85.184 (6.7)83.4-85.10.725
TBil0.76 (0.7)0.64-0.880.78 (0.7)0.70-0.870.444
CRP1.8 (6.3)1.11-3.332.0 (7.0)1.43-3.310.379
NLR5.2 (7.2)4.7-6.65.8 (6.9)5.10-6.400.584
PLR139 (100)127-154137 (87)131-1510.947
PNR25 (21)22.7-28.224 (19)21.6-27.40.462
WLR6.9 (7.6)6.20-8.107 .3 (7.6)6.60-8.100.697
WNR1.3 (0.3)1.30-1.401.3 (0.2)1.30-1.30 0.731
Appendix length60 (24)60-6560 (20)60-650.633
Appendix width9 (5)8-1011 (7)10-12< 0.001
Hospital stay2 (2)2.0-2.02 (3)2.0-2.00.003
Time to admission (h)24 (33)17-4836 (60)18-480.348

We aimed to evaluate the correlation between the pre-admission interval and the COVID-19 pandemic. We used telephone interviews of the patients included in the study to obtain the interval between initiation of the pain and admission to the hospital in both groups. In total 60 patients gave accurate answers to the questions that we asked. The pre-admission interval in the pre-COVID-19 and the COVID-19 groups were 4 h to 96 h (median: 24, IQR: 33, 95%CI: 17-48) and 4 h to 192 h (median: 36, IQR: 60, 95%CI: 18-48), respectively. This difference in the pre-admission intervals between the groups was not statistically significant (P = 0.348).

We evaluated the pre-admission intervals of the patients regardless of the COVID-19 or pre-COVID-19 period. The pre-admission intervals of the patients with and without perforation were 9 h to 192 h (median: 72, IQR: 48) and 4 h to 120 h (median: 18, IQR: 24), respectively (P < 0.001). In the pre-COVID-19 period, the median pre-admission time interval of the perforated and non-perforated AAp cases were 48 h (IQR: 36) vs 20 h (IQR), respectively (P = 0.048). During the COVID-19 pandemic, the median pre-admission intervals of the patients with perforated and non-perforated AAp were 72 h (IQR: 48) vs 12 h (IQR: 16), respectively (P < 0.001).

DISCUSSION

Since the World Health Organization declared COVID-19 as a public health emergency of international concern (i.e., a pandemic), 236132082 people have been infected with COVID-19, and 4822472 (2.04%) people have died due to severe COVID-19 infection or complications related to it. The recommendations of wearing a mask, social distancing, and social isolation were effective in controlling the spread of the disease. Despite all the preventive measures, COVID-19 had devastating effects on the global health and socio-economic status[4]. In other words, COVID-19 became a serious public health problem that threatened the physical, psychological, and social well-being of individuals globally.

The fear of COVID-19 infection has prevented people who are seriously ill to seek medical attention[2]. This has led to a delay in the diagnosis and the management of life-threatening conditions such as myocardial infarction, embolism, AAp, acute cholecystitis, perforation, trauma, and cancers[27-30]. Nourazari et al[31] showed that there was a 32% drop in the rate of emergency department admissions during the COVID-19 pandemic when compared to previous periods. The results of the study by Göksoy et al[32] showed that there was a 25% drop in admissions to emergency surgery, and 20% of the patients admitted refused the surgical treatment recommended by the attending physicians. Furthermore, they stated that the majority of surgeons preferred open surgical procedures during the COVID-19 pandemic[32].

AAp is one of the most common causes of emergency department admissions, and rapid diagnosis and management are crucial factors regardless of the conditions. The current literature regarding ”COVID-19 and AAp” emphasize three main arguments: (1) Delay in hospital admissions (prolongation of the pre-admission period) and in-hospital delay of the patients (prolongation of the preoperative period due to overwhelming work load of the hospital staff and facilities) until the definitive treatment is performed; (2) Increase in complication rates related with AAp (such as perforation, abscess formation, and plastron); and (3) Change in the treatment modality (open vs laparoscopic or surgical vs medical therapies) increasing the complication rate in the postoperative and post-treatment course. We would like to evaluate these main arguments in accord with our results.

