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  • Review Article
  • OPEN ACCESS

Impact of COVID-19 on Patients with Inflammatory Bowel Disease

  • Paula A. Ambrose and
  • Wendy A. Goodman* 
 Author information  Cite
Journal of Exploratory Research in Pharmacology   2022;7(1):37-44

doi: 10.14218/JERP.2021.00014

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in Wuhan, China, in late 2019. Responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2 is one of three structurally similar beta-coronaviruses that can cause a strong upregulation of cytokines referred to as cytokine release syndrome (CRS). Unresolved CRS leads to respiratory symptoms, including pneumonia, and in more severe cases, acute respiratory distress syndrome (ARDS). Although COVID-19 is widely known for these hallmark respiratory symptoms, it also impacts the gut, causing gastrointestinal (GI) tract inflammation and diarrhea. COVID-19’s GI symptoms may be due to the high intestinal expression of angiotensin converting enzyme-2 receptors, which are for the binding of SARS-CoV-2 viral particles. Reports have shown that SARS-CoV-2 can be passed through fecal matter, with one study finding that 48.1% of COVID-19 patients expressed viral SARS-CoV-2 mRNA in their stool. Given that the GI tract is a target tissue affected by COVID-19, this causes concern for those with underlying GI pathologies, such as inflammatory bowel disease (IBD). Regrettably, there have been only limited studies on the impact of COVID-19 on gut health, and the impact of COVID-19 on intestinal inflammation among IBD patients remains unclear. In particular, questions regarding susceptibility to SARS-CoV-2 infection, clinical impact of COVID-19 on IBD, and the potential influence of age, sex, and immunosuppressant medications are still poorly understood. An improved understanding of these issues is needed to address the unique risks of COVID-19 among IBD patients, as well as the potential impact of SARS-CoV-2 on the host intestinal microbiota.

Keywords

Inflammatory bowel disease, COVID-19, SARS-CoV-2, ACE-2, Crohn’s disease, Ulcerative colitis

Introduction

Coronaviruses undergo frequent mutations, leading to increased genetic diversity and recombination capabilities, frequent human-animal host interactions, and relatively high rates of human infectivity.1–3 Severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, is a novel beta-coronavirus that was first identified in Wuhan, China, in late December of 2019 and subsequently caused a worldwide pandemic.4 The World Health Organization (WHO) officially designated the new coronavirus strain for a pandemic on March 11, 2020. As of August 1, 2021, this pandemic has reached approximately 200 countries and resulted in more than 198 million cases (coronavirus disease 2019, COVID-19, dashboard).5

Infection with SARS-CoV-2, the virus causing COVID-19, leads to the rapid release of cytokines, chemokines, and other pro-inflammatory mediators,6,7 a process known as cytokine release syndrome (CRS).8 Similar to genetically-related coronaviruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) 2012,9–11 SARS-CoV-2 infection results in damaging respiratory symptoms, including cough, shortness of breath, chest tightness, sore throat, and nasal congestion, pneumonia, acute respiratory distress syndrome (ARDS). The non-respiratory symptoms include fever, fatigue, myalgia, dyspnea, abdominal pain, loss of appetite, nausea, vomiting, and diarrhea. In the most severe cases, COVID-19 can lead to sepsis, multi-organ dysfunction, and death.7,12–14

SARS-CoV-2 enters human host cells through interactions of its surface spike glycoprotein (“S” protein) with the binding domain of the host-expressed angiotensin converting enzyme 2 (ACE)-2 receptor,15–17 a broadly expressed metallopeptidase. In particular, ACE-2 is highly expressed by airway epithelial cells and intestinal enterocytes,18,19 leading to high rates of SARS-CoV-2 infection in the respiratory tract and intestine.20–23 Because of this, a significant number of patients experience gastrointestinal (GI) symptoms.24–27

Because SARS-CoV-2 directly infects intestinal enterocytes in the gut, it is critical to understand how it may influence the clinical course of chronic intestinal diseases, such as inflammatory bowel disease (IBD). IBD is comprised of two primary diseases, Crohn’s disease (CD) and ulcerative colitis (UC), with distinct pathophysiologies, as well as other, non-classified forms.28 Inflammation from UC affects the superficial mucosa of the large intestine, generally occurs in a continuous pattern from the rectum to proximal colon, and is characterized by erythema, altered vascularization, bleeding, granularity, erosions, and ulcerations.29,30 In contrast, CD can impact any portion of the GI tract, leading to chronic, discontinuous, transmural inflammation that can reach the muscularis.31,32 Both UC and CD are mixed autoimmune/auto-inflammatory conditions with strong genetic and environmental susceptibilities. They can both cause chronic, relapsing and remitting inflammation in the GI tract, ultimately leading to irreversible tissue damage.28 It is estimated that 6.8 million people are affected by IBD worldwide.33 Medications for IBD include several classes of immunosuppressants, which can lead to increased susceptibility to opportunistic infections.34,35

How COVID-19 affects those with IBD is still unclear, but several studies have detected SARS-CoV2 viral RNA in stool samples obtained from COVID-19 infected patients (from 55 to 67%).36–38 This further supports SARS-CoV-2 infection of cells in the GI tract, which are often damaged in IBD patients. Thus, COVID-19 infection in IBD patients is likely to exacerbate pre-existing intestinal inflammation and GI symptoms.

This review will explore the interactions between SARS-CoV-2 infection and intestinal inflammation in the IBD population, including issues of how age, sex, pregnancy, medication status, and concomitant comorbidities may impact the clinical course of COVID-19 in IBD patients.

