From the end of December, the world is facing the threat of a new zoonosis caused by Severe Acute Respiratory Syndrome - Coronavirus – 2 (SARS CoV-2) which gave rise to a pandemic which is currently ongoing. The Bergamo province has been one of the most affected regions worldwide with an increase in the mortality rate in the first trimester of 2020 of + 568% [
- Fagiuoli S
- Lorini FL
- Remuzzi G
- Unit Covid-19 Bergamo Hospital Crisis
Adaptations and Lessons in the Province of Bergamo.
N Engl J Med. 2020 May 5;
We describe a case of fatal intestinal infarction whit a difficult diagnosis, which was made possible throughout by using innovative technique.
A 62-year-old unconscious man was admitted to the Emergency Department of Papa Giovanni XXIII Hospital (Bergamo, Italy) with severe hypotension during the month of April 2020. The recent medical history reported by phone from his wife included three days of abdominal pain and bilious vomiting. The patient's main comorbidities were obesity, arterial hypertension, diabetes mellitus type 2 and hepatic cirrhosis (non-alcoholic steatohepatitis + hepatitis B). Blood tests revealed an increase in the blood levels of leukocytes (primarily neutrophils) and C-reactive protein blood levels, altered renal and liver function tests, and D-dimer levels increased of > 75-fold above the upper limit of normal. Owing to the rampage of the pandemic in our area, the patient was tested for SARS CoV-2and found negative in nasopharyngeal swab and bronco-alveolar lavage.
Chest CT was unremarkable while abdominal CT findings were highly suggestive for small bowel ischemia; moreover, thromboembolic filling defects in inferior vena cava and superior mesenteric vein were found (Fig. 1). The patient underwent small intestine resection, but eventually died for refractory septic shock 12 hours after surgery. The histological examination on the resected small bowel showed complete ischemic necrosis of the mucosal layer and acute perivisceral inflammation; the mesenteric vessel was characterized by complete recent thrombosis and inflammatory infiltration of the endothelium (Fig. 2). These histological findings, in particular the severe endothelial inflammation, were not what one might expect to find in a true intestinal infarction and, combined with the time period, the pandemic situation in our area and the recent experience in our center caused strong suspicion of COVID 19 infection. For this reason we decided to perform on resected small bowel an ISH (in situ hybridization) on the resected small bowel specimen, using the RNAscope technology(ACD, Advanced Cell Diagnostics), an RNA in situ hybridization technique described previously [
]. This method that enables the detection of the SARS-CoV-2 spike protein mRNA by means of the VnCov2019- S probe (Fig. 3).
- Wang F
- Flanagan J
- Su N
- Wang L-C
- Bui S
- Nielson A
- et al.
RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues.
J Mol Diagn. Jan. 2012; 14: 22-29
Paired double Z oligonucleotide probes were designed against target RNA using custom software. The following probe was used : V-nCoV2019-S, 848568, NC_045512.2, 20 pairs, nt 21631-23303. The RNAscope 2.5 LSX Reagent Kit-Brown IVD Automation (Leica BOND III ) was used according to the manufacturer's instructions. FFPE tissue section samples were prepared according to manufacturer's recommendations.
The RNA ISH assay confirmed SARS CoV-2 presence in the intestinal mucosa giving us the possibility of a direct visualization of the virus while retaining tissue morphology, a feature that is lost in other methods such as PCR.
Facing a pandemic emergency is a very hard challenge, beginning with the difficulties of employing accurate diagnostic tools [
]. Gastrointestinal symptoms have been described shortly after the SARS CoV-2 outbreak [
- Patel R
- Babady E
- Theel ES
- Storch GA
- Pinsky BA
- St George K
- et al.
Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS-CoV-2/COVID-19.
mBio. 2020; 11 (26)
] and reported to be self-limiting in the vast majority of patients, but with the possibility of being linked to a high risk of complications. Furthermore, there is growing evidence of a link of COVID-19 to coagulopathy [
- Jin X
- Lian J-S
- Hu J-H
- Gao J
- Zheng L
- Zhang Y-M
- et al.
Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms.
Gut. 2020 Mar 24;
] and a state of hypercoagulability has been demonstrated by thromboelastography [
- Guan W-J
- Ni Z-Y
- Hu Y
- Liang W-H
- Ou C-Q
- He J-X
- et al.
Clinical Characteristics of Coronavirus Disease 2019 in China.
N Engl J Med. 2020 Feb 28;
]. This state could also be the explanation of the diffuse thrombosis found in peripheral pulmonary vessels post-mortem by our pathology department [
- Panigada M
- Bottino N
- Tagliabue P
- Grasselli G
- Novembrino C
- Chantarangkul V
- et al.
Hypercoagulability of COVID-19 patients in Intensive Care Unit. A Report of Thromboelastography Findings and other Parameters of Hemostasis.
J Thromb Haemost. 2020 Apr 17;
] Thus, a link between the intestinal ischemia in our patient and COVID-19 infection is highly probable.
- Carsana L
- Sonzogni A
- Nasr A
- Rossi R
- Pellegrinelli A
- Zerbi P
- et al.
Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy.
medRxiv. 2020 Apr 22; (2020.04.19.20054262)
Declaration of Computing Interest
Authors declares no conflict of interest and no financial support for this study.
- Adaptations and Lessons in the Province of Bergamo.N Engl J Med. 2020 May 5;
- RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues.J Mol Diagn. Jan. 2012; 14: 22-29
- Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS-CoV-2/COVID-19.mBio. 2020; 11 (26)
- Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms.Gut. 2020 Mar 24;
- Clinical Characteristics of Coronavirus Disease 2019 in China.N Engl J Med. 2020 Feb 28;
- Hypercoagulability of COVID-19 patients in Intensive Care Unit. A Report of Thromboelastography Findings and other Parameters of Hemostasis.J Thromb Haemost. 2020 Apr 17;
- Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy.medRxiv. 2020 Apr 22; (2020.04.19.20054262)
Published online: June 09, 2020
Accepted: May 16, 2020
Received: May 13, 2020
© 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.