The hospital admissions in the COVID-19 era are a matter of debate. The hospital admission rates have dropped during the quarantine. We evaluated 25 studies related with COVID-19 and AAp, and 23 of these articles reported that there was a 24% (IQR: 15%-39%; min-max: 5.4%-81%) drop in the hospital admissions due to AAp during the quarantine regulations[1-4,10,12,14-22,33-39]. In only 1 of the 25 studies, there was a 7% increase in the hospital admissions[40]. The results of our study have shown that there was a 44.8% increase in the hospital admissions due to AAp and subsequent appendectomies that were performed. The studies emphasized that the reasons for the drop in the hospital admissions were due to fear of disease transmission and the perception that the hospitals were sources of the disease. This has caused an increase in the rate of pre-admission self-medication with antibiotics and nonsteroidal anti-inflammatory drug use.

Gao et al[2] showed that pre-admission self-medication with antibiotics increased by 8.7 fold in the COVID-19 period when compared to the pre-pandemic period [odds ratio (OR): 8.7; 55.2% vs 12.4%; P < 0.001]. The results of the study by Yang et al[4] showed that pre-admission antibiotic use increased by 2.76 fold during the pandemic when compared to the pre-pandemic period (OR: 2.76; 18.9% vs 7.8%; P = 0.011). In our study we found an increase in the hospital admissions due to AAp because the municipal hospital in our city was re-organized as the pandemic hospital while our institution treated all the non-COVID-19 emergencies in our city. In larger metropolitans, even the private hospitals were organized as pandemic hospitals because of the overwhelming cases.

The second argument is the hypothesis that the COVID-19 pandemic caused a prolongation of the re-admission period of the patients. This may be due to hesitation of the patients to seek medical help or may be related with overwhelmed hospitals that could not provide the necessary medical care for these patients. Twenty-five studies have been evaluated COVID-19 and AAp, and six of these studies stated that the interval between the initiation of symptoms and hospital admission had been prolonged[1,2,4,15,17,36]. Particularly, in 2 of these 6 studies, this difference in pre-admission intervals during the COVID-19 pandemic was evaluated and confirmed with different regression models.

Gao et al[2] stated that prolonged pre-hospital intervals (OR: 1.075; P = 0.005) and reluctance of patients towards the recommended surgical/medical therapy (OR: 1.848; P = 0.007) were independent risk factors for increased rates of complicated AAp. Similarly, Rudnick et al[17] found that prolongation of the interval between initiation of symptoms and hospital admission was an independent risk factor for development of complicated AAp (OR: 1.139; P = 0.032). In various other studies it was reported that there was no statistically significant difference in the pre-admission intervals between the pandemic and pre-pandemic periods[18,19,22,37]. However, detailed analysis of the results of these studies showed that pre-admission intervals were longer during the pandemic period[18,19,22,37].

In our study the pre-admission intervals in the pre-pandemic and pandemic periods were 24 h and 36 h, respectively. Our literature analysis showed that there is only one study that reported a prolonged pre-admission interval in the pre-pandemic period[40]. On the other hand, overwhelming circumstances during the pandemic may have delayed the intended surgical treatment planned for the patients. Of the 25 studies regarding AAp during COVID-19, we found 5 studies reporting the intervals before the operation. Three of these studies reported a prolonged interval before the planned operation[4,35,37]. On the other hand, prolonged preoperative intervals were reported during the pre-pandemic period in two studies[15,18]. There were two studies that concluded that the diagnostic process was prolonged during the COVID-19 period[10,13]. One important point that should be emphasized regarding the reported intervals in studies is that all were self-reported intervals. This means that the patients were retrospectively interviewed, and they stated the intervals if they remembered them accurately. Similarly, in the present study we interviewed our patients by telephone and tried to obtain similar information. Only 60 patients could accurately remember the pre-admission and preoperative intervals. Therefore, the results of these studies (including our own) should be evaluated with a certain level of skepticism.

