key: cord-0947908-zv7er2vq
authors: Magro, Fernando; Nuzzo, Alexandre; Abreu, Cândida; Libânio, Diogo; Rodriguez‐Lago, Iago; Pawlak, Katarzyna; Hollenbach, Marcus; Brouwer, Willem P.; Siau, Keith
title: COVID‐19 in gastroenterology: Where are we now? Current evidence on the impact of COVID‐19 in gastroenterology
date: 2021-06-30
journal: United European Gastroenterol J
DOI: 10.1002/ueg2.12115
sha: 650f134966f13ea1bee9435b3edc62a548bb281f
doc_id: 947908
cord_uid: zv7er2vq

BACKGROUND: The COVID‐19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health‐related consequences worldwide. In this context, gastroenterology patients and healthcare systems and professionals have seen their routines changed and were forced to adapt, adopting measures to minimize the risk of infection while guaranteeing continuous medical care to chronic patients. OBJECTIVE: At this point, it is important to evaluate the impact of the pandemic on this field to further improve the quality of the services provided in this context. METHODS/RESULTS/CONCLUSION: We performed a literature review that summarizes the main aspects to consider in gastroenterology, during the pandemic crisis, and includes a deep discussion on the main changes affecting gastroenterology patients and healthcare systems, anticipating the pandemic recovery scenario with future practices and policies.

Since the emergence of the SARS-CoV-2 virus in December 2019, 1 the COVID-19 pandemic has spread globally with far-reaching consequences on every echelon of society. As of 20 April 2021, COVID-19 has infected over 140 million people and claimed at least 3 million lives. 2 Controlling the pandemic has been at the forefront of the World Health Organization (WHO) and international communities.

As countries implement public health reforms which reverberate through healthcare, social, education, travel, and economic sectors, [3] [4] [5] [6] the gastroenterology community has also been forced to accommodate sweeping adaptations.

Specific to gastroenterology, stakeholders affected by include patients, healthcare professionals (HCPs), researchers, societies, and health policy makers. [7] [8] [9] On this setting, the susceptibility, monitoring, diagnosis, and treatment of patients with chronic gastrointestinal (GI) diseases are major concerns. [10] [11] [12] Regarding diagnosis, endoscopy is one of the most affected procedures and the impact of the decrease of procedures is yet to be determined. 13, 14 Gastroenterologists have seen their clinical routine disturbed by the pandemic with adaptations in patients' management and evidence of burnout and mental health among HCP. 10, 15 Telemedicine became a reality, 16, 17 and team and scientific meetings were adapted to virtual format, 18 as well as medical training and learning. 15 The vaccination process is now a priority, and the conditions in which GI patients shall be managed must be clarified. This article intends to provide a global perspective on the major changes that have been affecting gastroenterology during the pandemic, while providing a deep discussion on their impact on patients, healthcare systems, and professionals, considering all the lessons learned and the management plan for the pandemic, in the next years.

