COVID-19 infection causing residual gastrointestinal symptoms – a single UK centre case series

Introduction

Although COVID-19 was first recognised as an acute respiratory illness, asymptomatic infection is increasingly being appreciated, as is involvement in extra-pulmonary body systems.¹ Acute gastrointestinal (GI) symptoms with COVID-19 infection have been reported extensively in the literature, and may even precede the classic COVID-19 symptoms¹ of fever, breathlessness, cough, and anosmia, as adeptly summarised by Zhong et al,² who suggest that the pathophysiology of GI manifestations is due to the presence of angiotensin converting enzyme 2 (ACE-2) receptors throughout the GI tract. Meta-analysis of 60 studies and 4,243 patients by Cheung et al³ has estimated that 17.6% of patients with acute COVID-19 infection have GI symptoms. Silva et al⁴ in their systematic review of 43 studies and 18,246 patients found that diarrhoea was the most common symptom, affecting 11.5% of patients, followed by nausea and vomiting, affecting 6.3%, and abdominal pain, affecting 2.3% of people. Similarly, Parasa et al⁵ in their systematic review and meta-analysis of 29 studies report that approximately 12% of patients with acute COVID-19 infection have GI symptoms, including diarrhoea, nausea and vomiting, and that SARS-CoV-2 RNA was detected in the stool of 41% patients; they proposed a potential faecal-oral route of transmission.

These figures are comparable to what is known about gastrointestinal symptoms in other acute viral respiratory infections. Minodier et al⁶ showed in 2017 that among patients in primary care with positive PCR for common respiratory viruses, 14% reported diarrhoea, 8.5% vomiting, 31.7% nausea and 34.1% abdominal pain. However, in this study these symptoms were not always supported by the presence of respiratory virus in stool PCR, suggesting an alternative mechanism for symptoms.

Interestingly, with COVID-19, studies have found patients who experienced GI symptoms were more likely to have a more severe COVID-19 illness, with more need for intensive care admission and ventilation,^7,8 thus supporting the need for further characterisation of this association.

Despite this wealth of information, with COVID-19 still being a relatively new disease, the long-term sequelae are less well characterised. Lopez-Leon et al⁹ conducted a systematic review of long-term symptoms, with a meta-analysis of 15 studies with over 100 patients in each and 47,910 in total, with a maximum follow up duration of 110 days post viral infection. They reported a 12% long-term prevalence of digestive disorders and 16% prevalence of nausea or vomiting among over 50 other persisting symptoms. Nasserie et al¹⁰ conducted a systematic review describing persistent symptoms (lasting >60 days) in COVID-19 and found that 72.5% of the 9,751 patients included in the analysis described at least one persisting symptom, with breathlessness and fatigue being most common; however, no GI symptoms were mentioned. Arnold et al¹¹ in one of the few UK studies followed up 110 patients for 12 weeks after their acute illness and found that 74% had at least one residual symptom, again with respiratory symptoms most common, and only 2% having residual diarrhoea and 2% abdominal pain.

There is a paucity of UK data on the acute and particularly chronic GI manifestations of COVID-19 infection. Post-infectious irritable bowel syndrome (PI-IBS)¹² is a recognised and common phenomenon whereby GI symptoms can persist for years following enteric infection, although there is limited understanding of its pathophysiology. PI-IBS was first described in 1950 by Stewart¹³ as a post-dysentery non-ulcerative colitis that persisted after clearance of the offending organism, which did not respond to further antibiotics and had a slow natural improvement. Since then various bacterial pathogens have been implicated in the development of PI-IBS, including Campylobacter, Shigella, Salmonella and Escherichia coli, as well as presumptive viral gastroenteritis, which may cause a more transient form of PI-IBS.¹⁴ Meta-analysis by Thabane et al¹⁵ has shown that the risk of developing IBS increases six-fold after a GI infection and remains elevated for 2–3 years post-infection. The risk of PI-IBS seems to correlate with the severity of the acute enteric infection, and seems to be higher among females, with increasing age, in those with mental health problems and in carriers of the TLR9, CDH1 and IL6 genes.¹²

With GI and multisystem involvement becoming increasingly recognised with acute and chronic COVID-19, and PI-IBS being a recognised outcome following other viral illnesses, we hypothesise the existence of a post-COVID-19 irritable bowel syndrome (COVID-19-PI-IBS), and sought to begin exploration for this with a patient symptom survey.