Interaction of SARS-CoV-2 with intestinal ACE-2

A significant proportion of COVID-19 patients experience digestive symptoms, suggesting that SARS-CoV-2 may directly affect the GI tract.39 Under homeostatic conditions, the ACE-2 receptor and its interactions with components of the renin/angiotensin system are responsible for maintaining gut homeostasis and the physical integrity of the intestinal mucosa.40 In healthy individuals, ACE-2 is most highly expressed in the intestinal epithelial cells (IECs) of the small intestine,41 and it is moderately expressed in the submucosal layers of the colon.23,42–44

The ability of SARS-CoV-2 to infect and replicate within ACE-2-expressing intestinal enterocytes has been observed in multiple human and animal studies (reviewed in).20 Among the experimental evidence supporting viral infection of IECs, in vitro studies have shown that SARS-CoV-2 can effectively enter and replicate in colonic epithelial cell lines.45,46 Several studies have also confirmed SARS-CoV-2 replication in primary IECs using small intestinal organoid models.44,47,48 Collectively, these studies indicate that there is efficient and direct interaction of SARS-CoV-2 with ACE-2-expressing cells in the GI tract.

SARS-CoV-2 infection of the intestine causes injury to host cells, including epithelial enterocytes, and exacerbates the epithelial damage and inflammation already present in patients with active forms of IBD. In particular, recent studies have shown COVID19-associated damage to colonic enterocytes, which leads to infiltration of antibody-secreting plasma cells and interstitial edema.22,49 Other studies have shown increased levels of calprotectin, a biomarker of intestinal inflammation,50 in fecal samples from COVID-19 patients who experience diarrhea compared to those who do not.51–53 Interleukin 18 (IL-18), a pro-inflammatory cytokine usually upregulated in human and experimental IBD,54–57 is elevated in feces and serum samples from COVID-19 infected individuals compared to the general population.58 This further suggests that SARS-CoV-2 infection can worsen pre-existing intestinal inflammation if the individual is experiencing an active form of IBD when infected.59,60

Several studies have suggested that increased expression of ACE-2 may be correlated with worse clinical outcomes of COVID-19, as well as increased risk of infection.61–63 However, the potential regulation of ACE-2 expression and function in response to chronic intestinal inflammation is not well-understood.

Recent studies have examined potential alterations in the levels of intestinal ACE-2 expression in patients with IBD. One of them, a large, multi-center study of >800 IBD patients and >100 non-IBD controls, found that intestinal ACE-2 mRNA expression increased in colonic samples from patients with active UC, but decreased in small intestinal samples from patients with active CD.64 In both cases, ACE-2 expression was normalized in patients responding to cytokine-directed therapies. These data suggest that cytokine-driven intestinal inflammation may impact ACE-2 expression, and that ACE-2 may be differentially regulated and have distinct functions in the small intestine versus the colon.64 A separate study comprising 129 IBD patients in Germany supported these findings, as mRNA and protein levels of ACE-2 were reduced in inflamed CD patient ilea.65 Intriguingly, this study also found that toll-like receptor (TLR)-dependent signaling regulated intestinal ACE-2 expression, suggesting that microbes, such as Citrobacter rodentium may regulate ACE-2 expression in the GI tract.65 Increasing evidence indicates that SARS-CoV-2 infection is associated with alterations in the intestinal microbiome.58,66 As an example, Coprobacillus, a gut bacterium that has been associated with severe COVID-19, was recently shown to increase ACE-2 expression in the intestine of mice, potentially contributing to the worsening of inflammation in the GI tract.67 Collectively, these studies suggest the potential for reciprocal viral/microbial regulatory networks in SARS-CoV-2-infected intestinal tissues.

Interestingly, IBD patients have increased levels of soluble ACE-2, a competitor for SARS-CoV-2 binding,68 in their peripheral blood;69 this may confer some levels of protection from direct SARS-CoV-2 infection of the GI tract. Taken together, these findings suggest that ACE-2 expression may be regulated by SARS-CoV-2 viral entry, and that the up-regulated expression of ACE-2 is an important contributor to COVID-19 clinical outcomes. More studies are needed to further investigate the potential for IEC damage in both types of primary IBD patients as well as the general population in response to COVID-19 infection.

Direct and indirect effects of COVID-19 on IBD patients

Immunomodulatory agents, including targeted biologics, are commonly used for the long-term management of IBD. Clinical guidance for IBD patients during the COVID-19 pandemic includes remaining on existing therapies to avoid disease flares (crohnscolitisfoundation.org); however, long-term use of immunosuppressant medications may lead to an increased susceptibility to infections from fungal, parasitic, viral, and bacterial pathogens.34,35,70 These factors raise concern regarding potentially increased susceptibility to SARS-CoV-2 within the IBD population.71 However, most studies to date have observed comparable risk of COVID-19 among the IBD and non-IBD populations,72–75 suggesting that IBD itself does not confer an increased risk of COVID-19 infection.

Multiple studies have identified male sex and advanced age (>60 years of age) as independent risk factors for COVID-19 infection, as well as severe morbidity and high mortality in both the general population and IBD patients.76–79 To determine the potential effects of sex and age on the risk of COVID-19 among the IBD population, a retrospective cohort study was performed using analytic data from 30,911 IBD patients enrolled in the Veterans Affairs Healthcare System.78 The majority of the cohort was male (90.9%), with a median age of 65, and 78.6% Caucasian. There were 58% of the cohort with UC and 42% with CD. There were also 649 patients (2.1% of the total IBD cohort) diagnosed with SARS-CoV-2 infection during a median follow-up period of 10.7 months.78 The study found that the majority of SARS-CoV-2-infected IBD patients were above the age of 65 and male; however, this was most likely due to the demographic breakdown of this cohort.

