Acute Acalculous Cholecystitis Caused by Candida Albicans in a COVID-19 Patient: A Case Report


 BackgroundAcute acalculous cholecystitis is a necro-inflammatory disease of the gallbladder with multifactorial pathogenesis and is associated with high morbidity and mortality rates. Severe acute respiratory syndrome coronavirus 2 has been declared a pandemic that causes coronavirus disease-19 (COVID-19). Although many COVID-19 patients reported gastrointestinal symptoms such as anorexia, nausea, vomiting, and diarrhea, there was no evidence about the gallbladder and biliary tract involvement in the literature to date. Case ReportA 71-year-old male was admitted to our facility and found to be positive for COVID-19. He received appropriate COVID-19 treatment with dexamethasone, remdesivir, and convalescent plasma. The patient continued to be lethargic, weak, and had elevated inflammatory markers. The arterial blood gas (ABG) panel showed metabolic acidosis with respiratory compensation, and the patient appeared to be overcompensating because of his hypoxia. Consequently, the patient was transferred to the intensive care unit (ICU) for intubation and mechanical ventilation. The total bilirubin started to increase over the following days and reached 8 mg/dL. The ultrasound did not show cholelithiasis. The bile culture grew Candida albicans, and the patient was diagnosed with acalculous Candida cholecystitis. The patient had a significant deterioration in clinical status and expired after being transferred to comfort care.ConclusionLong-term complications of COVID-19 are still unknown. This case suggests the incidence of a fungal infection involving the gallbladder. Future research could help facilitate a better pathophysiological understanding of those complications.


Introduction
Acute acalculous cholecystitis (AAC) is a necro-in ammatory disease of the gallbladder with multifactorial pathogenesis [1]. It accounts for approximately 10% of all acute cholecystitis cases and is associated with high morbidity and mortality rates of around 30% [range, 10% -90%] with early or late diagnosis, respectively. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has not been previously identi ed in humans, and it is responsible for the coronavirus disease-19 (COVID- 19) infection. The rst case was identi ed in Wuhan, China, in December 2019, and it has spread to many countries around the world and was declared a global pandemic on March 11, 2020, by the World Health Organization (WHO) [2,3]. Many COVID-19 patients reported gastrointestinal symptoms such as anorexia, nausea, vomiting, and diarrhea. However, to our knowledge, there has been no evidence of the gallbladder and biliary tract involvement with COVID-19. Therefore, we report a case of acute acalculous cholecystitis caused by Candida albicans in a patient with COVID-19 infection.

Case Report
This was a 71-year-old male with a past medical history of benign prostatic hyperplasia (BPH), essential hypertension, and hyperlipidemia who was admitted to Piedmont Columbus Regional Midtown (PCRM) in Columbus, Georgia, United States, with a chief complaint of shortness of breath that started a week ago and has been worsening in the last 24 hours. The patient's weight was 80. 3

Discussion
The etiology of AAC is multifactorial and likely results from bile stasis or ischemia (or both) [4]. Bile stasis can be caused by fasting, obstruction, postsurgical/procedural irritation, or total parenteral nutrition (TPN). The growth of organisms is ordinarily inhabited by the normal human bile salt concentration of 12% present in the gallbladder. However, the presence of cholestasis reduces this concentration, which may permit bacteria to proliferate in the biliary system [5,6]. Gastrointestinal symptoms have been reported with COVID-19. In a meta-analysis of 4243 patients with COVID-19, the prevalence of gastrointestinal symptoms was 17.6%, including loss of appetite, nausea/vomiting, diarrhea, and abdominal pain [7]. Acalculous cholecystitis has been reported previously after an acute infection with Epstein Barr virus (EBV) [8]. Also, a case of acute acalculous cholecystitis has been reported in a COVID-19 patient but with no pathogen identi cation [9]. Our case represents an acute acalculous cholecystitis possibly associated with COVID-19, and the causative organism was identi ed as Candida albicans.
Candida albicans in the gallbladder is thought to be a consequence of ascending migration of the organism within the biliary tract or hematogenous seeding during candidemia. In a retrospective chart review of 27 Patients with Candida spp isolated from the gallbladder or biliary tract, only 3 of 27 patients had candidemia, and 22 of 27 patients were colonized with Candida at other sites including sputum, urine, peritoneal uid, catheter tip, and other sites [10]. An epidemiological study also found that patients presenting with severe forms of COVID-19, especially those who required mechanical ventilation, were at increased risk of developing candidemia [11]. It has been proposed that SARS-CoV-2 may increase intestinal permeability, potentially by causing damage to enterocytes and to the epithelial layer. This disruption of the intestinal mucosal barrier in COVID-19 patients could be an additional risk factor for candidemia by facilitating Candida species' translocation from the gut lumen to the bloodstream [12,13,14]. In our case, COVID-19 could have been associated with gut disruption resulting in Candida's translocation and, consequently, dissemination to the gallbladder. Although there was no fungal growth in the blood cultures, the possibility that our patient experienced candidemia could not be ruled out due to prior amphotericin B exposure.
Fungal organisms are an infrequent cause of gallbladder infections. Predisposing factors that could increase the risk of acute acalculous Candida cholecystitis include critical illness with prolonged hospitalization, malignancy, prolonged broad-spectrum antibiotic therapy, immunosuppression, treatment with histamine (H 2 )-receptor antagonists, gastric achlorhydria, diabetes mellitus, total parenteral nutrition, and intraabdominal surgery [15,16]. Our patient had multiple predisposing factors, including prolonged hospitalization, being on multiple broad-spectrum antibiotics, and receiving total parenteral nutrition.
De nitive treatment of AAC consists of cholecystectomy or, in poor surgical candidates, cholecystostomy. Alternatively, endoscopic retrograde cholangiopancreatography (ERCP) is an effective treatment option for patients who cannot tolerate surgery or cholecystostomy. In addition to drainage, patients on broadspectrum antimicrobials can be narrowed, based on the results of aspirated bile cultures [17]. In our case, cholecystectomy was not a feasible option considering the patient's COVID-19 infection and unstable condition. Therefore, cholecystostomy was performed through interventional radiology.
AAC can be associated with multiorgan dysfunction in critically ill patients [18,19]. Critically ill patients who are admitted to intensive care units have been found to have high mortality rates (38% − 80%), likely because of the disseminated Candida infection and candidemia [16,18]. In a retrospective, unmatched, observational cohort study of 24 patients who underwent an open cholecystectomy for AAC, the median total Sequential Organ Failure Assessment (SOFA) score three days before cholecystectomy was 7.5 and increased to 10.5 (P < 0.0001) by the day of cholecystectomy, which indicated developing multiorgan dysfunction [19]. Our patient had a multiorgan failure, which could be the consequence of the combination of COVID-19 infection and AAC.

Conclusion
We report a case of AAC caused by Candida albicans in a patient with a COVID-19 infection. This case cannot establish a correlation between COVID-19 and AAC. However, considering that the long-term complications of COVID-19 are still unknown, future research could help facilitate a better pathophysiological understanding of those complications and provide a more precise explanation of the long-term effects of COVID-19.

Declarations
Funding The authors received no funding for this publication.

Con icts of Interest/Competing Interests
All the authors report no potential con icts of interest.

Availability of Data and Material
Not applicable.
Code Availability Not applicable.

Authors' Contributions
The rst draft of the manuscript was written by Haytham Wali, and all authors commented on previous versions of the manuscript. All authors read and approved the nal manuscript.

Ethics Approval
The Columbus Regional Research Integrity Panel has con rmed that no ethical approval is required.

Consent to Publish
The relatives of the patient have consented to the submission of the case report to the journal.