Acute cholecystitis is an emergency condition, most commonly the result of gallbladder disease, and is usually presented with right upper abdominal pain, pain in the right shoulder, nausea, vomiting, and occasionally fever. During 2012, in the United States, it was the sixth most common gastrointestinal and pancreatic diagnosis from emergency department visits, accounting for a total of 651,829 emergency department visits and 389,180 hospital admissions, amounting to 0.7 per 100,000 mortality rate (1).

According to the World Emergency Surgery Association (WSES) (2) and the Tokyo Guidelines (3), early laparoscopic surgery is the gold standard and should be performed as soon as the diagnosis is made and the choledocholithiasis risk is evaluated. This approach results in a shorter length of stay (LOS), fewer complications in comparison to late cholecystectomy, and generally decreased recurrence rates. Patients who are at high risk of morbidity or mortality should undergo conservative treatment and in case of failure, percutaneous cholecystostomy (PC) could serve as an alternative (2, 3).

During 2019, a new coronavirus named SARS-CoV-2 was identified. The related disease had a great social and financial global impact and was soon recognized as a pandemic (4). During such times, the worldwide healthcare systems and the management of surgical interventions were compromised. Due to the increased rate of hospitalizations, many organizations amended their guidelines to limit admission rates, so that they could free up space for possible patients infected with COVID-19 and limit patient exposure in a heavily infected environment. Based on this, organizations such as the British Intercollegiate General Surgery Guidance (BIGSG) (5), the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) (6), and the European Association for Endoscopic Surgery (EAES) (7) have stated that a more conservative approach to surgery, which means antibiotic therapy, PC, and “watchful waiting,” is preferred, whenever possible, in acute cholecystitis (5–7). On the other hand, WSES highly suggests that laparoscopic cholecystectomy should remain the standard of care even in the setting of the COVID-19 pandemic and warns against the excessive use of PC (8).

The rationale for this study is that no systematic review currently examines the shift toward a more conservative approach in the management of acute cholecystitis and the related outcomes in the COVID-19 era. This research aims to assess the impact of COVID-19 on acute cholecystitis management and its treatment.

A systematic review of the literature was performed. The studies evaluating the management of acute cholecystitis during the COVID-19 period, as well as those comparing COVID-19 and non-COVID-19 periods, were included. Case reports, case series, abstracts, congress proceedings, and non-English language reports were excluded from our review. Studies with less than 15 patients were also excluded. The outcome measures taken into consideration were the rates of different management strategies during both the pandemic period and as a comparison between COVID-19 and pre-COVID-19 period. The rates of complications and mean LOS during those periods were also examined.

During the COVID-19 era, there have been numerous modifications in the approach of emergent cases in every medical specialty and especially in situations with potential surgical intervention. Before the outbreak of this viral pandemic, laparoscopic cholecystectomy was the gold standard treatment in most patients diagnosed with acute cholecystitis. There are several studies in the current literature that suggest emergent surgery in acute cholecystitis, and the WSES further emphasizes that early laparoscopic cholecystectomy should be performed as soon as possible but can be safely performed up to 10 days after the onset of symptoms (2). However, early laparoscopic intervention is significantly associated with a shorter hospital stay, fewer complications, and operational costs (2, 27). Following the virus's global spread, guidelines regarding acute abdominal incidents were modified. Indeed, the BIGSG on COVID-19 stated that during the COVID-19 pandemic, whenever non-operative management is possible (such as for early appendicitis and acute cholecystitis), this should be performed. BIGSG recommended either non-surgical management or the utilization of a PC tube for the management of acute biliary disease (5). Similarly, other surgical societies, such as the SAGES and EAES, have also advocated for a more patient- and hospital-centered approach, which suggests conservative treatment whenever appropriate (6, 7).

With regard to the above, numerous hospitals considered altering their initial approach. This shift was mainly attributed to the fact that laparoscopy is an aerosol-forming procedure and carries a potential risk for transmission of SARS-CoV-2 to healthcare professionals (28). As a result, several hospitals began their treatment with antibiotics and “watchful waiting” while others performed PC. As a matter of fact, this potential risk was investigated and the results revealed a greater benefit in favor of laparoscopy with no reason of replacing it with laparotomy due to COVID-19 infection (28).