In contrast to frequent infections among older adults, COVID-19 has been known to affect children and adolescent populations the least of all age groups.80 In a cohort study by Ludvigsson et al., less than 1 in 1,000 pediatric IBD patients (<18 years old) was admitted to the hospital for COVID-19.79 However, pediatric IBD still led to an increased risk for COVID-19 hospitalization by a factor of 2.93 (incidence rate [95% CI] per 1,000 person-years (PY): 1.8 [0.4–3.3]) when matched with the general population (incidence rate [95% CI] per 1,000 PY: 0.6 [0.2–1.0]).79

In addition to advanced age, male sex, and medication-associated immunosuppression, conditions including obesity, diabetes, peripheral vascular disease, chronic kidney disease, and chronic obstructive pulmonary disease are also significant risk factors for SARS-CoV-2 infection.81–86 Many of these conditions are common comorbidities in IBD patients,72,87 potentially increasing these individuals’ risk of contracting COVID-19 or developing a more severe clinical course. A recent study of 79 IBD patients with confirmed SARS-CoV-2 infections identified IBD-associated hypertension as a significant risk factor for COVID-19, in addition to age >65 years and the presence of active disease.76

Although most studies have found that individuals with IBD are not at increased risk of contracting COVID-19, IBD does likely increase the severity of COVID-19, particularly in terms of hospitalization and pneumonia.76,77,79 However, the risk for especially severe outcomes, such as admission to the intensive care unit (ICU), ventilation, and death, appears to be similar to that of the general population.76,77,79 The largest study to date of IBD patients with COVID-19, the SECURE-IBD cohort study, reported that one-third of the total patient cohort (476 out of 1,760 individuals) was hospitalized due to COVID-19 complications, and that 63 patients died.77 In a smaller cohort study, 46% of IBD patients infected with SARS-CoV-2 developed pneumonia; 44% of these individuals required respiratory assistance, 28% had to be hospitalized, and 16% died.76 Hospitalization and the need for respiratory assistance were observed mostly among patients with active disease (16% of the overall cohort) compared to those whose IBD was in remission (p<0.001 for both).76 In addition to hospital reporting and testing, one point that Khan et al. mention is that at the time of the SECURE-IBD studies, hospitals may have only reported their most severe cases (ICU, ventilation, death). All of these factors could have influenced potentially inaccurate numbers of cases amongst the IBD population.

Since primary IBD encompasses both CD and UC, it is reasonable to ask whether one or the other affects COVID-19 differently in terms of severity. Ludvigsson et al. observed a similar risk of hospitalization as well as the risk of developing severe COVID-19 among UC and CD patients.79 In contrast, Bezzio et al. found that UC was associated with worse outcomes, particularly for COVID-19-related pneumonia, compared to CD.76 A potential explanation for differing results between these studies could be that the majority of CD patients, but not UC patients, in the Ludvigsson study had an additional autoimmune co-morbidity, potentially contributing to an even greater risk of SARS-CoV-2 infection as well as significantly worse clinical outcomes. Interestingly, the study by Bezzio et al. found that 100% of UC patients enrolled in treatment for severe acute colitis flares tested positive for COVID-19 prior to treatment, and that all of these individuals eventually developed COVID-19 pneumonia.76 These findings, although representing only a small sample size, suggest that COVID-19 may worsen intestinal inflammation in UC patients.

In conclusion, studies have not consistently revealed any significant differences in the prevalence of SARS-CoV-2 infection among individuals in the IBD patient population compared to the general population. However, IBD patients may be at increased risk for hospitalization and severe COVID-19, particularly if they have active disease at the time of SARS-CoV-2 infection. There is a clear need for additional studies that include more diverse patient cohorts before any definitive conclusions can be drawn.

Impact of therapeutics on IBD patients with COVID-19

Pharmacological agents used in the treatment of IBD are immuno-modulatory and include biologics, such as vedolizumab (VDZ, targeting the α4β7 integrin), ustekinumab and tofacitinib; cyclosporine; 5-aminosalicylic acid (5-ASA, i.e. mesalazine); corticosteroids; thiopurines; and methotrexate (MTX).88–90 These agents are broadly immunosuppressive, leaving IBD patients at risk for adverse outcomes of infection.34,35,78 Nevertheless, most studies have found that the rate of SARS-CoV-2 infection is comparable between the general population, the IBD population, and IBD patients receiving biologics, corticosteroids, or combination therapies.76,91

Several studies have asked if common IBD medications, including biologics, may affect the clinical course of COVID-19. In the large-scale VAHS study, COVID-19-associated hospitalization was highest among patients co-treated with anti-TNF and MTX (incidence rate of 7.42 per 10,000 person-years, 95% CI 2.79 to 19.77).78 The majority of IBD patients who were administered VDZ were also co-administered corticosteroids78 and therefore it is difficult to interpret if the risk of infection increased due to corticosteroids or due to VDZ independently. In a separate study, corticosteroid use among IBD patients increased the risk of COVID-19-associated pneumonia, especially when the patient had active inflammation.76 Interestingly, Khan et al. also determined that IBD patients who were not on medication were surprisingly more prone to severe COVID-19 compared to those on mesalazine.78 This finding contradicts the SECURE-IBD study that determined that those on mesalazine were more prone to severe COVID-19 outcomes,77 highlighting the need for larger-scale studies with expanded demographic data.