SARS-CoV-2 infection is dependent on cell entry; this occurs via the binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE-2) receptor, and cleavage of S-protein by transmembrane serine protease 2 (TMPRSS2). Although expressed in the respiratory tract, 19 ACE-2 and TMPRSS2 are highly expressed in the brush border of enterocytes and the evidence of SARS-CoV-2 intestinal infections highlights the potential influence of the gut inflammatory response. 20, 21 Indeed, multiple in vitro and in vivo animal studies showed that SARS-CoV-2 can enter and replicate in enterocytes. 22, 23 This has been confirmed in several human studies through detection of viral RNA, subgenomic RNA, antigens, and virions in intestinal tissue samples. The prolonged detection of viral RNA in fecal samples, in about half of patients with COVID-19 21, 23, 24 provides further evidence for the relation between SARS-CoV-2 and enterocytes. Viral RNA is detectable in stools, for a median time of 28 days, persisting for a mean of 11 days, after negative nasopharyngeal swab PCR testing. 21, [25] [26] [27] In some cases, peak concentrations were higher than those in pharyngeal swabs. The analysis of human excrements in sewage content are being considered as a strategy to estimate the prevalence of COVID-19 and evaluate emerging virus strains. 28 These evidences of the presence of SARS-CoV-2 in intestinal tissues and fecal samples have raised concerns about a potential fecal-oral transmission. 21, [29] [30] [31] According to histological analyses, the replication of SARS-CoV-2 in enterocytes causes tissue inflammatory infiltration, usually without major injury. 21, 23, 32 The possibility of gut inflammatory response is supported by the occurrence of diarrhea and increased concentrations of calprotectin in stools of patients with COVID-19, 33 and high concentrations of enterocyte-specific cytokines (IL-18), in severe COVID-19 patients. 23, 34 Fecal microbiota analyses have shown a significant and prolonged effect of SARS-CoV-2 infection on dysbiosis, including depletion of commensals and selection of opportunistic pathogens, which correlate with inflammatory markers and disease severity. 35, 36 Multiple largescale meta-analysis have reported GI symptoms and elevation of liver enzymes, in patients with COVID-19. This arises either as a result of SARS-CoV-2 infection or of adverse events caused by drugs. 37, 38 Diarrhea is the most common GI symptom (2%-16.5%); it can persist for 1-9 days and has been associated to viral RNA detection in stools. 21, 23, 29 The mechanism of diarrhea is unknown and may involve changes in gut microbiota, gut epithelial inflammation, and release of virulent antigens. 23, 39 Other common GI symptoms include nausea, vomiting, anorexia, and abdominal pain, whereas rare cases of GI bleeding and ischemic injury have been reported. 29, 33, 40 In a propensity-score matched study, COVID-19 patients had higher rates of GI complications including mesenteric ischemia, suggesting a different phenotype for COVID-19 when compared with conventional acute respiratory distress syndrome (ARDS). 41 However, it remains inconclusive whether GI symptoms are related to severity of COVID-19. 21, 23, 42, 43 As GI signs may be present at the onset of the disease, COVID-19 may be considered as a differential diagnosis, even in the absence of respiratory symptoms. 44 Subacute or chronic diarrhea have been observed in 0.9%-10.5% of patients suffering from post-acute COVID-19. 24, 45, 46 The subacute and long-term consequences of COVID-19 on the GI system, including post-infectious irritable bowel syndrome (IBS), are still being studied (NCT04691895). A population-based survey, including 2704 people from 33 countries, revealed that 5% of respondents MAGRO ET AL.

-751 developed IBS-like symptoms during the first 3 months of the COVID-19 pandemic. Patients with IBS prior to the COVID-19 pandemic (11%) reported significantly worse emotional, social, and psychological well-being, compared with non-IBS respondents. 47 GI symptoms can also be a consequence of the socio-cultural changes that emerged during the COVID-19 pandemic. In fact, lockdowns and social distancing are modifying behaviors that are being associated with unhealthy eating habits, decreased physical exercise, decreased patient interactions with medical services, increased anxiety and alcohol consumption (or relapse in abstinent patients). All these events may have negative impact on GI and liver health [48] [49] [50] and are important to re-emphasize to our patients.

The COVID-19 pandemic has disrupted our medical routines and impacted a wide variety of medical activities, resulting in an exponential increase of telemedicine. 51, 52 A US study revealed that, during the pandemic, 94% of GI/hepatology visits were virtual via telemedicine, compared to only 5% 2 weeks before the onset of Overall, the pandemic is affecting general Gastroenterology services with impact on patients, HCPs, and policy makers. 53 Outpatient care has evolved, and patients have seen their appointments delayed and their visiting rights restricted.

