Abstract

The COVID-19 pandemic involved the globe and resulted in major mortalities mainly affecting the respiratory system. Initially thought to be respiratory disease it was later postulated and confirmed the involvement of gastro-intestinal tract (GIT) and its contribution to the complications and mortalities. Herein we present five cases of severe COVID-19 infection with GI involvement and their management with literature review.

Keywords: COVID-19, Acute Abdomen

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Introduction

An outbreak of coronavirus 2019 (COVID-19) infection, caused by severe acute respiratory syndrome virus (SARS-CoV-2), has rapidly spread from China to almost all over the world. Unfortunately, the number of infected people is rising with increased mortality.

Patients can be asymptomatic or symptomatic with various degrees of severity. Gastro-intestinal (GI) involvement is documented in the literature, the incidence of which initially ranged from 3% to currently 20% with vague presentations like abdominal pain, nausea, and vomiting. Evidence is accumulating that GI symptoms are more; and SARS-CoV-2 can be detected in feces in about 50% of infected subjects [1]. It is reported that sometimes those GI symptoms may precede couple of days prior to the diagnosis of COVID-19 [2].

The prognosis of patients with COVID-19 with gastrointestinal symptoms is still largely unknown. Studies implied that these patients may have worse clinical outcome than those without digestive symptoms, emphasizing the importance of symptoms such as diarrhea to diagnose COVID-19 early [3]. Pan et al [4] also showed that as the severity of the disease increased, digestive symptoms became more pronounced. A multicenter and cross-sectional study demonstrated that approximately 50 % of patients experienced symptoms such as diarrhea, nausea, vomiting, and abdominal pain. Furthermore, the time from onset of gastrointestinal symptoms to hospital presentation is delayed compared to respiratory symptoms (9.0 vs. 7.3 days) [5].

Wang and colleagues found that patients admitted to the intensive care units (ICU) were more likely to have abdominal pain and loss of appetite compared with non- ICU patients [6]. Mao et al [3] did subgroup analyses to investigate the difference in gastrointestinal symptoms between patients with severe and non-severe COVID-19. They found a higher prevalence of abdominal pain in patients with severe COVID-19 than in those with non-severe group [3].

Here we present 5 patients who were diagnosed with COVID 19 and found to have surgical acute abdomen with perforated viscus. Literature review of reported cases in the world was done to investigate any correlation between COVID 19 and pneumoperitoneum and predict the outcome of such patients.

Patient cases

Case 1

38 Years old previously healthy male patient presented with respiratory symptoms, COVID-19 PCR was positive, the patient respiratory symptoms kept worsening and he required endotracheal intubation. 26 Days post ICU admission for COVID-19 pneumonia, the patient was found to have abdominal distension and sigmoid colon perforation diagnosed after CT Abdomen. He underwent exploratory laparotomy and Hartmann procedure. Patient showed full recovery and was discharged home.

Case 2

40 years old male known to have diabetes mellitus and hypertension was admitted to the medical intensive care unit as a case of COVID-19 pneumonia requiring intubation for ventilatory support. One week later, he was found to have abdominal distension and CT scan showed distension of the cecum and ascending colon (Pseudo-obstruction). The patient was treated conservatively, and the abdominal distension became significantly less. However few days later the patient succumbed due to respiratory complications.

Case 3

34 Years old previously healthy male patient presented to ED with respiratory symptoms due to COVID-19 pneumonia that required endotracheal intubation, 8 days later he was found to have abdominal distension. Chest X- ray showed pneumoperitoneum and the patient was taken to the operating room for exploratory laparotomy which showed transverse colon perforation and was treated with primary repair. Few days later the patient was improving and was extubated and discharged home.

Case 4

53 years old previously healthy male patient admitted to the medical intensive care unit as a case of severe COVID-19 pneumonia requiring ventilatory support. Four days later, patient had increased abdominal distension and peak airway pressures. CT scan of the chest and abdomen showed multiple segmental pulmonary embolisms, pneumomediastinum and pneumo-retroperitoneum. The patient was managed non operatively. However, one month later, he expired due to COVID related complications and multi-organ failure.

Case 5

47 years old with severe COVID-19 pneumonia on mechanical ventilation developed increasing abdominal distension. Chest X-ray was significant for free air under the diaphragm whereas, CT scan of the abdomen with contrast showed pneumoperitoneum, pneumomediastinum as well as free fluid in all four quadrants of the abdomen. The patient was managed non operatively as the pneumoperitoneum was attributed to extension of pneumomediastinum possibly due to tracheo-bronchial tree injury. The patient remained hospitalized for two months and recovered completely from COVID pneumonia.

Method

Literature search was done using PubMed, Google Scholar, Cochrane, to look for articles that reported GI symptoms (acute abdominal pain) and COVID 19 in English language. Papers that reported positive COVID 19 and pneumoperitoneum or suspicion of perforated viscus were included.