Interestingly, a recent study found that anti-TNF therapeutics as well as VDZ are associated with lower antibody levels following either Pfizer-BioNTech or NIH-Moderna COVID-19 vaccination. This suggests that IBD patients receiving these therapies may exhibit reduced vaccine efficiency.92 In this study, sero-prevalence tests for antibodies against SARS-CoV-2 S and RBD proteins were compared among healthy controls and IBD patients receiving either COVID-19 mRNA vaccine. There were 84.6% of the IBD cohort with sufficient levels of both anti-RBD and anti-S antibodies, indicating that for the majority of IBD patients, vaccine efficacy was not significantly affected by their medications.92 However, lower sero-prevalence index levels were observed in IBD patients who were taking anti-TNF (anti-RBD total Ig: p=0.0299) and VDZ (anti-RBD total Ig: p=0.0069, anti-RBD IgG: p=0.045, and anti-S IgG: p=0.0043), compared to controls.

Recently, the American Gastroenterological Association and the European Crohn’s and Colitis Organization highly advise that IBD patients stop or reduce their use of corticosteroids during the pandemic as more research has been eluding to their association with severe COVID-19 clinical outcomes, such as ventilation, ICU, and death.93,94 In contrast, the WHO recommends corticosteroid use only for patients with severe COVID-19, as steroid use in non-severe disease increases the risk of developing severe disease (reviewed in95). More studies need to be conducted on the effects of immunosuppressant use at different time points in COVID-19 before, during, and after treatment in order to better understand how IBD medication can affect COVID-19 severity in IBD patients.

Interestingly, a recent clinical trial sponsored by the University of Oxford (RECOVERY trial, NCT04381936) found that low dosages of the glucocorticoid receptor-activating corticosteroid, dexamethasone (DEX), reduced death from COVID-19 in up to 1/3 of hospitalized patients experiencing severe respiratory symptoms.96 However, corticosteroids are the medication class most often associated with greater disease severity among IBD patients with COVID-19.76–78 Few studies have compared the outcomes for patients who were given corticosteroids before versus after contracting COVID-19, or at different time points in COVID-19 treatment, potentially accounting for disparate results between the RECOVERY trial and other published studies.77,78

IBD, pregnancy, and COVID-19

Women are more prone to infection during pregnancy and unrestrained intestinal inflammation during pregnancy is highly associated with adverse fetal outcomes.97,98 Therefore, avoidance of chronic infections, particularly intrauterine infections, is crucial for successful pregnancies.99–101 ACE-2 receptors are not only found in the intestinal and respiratory tracts, but also in the uterine endometrium.102 Despite the expression of endometrial ACE-2, pregnancy itself does not appear to be associated with an increased risk of contracting COVID-19.103

Among the general (non-IBD) population, pregnant women with COVID-19 during the third trimester have an increased risk of being hospitalized.104 Another study found that compared to the general population, pregnant women with COVID-19 were five times more likely to be admitted to the ICU during the second half of pregnancy.105 Collectively, these studies indicate that SARS-CoV-2 infection during pregnancy, specifically during the third trimester, is particularly deleterious for pregnant women.

Relatively few studies have been conducted on how SARS-CoV-2 infection affects IBD pregnancies. In a study by Selinger et al., a cohort of pregnant women with IBD was followed and observed to have low incidence rates of COVID-19 and low adverse pregnancy outcomes.106 Female IBD patients at reproductive age are routinely counseled to plan pregnancies for times when their IBD symptoms are in remission, and therefore, pregnant IBD patients who contract COVID-19 are unlikely to have active disease. Regardless, low rates of SARS-CoV-2 infectivity and minimal adverse outcomes may be due to pregnant IBD patients being particularly cautious of social interaction during the pandemic, thereby limiting exposure risk.

The question of whether pregnant IBD patients should continue corticosteroid use during the COVID-19 pandemic is controversial. Cyclosporine is of particular concern since it crosses the placenta during pregnancy and is detectable in neonatal serum samples.107 Cyclosporine is frequently considered a “last resort” therapy for pregnant COVID-19 patients since it has been long-associated with hypertension108 and is also known to increase risk of pregnancy complications, including gestational diabetes, pre-term birth, and low birth weight.109 In a recent case report, a 26-year-old pregnant UC patient experienced acute disease flares and was treated with intravenous cyclosporine and steroid, then later tapered to oral corticosteroids.109 Her symptoms reemerged every time when she was put on oral corticosteroids and she was admitted to the hospital three times. On the third admission, she had severe chest pain and tested positive for COVID-19. She discontinued corticosteroids and re-started IV cyclosporine; however, by day nine of her third admission, she had a spontaneous abortion. Although larger-scale studies are clearly warranted, this case highlights the potential danger of cyclosporine use in pregnant IBD patients after COVID-19 diagnosis.110

Future directions

Although we understand far more about the course of COVID-19 in IBD patients than we did at the outset of the pandemic, more work needs to be done. Higher levels of serum soluble ACE-2 (i.e., IBD patients) and estrogen (i.e. in women) may have a potential protective effect against SARS-CoV-2 infection due to the ability to control viral entry and replication. Unquestionably, more research is warranted and is necessary to better understand the complicated interactions between SARS-CoV-2, intestinal ACE-2 receptor, and IBD.

Conclusions

Based on recent studies and because SARS-CoV-2 is still a novel virus, there appear to be no significant safety concerns for IBD patients taking immunomodulatory treatments. The risk of SARS-CoV-2 infection for the general IBD population without additional comorbidities is not significantly increased; however, active IBD patients with SARS-CoV-2 infection are strongly associated with severe COVID-19 pneumonia. Those with active IBD remain most at-risk for hospitalization, but there is no increased risk of death.76,78,79 However, there appears to be an inherent risk in those patients who are particularly immunocompromised, such as those who are pregnant, of advanced age, or with significant comorbidities. Until more data is available, treatment options such as corticosteroids should be avoided for COVID-19 treatment in those populations as there is some evidence that the treatment increases the risk for severe COVID-19. As the proportion of vaccinated people increases, some of these concerns may be mitigated; however, more research is needed regarding vaccine efficacy among immunocompromised patients to better understand its safety and efficacy.