Healthcare systems were forced to implement measures to minimize the risk of virus spread: the services were reconfigured with changes affecting patients' triaging, healthcare personnel (redeployment, "shielding" of vulnerable HCP), medical and technical training, and Protective Personal Equipment (PPE). All this in a changing policy environment with tremendous pressures on policy makers to issue guidance on the pandemic and to manage the vaccination process.

The increased susceptibility of IBD patients, per se, to infections was a matter of debate even before the pandemic crisis. 54, 55 This increased risk can be modulated by many factors including medications such as steroids, immunosuppressive, or biologic therapies. 56 Despite previous evidence, both physicians and patients have been facing challenges while unveiling how to adapt to Reassuringly, IBD patients do not appear to be at increased risk of SARS-CoV-2 infection compared to the general population. [57] [58] [59] [60] [61] The discussion has been focused on the overexpression of the ACE-2 receptor in the colonic mucosa and its downregulation in the small bowel. 62, 63 Available data seem to indicate that factors such as IBD phenotype, disease location, or the degree of mucosal inflammation do not influence the risk of infection. Although IBD does not increase risk of transmission, certain classes of treatments seem to be associated with increased severity and mortality from COVID-19. 64, 65 The outcome of the infection and factors affecting the risk of infection with SARS-CoV-2 are somehow conflicting. Data from the SECURE registry, a prospective, international, and collaborative database, showed that the sex-standardized mortality ratio was similar to that of the general population, 66 but updated data suggested that mortality in IBD might be higher (data not published). 67 However, a separate multicenter analysis of 232 patients did not find differences in hospitalization or mortality risk. 68, 69 In this context, the risk of severe COVID-19 in patients with IBD (defined as ICU admission, use of mechanical ventilation, or death) seems to be driven by the same risk factors as in the general population. While age appears to confer additional prognostic risk as in the general population, this risk is not increased in IBD per se, 64, 66, 70, 71 as observed in subjects with concomitant non-IBD comorbidities. 58, 64, 66, 70 However, some factors demand particular attention. It has been demonstrated, across different cohorts, that steroids increase the risk of infection and that active disease should be considered as a risk factor. 66, 68, 70 In addition, thiopurines have been identified as the major responsible for the increased risk of viral infections in IBD patients. [54] [55] [56] 72 The SECURE-IBD registry found that thiopurines either as monotherapy or in combination with anti-TNF inhibitors were associated with more severe disease. 73 Some authors have also reported an increased risk of severe disease among patients with ulcerative colitis (UC) 60, 70, 74 and in those receiving aminosalicylates, 66 Regarding the daily care of these patients, telemedicine has now arrived in the field of IBD, with new tools and devices that will enable the development of the forthcoming models of patients care. 83, 84 The reduction of endoscopic procedures resulted in a maximum decrease of 46.3% in new diagnoses and in a decrease of 25.5% in indefinite and low-grade dysplasia diagnoses. 85 In terms of monitoring, noninvasive biomarkers have been included as targets of IBD management, in the recent STRIDE-II recommendations. 86 In this setting, it is expected that the implementation of remote monitoring, with PROMS and point of care tests, will become more widely utilized in the upcoming years 87 ( Figure 1 ).

Within the liver, ACE-2 is expressed predominantly in cholangiocytes (59.7% of cells) and to a lesser extent, hepatocytes (2.6% of cells). 88 Liver injury associated with COVID-19 is typically hepatocellular in nature with transaminitis. 89, 90 Possible causative mechanisms include: direct hepatocytopathic effect of SARS-CoV-2, liver engorgement from increased pulmonary pressure, drug-induced liver injury, or ischemic hepatitis. 91 Two recent meta-analyses showed that the prevalence of "COVID-19 acute liver injury" in hospitalized patients was about 24%-27%, and that 2% of patients developed chronic liver disease (CLD). Acute liver injury was associated with poor outcomes and was found in 45% of patients with severe COVID-19 and in 20% of non-severe COVID-19 patients. 89, 90 An important sidenote here is that the definitions of "severe COVID- 19" or "acute liver injury" were heterogeneous across studies. Of note is also the increase of mortality and liver disease severity associated with the decrease of liver transplantation procedures due to patient's vulnerability, scarcity of deceased donor organs, and to imposed restrictions to decrease virus transmission. 92, 93 Chronic liver disease

The overall mortality rate for COVID-19 is estimated at 0%-2% in CLD patients, 89, 90 with risk factors comprising cirrhosis, alcoholrelated liver disease (ALD), increasing age, obesity, and diabetes.