Statistical methods

Descriptive statistics in the form of mean and standard deviations for interval variables such as age and frequency with percentages for categorical variables were reported. Student t tests were applied to see significant mean age difference according to gender and comorbidity. P value 0.05 (two tailed) was used statistically significant level. SPSS 26.0 statistical package was used for the analysis.

Results

We found 23 cases from 17 publications. All were COVID 19 positive and were of 54.1±19.3 years of age, 8 being females (34.8%) and 15(65.2%) male patients. 13 patients (56.5%) had at least one comorbidity. The mean age of the comorbid patients was more than those without any comorbidity (63.0±18.8 years vs female 42.0±15.3 years, p=0.008) whereas; there was no statistical difference between mean age according to gender (male 54.3±18.8 years) vs female (53.9±21.5 years, p=0.96).

CT abdomen was performed for 17 (73.9%) patients, X-ray for 16 (67.6%) and one patient had the US. Distention was the most common gastrointestinal symptom in 12 patients (52.1%), pain 8 (34.8%), incidental findings of pneumoperitoneum in 2(8.7%), and hemodynamic instability in 2 (8.7%). 18 patients (78.3%) had primary while 5 patients (21.7%) had secondary pneumoperitoneum. The most common perforated organ was colon 10 (43.4%), in the frequency of cecum 4(17.4%), and then right colon 2(8.7%), transverse colon 1(4.3%), left colon 1(4.3%), and sigmoid, rectum and not identified were 2 (8.7%) each. Small bowel perforation was less common and accounted for only 4(17.4%) patients, where duodenum, jejunum, and ileum were 1 (4.3%) each.

Conservative treatment was carried out in 9 patients (39.1%); however, surgery was performed in 14 patients (60.9%). Seven (30.4%) patients died, 12 (52.1%) were discharged, 3 (13%), with one patient was not described.

Patients’ details are given below in Table 1 [7-22].

