Pseudomembranous Colitis in a Coronavirus Disease 19 positive patient : not a simple issue.

doi:10.21203/rs.3.rs-2062655/v2

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Pseudomembranous Colitis in a Coronavirus Disease 19 positive patient : not a simple issue.

https://doi.org/10.21203/rs.3.rs-2062655/v2

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Since its emergence, Coronavirus Disease (Covid-19) rapidly spread worldwide and was responsible for a global pandemic. Although it was initially considered a respiratory disease, recent studies have evidenced that Covid-19 had serious systemic adverse effects involving major organs, including those of the digestive system. Histological lesions associated with these manifestations have rarely been reported. We, herein, present a singular case of pseudomembranous colitis (PMC), proven histologically, in a 73-year-old Covid-19 positive female patient. We aim to study the clinico-pathological characteristics of this association. A 73-year-old Covid positive patient was intubated and put on intravenous antibiotherapy after the deterioration of her respiratory function. Ten days after admission, the patient presented abdominal distension and melena. An abdominal tomography scan showed a left mesenteric infarction related to a thrombosis at the origin of the left mesenteric artery. A left hemicolectomy was performed in emergency. Macroscopic examination of the hemicolectomy specimen showed an edematous colonic mucosa, with multiple ulcerations covered by a whitish necrotic coating reminiscent of false membranes. Histological examination confirmed the diagnosis of PMC. The patient presented a septic shock and died six days after the operation. The PMC could have resulted from the use of antibiotics. However, the direct involvement of Covid-19 in the occurrence of this PMC cannot be excluded. Further studies are needed to evaluate the direct correlation between Covid-19 and PMC.

Pseudomembranous colitis

Coronavirus Disease 19

Clostridium difficile infection

Intestinal ischemia

Coronavirus Disease (Covid-19), first arising in Wuhan, China, in December 2019, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its emergence, it rapidly spread worldwide and was responsible for a global pandemic. By the first of September 2022, the World Health Organization (WHO), had recorded more than 600 millions confirmed cases, with six millions deaths all around the world(1). Although it was initially considered a respiratory disease, recent studies have evidenced that Covid-19 had serious systemic adverse effects involving major organs, including those of the digestive system (2). We, now, consider that up to 40% of Covid-19 patients presented gastrointestinal symptoms, including diarrhea, nausea, vomiting, and abdominal pain(3). Histological lesions associated with these manifestations have rarely been reported. We, herein, present a singular case of pseudomembranous colitis (PMC), proven histologically, in a 73-year-old Covid-19 positive female patient. We aim to study the clinico-pathological characteristics of this association.

A 73-year-old hypertensive diabetic female patient, presented during the pandemic,fever, chest pain and dyspnea. A real time reverse transcription polymerase chain reaction (RT-PCR) SARS-CoV-2 nasopharyngeal test was performed. The result came back positive. The patient was put on antibiotherapy and home oxygen therapy. As her condition worsened, she presented to our emergency department ten days later. Physical examination revealed an increased respiratory rate with an oxygen saturation of 80%. A chest tomography was performed and showed pneumopathy lesions suggestive of Covid-19 with 75% pulmonary involvement. With the exacerbation of the respiratory function, the patient was intubated and started to receive intravenous antibiotic therapy. Ten days after admission, the patient presented abdominal distension and melena. An abdominal tomography scan showed a left mesenteric infarction related to a thrombosis at the origin of the left mesenteric artery (Fig. 1). A left hemicolectomy was performed in emergency. Macroscopic examination of the hemicolectomy specimen showed an edematous colonic mucosa, with multiple ulcerations covered by a whitish necrotic coating reminiscent of false membranes (Fig. 2). Histological examination revealed focal and superficial ulcerations covered by deposits of fibrin, mucus and altered neutrophil cells, resulting in the classic “volcanic-like eruption” appearance. Intercryptic necrosis was also noted (Fig. 3). The rest of the colonic wall was edematous, congested and focally necrotic. The diagnosis of pseudomembranous colitis was established. No testing for Costridium difficilae (CD) has been undergone. The patient presented a septic shock and died six days after the operation.