Patients with metabolic-associated fatty liver disease (MAFLD) may also be at higher risk. 94 As expected, rates of acute-on-chronic liver failure (ACLF) and severe COVID-19 disease course increase with the stage of liver disease, according to the Child-Pugh classification. 94 In the setting of the pandemic, the lack of physical activity, mental health issues, and increased alcohol consumption can contribute to the increase of ALD and MAFLD burdens. 95

Immunosuppression is associated with increased risk of acquiring SARS-CoV-2. A recent study showed a hospital admission rate of 84% in liver transplant recipients, and a mortality rate of 20%, with respiratory failure as the most prevalent cause of death. 96 However, studies highlighted the possible protective effect of calcineurin inhibitors and potential deleterious effects of mycophenolate mofetil. 96, 97 The protective effect of immunosuppressants may be due to mitigation of the cytokine storm. In a European/American retrospective study of 110 patients with autoimmune hepatitis (AIH), patients with COVID-19 were not at increased risk for worse outcomes with an overall all-cause mortality rate of 10%, and 22% for F I G U R E 1 Main changes on the management of IBD patients during the COVID-19 pandemic. IBD, inflammatory bowel disease; PRO, patient reported outcomes MAGRO ET AL.

-753 hospitalized patients. 98 In this study, 92% of patients were on immunosuppressants. The authors concluded that immunosuppression was protective for liver injury and did not predispose to a more severe disease course. 98 

Even though causality cannot be confirmed, pathophysiological findings seem to indicate that the pancreas is affected by COVID-19. 99 In fact, ACE-2 receptor is expressed in the exocrine and endocrine pancreas 100,101 and SARS-CoV-2 infects and replicates in pancreatic cells. 102 In the early stages of the pandemic, a few studies reported increased levels of lipase and amylase, in COVID-19 patients (9 of 52 patients) with severe pneumonia. 103 This evidence led to the hypotheses that COVID-19 infection could directly result in acute pancreatitis (AP). The publication of reports on cases of COVIDinduced pancreatitis corroborated that theory. [104] [105] [106] However, in most cases, lipase levels were less than three times higher than the upper limit-of-normal (ULN), and patients showed no typical symptoms of pancreatitis. Thus, these reports lacked specificity for the diagnosis of AP. 107,108 Also on this setting, a US multicenter study reported hyperlipasemia in 12.1% of hospitalized COVID-19 patients; in this study, 2.2% of patients presented lipase levels three times higher than the ULN and no patient developed AP. 109 Comparable data were reported in Asian 110 and German patients, 111 and in other US study. 112 However, a large retrospective study analyzed 48,012 patients who were admitted during the COVID-19 pandemic.

Some 189 had evidence for AP and, 32 from this cohort were COVID-19 positive. In patients with COVID-19, the cause of AP was more often undetermined. 113 Moreover, in a prospective study from China, 12.6% of patients with COVID-19 pneumonia developed AP, which was a risk factor for severe illness and mortality. 114 These findings were confirmed by a large prospective UK study that determined COVID-19 as a risk factor for severe AP, with worse clinical outcome. 115 To conclude, increased amylase or lipase levels might not be associated with AP in COVID-19 and may be a consequence of concurrent clinical conditions. There is no evidence for a COVID-19induced AP. 99, 116, 117 

The largest challenge during the first wave of the COVID-19 pandemic was the high asymptomatic carrier rate, along with the lack of effective means to detect the virus.