Table: 1

No Study Age Gender Initial COVID status Intub-ated Initial GI symptom Image finding Perforated organ Duration from COVID positive to GI Symptoms COVID Treat-ment Y=1 N=0 Diagnosis Conser-vative=0 Surgery=1 ASA Surgery/Outcome
1 Al-Qahtani 38 Male Positive Yes Abdominal distension Pneumo-peritoneum and free fluid Sigmoid 26 days 1 Sigmoid perforation 1 Life saving Exploratory Laparotomy and Hartmann procedure/ Discharge
2 Al-Qahtani 33 Male Positive Yes Abdominal distension Pneumo-peritoneum Transversecolon 8 days 1 TransverseColon perforation 1 III E Exploratory Laparotomy, primary repair/Discharge
3 Al-Qahtani 47Male Positive Yes None Pneumo-peritoneum with pneumo- mediastinum None 34 days 1 Pneumo-mediastinum 0 - None
4 Al-Qahtani 53Male Positive Yes None Pulmonary embolism, Surgical emphysema, pneumo-mediastinum with pneumo-retroperitoneum None 15 days 1 Pneumo-mediastinum 0 - None
5 Al-Qahtani 46 Male Positive Yes Abdominal Distension Extensive surgical emphysema, extensive pneumo-mediastinum extending intra-abdominal and pre-peritoneally None 15 days 1 pneumo-mediastinum 0 - NoneSpread of pneumomediastinum leading to presence of air preperitoneal, intra and retro peritoneal
6 Paramythiotou [7] et al 2020 50 Female Positive Yes None Pneumo-peritoneum Lung 45 days 1 Respiratory failure 0 - presence of a large quantity of free air in the peritoneum attributed to spreading of air from the lung/ Expired
7 Gartland et al [8], 2020 47 MaleDM Positive Yes Abdominal Distension Small bowel ischemia and perforation, patent mesenteric vessels Ileum 14 days 1 Bowel necrosis and terminal ileal perforation 1 Life saving Exploratory laparotomy, bowel Ischemia and perforation/ Expired
8 Kangas-Dick et al [9] 2020 74Male Positive Yes Abdominal distension Pneumo-peritoneum and free fluid Proximal GI tract perforation 5 days 1 Bowel perforation 1 - No surgery/Expired
9 Giuffre et al [10], 2020 87 Femalewithpolymyalgia rheumatica, giant cell arteritis Positive No Abdominal distension and rectal bleeding wall thickening of the lower third of the rectum with free perivisceral air Perforated rectum Same day 1 Perforated rectum 0 - No surgery/Expired
10 De Nardi et al [11], 2020 53 Male,Hypertension,paroxysmal supraventricular tachycardia Positive No Abdominal pain and distension, Diarrhea Massive pneumo- peritoneum Ascending colon 13 days 1 Cecal distension and perforation 1 Life- saving Exploratory Laparotomy, right Hemicolectomy/ Discharged
11 Neto et al [12], 2020 80 Female,Hypertension Positive Yes Diffuse abdominal pain and stiffness Pneumo- peritoneum, free fluid in abdomen Sigmoid Same day 1 reduced visceral per-fusion in the entire gastrointestinal tract and four punctate lesions in the sigmoid colon, with fecal content into the cavity 1 Life- saving Exploration Laparotomy, recto-sigmoidectomy terminal Colostomy/ Expired
12 Parhar et al [13], 2020 36 FemaleHypertension Positive Yes Fever and elevated White cell count Free air under diaphragm Cecum and ascending colon perforation Few days 1 Cecum and ascending colon perforation 1 Life saving Exploration Laparotomy Right hemicolectomy and loop ileostomy were performed
13 Rojo et al [14], 2020 54 FemaleDM, HTN Positive Yes Hemodynamic instability Active bleeding from cecum and free air Cecal perforation 15 days 1 Cecal ulceration with perforation 1 Life Saving Right hemicolectomy/ Expired
14 Winnicka and Shenoy M [15], 2020 73 MaleCAD, PVD, DM, Obesity Positive Yes no GI symptoms, incidental findings of air under diaphragm Free air under diaphragm Unknown 16 days 1 - 0 - No surgical procedure/ Discharge
15 Guo et al [16], 2020 40 Female Un-known then positive Yes Nausea, vomiting, epigastric pain Pneumo-peritoneum Posterior duodenal wall perforation Not mentioned 1 Duodenal perforation 1 - Laparotomy, closure of perforation, Discharged
16 Lotti et al [17], 2020 72 Male, HTN, Diverticulosis Positive No Abdominal pain Pneumo-peritoneum Jejunal diverticulum perforation Same day presentation 1 Jejunal diverticulum perforation 1 - Laparotomy Jejunal resection/ Discharge
17 Sharma et al [18], 2020 47 Male, DM, HTN Positive Yes no GI symptoms, incidental findings of free air Pneumo- peritoneum, Pneumo-mediastinum and subcutaneous emphysema None 10 days 1 - 0 - No surgical intervention/Discharge
18 Bhattacharjee et al [19], 2020 45, MaleHTN Un-known than positive No Abdominal pain and distension Free air under diaphragm Unknown initial presentation with GI symptom, diagnosed with covid on routine swab 1 Sealed hollow viscus perforation 0 - No surgical intervention/Discharge
19 Verma et al [20], 2020 60 FemaleHypo-thyroidism Positive No Abdominal pain and distension, generalised peritonitis Free air under diaphragm Upper third of rectum 11 days 1 Rectal perforation 1 laparotomy and transverse colostomy/Discharge
20 Verma et al [20], 2020 24 FemalePost C-section Un-known than positive No abdominal pain, vomiting and distention of abdomen Massive pneumo- peritoneum Anterior wall of cecum Same day 1 Cecal perforation 1 - Laparotomy, primary closure with loop ileostomy/Discharge
21 Verma et al [20], 2020 21Male Positive No vomiting and distention of abdomen Pneumo- peritoneum Anterior wall of stomach Same day 1 Gastric perforation 1 - laparotomy, Graham's patch closure of perforation/Discharge
22 Nahas et al [21]2020 92 MaleHTN, CKD, Colonic malignancy Positive No Diffuse abdominal pain Pneumo-peritoneum with no collection and distended bowel loops Descending colon Same day 1 Descending colon perforation 5 cms from previous colostomy site 1 - Laparotomy, resection and terminal-colostomy/Expired
23 Persiano et al [22],2020 73 MaleIHD, CKD,NIDDMHTN Un-known than Positive No fever and Diarrhea,abdominal distention and tenderness Pneumo-peritoneum with no collection and distended bowel loops Ascending colon 11 days 1 Ascending colon perforation 1 - Laparotomy and right Hemicolectomy/Discharged
Table 1.

Discussion

Almost 20% of COVID-19 patients have abdominal symptoms ranging from mild generalized pain, nausea, vomiting, to significant and acute surgical abdomen. The proportion of acute abdominal pathologies has increased from 32.7% to 50.5%, and demonstrated an increase in the severity of these pathologies 7.9% to 19.7%, and an associated trend for increased need for surgical intervention 26.3% to 47.6% in one study [23].

The most common perforated organ was the colon as one would assume small bowel would be the most common organ. 60% of patient had surgical intervention with high mortality reaching to 30%. This could be explained partially to the fact that some had late diagnosis, or they were in septic shock and poor outcomes to start with. However, 52% of patient who underwent surgery had good outcome and sent home after prolonged hospital course [3].