Abbreviations

ACE: 

angiotensin converting enzyme

CD: 

Crohn’s disease

COVID-19: 

coronavirus disease 2019

CRS: 

cytokine release syndrome

GI: 

gastrointestinal

IBD: 

inflammatory bowel disease

ICU: 

intensive care unit

IEC: 

intestinal epithelial cells

SARS-CoV-2: 

severe acute respiratory syndrome coronavirus 2

TNF: 

tumor necrosis factor

UC: 

ulcerative Colitis

VDZ: 

vedolizumab

Declarations

Acknowledgement

None.

Funding

NIDDK R01DK128143-01 (to WAG), NIDDK R03DK123579 (to WAG), Crohn’s and Colitis Foundation Senior Research Award # 635911 (to WAG), Crohn’s and Colitis Foundation Student Research Fellowship Award #869119 (to PAA).

Conflict of interest

The authors have no conflicts of interest related to this publication.

Authors’ contributions

Drafted the manuscript (PAA), critical revision of the manuscript (WAG), supervision (WAG).

References

  1. de Haan CA, van Genne L, Stoop JN, Volders H, Rottier PJ. Coronaviruses as vectors: position dependence of foreign gene expression. J Virol 2003;77(21):11312-11323 View Article
  2. Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol 2015;1282:1-23 View Article
  3. Weiss SR, Navas-Martin S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev 2005;69(4):635-664 View Article
  4. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579(7798):270-273 View Article
  5. Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 2020;20(5):533-534 View Article
  6. Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Moller R, et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell 2020;181(5):1036-1045.e1039 View Article
  7. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395(10223):507-513 View Article
  8. Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020;368(6490):473-474 View Article
  9. He B, Zhang Y, Xu L, Yang W, Yang F, Feng Y, et al. Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China. J Virol 2014;88(12):7070-7082 View Article
  10. Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet 2003;361(9371):1767-1772 View Article
  11. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012;367(19):1814-1820 View Article
  12. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020;382(18):1708-1720 View Article
  13. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497-506 View Article
  14. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382(8):727-733 View Article
  15. Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 2020;581(7807):215-220 View Article
  16. Shang J, Wan Y, Luo C, Ye G, Geng Q, Auerbach A, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A 2020;117(21):11727-11734 View Article
  17. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020;367(6485):1444-1448 View Article
  18. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004;203(2):631-637 View Article
  19. Tian S, Xiong Y, Liu H, Niu L, Guo J, Liao M, et al. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod Pathol 2020;33(6):1007-1014 View Article
  20. Guo M, Tao W, Flavell RA, Zhu S. Potential intestinal infection and faecal-oral transmission of SARS-CoV-2. Nat Rev Gastroenterol Hepatol 2021;18(4):269-283 View Article
  21. Ong J, Young BE, Ong S. COVID-19 in gastroenterology: a clinical perspective. Gut 2020;69(6):1144-1145 View Article
  22. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology 2020;158(6):1831-1833.e1833 View Article
  23. Zhang H, Kang ZJ, Gong HY, Xu D, Wang J, Li ZX, et al. Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process. Gut 2020;69(6):1010-1018 View Article
  24. Chen A, Agarwal A, Ravindran N, To C, Zhang T, Thuluvath PJ. Are gastrointestinal symptoms specific for Coronavirus 2019 infection? A prospective case-control study from the United States. Gastroenterology 2020;159(3):1161-1163.e1162 View Article
  25. Dong ZY, Xiang BJ, Jiang M, Sun MJ, Dai C. The Prevalence of gastrointestinal symptoms, abnormal liver function, digestive system disease and liver disease in COVID-19 infection: a systematic review and meta-analysis. J Clin Gastroenterol 2021;55(1):67-76 View Article
  26. Luo S, Zhang X, Xu H. Don’t overlook digestive symptoms in patients with 2019 Novel Coronavirus Disease (COVID-19). Clin Gastroenterol Hepatol 2020;18(7):1636-1637 View Article
  27. Ng SC, Tilg H. COVID-19 and the gastrointestinal tract: more than meets the eye. Gut 2020;69(6):973-974 View Article
  28. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009;361(21):2066-2078 View Article
  29. Kobayashi T, Siegmund B, Le Berre C, Wei SC, Ferrante M, Shen B, et al. Ulcerative colitis. Nat Rev Dis Primers 2020;6(1):74 View Article
  30. Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet 2017;389(10080):1756-1770 View Article
  31. Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet 2012;380(9853):1590-1605 View Article
  32. Roda G, Chien Ng S, Kotze PG, Argollo M, Panaccione R, Spinelli A, et al. Crohn’s disease. Nat Rev Dis Primers 2020;6(1):22 View Article
  33. Jairath V, Feagan BG. Global burden of inflammatory bowel disease. Lancet Gastroenterol Hepatol 2020;5(1):2-3 View Article
  34. Kirchgesner J, Lemaitre M, Carrat F, Zureik M, Carbonnel F, Dray-Spira R. Risk of Serious and opportunistic infections associated with treatment of inflammatory bowel diseases. Gastroenterology 2018;155(2):337-346.e310 View Article