Even though the incidence of asymptomatic cases varies across studies (from 1.6% to 56.5%), it has been early recognized that these patients are potentially infective. 118 It became clear that, although endoscopy is a high-risk aerosol generating procedure, the adoption of protective measures reduces infective transmission. [119] [120] [121] This improved with the availability of nasopharyngeal antigen testing, followed by rapid point of care tests, although false negative rates remain high.

Anyway, the first wave led to a marked decrease in endoscopy activity as elective procedures were curbed to minimize footfall and hospital transmission. The redistribution of HCP and lack of PPE were initial contributory factors. Several societies worldwide were quick to issue guidance on prioritizing activity and patient risk stratification for procedures. [119] [120] [121] This marked reduction in activity (to 10%-15% of pre-COVID-19) included also cancer screening procedures. 13 The selective control of indications for GI endoscopy led to an increase in cancer detection rate per procedure and to a concerning decrease in colorectal cancer diagnosis (of 72% in the United Kingdom and 50% in the Unitesd States). 13, 122 In the United Kingdom, colorectal and esophageal cancer deaths will increase 15% and 6%, respectively, in the next 5 years. 123 After the first wave, endoscopy departments faced the challenges of reconfiguring services to adapt, revert to pre-pandemic levels of activity, and address waiting list backlogs (Table 1) . Patients were discouraged to attend hospitals and started avoiding healthcare contacts (and/or having access difficulties), given that the risk of contracting COVID-19 was perceived as high, outweighing the risk of a delay in cancer diagnosis. 124 Since the start of the pandemic, overall cancer diagnoses decreased in the United States, not meaning that the actual incidence of cancer has dropped. Undiagnosed cancers summed up with those that where deprioritized to preserve clinical capacity for COVID-19 patients, with delayed surgeries and less frequent chemotherapy and/or radiotherapy, are matter of serious concern. 125 The impact of these tendencies is predictable if we acknowledge that even a slight 3-month delay in cancer diagnosis The impact of these measures will be further improved by proper patient education programs that are being adapted to the digital format in many hospitals. 127 The pandemic had also a negative impact on endoscopy training worldwide. 128, 129 The decrement of case volume, PPE shortage, exclusion from endoscopy procedures, or redeployment to another clinical area were the main challenges that endoscopy trainees had to 754 -UNITED EUROPEAN GASTROENTEROLOGY JOURNAL face. 128, 130 The substantial reduction of hands-on opportunities disrupted further endoscopy skills development. Additional concerns stemmed from the potential endoscopy training prolongation and from the lack of institutional support for trainees' emotional health care. 128, 131, 132 All this has been translated into growing frustration, anxiety (52.4%), and even burnout (18.8%), among endoscopy trainees. 128, 131 These conclusions became a call for prompt reorganization of the training path by involving societies, endoscopy units, and course directors. 133 So far, the visible changes regarding endoscopy training are strongly related to the translocation of endoscopic education to online platforms, shifting the focus to cognitive skills development. 133 Learning resources were developed and released on the websites of the major GI and endoscopy societies. In addition, trainees can have close contact with experts and access to public discussions, during interactive webinars or conferences, which also became a new virtual reality. Also, podcast series created by journals (Endoscopy, GIE) are gaining popularity. Social media platforms (Twitter and LinkedIn) opened new learning and sharing opportunities, including international collaboration and experience sharing. 134 However, patient-based endoscopy exposure for technical skills development remained the greatest concern for endoscopy trainees. 135 The emergence of international and national position statements on GI endoscopy, during COVID-19 pandemic, led to the adaptation of endoscopy units, providing safety along with highquality procedures performance. 136 The increment of endoscopy case volume, with prior-to-procedure testing, along with vaccination and adequate PPE, may allow incorporating advanced fellows back into the endoscopy room. 133 Adaptative strategies have included: simulation-based teaching programs, 137 non-technical skills teaching, resilience training and emotional support for staff and trainees, distance mentorship, proposals to move away from emphasizing minimum procedure numbers toward competency-based curricula backed by competency assessment tools. 137 As examples of simulators, we highlight Endoscopic Retrograde Cholangiopancreatography and Endoscopic ultrasound, that are being used as alternatives for upper and lower GI endoscopy and advanced procedure. 150 and several European countries suspended the administration of the AstraZeneca vaccine, in some groups of the general population, such as people below 60 or 55 years of age.