Theory

There are many hypotheses why COVID-19 appears to cause digestive symptoms, but, the exact molecular mechanism needs to be further investigated. A study conducted by Xiao et al [24], demonstrated results favoring gastrointestinal viral replication with potential fecal-oral route of transmission. Upon endoscopy and biopsy, the study also found that SARS-CoV-2 RNA was detected with positive staining of the viral nucleocapsid protein in gastric, duodenal, and rectal epithelium. These findings further support the evidence of replication of infectious virions occurring within the gastrointestinal tract [24].

It is postulated the role of angiotensin converting enzyme 2 (ACE-2) receptor in the pathogenesis of abdominal pain [25]. The virus binds to the ACE-2 receptor, which can be found in the lungs and various GI system including intestine, by which the virus gains cellular entry and create the potential for viral replication5. Zhang et al found that successful virus entry of SARS-CoV-2 depends not only on the presence of ACE-2 cell receptor; but also, the cellular serine protease, transmembrane protease serine 2 (TMPRSS2), which cleaves the S protein of human coronaviruses on the cell membrane) [26]. Both of these protein molecules are critical for fusion of viral and the cellular membranes [26]. ACE-2 and TMPRSS2 are co-expressed in lung alveolar type 2 cells and esophageal upper epithelial type II cells. It is also highly expressed in the ileum and colon which suggests that the virus can invade enterocytes of the digestive tract [1], and cause primary damage to GI tract. Davidson et al found that the binding affinity of ACE-2 to the outer domain of SARS-CoV-2 is ~10–20 times higher than that of SARS-CoV [27]. It is postulated that binding of SARS-CoV-2 with ACE-2 receptors in the gastrointestinal tract reduces the level of available receptors, which affects the absorption of tryptophan, and ultimately destroys the steady state of the intestinal flora [28,29].

There could be a direct injury of the gastrointestinal system due to a chain of inflammatory response. Villapol showed that any changes in intestinal dysfunction would induce changes in intestinal microbes, hence, an increase in inflammatory cytokines [29]. Once within a cell, the virus activates the intracellular immune system, which causes immune and non-immune cells to release large amounts of pro-inflammatory cytokines that activate a cytokine storm and result in damage to the host [30]. Huang et al found that the plasma cytokine and chemokine levels of COVID-19 patients were higher than those of healthy people [31]. The plasma level of certain cytokines such as IL-2, IL-7, IL-10, granulocyte colony stimulating factor (GSCF), and recombinant human interferon-induced protein-10 (IP-10), MCP-1, macrophage inflammatory protein-1A (MIP-1A), and TNF were high in levels of patients with severe disease than the level of cytokines of patients without severe disease [31].

Bhayana et al [32] suggested a role of ACE2 receptor and the possibility of direct vascular invasion by the virus or occlusion resulting from the microthrombus formation and causing mesenteric vessel ischemia (occlusive or non-occlusive), renal vessels infarcts, appendagitis, and omental infarcts [33]. Other Non-thrombotic events cause peritonitis, colonic distension, and colitis, and pancreatitis which have been reported in association with COVID-19 [5].

In general, presence of co-morbidities is associated with poor outcomes in patients with COVID-19. This may have implications for the management of patients with pre-existing digestive diseases [3]. Autopsy studies are important to help investigate histopathological changes in the gastrointestinal tract in patients with COVID-19. Only one autopsy report with details of gastrointestinal pathology has been published in an 85-year-old man with COVID-19, which showed segmental dilatation and stenosis in the small intestine [34]. Further studies are needed to clarify whether this finding is secondary to COVID-19 or a pre-existing gastrointestinal comorbidity [3].

Conclusion

There is evidence of COVID-19 involving the gastrointestinal tract and increases the morbidity and mortality if intestinal perforation ensues. A high grade of suspicion should be kept in mind as the sick patients are already ventilated and the GI pathology further aggravates the precarious condition. Although surgical intervention carries high mortality but provides the only chance of cure if carried out judiciously.

Declarations

Data Availability

The data is available with corresponding author and all the references have been mentioned in the “Reference Section.”

Conflicts of Interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

Funding Statement

No funding.

Supplementary Materials

No supplementary material used.

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How to Cite
Al-qahtani, J., Al-Kuwari, H. ., Sameer, M., Alobaidi, M., Ali, S. M., & Singh, R. (2022). Acute Abdomen in the ERA of COVID 19: Case Series and Literature Review. International Journal of Innovative Research in Medical Science, 7(09), 492–497. https://doi.org/10.23958/ijirms/vol07-i09/1490

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Copyright © 2022 Jowhara Al-qahtani Haya Al-Kuwari Mohammed Sameer Mohammed Alobaidi Syed Muhammad Ali Rajvir Singh this is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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