The impact of the COVID-19 pandemic on the use of radiologic imaging modalities for the diagnosis of AAp is another argument that should be emphasized. Analysis of the results of the study reported by Ganesh et al[12] showed that the use of radiologic imaging modalities such as CT or magnetic resonance imaging have increased by 42 fold during the pandemic period (OR: 42; 60.9% vs 100%;). Somers et al[16] reported that radiologic imaging modalities have been used 1.26 times more frequently during the COVID-19 period (OR: 1.26; P = 0.007). The authors stated that all three radiological instruments (US, CT, and magnetic resonance imaging) are used more frequently during the COVID-19 period. Antakia et al[18] reported that during the COVID-19 pandemic, they have used CT 2.6 times more frequently (OR: 2.6; P = 0.008), but the use of US was reduced by 1.6 fold (OR: 1.6; P = 0.227). Khan et al[13] showed that US was performed less frequently, and use of CT for the diagnosis of AAp increased during the pandemic period (OR: 3.7; P < 0.001).

The COVID-19 pandemic changed the way we evaluate the patients. Patients who are admitted to the emergency departments with various major complaints who have concomitant respiratory symptoms and/or a fever are initially evaluated by thorax CT. Therefore, any patient with an abdominal complaint receives both thorax and abdominal CT during the evaluation process. This may be the reason explaining the increased CT use during the pandemic period. In contrast to the majority of the studies, Romero et al[41] reported that the use of CT dropped by 61% during the COVID-19 pandemic. In our study we found that radiologic evaluation for the diagnosis of AAp in the pre-pandemic and pandemic periods were 96.7% and 86.8%, respectively (P = 0.001). This drop in the use of radiologic evaluation in our study can be due to two factors. First, the delay in the hospital admissions of the patients led to prominent symptoms that did not need any radiologic evaluation. The second reason can be due to the fact that these patients were evaluated in other centers or private hospitals where the radiologic modalities were performed and the patient was sent to our institution once the diagnosis was established.

We would like to emphasize the impact of the pandemic on the occurrence of complications (perforated AAp, gangrenous AAp, and peri-appendicular abscess) seen during the course of AAp. In the literature, there is no consensus on the definition of complications (plastron, abscess, phlegmon, gangrene, perforation, peri-appendicular abscess, pelvic abscess, and severe peritonitis) that are related to AAp. Ten of the 25 studies that are related to the COVID-19 pandemic and AAp reported that perforation rates significantly increased during the pandemic period (5.0%-45.6%)[1-4,9,13,15,16,40]. In addition, another 2 of the 25 studies reported an increase in the perforation rates (17.5%-31.0%) that did not reach statistical significance[37,38]. Interestingly, perforation rates were reported to be reduced (5.0%-10.7%) during the COVID-19 pandemic in two studies[14,17]. Five studies in our literature review reported that peri-appendicular and pelvic abscess rates (5.6%-33.9%) increased during the pandemic period[2,13,17,18,35]. Some of the studies reported all complications as “complicated AAp”. In 12 studies, the frequency of complicated AAp (15.9%-64.4%) was reported to be increased during the pandemic period. Nine of the 12 studies reported that the pre-admission interval was longer during the pandemic period. Only two studies used a logistic regression model and showed that longer pre-admission intervals were a risk factor for the development of complicated AAp[2,17]. Analysis of the results of all these studies showed that the delay in hospital admissions during the COVID-19 pandemic was correlated with the incidence of complicated AAp.

Negative appendectomy is an important concept in the treatment of AAp. This has been a matter of debate, and the consensus states that there should be a balance between negative appendectomy and perforated AAp rates to ensure patient safety. Ten of the 25 studies that were reviewed gave their results regarding negative appendectomy rates. The results of these studies showed that negative appendectomy rates dropped during the COVID-19 pandemic[1,6,13-16,18,33,34,39]. Five of the ten studies stated that this drop showed statistical significance. In our study, we observed that negative appendectomy dropped by 2.6 times during the pandemic period (OR: 2.6; 16.9% vs 7.2%; P = 0.003). These results suggested that during the pandemic period the patients were more meticulously evaluated before establishing the diagnosis and performing surgery for AAp. Another reason can be attributed to the fact that patients did not come to the hospital until the definitive symptoms of AAp developed because of the reluctance due to the COVID-19 pandemic.