Despite these concerns, vaccine effectiveness seems to be the key concern, rather than safety. All the entities and experts recom- At this point, it is vital to understand if immunosuppressive agents mitigate or even prevent side effects related to vaccine immunogenicity, in IBD patients. 157 In fact, COVID-19 vaccines efficacy might be reduced in IBD patients treated with immunosuppressants, biologicals, or corticosteroids. Several studies found that patients with COVID-19 infection, treated with infliximab, have a blunted anti-SARS-CoV-2 response, 158,159 that is further reduced with concomitant immunomodulator use. 158 However, a blunted response does not equate to vaccine failure. This effect was not observed with vedolizumab. 160 Another concern is the possibility of an accelerated wanning of protective antibody titers, in patients treated with immunosuppressants, as verified with common vaccines (hepatitis B, measles, pertussis). [161] [162] [163] In this context, the International Organization for the study of Inflammatory Bowel Disease advises that maintenance therapies should not be withheld. 9 Thus, patients shall be vaccinated as soon as possible 155 vaccines, as all other highly vulnerable people. 165 Recent concern has been raised about variants of SARS-CoV-2 that may escape current vaccines, as changes in SARS-CoV-2 spike can alter neutralization sensitivity and reduce vaccine efficacy. 166, 167 New SARS-CoV-2 variants are emerging rapidly, such as B. 

This article presents an overview of COVID-19 in Gastroenterology, the lessons learned so far, in the scope of this specialty, as well as implications to the future 169 ( Figure 3 ).

It is now clear that GI manifestations are common in COVID-19

patients, but without established relation with disease severity. 20 These manifestations can be further aggravated by the reduction of patients' contact with medical services and by the sedentary lifestyle adopted by the majority of the population, during lockdowns.

GI patients, as others, have been also affected by the reduction of the frequency of medical attendances, with a wide range of consequences, such as progression or decompensation of chronic diseases, late diagnosis of complications, and failure in monitoring medical treatments. In this setting, we highlight, with great concern, the difficulties concerning viral hepatitis control as defined by WHO, that aimed at a reduction of newly infected persons and related mortality by 90% and 65% respectively, by 2030. The pandemic crisis is affecting the achievement of this goal mainly by decreasing diagnosis, access to treatment and harm reduction programs. 170 In this scenario, telemedicine was explored to mitigate the effects of the pandemic on the care provided to chronic GI patients and allowed medical monitoring in a remote format. 17 We predict that, considering its recent developments and indicators, such as reduction of costs and administrative burdens, telemedicine can remain a valid strategy for IBD patients, in combination with conventional visits, both for continuous care and procedure's monitoring (Figure 3 ). 16 However, it is mandatory to observe how telemedicine will evolve and impact the whole management, while guaranteeing individual accessibility. 83 (Figure 3 ). 171 Considering that endoscopy is a core diagnosis and treatment modality for GI pathology, these readjustments are vital. Even though, the widespread use of point-ofcare testing to cohort patients, may obviate the need for aerosol generating procedure PPE and room turnover precautions.

