Abstract
Background/Aim: COVID-19 is rapidly spreading, and due to the high morbidity and mortality caused by the pandemic many Governments have introduced social restrictions. Those measures combined with infection-related patient anxiety, led to hiding other diseases. The aim of this study was to evaluate the impact of COVID-19 on numbers and severity of acute appendicitis cases referred during the pandemic. Patients and Methods: Between March 2019 and March 2021, all patients who underwent appendectomy in Tor Vergata Hospital, Rome were included. Patients were divided in two groups (COVID-19/pre-COVID-19). Clinical features, intraoperative findings, hospital stay, and histologic examination data were included in the retrospective analysis. Results: Out of 334 admitted patients, 36 (10.7%) had a diagnosis of acute appendicitis (COVID-19 group) vs. 59(11.2%) in the pre-COVID-19 group. The COVID-19 group presented significantly longer hospitalization, incidence of appendicular abscess, perforation, and severity of inflammation at univariate analysis p=0.002, p=0.021, p=0.001, p=0.006, p=0.001, respectively. At multivariate analysis, appendicular abscess (p=0.015) and higher serum levels of C reactive protein (p<0.008) were associated with prolonged hospital stay. Conclusion: This study highlights the correlation between COVID-19 pandemic and the severity of acute appendicitis presentations.
Since the first cases of SARS-CoV-2 infection were described in Wuhan, Hubei province, China, during late 2019, the new coronavirus rapidly spread worldwide causing an unusual type of pneumonia (1). Due to extremely rapid human-to-human transmission, on March 11, 2020, the World Health Organization declared the outbreak of a global pandemic (1-2). Many governments struggled to intercept the spread of SARS-CoV-2 by utilizing different strategies (3).
Healthcare systems shifted resources towards COVID-19 patients and adopted measures to preserve hospital capacity and increase intensive care unit beds availability during the emergency (3). These restrictions have been associated with a decrease in or cessation of most non-COVID-19 health services with a significant impact on daily practices (4-5). In addition, authorities instructed the public to stay at home and avoid visiting local clinics and hospitals as much as possible while recommending increased application of telemedicine-based practice (6). Moreover, infection-related patient anxiety played a major role in avoiding hospitalization or access to healthcare facilities (7-9). Potentially, all these factors combined led to hidden disease (10) and delayed diagnoses and treatments (11, 12). Nonetheless, urgent or emergent medical conditions continue to appear during the current outbreak and diagnoses should still be made promptly. Delayed diagnosis and treatment of non-COVID-19 disease can lead to significant morbidity that may overweigh the harm caused by SARS-CoV-2 infection (13, 14).
While most published studies regarding SARS-CoV-2 infection have explored viral transmission, pathogenesis, treatments and outcomes, the effective impact on other disease requires further investigation (15-17).
Acute appendicitis represents 4.5% of abdominal pain occurrences and the most common emergency any general surgeon faces in practice (18, 19). In western countries, the lifetime risk of acute appendicitis is calculated to be 1 in 15 individuals (19). Severity and associated morbidity can be correlated with the period between signs and symptoms onset to treatment initiation (19).
We hypothesize that COVID-19 restrictions have resulted in a significant impact on the number of patients presenting to the Emergency Department with a diagnosis of acute appendicitis. Moreover, patients admitted to the emergency department present with advanced stages and severity of the disease due to pandemic-related delayed diagnoses and treatments.
The aim of the study was to evaluate the impact of COVID-19 on number, severity, and length of hospitalization of acute appendicitis patients treated during the pandemic.
Patients and Methods
The study was conducted as a retrospective, cohort investigation of acute appendicitis patients undergoing surgery at Policlinico Tor Vergata hospital of Rome, Italy. The study was approved by the local Ethical Committee of Fondazione Policlinico Tor Vergata (reference 122/20). The requirement for informed consent was waived by the committee in light of the retrospective and anonymous nature of the study.
All patients admitted to the surgical Emergency Department with a suspicion of acute appendicitis, and consequently undergone appendicectomy between March 11, 2019, and March 11, 2021 were identified and data were collected for the analysis.