  35. Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2014;8(6):443-468 View Article
  36. Chen Y, Chen L, Deng Q, Zhang G, Wu K, Ni L, et al. The presence of SARS-CoV-2 RNA in the feces of COVID-19 patients. J Med Virol 2020;92(7):833-840 View Article
  37. Wu Y, Guo C, Tang L, Hong Z, Zhou J, Dong X, et al. Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol 2020;5(5):434-435 View Article
  38. Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ 2020;369:m1443 View Article
  39. Sultan S, Altayar O, Siddique SM, Davitkov P, Feuerstein JD, Lim JK, et al. AGA Institute rapid review of the gastrointestinal and liver manifestations of COVID-19, meta-analysis of international Data, and recommendations for the consultative management of patients with COVID-19. Gastroenterology 2020;159(1):320-334.e327 View Article
  40. Garg M, Royce SG, Tikellis C, Shallue C, Batu D, Velkoska E, et al. Imbalance of the renin-angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target?. Gut 2020;69(5):841-851 View Article
  41. Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun 2020;526(1):135-140 View Article
  42. Du M, Cai G, Chen F, Christiani DC, Zhang Z, Wang M. Multiomics Evaluation of gastrointestinal and other clinical characteristics of COVID-19. Gastroenterology 2020;158(8):2298-2301.e2297 View Article
  43. Xu J, Chu M, Zhong F, Tan X, Tang G, Mai J, et al. Digestive symptoms of COVID-19 and expression of ACE2 in digestive tract organs. Cell Death Discov 2020;6:76 View Article
  44. Zang R, Gomez Castro MF, McCune BT, Zeng Q, Rothlauf PW, Sonnek NM, et al. TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Sci Immunol 2020;5(47):eabc3582 View Article
  45. Chu H, Chan JF, Yuen TT, Shuai H, Yuan S, Wang Y, et al. Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study. Lancet Microbe 2020;1(1):e14-e23 View Article
  46. Stanifer ML, Kee C, Cortese M, Zumaran CM, Triana S, Mukenhirn M, et al. Critical role of Type III interferon in controlling SARS-CoV-2 infection in human intestinal epithelial cells. Cell Rep 2020;32(1):107863 View Article
  47. Lamers MM, Beumer J, van der Vaart J, Knoops K, Puschhof J, Breugem TI, et al. SARS-CoV-2 productively infects human gut enterocytes. Science 2020;369(6499):50-54 View Article
  48. Zhou J, Li C, Liu X, Chiu MC, Zhao X, Wang D, et al. Infection of bat and human intestinal organoids by SARS-CoV-2. Nat Med 2020;26(7):1077-1083 View Article
  49. Qian Q, Fan L, Liu W, Li J, Yue J, Wang M, et al. Direct evidence of active SARS-CoV-2 replication in the intestine. Clin Infect Dis 2021;73(3):361-366 View Article
  50. Magro F, Lopes J, Borralho P, Lopes S, Coelho R, Cotter J, et al. Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels. Gut 2019;68(4):594-603 View Article
  51. Effenberger M, Grabherr F, Mayr L, Schwaerzler J, Nairz M, Seifert M, et al. Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut 2020;69(8):1543-1544 View Article
  52. Ojetti V, Saviano A, Covino M, Acampora N, Troiani E, Franceschi F, et al. COVID-19 and intestinal inflammation: Role of fecal calprotectin. Dig Liver Dis 2020;52(11):1231-1233 View Article
  53. Udeh R, Advani S, de Guadiana Romualdo LG, Dolja-Gore X. Calprotectin, an emerging biomarker of interest in COVID-19: a systematic review and meta-analysis. J Clin Med 2021;10(4):775 View Article
  54. Kanai T, Watanabe M, Okazawa A, Nakamaru K, Okamoto M, Naganuma M, et al. Interleukin 18 is a potent proliferative factor for intestinal mucosal lymphocytes in Crohn’s disease. Gastroenterology 2000;119(6):1514-1523 View Article
  55. Kanai T, Watanabe M, Okazawa A, Sato T, Yamazaki M, Okamoto S, et al. Macrophage-derived IL-18-mediated intestinal inflammation in the murine model of Crohn’s disease. Gastroenterology 2001;121(4):875-888 View Article
  56. Pizarro TT, Michie MH, Bentz M, Woraratanadharm J, Smith MF, Foley E, et al. IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn’s disease: expression and localization in intestinal mucosal cells. J Immunol 1999;162(11):6829-6835
  57. Sivakumar PV, Westrich GM, Kanaly S, Garka K, Born TL, Derry JMJ, et al. Interleukin 18 is a primary mediator of the inflammation associated with dextran sulphate sodium induced colitis: blocking interleukin 18 attenuates intestinal damage. Gut 2002;50(6):812-820 View Article
  58. Tao W, Zhang G, Wang X, Guo M, Zeng W, Xu Z, et al. Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18. Med Microecol 2020;5:100023 View Article
  59. Wang P, Zhu S, Yang L, Cui S, Pan W, Jackson R, et al. Nlrp6 regulates intestinal antiviral innate immunity. Science 2015;350(6262):826-830 View Article
  60. Zhu S, Ding S, Wang P, Wei Z, Pan W, Palm NW, et al. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature 2017;546(7660):667-670 View Article
  61. Kragstrup TW, Singh HS, Grundberg I, Nielsen AL, Rivellese F, Mehta A, et al. Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients. PLoS One 2021;16(6):e0252799 View Article
  62. Pinto BGG, Oliveira AER, Singh Y, Jimenez L, Goncalves ANA, Ogava RLT, et al. ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. J Infect Dis 2020;222(4):556-563 View Article