Pseudomembranous colitis (PMC), a severe acute colonic inflammatory disease, is mainly caused by Clostridium difficile infection (CDI) (4). Nevertheless, it can be caused by a wide range of conditions including: ischemic colitis (IC), collagenous colitis, inflammatory bowel disease, Behçet disease, infections (Entamoeba histolytica, Escherichia coli O157:H7, Cytomegalovirus), medications and drugs (5).

The emblematic histological sign of PMC consists in the presence of laminated pseudomembranes made up of exudates of fibrin, mucus, altered neutrophils and necrotic epithelial cells, lying on the surface of ulcerated crypts the characteristic aspect of volcanic eruption or pseudo-Mushroom (6). Erosions, ulcerations, mucosal necrosis, hemorrhage and hyalinization within the lamina propria, crypt destruction, and crypt abscesses are also common findings(4).

CDI represents the leading cause of PMC. Several cases of CDI have been reported in Covid-19 positive patients (7). The use of antibiotics in COVID-19 pneumonia enhances the risk of antibiotic-associated diarrhea, mainly CDI (8). Our patient had received antibiotic therapy, first orally and then intravenously. This would have favored the occurrence of CDI and therefore PMC.

However, CDI have been recorded in Covid-19 patients with no history of antibiotherapy (7). This suggests that Covid-19 itself can promote the occurrence of PMC independently of the use of antibiotic therapy. In fact, the intestinal inflammation caused by Covid-19 could predispose to coinfection with other gastrointestinal pathogens, including CDI (9). Besides, COVID-19 can cause an alteration of the fecal microbiota composition with the enrichment of opportunistic pathogens and depletion of beneficial commensals (8). Deregulation of the innate and the adaptive immune response due to the replication of SARS-CoV-2 virus can also promote the occurrence of CDI (7).

It is well known that Covid-19 has a vascular tropism, causing coagulation abnormalities, thromboembolic complications especially ischemic colitis (10). Therefore, apart from causing CDI, Covid-19 can lead to PMC by means of IC. Indeed, in the case we report, the patient had a mesenteric infarction with thrombosis of the left mesenteric artery. This could explain the onset of PMC. Ischemia as a cause of PMC is not a novel concept, but it is often under-diagnosed, owing to the strong association of PMC with CDI(4). However, since no CDI testing had been performed in our case, the occurrence of CDI is not excluded and its involvement in PMC can not be ruled out.

Histological study can help to distinguish the different causes of PMC(5). However, there are no pathognomonic signs to determine with certainty the PMC’s specific etiology. In CDI, acute crypt injury and dilation are common. The upper lamina propria is usually involved and pseudomembranes are focal. However, hyalinization and hemorrhage of the lamina propria, full-thickness mucosal necrosis and diffuse pseudomembranes seem to be significantly more associated with ischemic colitis than CDI in PMC (11). Of all these findings, hyalinization of the lamina propria was most specific for IC (5). A thickened subepithelial collagen band > 10 µm and intraepithelial lymphocytosis may point to collagenous colitis as an etiology (5). In inflammatory bowel disease, architectural distortion, glandular atrophy and basal plasmacytosis are suggestive of this etiology.

Microscopic examination did not show any cryptic abscesses that could have suggested CDI as an etiology. Similarly, it did not show hyalinization of the lamina propria or transmural necrosis suggestive of an ischemic origin. However, the diffuse pseudomembranes were a sign in favor of ischemic origin.

In the case we present, PMC could be secondary to the ischemia caused by the thrombosis of the left mesenteric artery. However, since no CD’s testing had been performed, CDI cannot be excluded. It could have been promoted by the use of antibiotics or by the Covid-19 itself.

Coronavirus can be responsible for various intestinal manifestations. We presented a singular case of histologically proven PMC in a Covid-19 positive patient. It could be secondary to the use of antibiotics. But the direct involvement of Covid-19 in the occurrence of this PMC cannot be excluded. Further studies are needed to evaluate the direct correlation between Covid-19 and PMC.

Author contribution statement

All authors listed have significantly contributed to the investigation, development and writing of this article.

Funding statement

This research did not receive any specific grant from funding agencies in the public, commercial, or non-profit sectors.

Competing interest statement

The authors declare no conflict of interest.

Additional information

No additional information is available for this paper.

Conflict of interest :The authors declare no conflicts of interest.

Fundings: none.

Consent : Informed consent was obtained from the patient to publish these images.

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No competing interests reported.

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