Another point that needs to be emphasize is the impact of the COVID-19 pandemic on the demographic, clinical, and laboratory parameters of the patients with AAp. All 25 studies that have been analyzed in our literature search have shown that pandemic and pre-pandemic periods did not differ significantly in terms of age and body mass index. However, one study reported that significantly older patients were admitted to the hospital for AAp during the COVID-19 period[13]. Differences in gender were analyzed in four studies in the literature. Three of these studies stated that female gender was predominant[13,17,20], and in the remaining study male gender was the predominant gender during hospital admissions related to AAp[38]. One study reported that the American Society of Anesthesiologists scores were higher in the pre-pandemic period[18]. In another study, the comorbidity rate was higher in patients treated for AAp during the COVID-19 pandemic[3]. The frequency of smokers were not different in patients in the COVID-19 and pre-COVID-19 periods[15,18,38].

The data regarding the leukocyte counts were presented in 18 studies, and 14 of them showed no difference before and after the COVID-19 pandemic. Three studies showed lower WBC counts in patients with AAp during the pandemic period[13,14,41]. One study reported a higher WBC count in patients with AAp during the COVID-19 pandemic[22]. CRP levels were reported in 12 studies, and in 3 of these studies the CRP levels were significantly different between the COVID-19 and pre-COVID-19 periods[1,13,40]. In one of these studies CRP was significantly higher in patients with AAp in the COVID-19 period, and in the remaining two studies it was higher in AAp cases in the pandemic period. Gao et al[2] have suggested that the CRP levels and WBC count did not show significant changes because of the high rate (reaching 55% of the patients) of pre-admission self-medication with antibiotics during the COVID-19 pandemic. In the literature, studies are usually retrospective in nature, and there is no data regarding the nonsteroidal anti-inflammatory drug and antibiotic use of the patients. For this reason, we believe that there is no data to support the hypothesis of Gao et al[2].

We have analyzed all markers of inflammation that have been mentioned above, and we could not find a significant difference between the two different time intervals. When the pandemic and pre-pandemic periods are internally grouped according to the perforation status of the patients, inflammatory markers are found to be significantly elevated in patients with perforated AAp. For this reason, prospective studies are needed to further evaluate this specific topic.

Furthermore, COVID-19 causes multisystem inflammatory syndrome that can occasionally manifest itself as acute abdomen, especially in vulnerable populations such as children. It is the result of immune dysregulation and causes gastrointestinal symptoms that mimic AAp. Multiple systemic inflammatory reaction during or after COVID-19 generally implies active infection or complication of COVID-19 that is misdiagnosed as AAp[42]. In the present study, the pre-admission duration in both AAp and perforated AAp increased during the pandemic period when compared to the pre-pandemic period. Furthermore, the US and histopathologic confirmation rate of AAp increased, while the negative appendectomy rate decreased. Our results suggest that during the pandemic period, the surgical team took more time in diagnosing AAp, which increased preoperative waiting period. This is also reflected as the increase in the perforation rates in our patients. Therefore, our diagnostic accuracy increased during the pandemic, which rules out COVID-19 related multiple systemic inflammatory reaction.

Although the studies related to the association of AAp and COVID-19 infection are lacking, it is quite possible that dysregulated inflammatory reaction in infected patients may cause expansion of the Peyer patches causing lymphoid hyperplasia related obstruction of the appendiceal lumen leading to increased incidence of AAp. In accordance with our study, the case series presented by Anderson et al[42] showed that there was increased lympho-histiocytic infiltration in the submucosa and mesoappendix.

The treatment modality of choice for patients with AAp during the COVID-19 pandemic is also a matter of debate and needs to be clarified. The two alternatives are appendectomy vs NOM. The studies performed in the last two decades show that the two treatment alternatives have no superiority over the other. This discussion is crucial during the COVID-19 pandemic. The metanalysis published by Emile et al[43] suggests that during the COVID-19 pandemic patients treated with NOM had significantly lower complication rates and a shorter duration of hospitalization. However, it has been shown that in young, male, and complicated AAp patients, the success of NOM is lower than appendectomy. The authors have shown that the success rate of NOM did not change significantly between the pre-pandemic and pandemic periods. Yang et al[44] recently published the results of their meta-analysis regarding AAp in the pre-COVID-19 period and showed that NOM reduced complication rates and duration of hospitalization in both complicated and non-complicated AAp. Furthermore, they showed that appendectomy was a highly effective treatment with reduced relapse rates. Javanmard-Emamghissi et al[45] performed a multicentric study regarding AAp during the COVID-19 pandemic and found that complication rates and duration of hospitalization was significantly lower in the patients with AAp who received NOM.