Data were extracted from patient records and included demographic and clinicopathological variables. White blood cells (WBCs) count, percentage of neutrophils and C reactive protein (CRP) value collected from blood test performed at hospital admission were reported for each patient (20). Number of previous hospital admissions due to conservatively-treated acute appendicitis were reported. Signs, symptoms, and duration between the onset of symptomatology and admission to healthcare were reported as well. Alvarado scores were calculated and reported for the analysis (21). The performed radiological exam, abdominal CT scan or sonography in unclear cases, were reported. Surgical data for analysis were collected from surgical procedure notes. Surgical procedure duration was reported in minutes and the surgical approach was distinguished between laparoscopic appendectomy, open appendectomy or converted. Severity of appendicitis was reported according to surgical notes; presence of peritonitis and number of abdominal quadrantes involved in the phlogistic process, presence of free fluid in abdomen and its type (e.g., exudative, pus or faecalis), reported as categorial variables. Additionally, perforation of the appendix and/or presence on abdominal abscesses detected during the abdominal exploration were reported. Methods for closure of appendix stump were reported as categorial variables (e.g., endo loop knots, surgical suture, or automated mechanical suture). Need for abdominal surgical drainage or re-operation, and related causes were collected and analyzed. The report included whether the surgical procedure was performed by a trainee or a senior surgeon. WBCs count, percentage of neutrophils and value of CRP collected from the first blood test performed after surgery were recorded. Types of appendicitis were reported from pantological examination of the appendix, performed routinely by an expert pathologist, and categorized as: inflamed, acute suppurative, gangrenous and necrotic. Length of hospital stay was considered from the date of the surgical procedure to hospital discharge, reported in days.
The goal of the study was to compare the incidence of acute appendicitis before and during the pandemic and evaluate changes in the characteristics or severity of patients diagnosed with appendicitis during the COVID-19 emergency compared to beforehand.
In order to assess these aims, our cohort was split into two different groups. Patients presenting in the 12 months prior to the declaration of pandemic were designated as pre-COVID-19 group, while those presenting in the following 12 months were designated as COVID-19 group. This corresponded to March 10, 2019 – March 10, 2020, for the former and March 11, 2020 – March 11, 2021, for the latter. A 12-month period was determined in order for the change in incidence not to be temporal or seasonal in nature, rather than due to COVID-19.
Statistical analysis. All data were collected into the EXCEL database (Microsoft, Washington, DC, USA). For continuous variables, we calculated and used medians and interquartile ranges. T-test was performed to determine whether there were significant differences between the two groups. Categorical data were reported in numbers and percentages. Analyses to determinate significant differences between the two groups were performed using the Fisher’s exact test in case of dichotomous variable or Monte Carlo test for non-dichotomous variable. Variables with p-values <0.05 were considered statistically significant. Cox regression was used for multivariate analysis. All the statistical analysis was performed in SPSS statistical package version 23.0 (SPSS Inc., Chicago, IL, USA).
Results
From March 11, 2019, to March 11, 2021, 858 patients were admitted to the Emergency Surgical Department at PTV university of Rome Tor Vergata; 524 (61.07%) before the pandemic and 334 (38.93%) during the COVID-19 pandemic. Out of 334 patients admitted during the global pandemic, 36 (10.77%) were admitted with a diagnosis of acute appendicitis versus 59 (11.24%) in the previous year; p=0.911 (30.55%) patients in the COVID-19 group and 26 (44.06%) in the control group were females, p=0.209. Median age was, respectively, 41.4 [26.5-61.9] and 37.1 [28.2-56-4] years during the pandemic and in the previous period, p=0.629.
Among the COVID-19 group, for 27 (75%) patients this was the first admission to the emergency department for acute appendicitis, 7 (19.4%) had a history of a previous admission and 2 patients presented twice or more to the surgical department. Differently, in the pre-pandemic group, 53 (89.8%) were first accesses, 5 (8.5%) a single previous access, and 1 (1.7%) presented two or more accesses to surgical department, showing a statical significant difference: p=0.039.
Median durations between symptomatology onset and admission to healthcare during the pandemic were longer, 2 days [1-4] versus 1 [0-2] in the pre-COVID-19 group, p<0.001. Only 14 (38%) patients underwent preoperative abdominal ultrasound during the pandemic while in the pre-pandemic period, 40 (67.8%) patients received diagnosis of acute appendicitis with sonography method; p=0.008. Moreover, 28 (77.7%) patients in the COVID-19 group and 34 (57.6%) in the pre-COVID-19 underwent abdominal CT scan before surgery, p=0.044.
The Alvarado score showed a statistically significant difference between the groups (p=0.001) and its distribution is resumed in Table I. Admission blood tests are reported in Table II with relative p-values.
Pre-operative Alvarado score between COVID-19 and pre-COVID group.
Blood test between COVID-19 and pre-COVID group.
Surgical procedure duration was longer during the pandemic period with a median of 86 minutes [70-107] versus 60 min [50-80] in the pre-COVID-19 era, showing a statistically significant difference; p<0.001. The surgeon, a senior or a trainee, did not show a difference between the groups with p-value=0.225; 10 procedures (27.8%) were performed by an in-training surgeon during the pandemic and 10 (17.2%) in the control group.
