BMJ Open Gastroenterol: first published as 10.1136/bmjgast-2020-000434 on 9 June 2020. Downloaded from Case report Pneumatosis intestinalis in COVID-19 Simone Meini ,1 Chiara Zini,2 Maria Teresa Passaleva,1 Anna Frullini,1 Francesca Fusco,2 Roberto Carpi,2 Fiorella Piani1 To cite: Meini S, Zini C, ABSTRACT coexpressed not only in alveolar type 2 cells, Passaleva MT, et al. Introduction COVID-19 is a respiratory illness due to but also in the enterocytes of the ileum and Pneumatosis intestinalis in novel severe acute respiratory syndrome coronavirus COVID-19. colon, suggesting that the virus can invade BMJ Open Gastro 2 (SARS-CoV -2), described in December 2019 in 3 2020;7:e000434. doi:10.1136/ the digestive tract. Wuhan (China) and rapidly evolved into a pandemic. bmjgast-2020-000434 Faecal–oral transmission is a possible route Gastrointestinal (GI) tract can also be involved. of SARS- CoV-2 transmission: SARS- CoV-2 Case presentation A 44- year- old man was hospitalised Received 4 May 2020 for COVID-19- associated pneumonia. A rapid recovery can be detected in stool in about 50% of Revised 19 May 2020 patients with COVID-19; however, there is Accepted 29 May 2020 of respiratory and general symptoms was observed after 1 week of treatment with lopinavir/ritonavir plus no clear correlation between gastrointes- hydroxychloroquine and broad-spectrum antibiotics tinal (GI) symptoms and detectable virus in 3 4 (piperacillin–tazobactam plus teicoplanin). No GI the stool. It has been reported that up to symptoms were reported during hospitalisation, but 11.4% of patients with COVID-19 present a lung contrast-enhancement CT (CE-CT) excluding with at least one GI symptom, such as nausea, thromboembolism showed, as collateral finding, vomiting or diarrhoea: they present fever intraperitoneal free bubbles not present on a previous CT over 38.5°C, fatigue, shortness of breath and examination; the subsequent abdominal CE-CT described headache more frequently than patients pneumatosis intestinalis (PI) involving the caecum and the without GI symptoms; moreover, aspartate right colon. Ciprofloxacin plus metronidazole was started, copyright. aminotransferase (AST) resulted significantly and the 2-week follow-up CT showed the complete 5 resolution of PI. increased in this subgroup. Discussion The pathogenesis of PI is poorly understood. It is therefore increasingly evident that PI involving the caecum and right colon has been although COVID-19 is mainly an acute described for HIV and Cytomegalovirus infections, but, respiratory disease, the GI system can be to our best knowledge, never before in COVID-19. We involved. Unfortunately, knowledge about hypothesise a multifactorial aetiopathogenesis for PI, with the extrapulmonary involvement is scarce, a possible role of the bowel wall damage and microbiota and it is of utmost importance that every http://bmjopengastro.bmj.com/ impairment due to SARS-CoV -2 infection, and we suggest previously unknown clinical expression is a conservative management in the absence of symptoms. promptly reported, in order to assist other clinicians who could again meet it, and to allow to better understand the pathogenesis of a still elusive infectious syndrome. INTRODUCTION Starting in December 2019 from Wuhan (Hubei province, China), a novel corona- CASE PRESENTATION virus, designated severe acute respiratory A 44- year- old man presented to the emer- syndrome coronavirus 2 (SARS-CoV -2), has gency department on 20 March 2020, after 9 on September 26, 2021 by guest. Protected caused an international outbreak of a respira- days of persisting fever over 39°C, productive © Author(s) (or their employer(s)) 2020. Re- use tory illness (COVID-19), rapidly evolving into cough and chest pain, despite treatment with permitted under CC BY- NC. No a pandemic. amoxicillin–clavulanate and paracetamol. No commercial re- use. See rights The clinical spectrum varies from asymp- GI symptoms were reported. Clinical history and permissions. Published tomatic or self- limiting mild forms, occur- was negative; no smoking history or drugs by BMJ. ring in most cases, to severe progressive use was reported. The patient reported only 1Medicina Interna, Azienda USL Toscana centro, Ospedale Santa pneumonia with acute respiratory distress about an isolated anal fissure, sometimes Maria Annunziata, Firenze, Italy syndrome requiring mechanical ventilation slightly bleeding, diagnosed 20 years ago. 2Radiologia, Azienda USL and intensive care support, to sepsis or septic COVID-19 was diagnosed by reverse Toscana centro, Ospedale Santa shock, ultimately causing death.1 It has been transcriptase-PCR (RT-PCR) testing for Maria Annunziata, Firenze, Italy described2 that SARS- CoV-2 uses the ACE2 SARS-CoV -2 on nasopharyngeal swab. At