  63. Reindl-Schwaighofer R, Hodlmoser S, Eskandary F, Poglitsch M, Bonderman D, Strassl R, et al. ACE2 elevation in severe COVID-19. Am J Respir Crit Care Med 2021;203(9):1191-1196 View Article
  64. Potdar AA, Dube S, Naito T, Li K, Botwin G, Haritunians T, et al. Altered intestinal ACE2 levels are associated with inflammation, severe disease, and response to anti-cytokine therapy in inflammatory bowel disease. Gastroenterology 2021;160(3):809-822.e807 View Article
  65. Patankar JV, Chiriac MT, Lehmann M, Kühl AA, Atreya R, Becker C, et al. Severe acute respiratory syndrome Coronavirus 2 attachment receptor angiotensin-converting enzyme 2 is decreased in Crohn’s disease and regulated by microbial and inflammatory signaling. Gastroenterology 2021;160(3):925-928.e924 View Article
  66. Gu S, Chen Y, Wu Z, Chen Y, Gao H, Lv L, et al. Alterations of the gut microbiota in patients With Coronavirus disease 2019 or H1N1 Influenza. Clin Infect Dis 2020;71(10):2669-2678 View Article
  67. Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology 2020;159(3):944-955.e948 View Article
  68. Batlle D, Wysocki J, Satchell K. Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy?. Clin Sci 2020;134(5):543-545 View Article
  69. Garg M, Burrell LM, Velkoska E, Griggs K, Angus PW, Gibson PR, et al. Upregulation of circulating components of the alternative renin-angiotensin system in inflammatory bowel disease: A pilot study. J Renin-Angio-Aldo S 2015;16(3):559-569 View Article
  70. Beaugerie L, Kirchgesner J. Balancing benefit vs risk of immunosuppressive therapy for individual patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2019;17(3):370-379 View Article
  71. Bossa F, Carparelli S, Latiano A, Palmieri O, Tavano F, Panza A, et al. Impact of the COVID-19 outbreak and the serum prevalence of SARS-CoV-2 antibodies in patients with inflammatory bowel disease treated with biologic drugs. Dig Liver Dis 2021;53(3):277-282 View Article
  72. Allocca M, Fiorino G, Zallot C, Furfaro F, Gilardi D, Radice S, et al. Incidence and patterns of COVID-19 among inflammatory bowel disease patients from the Nancy and Milan cohorts. Clin Gastroenterol Hepatol 2020;18(9):2134-2135 View Article
  73. Gubatan J, Levitte S, Balabanis T, Patel A, Sharma A, Habtezion A. SARS-CoV-2 testing, prevalence, and predictors of COVID-19 in patients with inflammatory bowel disease in Northern California. Gastroenterology 2020;159(3):1141-1144.e1142 View Article
  74. Khan N, Patel D, Xie D, Pernes T, Lewis J, Yang YX. Are patients with inflammatory bowel disease at an increased risk of developing SARS-CoV-2 than patients without inflammatory bowel disease? results from a nationwide Veterans’ affairs cohort study. Am J Gastroenterol 2021;116(4):808-810 View Article
  75. Taxonera C, Sagastagoitia I, Alba C, Manas N, Olivares D, Rey E. 2019 novel coronavirus disease (COVID-19) in patients with inflammatory bowel diseases. Aliment Pharmacol Ther 2020;52(2):276-283 View Article
  76. Bezzio C, Saibeni S, Variola A, Allocca M, Massari A, Gerardi V, et al. Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study. Gut 2020;69(7):1213-1217 View Article
  77. Brenner EJ, Ungaro RC, Gearry RB, Kaplan GG, Kissous-Hunt M, Lewis JD, et al. Corticosteroids, but not TNF antagonists, are associated with adverse COVID-19 outcomes in patients with inflammatory bowel diseases: results from an international registry. Gastroenterology 2020;159(2):481-491.e483 View Article
  78. Khan N, Mahmud N, Trivedi C, Reinisch W, Lewis JD. Risk factors for SARS-CoV-2 infection and course of COVID-19 disease in patients with IBD in the Veterans Affair Healthcare System. Gut 2021;70:1657-1664 View Article
  79. Ludvigsson JF, Axelrad J, Halfvarson J, Khalili H, Larsson E, Lochhead P, et al. Inflammatory bowel disease and risk of severe COVID-19: A nationwide population-based cohort study in Sweden. United Eur Gastroenterol J 2021;9(2):177-192 View Article
  80. Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr 2020;109(6):1088-1095 View Article
  81. de Lusignan S, Dorward J, Correa A, Jones N, Akinyemi O, Amirthalingam G, et al. Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study. Lancet Infectious Diseases 2020;20(9):1034-1042 View Article
  82. Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J, Duhamel A, et al. High prevalence of obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity (Silver Spring) 2020;28(7):1195-1199 View Article
  83. Steed H, Walsh S, Reynolds N. A brief report of the epidemiology of obesity in the inflammatory bowel disease population of Tayside, Scotland. Obes Facts 2009;2(6):370-372 View Article
  84. Zhang J, Wang X, Jia X, Li J, Hu K, Chen G, et al. Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China. Clin Microbiol Infect 2020;26(6):767-772 View Article
  85. Zhao Q, Meng M, Kumar R, Wu Y, Huang J, Lian N, et al. The impact of COPD and smoking history on the severity of COVID-19: A systemic review and meta-analysis. J Med Virol 2020;92(10):1915-1921 View Article
  86. Zheng Y, Xu H, Yang M, Zeng Y, Chen H, Liu R, et al. Epidemiological characteristics and clinical features of 32 critical and 67 noncritical cases of COVID-19 in Chengdu. J Clin Virol 2020;127:104366 View Article