A multicentric study organized by the Italian Association of Surgery in 66 countries with contributions of 706 surgeons showed that during the pandemic surgeon preference of treatment modality for non-complicated AAp shifted from laparoscopic approach (57.2% vs 22.5%) to open appendectomy (7.2% vs 15.0%) or NOM (6.6% vs 23.7%)[46]. Furthermore, surgeons participating in the study stated that their preferred treatment for complicated AAp shifted from laparoscopic appendectomy (62.5% vs 33.7%) to open appendectomy (14.0% vs 28.1%), NOM (2.4% vs 5.3%) or NOM and percutaneous drainage (21.1% vs 32.9%). The guidelines of the American College of Surgeons recommend the use of oral/parenteral antibiotics as the first line treatment of patients with complicated or non-complicated AAp during the COVID-19 pandemic. These guidelines that recommend appendectomy should be performed in patients with a relapse of the disease[34]. Also, it is suggested that in patients with abscess, perforation, or failure to NOM minimally invasive or conventional surgical treatment should be performed[34].

Moletta et al[47] analyzed various treatment guidelines and recommendations for AAp published during the COVID-19 pandemic and stated that in non-complicated AAp, NOM should be performed. On the other hand, in complicated cases and in patients whom NOM failed, surgical therapy should be the treatment of choice[44]. Our literature review including 25 studies showed that in 6 studies the rate of NOM increased during the COVID-19 pandemic. Our experience regarding NOM is very limited. Therefore, we cannot share any data regarding NOM in AAp in our study. However, in our opinion and clinical practice, we do not use NOM for elderly patients (because of high rates of complicated AAp), patients with complicated AAp, and patients who refuse to choose NOM. In our opinion, during the COVID-19 pandemic, instead of a considerable duration of hospitalization and parenteral antibiotic use, we recommend appendectomy especially in patients with complicated AAp.

The efficacy of laparoscopy in the treatment of AAp has been extensively studied in patients and in specialized groups such as gravid patients, pediatric patients, elderly patients, and non-complicated AAp patients. Jaschinski et al[48] performed a systematic review for the Cochrane database and showed that laparoscopic appendectomy was associated with reduced surgical site infections, shorter duration of hospitalization, earlier return to work, and better quality of life when compared to conventional appendectomy. However, the intraabdominal abscess rate was higher in laparoscopic appendectomy. The main concern of the physicians regarding laparoscopy during the pandemic is aerosolization of the virus and risk of transmission due to insufflation and exsufflation of the abdomen. Moletta et al[47] analyzed different guidelines and four original studies. They concluded that laparoscopic surgery can be performed provided that the medical staff take the necessary precautions, and the fume extraction-ventilation of the operating room is provided. The authors stated that laparoscopy is based upon the creation and maintenance of a pneumoperitoneum, and the use of energy devices results in formation of smoke bioproducts. Aerosolization of blood born viruses has been previously detected in surgical smoke during laparoscopy. Therefore, a potential risk of aerosol exposure must also be considered for COVID-19 even though it is not currently demonstrated. In conclusion, there is no clear cut evidence showing increased risk of disease transmission during laparoscopy, and therefore there is no reason to stop laparoscopic procedures[49].

The postoperative complications and prolonged postoperative antibiotic therapy and hospital stay is another argument regarding the COVID-19 pandemic and AAp. Fourteen articles in our literature presented data regarding the duration of hospital stay in AAp during the pandemic. Ten of these studies showed no difference in duration between the different time intervals[4,13,19-22,35,36,39,40], while one study reported a prolonged hospital stay[1] and another study reported that the duration was shorter during the pandemic[14]. In addition, three studies reported that although there was no statistical difference, the duration of hospitalization during the pandemic tended to be longer[3,10,18]. Seven studies reported data regarding postoperative complications, and five of these studies reported that the rate of complications did not change. In one study, surgical site infection rate (1.9% vs 6.9%) was found to be increased during COVID-19 pandemic. In another study, the postoperative complication rates (25.0% vs 16.7%) were found to be reduced during the pandemic. In the present study, we found that the duration of hospital stay was longer in patients treated during the COVID-19 pandemic (P = 0.003). This was related with the high rates of complicated AAp observed during this period. In the present study, we could not find a significant difference in terms of duration of postoperative antibiotic use and complication rates.