In the COVID-19 group, 30 (83.3%) procedures were performed laparoscopically, 2 (5.6%) conversion in open surgery and 4 (11.1%) cases were performed in upfront open surgery, versus 51(87.9%), 6 (10.3%) and 1 (1.7%), respectively, in the control group; p=0.262.
Intraoperative findings as appendicular abscess, peritonitis, appendicular perforation, and use of abdominal drain tube are resumed in Table III with relative p-values. In addition to the significant increase in peritonitis cases during the pandemic, also the extent of inflammation, depicted by the number of involved abdominal quadrants, was significantly higher with a p<0.001. Abdominal extension of peritonitis and presence of abdominal free fluid and its type are summarized in Table IV. Staging of acute appendicitis at pathological examination was advanced in the pandemic group, showing a statistically significant difference, p<0.001. Pathological classifications of acute appendicitis are resumed in Table V.
Intra-operative findings between COVID-19 and pre-COVID group.
Intra-operative peritonitis extension between COVID-19 and pre-COVID group.
Pathological acute appendicitis classification between COVID-19 and pre-COVID group.
Additionally, methods for closure of appendix stump were significantly different between the groups; p=0.002. During the pandemic we reported an increased use of Endo-GIA staplers; 69.4% versus 36.2% in the control group. One patient in the COVID-19 group received a tobacco pouch suture during an open appendectomy. Contrastingly, closure of appendicular stump using Endo-loops was lower in the COVID-19 group; 13.9% versus 53.4% in the pre-COVID-19 group.
Six months reoperation rates were similar among the groups; p=1.000. One patient (2.8%) underwent a second surgery due to adhesive small bowel obstruction during the pandemic. Differently, in the control group 1 patient (1.7%) underwent right hemicolectomy due to malignancy at pathological examination of appendix. Post-operative blood tests are reported in Table II with relative p-values. Hospital acquired infection rate was 2.8%; 1 patient experienced a mild pneumonia and was discharged in 13th post-operative day, and its length of hospital stay was excluded from the statistical analysis.
Length of hospital stay was longer in the COVID-19 group, with a median of 5 [3-6] days versus 3 [2-4] days in the control group, showing a significant increase with p=0.002. A logistic regression was performed to evaluate the effects of perioperative variables on length of stay. Length of stay was classified as a dummy variable and a median value of 3 was set as the cutoff. All variables with p<0.100 were included in the multivariate analysis. The logistic regression model was statistically significant, χ2(4) = 33.449, p<0.0005. The model explained 42.6% (Nagelkerke R2) of the variance in length of stay and correctly classified 75.9% of cases. Appendicular abscess (p=0.015) and preoperative higher serum level of C reactive protein (p<0.008) were the variables associated with prolonged stay.
Discussion
Since the beginning of SARS-CoV-2 pandemic, routine healthcare and daily life changed dramatically worldwide (24, 25). The pandemic and its consequential restrictions led to high numbers of missed or delayed diagnoses as well as delays in treatment (10-12). Many authors tried to estimate the impact of COVID-19 pandemic on non-COVID-related disease, yet the true extent must still be investigated (15-17, 26). Nowadays, we begin to evaluate the first effects of COVID-19 on non-virus-related diseases (11, 13, 27). In fact, during this emergency period, even access to the surgical emergency department suffered a sharp decline (7, 28-30). Comparably with published data, in our analysis we recorded a reduction of roughly 40% in admissions to the emergency surgical department (28-34). Moreover, the fear of contracting COVID-19 as well as the encouragement by the authorities to avoid unnecessary presentations to the emergency department could explain the reduction in absolute numbers of accesses to the hospital (10, 35).
Differently, median age, sex and incidence did not show significant differences during the different periods. Due to the period comparability, without seasonal or demographic differences between the groups, we did not observe variation in incidence, as similarly reported by numerous studies (36, 37).
Many authors published suggestions on the management of acute appendicitis during the COVID-19 pandemic, advising to favor non-operative management when possible (38, 39). As reported in the literature, non-operative treatment for acute appendicitis presents a variable incidence of recurrence risk (40). In our study, we report a significant increase in the number of previous surgical emergency department accesses for lower right quadrant abdominal pain. This could be potentially explained by the preferred non-operative approach adopted during the pandemic, even in complicated acute appendicitis, leading to an increased recurrence rate before appendectomy. Furthermore, the duration between symptoms onset and admission to healthcare during the pandemic was longer. Probably, the delayed presentation could be related to the fear of contracting COVID-19 and the encouragement from authorities to avoid unnecessary hospital admissions (10, 35, 41). Despite the significantly higher Alvarado score in the Pandemic group, we did not observe a reduction of abdominal imaging prior to surgery. Assumingly, physicians tried to identify as many uncomplicated appendicitis cases as possible in order to apply non-operative management during the pandemic, as suggested in many studies (40-42). Moreover, an increased number of patients was subjected to abdominal CT scans. Although conceptually incorrect, healthcare personnel’s fear of contracting the virus led to the favoring CT scans over abdominal ultrasound in order to reduce contact with the patient as much as possible (9, 42).