Overall, the scientific and medical communities are also concerned about the impact of COVID-19 on medical education and training. 15, 130 Several tools have been developed and implemented to provide long distance classes and training, and despite all the associated advantages, the lack of hands-on training will impair skills development. Moreover, this loses the element of social interactivity, which is not only important for feedback and learning, but also emotional support, which can affect emotional health. 130, 131 It is -759 researchers, from 64 countries, attended the e-symposium "Vaccinology in the age of pandemics". This is a good example of the importance of digital media technologies for scientific discussion, in this period of social and traveling constraints. We believe, from our experience in the GI area, that, after the pandemic, most scientific meetings will keep a virtual component ( Figure 3) . Although, we admit that virtual events cannot fully simulate the networking that is provided by regular science conferences, in which colleagues can discuss all the aspects of their research, in person. The pandemic has also fostered international research collaborations and the establishment of prospective databases, like SECURE-IBD, SECURE-Liver, COVID-HEP that are sources of important information for HCPs, policy makers, and patients.

At this point of the pandemic, researchers, physicians, and governments are focused on vaccination. Evidence shows that a careful evaluation of chronic GI patients regarding corticosteroids and immunosuppressants will guarantee safety and efficacy, during the vaccination process. 155 However, even if group immunity is achieved in some regions, general population shall be aware of the need to keep sanitary (hands washing and masks) and social distance rules, to further reduce the risk of SARS-CoV-2 dissemination. Anyway, the COVID-19 "vaccine passport" is being discussed worldwide with the objective of allowing for citizens who were vaccinated or who tested negative, or recovered from the virus, to travel between countries with minimum risks.

Future research will further increase the knowledge on SARS-CoV-2 and COVID-19 and guide patients' management. We highlight the need to clarify the role of the GI tract on severe COVID-19 forms and on virus multiplication, as well as post-COVID complications such as IBS and dysbiosis.

In conclusion, the pandemic crisis has created unprecedent challenges for gastroenterologists and GI patients. One year after the first lockdowns worldwide, the impact of COVID-19 on healthcare systems, disease's courses and diagnosis and on education and training were evaluated, and are herein discussed in detail, enabling supported decisions. We believe that we have gathered enough knowledge to assume that some of the adopted measures presented evident benefits, such as those related with telemedicine and online learning, while others showed to have negative impact in patients such as those related with endoscopic procedures and excessive reduction of medical attendances (Figure 3 ). Thoughtful decisions shall be now made regarding the transition to normality, in order to guarantee the best care possible for chronic GI patients, while taking advantage of the technological tools that can reduce disease burdens for patients and HCP and systems.

The 

IR-L has received financial support for traveling and educational activities from or has served as an advisory board member for MSD, 

The data underlying this article will be shared on reasonable request to the corresponding author. 

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COVID-19 pandemic: its impact on liver disease and liver transplantation

Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: an international registry study

New dimensions for hospital services and early detection of disease: a Review from the Lancet Commission into liver disease in the UK

Protective role of tacrolimus, deleterious role of age and comorbidities in liver transplant recipients with covid-19: results from the ELITA/ELTR multi-center European study

Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients

Outcome of COVID-19 in patients with autoimmune hepatitis: an international multi-centre study

COVID-19 and acute pancreatitis: examining the causality

ACE2 expression in pancreas may cause pancreatic damage after SARS-CoV-2 infection

SARS-CoV-2 receptor angiotensin I-converting enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature

SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas

Pancreatic injury patterns in patients with coronavirus disease 19 pneumonia

COVID-induced pancreatitis: case report

Coronavirus Disease-19 (COVID-19) associated with severe acute pancreatitis: case report on three family members

Coronavirus disease-19 (COVID-19) associated with acute necrotising pancreatitis (ANP)

Increased amylase and lipase in patients with COVID-19 pneumonia: don't blame the pancreas just yet! Gastroenterology

Insufficient etiological workup of COVID-19-associated acute pancreatitis: a systematic review

Lipase elevation in patients with COVID-19

Pancreatic injury in COVID-19 patients

High lipasemia is frequent in Covid-19 associated acute respiratory distress syndrome

Marked elevation of lipase in COVID-19 disease: a cohort study

Prevalence, risk factors, and outcomes of hospitalized patients with coronavirus disease 2019 presenting as acute pancreatitis

Association between acute pancreatitis and COVID-19: could pancreatitis Be the missing piece of the puzzle about increased mortality rates?

SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study

Current evidence on pancreatic involvement in SARS-CoV-2 infection

Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes

A systematic review of asymptomatic infections with COVID-19

Gastrointestinal endoscopy during the COVID-19 pandemic: an updated review of guidelines and statements from international and national societies

Safe and valuable endoscopy in the COVID era

Endoscopy works during the pandemic of coronavirus COVID-19: recommendations by the Chinese Society of

Changes in the number of US patients with newly identified cancer before and during the coronavirus disease 2019 (COVID-19) pandemic

The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study

COVID-19 as a barrier to attending for gastrointestinal endoscopy: weighing up the risks

COVID-19 and cancer

Collateral damage: the impact on outcomes from cancer surgery of the COVID-19 pandemic

Propelling a new era of patient education into practice-cancer care post-COVID-19

Impact of COVID-19 on endoscopy trainees: an international survey

COVID-19 pandemic through the lens of a gastroenterology fellow: looking for the silver lining

The impact of COVID-19 on gastrointestinal endoscopy training in the United Kingdom

Outrunning burnout in a GI fellowship program during the COVID-19 pandemic

Tips from the battlefront: psychological support of patients with a chronic illness during the COVID-19 lockdown in four steps

The new virtual reality: advanced endoscopy education in the COVID-19 era

How to maximize trainee education during the coronavirus disease-2019 pandemic: perspectives from around the world. Gastroenterology

Gastrointestinal endoscopy and the COVID-19 pandemic: urgent issues in endoscopic retrograde cholangio-pancreatography and endoscopic training

ESGE and ESGENA Position Statement on gastrointestinal endoscopy and COVID-19: an update on guidance during the postlockdown phase and selected results from a membership survey

Considerations in performing endoscopy during the COVID-19 pandemic

Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Interim results of a phase 1-2a trial of Ad26.COV2.S covid-19 vaccine

Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, nonrandomised phase 1/2 studies from Russia

Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine

BNT162b2 mRNA covid-19 vaccine in a nationwide mass vaccination setting

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials

Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination

Thrombosis and thrombocytopenia after ChA-dOx1 nCoV-19 vaccination

Thrombotic thrombocytopenia after Ad26.COV2.S vaccination -response from the manufacturer

SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement

Winter is coming! Clinical, immunologic, and practical considerations for vaccinating patients with inflammatory bowel disease during the coronavirus disease-2019 pandemic

Brazilian IBD study group position statement on SARS-CoV2 vaccination

SARS-CoV-2 vaccination in IBD: past lessons, current evidence and future challenges

SARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting

British Society of Gastroenterology. A joint statement on vaccination for Sars-CoV2 in patients with liver disease

Do COVID-19 RNA-based vaccines put at risk of immune-mediated diseases? In reply to "potential antigenic crossreactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases

Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab

Antibody responses to SARS-CoV-2 infection are attenuated in infliximab-treated patients with IBD

Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD

Kinetics of anti-hepatitis B surface antigen titers after hepatitis B vaccination in patients with inflammatory bowel disease

Many inflammatory bowel disease patients are not immune to measles or pertussis

Aspects of inflammatory bowel disease during the COVID-19 pandemic and general considerations

EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

The effect of spike mutations on SARS-CoV-2 neutralization

Covid-19: Pfizer BioNTech vaccine reduced cases by 94% in Israel, shows peer reviewed study

COVID-19 and the digestive system

COVID-19 and viral hepatitis elimination programs: are we stepping backward?

Cancer screening tests and cancer diagnoses during the COVID-19 pandemic

COVID-19 in gastroenterology: where are we now? Current evidence on the impact of COVID-19 in gastroenterology