There are various limitations of the present study. The main limitation was the significant recall bias regarding the hospital admissions and interval to operation. The main reason for this is the telephone interview of the patients to receive these data. This is especially important for patients operated in the pre-pandemic era. The retrospective study design for obtaining the data analyzed in the present study is another limitation of our study. However, our results are striking because we observed a higher incidence of AAp as well as perforation rate during the COVID-19 era. In addition, our data regarding the COVID-19 infection rates in the pre- and postoperative period in our patients are missing, which should be noted as a limitation of our study.

CONCLUSION

The results of our study suggest that the complicated AAp rates increased, which led to a prolonged duration of hospitalization during the COVID-19 pandemic. The number of patients treated for AAp increased during the pandemic, which is attributed to the shift of role of the two state hospitals in our city. Fortunately, although the rate of complicated AAp increased, this did not increase the postoperative complication rates. Therefore, we can conclude that during global catastrophes such as the COVID-19 pandemic more complicated forms of the diseases such as AAp can be seen. Although the system is overwhelmed by the workload of the patients with COVID-19 infection, this should not change our attitude towards performing surgical therapy in these patients because any delay will lead to dismal consequences and prolonged hospital stays.

ARTICLE HIGHLIGHTS
Research background

Although emergency procedures were allowed during the coronavirus disease 2019 (COVID-19) pandemic provided that necessary precautions were taken in the operating theatre and inpatient wards, it was believed that there were serious disruptions in the management of patients with acute appendicitis (AAp).

Research motivation

AAp management is critical because AAp is the most common cause of acute abdominal pain, and appendectomy is the most frequent emergency procedure.

Research objectives

The present study aimed to comparatively evaluate the impact of the COVID-19 pandemic to the pre-pandemic period regarding patients who underwent appendectomy for AAp in terms of negative appendectomy and perforation rates. Our secondary aim was to evaluate the impact of the COVID-19 pandemic on the hospital admission rates of patients with AAp.

Research methods

Demographic, clinical, and histopathological characteristics of 223 patients (COVID-19 group) who underwent appendectomy with a preliminary diagnosis of AAp between March 2020 and July 2021 were compared with 154 patients (pre-COVID-19 group) who underwent appendectomy with the same indication between October 2018 and March 2020.

Research results

There was a 44.8% increase in the number of patients admitted to our hospital with a presumed diagnosis of AAp during the pandemic. Significant differences were found between pre-COVID-19 and COVID-19 groups in terms of procedures performed on the weekdays or weekends [odds ratio (OR): 1.76; P = 0.018], presence of AAp findings on ultrasonography (OR: 15.4; P < 0.001), confirmation of AAp in the histopathologic analysis (OR: 2.6; P = 0.003), determination of perforation in the appendectomy specimen (OR: 2.2; P = 0.004), the diameter of the appendix (P < 0.001), and hospital stay (P = 0.003).

Research conclusions

The results of our study suggest that the perforated AAp rates increased, which led to prolonged hospital stays during the COVID-19 pandemic. The number of patients treated with AAp increased during the pandemic, which is attributed to the shift of roles of the two state hospitals in our city. Fortunately, although the rate of complicated AAp increased, this did not increase our postoperative complication rates. Therefore, we can conclude that during global catastrophes such as the COVID-19 pandemic more complicated forms of the diseases such as AAp can be seen.

Research perspectives

This study has shown that even diseases that require emergency management, such as AAp, can be ignored during the COVID-19 pandemic. It is known that this situation is directly related to both patient behavior and the increased workload of healthcare professionals. The most important way to overcome this problem is to learn from the pandemic process, implement preventive measures properly, and create social awareness.

ACKNOWLEDGEMENTS

We would like to commend all healthcare professionals who were always on the frontlines. They took the courage and responsibility of treating all patients during these hard times despite risking their own lives. They are the real heroes.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Medicine, research and experimental

Country/Territory of origin: Turkey

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): 0

Grade C (Good): C, C

Grade D (Fair): D

Grade E (Poor): 0

P-Reviewer: Hernandez-Caballero A, Mexico; Leowattana W, Thailand S-Editor: Wang JJ L-Editor: Filipodia P-Editor: Wang JJ

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