Correspondence to receptor for cell entry and the serine protease admission, plain film of the chest showed Dr Simone Meini; TMPRSS2 for S protein priming: both these a right infrahilar opacity and a bilateral simonemeini2@ gmail. com proteins play a crucial role, and are highly peripheral reticular pattern. The following Meini S, et al. BMJ Open Gastro 2020;7:e000434. doi:10.1136/bmjgast-2020-000434 1 BMJ Open Gastroenterol: first published as 10.1136/bmjgast-2020-000434 on 9 June 2020. Downloaded from Open access laboratory studies resulted altered: C-reactive protein an almost complete remission of cough, and needing for (CRP) 16.64 mg/dL, procalcitonin (PCT) 0.29 ng/mL, very low flow oxygen support (1 L/min). CRP decreased ferritin 1966 ng/mL, D- dimer 1248 ng/mL, international to 3.43 mg/dL, and D-dimer to 1027 ng/mL. At the same normalized ratio (INR) 1.53, and lactate dehydroge- time, however, we observed altered levels of AST (143 nase (LDH) 380 U/L. Except for minimal neutrophilia, UI/L, after 2 days further increasing to 353 UI/L) and ALT the blood count was normal, and interleukin-6 levels (150 UI/L, then 378 UI/L), and hyperammonaemia (113 (<3.0 pg/mL), AST (38 UI/L), alanine aminotransferase μg/dL), with persisting normal values of cholinesterase, (ALT) (28 UI/L), and bilirubin (1.20 mg/dL) resulted bilirubin, and alkaline phosphatase; gamma- glutamyl within the normal limits. Hepatitis serological tests were transferase only slightly increased (71 UI/L). In the compatible with previous vaccination for hepatitis B virus. hypothesis of iatrogenic acute liver damage, we promptly Blood and urine cultures and Legionella pneumophila and interrupted the treatment with lopinavir/ritonavir and Streptococcus pneumoniae urinary antigens were negative. hydroxychloroquine, avoiding further administration of Lopinavir/ritonavir 400/100 mg plus hydroxychloro- paracetamol (last administration 48 hours earlier), main- quine 200 mg, both two times a day, were started. Given taining only therapy with teicoplanin, also because its the persistence of high fever and productive cough, putative efficacy to inhibit the first stage of SARS-CoV -2 and the slightly increased level of PCT, in suspicion of viral life cycle in human cells,6 and adding intravenous a secondary bacterial infection resistant to the previous acetylcysteine; moreover, enoxaparin was discontinued. therapy with amoxicillin–clavulanate, intravenous teico- Lactulose at an average daily dose of 25 mL was adminis- planin 400 mg one time a day (after loading dose) plus tered for the next 6 days. Ultrasound (US) examination of piperacillin–tazobactam 4.5 g three times a day were the abdomen did not report any particular finding. The started. Moreover, subcutaneous enoxaparin 4000 UI was lung high- resolution CT showed bi-basal dorsal consolida- administered one time a day for prophylaxis of venous tions associated with traction bronchiectasis, especially at thromboembolism. the level of right inferior lobe, compatible with COVID-19 After 6 days, the patient had a clear improvement of pneumonia (figure 1A); no particular abdominal finding general conditions, with resolution of fever from 48 hours, was depicted in the lower scans (figure 1B). copyright. http://bmjopengastro.bmj.com/ on September 26, 2021 by guest. Protected Figure 1 CT scans performed for the lung evaluation. (A) First lung CT coronal multiplanar reconstruction (MPR) shows ground glass areas with consolidation in association with bronchiectasis located especially at the level of right inferior lobe. (B) First CT axial abdomen image does not describe any particular finding. (C) Second lung CT coronal MPR demonstrates partial resolution of the consolidation previously described with residual ground glass opacity. (D) Second contrast-enhancement axial abdomen image shows free air bubble within the gastrohepatic space (arrows). 2 Meini S, et al. BMJ Open Gastro 2020;7:e000434. doi:10.1136/bmjgast-2020-000434 BMJ Open Gastroenterol: first published as 10.1136/bmjgast-2020-000434 on 9 June 2020. Downloaded from Open access Lung US examination performed regularly starting non- dependent portions mainly involving the caecum from the admission showed a progressive resolution of and the right colon, compatible with pneumatosis the subpleural consolidations. The patient completely intestinalis (PI); no filling defects were depicted in the recovered and did not report any other symptom; the lumen of abdominal aorta and its branches, no portal laboratory examinations repeated after 6 days from venous air was found, and no free fluid collection was the previous ones confirmed the normalisation of CRP found (figure 2A,B). (0.41 mg/dL), PCT (0.05 ng/mL) and AST (34 UI/L; Given the complete absence of symptoms