Additional safety precautions were recommended to avoid the possibility of virus transmission. Those measures concern mainly the prevention of pneumoperitoneum dispersion and potential viral spreading (29, 30), the safer operative technique with the proper evacuation of smoke developed from electrosurgery and ultrasonic surgery (29, 31), the disinfection of potentially contaminated devices and materials, and the usage of more protective equipment under each hospitals protocol. Finally, recommendations were proposed for the establishment of specific operating rooms for patients with COVID-19 regarding the risk of transmission between patients (29, 31, 32).

The various types of management of acute cholecystitis along with their outcomes were the topic of our systematic review. The studies were divided into two main categories with the first one focusing on different approaches exclusively during the COVID-19 outbreak, whereas in the second one, studies compared alternative managements before and after the start of the pandemic. In the first group, within a total of 218 patients with acute cholecystitis, there was a significantly high number of non-surgical treatments [160], of which 127 were only given antibiotics and 33 were treated with PC. In contrast, only a small number of patients [58] directly underwent surgery. The outcomes from most of the studies of the second category were similar. There was a notable change in the percentage of conservative management before (36.3%) and after (43.2%) the start of the pandemic. As a matter of fact, PC was frequently preferred on many occasions as a combination of potentially life-saving and less invasive treatment options, taking into consideration that it can serve as a bridge therapy allowing patients to survive severe disease and stabilize until they undergo a cholecystectomy (21). Moreover, in some cases, PC was chosen over surgery, taking into consideration the severity of pulmonary complications related to the disease (12, 33).

Treating patients conservatively as outpatients or inpatients does spare surgical capacity; however it renders the overall hospital stay much longer, and, in some cases, it reflects in more complicated cholecystitis. Our systematic review depicts that this is the result of both antibiotic therapy and PC. In the case of PC, the LOS was noted even longer which can be attributed to delay in PC insertion (20). In this setting, the WSES underlines that the extravagant use of PC jeopardizes the standard level of care and that this method should be reserved for only a small, selected subset of patients (8). The shift toward more conservative treatments was thought to minimize the risk of aerosol transmission of COVID-19 through laparoscopic procedures and, therefore, protect from the viral spread. However, this type of management is associated with extended hospitalizations and, therefore, longer viral exposure for the patients and the professionals. When comparing the two periods, several studies reported a higher rate of complications since the outbreak of COVID-19. More specifically, Fouad et al. (11) highlighted a statistically significant difference in intra-operative, post-operative, and non-surgical complications (predominantly pulmonary) during the pandemic compared to the pre-COVID-19 period. However, the longer LOS and complication rates during the COVID-19 period may be attributed to a prolonged duration of symptoms prior to admission, due to the patients' concern of possible virus transmission (11, 23).

The majority of studies were conducted during the onset of the pandemic, a period without straight facts about COVID-19. Nowadays, due to the contribution of many studies, knowledge has been acquired concerning both the transmission of the virus and the strategies that are necessary for the protection and risk minimization of healthcare providers. Therefore, it is a thought-provoking question whether the modifications in acute cholecystitis management analyzed in this review are still existent or whether treatment strategies have returned back to their prior state.

This systematic review has a number of limitations. First, our research was mainly based on retrospective studies with no available randomized trials, due to the ongoing status of the COVID-19 pandemic. Moreover, each study reports in different lockdown periods based on the country and the existing circumstances at the time of conduction, thus leading to a discrepancy in terms of quality and completeness of data between the studies. The fact that the observation period of the studies is not equally long should also be noted. In addition, this systematic review presents only the short-term outcomes of conservative treatment with no reference to the long-term recurrence rates of this approach. Finally, stratification of the results according to Tokyo grade could not be done as only a few studies used this classification.

In summary, the ongoing pandemic has had a tremendous impact on surgical emergencies, and thus, the management of acute cholecystitis could not pose an exception and has been dramatically affected. Most studies reported a tendency toward more conservative approaches, namely, the use of antibiotics or PC, for the treatment of acute cholecystitis, in comparison to the widely used early laparoscopic cholecystectomy in the pre-pandemic era. This review highlights that this approach is associated with a longer LOS and, in certain circumstances, higher complication rates. Due to the unknown course of the pandemic, future studies, especially randomized controlled trials, are compulsory to investigate the safety profile of non-surgical management for acute cholecystitis patients.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

KS and IL: conceptualization. MK: methodology. GK, KS, IL, and MK: literature review, writing—original draft preparation, and project administration. AI: validation, writing, reviewing, editing, and supervision. KS and MK: formal analysis. IL and GK: investigation. KS: resources. IL: data curation. GK: visualization. All authors have read and agreed to the published version of the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AM declared a shared affiliation with the authors KS, IL, and GK to the handling editor at the time of review.

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