  87. Novacek G, Weltermann A, Sobala A, Tilg H, Petritsch W, Reinisch W, et al. Inflammatory bowel disease is a risk factor for recurrent venous thromboembolism. Gastroenterology 2010;139(3):779-U114 View Article
  88. Beaugerie L, Kirchgesner J. Balancing benefit vs risk of immunosuppressive therapy for individual patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2019;17(3):370-379 View Article
  89. Kirchgesner J, Lemaitre M, Carrat F, Zureik M, Carbonnel F, Dray-Spira R. Risk of serious and opportunistic infections associated with treatment of inflammatory bowel diseases. Gastroenterology 2018;155(2):337-346.e310 View Article
  90. Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, et al. European Crohn’s and Colitis Organisation (ECCO). Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2014;8(6):443-68 View Article
  91. Burke KE, Kochar B, Allegretti JR, Winter RW, Lochhead P, Khalili H, et al. Immunosuppressive therapy and risk of COVID-19 infection in patients with inflammatory bowel diseases. Inflamm Bowel Dis 2021;27(2):155-161 View Article
  92. Wong SY, Dixon R, Martinez Pazos V, Gnjatic S, Colombel JF, Cadwell K, et al. Serologic response to messenger RNA Coronavirus disease 2019 vaccines in inflammatory bowel disease patients receiving biologic therapies. Gastroenterology 2021;161(2):715-718.e714 View Article
  93. Magro F, Rahier JF, Abreu C, MacMahon E, Hart A, van der Woude CJ, et al. Inflammatory bowel disease management during the COVID-19 outbreak: the ten do’s and don’ts from the ECCO-COVID taskforce. J Crohns Colitis 2020;14(14 Suppl 3):S798-S806 View Article
  94. Rubin DT, Feuerstein JD, Wang AY, Cohen RD. AGA clinical practice update on management of inflammatory bowel disease during the COVID-19 pandemic: expert commentary. Gastroenterology 2020;159(1):350-357 View Article
  95. Shuto H, Komiya K, Yamasue M, Uchida S, Ogura T, Mukae H, et al. A systematic review of corticosteroid treatment for noncritically ill patients with COVID-19. Sci Rep 2020;10(1):20935 View Article
  96. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Group RC, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384(8):693-704 View Article
  97. Broms G, Granath F, Linder M, Stephansson O, Elmberg M, Kieler H. Birth outcomes in women with inflammatory bowel disease: effects of disease activity and drug exposure. Inflamm Bowel Dis 2014;20(6):1091-1098 View Article
  98. van der Woude CJ, Ardizzone S, Bengtson MB, Fiorino G, Fraser G, Katsanos K, et al. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis 2015;9(2):107-124 View Article
  99. Favre G, Pomar L, Musso D, Baud D. 2019-nCoV epidemic: what about pregnancies?. Lancet 2020;395(10224):e40 View Article
  100. Hartert TV, Neuzil KM, Shintani AK, Mitchel EF, Snowden MS, Wood LB, et al. Maternal morbidity and perinatal outcomes among pregnant women with respiratory hospitalizations during influenza season. Am J Obstet Gynecol 2003;189(6):1705-1712 View Article
  101. Siston AM, Rasmussen SA, Honein MA, Fry AM, Seib K, Callaghan WM, et al. Pandemic 2009 Influenza A(H1N1) virus illness among pregnant women in the United States. Jama-J Am Med Assoc 2010;303(15):1517-1525 View Article
  102. Levy A, Yagil Y, Bursztyn M, Barkalifa R, Scharf S, Yagil C. ACE2 expression and activity are enhanced during pregnancy. Am J Physiol Regul Integr Comp Physiol 2008;295(6):R1953-1961 View Article
  103. Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ 2020;369:m1985 View Article
  104. Knight M, Bunch K, Vousden N, Morris E, Simpson N, Gale C, et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ 2020;369:m2107 View Article
  105. Badr DA, Mattern J, Carlin A, Cordier AG, Maillart E, El Hachem L, et al. Are clinical outcomes worse for pregnant women at >/=20 weeks’ gestation infected with coronavirus disease 2019? A multicenter case-control study with propensity score matching. Am J Obstet Gynecol 2020;223(5):764-768 View Article
  106. Selinger CP, Fraser A, Collins P, Gunn M, Chew TS, Kerry G, et al. Impact of the coronavirus infectious disease (COVID-19) pandemic on the provision of inflammatory bowel disease (IBD) antenatal care and outcomes of pregnancies in women with IBD. BMJ Open Gastroenterol 2021;8(1):e000603 View Article
  107. Claris O, Picaud JC, Brazier JL, Salle BL. Pharmacokinetics of cyclosporin A in 16 newborn infants of renal or cardiac transplant mothers. Dev Pharmacol Ther 1993;20(3-4):180-185 View Article
  108. Porter GA, Bennett WM, Sheps SG. Cyclosporine-associated hypertension. National High Blood Pressure Education Program. Arch Intern Med 1990;150(2):280-283 View Article
  109. Rosen MH, Axelrad J, Hudesman D, Rubin DT, Chang S. Management of acute severe ulcerative colitis in a pregnant woman with COVID-19 infection: a case report and review of the literature. Inflamm Bowel Dis 2020;26(7):971-973 View Article
  110. de Wilde AH, Zevenhoven-Dobbe JC, van der Meer Y, Thiel V, Narayanan K, Makino S, et al. Cyclosporin A inhibits the replication of diverse coronaviruses. J Gen Virol 2011;92(Pt 11):2542-2548 View Article
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Impact of COVID-19 on Patients with Inflammatory Bowel Disease

Paula A. Ambrose, Wendy A. Goodman
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