Surgical procedure duration was longer during the pandemic period. This could be related to advanced inflammatory processes observed in the COVID-19 group, as reported in our results.
Our analysis, in parallel with studies published in the literature, showed an increased number of intraoperative findings (appendicular abscess, peritonitis and appendicular perforation) as well as higher staging of acute appendicitis on pathological examinations and higher inflammatory indices on blood tests during the pandemic (28, 36). It has been described that patients presenting to the surgical department more than 1 day after the onset of signs and symptoms are at a higher risk of suffering from perforated appendicitis (43, 44). The higher incidence of appendicular perforation could be related to the prolonged duration from the onset of symptoms to treatment.
The use of an abdominal drainage tube was also significantly more frequent in the COVID-19 group. This could be explained by the higher incidence of advanced inflammatory processes, presence of abscess and appendicular perforation observed in our study and other published series (45-47). Due to increased incidence of severe abdominal inflammatory findings and more frequent appendicular perforations, the use of Endo-GIA stapler for securing the appendicular stump was preferred. This is in spite of the lack of a proven superiority over the endo-loop in laparoscopic appendectomy. Additionally, despite higher costs, mechanical suturing was chosen as it is faster and considered safer by many surgeons (48).
Notwithstanding cases with advanced inflammatory processes, no differences were reported in terms of surgical approach; laparoscopic, open or conversion. The choice was based on the acute appendicitis 2020 guidelines, which favor laparoscopic surgery even in complicated cases (49). Despite the increase in difficult cases, the surgeon choice, senior or in training, did not show a difference between the periods. This allowed the training of young surgeons during a challenging period for surgical practice, partly due to the reduction in numbers of surgical procedures (50-52).
Length of hospitalization was significantly higher in the COVID-19 group. The increased cases of complicated appendicitis and the advanced staging of the inflammatory process influenced the hospitalization (53). At multivariate analysis, appendicular abscess and plasma levels of C reactive protein seemed to be the major factors influencing hospitalization (53, 54). Our findings are in accordance with a recent report by Sevinç et al. (55).
There are several limitations to our study; the first wave of the COVID-19 pandemic was unexpected, and the healthcare system was not prepared to simultaneously provide care for COVID-19 and non-virus-related patients. This has likely led to guidelines not being followed at times, especially at the beginning of the pandemic when there were no suggestions for the management of acute appendicitis during the COVID-19 pandemic. Additionally, this is a single institution, retrospective analysis that was performed utilizing ICD codes in order to identify every patient with the diagnosis of acute appendicitis. Finally, the small number of patients admitted with acute appendicitis represented an intrinsic limitation.
In conclusion, this study highlights the direct correlation between COVID-19 pandemic and the severity of acute appendicitis presentations. The significant increase in the incidence of complicated acute appendicitis with advanced inflammatory processes and in longer hospitalization times indicates that these patients required earlier diagnosis and treatment. In light of the high healthcare costs associated with appendicitis hospitalization, the resources transferred to COVID-19 patients thus far and the likelihood of further COVID-19 waves, it is prudent to address these issues so that this does not reoccur.
Footnotes
Authors’ Contributions
Study conception and design: Marco Pellicciaro; Acquisition of data: Francesca Santori and Simona Grande; Analysis of data: Marco Pellicciaro and Marco Materazzo; Interpretation of data: Gianluca Vanni, Daniele Sforza, Di Cesare Tataiana, Ciancio Manuelli Matteo; Drafting of article: Marco Pellicciaro, Dario Venditti and Massimo Villa; Critical revision of literature: Marco Pellicciaro, Dario Venditti and Marco Materazzo. Clinical Case data acquisition: Gianluca Vanni, Daniele Sforza, Di Cesare Tatiana, Ciancio Manuelli Matteo. Supervision: Michele Grande. All the Authors read and approved the final version of the manuscript.
Conflicts of Interest
The Authors declare no conflicts of interest regarding this study.
- Received January 3, 2022.
- Revision received January 24, 2022.
- Accepted February 16, 2022.
- Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
