Introduction
Coronaviruses are non-segmented, enveloped, positive-sense, single-strand RNA viruses
[1 ] with six species known to lead to human disease. Cyclically, lethal coronaviruses
have appeared in recent years. This was the case with severe acute respiratory syndrome
coronavirus (SARS-CoV) in 2002 and with Middle East respiratory syndrome coronavirus
in 2012. In December 2019, a new unknown species of coronavirus, then identified as
SARS-CoV-2, was isolated and linked to cases of pneumonia detected in Wuhan [2 ]. After that, more than 800,000 of cases of SARS-CoV-2-related disease, called COVID-19,
were diagnosed all over the world, leading the World Health Organization (WHO) to
declare the infection a pandemic [3 ].
Italy has been one of the countries most affected by COVID-19, with more than 100,000
patients who have tested positive [3 ] resulting in significant and unprecedented consequences for the local health care
system. Indeed, in a few weeks, the SARS-CoV-2 outbreak has become a rapid driver
of striking changes in the health care system at local and national levels because
it is highly contagious, often requires hospitalization and critical care assistance,
and has a high rate of important mortality [4 ]. Infection transmission happens primarily through direct contact or air droplets
and patients at higher risk are those with underlying chronic conditions, including
diabetes, hypertension, and cardiovascular disease [5 ]
[6 ].
In this context, inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and
ulcerative colitis (UC), are chronic, relapsing inflammatory disorders of the gastrointestinal
tract resulting from a loss of homeostasis between the intestinal immune system and
the gut microbiome in genetically-predisposed individuals [7 ]. Although this has not been completely described [8 ]
[9 ], IBD patients may be more susceptible to COVID-19 because of their dysregulated
immune response and immunosuppressive treatments. As the risk of severe infections
(such as respiratory infections) is slightly higher in subjects receiving immunosuppressive
and/or biological therapies, it is expected that the same might occur with this infection
[10 ]. Furthermore, besides respiratory illness, the viral infection also can cause diarrhea.
Indeed, SARS-CoV-2 RNA has been detected in stool specimens [11 ], suggesting the possibility of the capacity for infection of gastrointestinal cells
and of a fecal-oral transmission route [12 ]
[13 ]. However, no specific recommendations exist for care of patients with IBD who have
COVID-19 and they should treated following the same rules provided by the WHO for
the general population [14 ].
Our IBD unit is a high-volume Italian and European IBD center and part of one of the
largest university hospitals in Italy. Since the beginning of the outbreak, our country
and in particular our hospital, has been extremely burdened by caring for patients
with COVID-19, with a consequent need to dramatically change management of patients
with IBD at every level. In the current study, we provide the first detailed observational
report about the short-term impact of the SARS-CoV-2 pandemic on management of endoscopic
procedures in a high-volume IBD Center.
Patients and methods
Study design
This was an observational prospective study reporting major clinical and organizational
changes in endoscopic management at the IBD Center – CEMAD (Centro Malattie Apparato
Digerent – Digestive Disease Center) of the Fondazione Policlinico Gemelli IRCCS,
Rome, Italy from January 31, 2020 to April 5, 2020.
Patients
All patients actively followed in the IBD center were included in the study. No informed
consent was required for this observational study. For each patient at the planned
schedule visit/therapeutic infusion/endoscopic procedure, the outcome of care was
evaluated as either “confirmed” if no modification was observed, “delayed for clinical
reasons,” “delayed for patient choice,” or rescheduled at a local IBD center.
Physicians, nurses and other personnel involved in the study
Working plans for all physicians, nurses, and administrative staff dedicated to endoscopic
management of the IBD Unit were included in the analysis.
Ethics approval
The study protocol was conducted in accordance with the principles of the Declaration
of Helsinki and approved by the Fondazione Policlinico Gemelli IRCCS Ethic Committee.
Results
Impact of COVID-19 at CEMAD on IBD outpatient service
IBD outpatient service is a good example of clinical organization for management of
chronic diseases [15 ]. The IBD center at CEMAD Fondazione Policlinico Gemelli IRCCS is one of the largest
centers in Italy by volume of patients, accounting for more than 1,500 patients actively
followed for biological therapy and administration of experimental drugs. Weekly schedules
include up to 150 biologic administrations, up to 20 procedures specifically for trials,
and about 250 follow-up visits.
The center provides multidisciplinary evaluations with access to psychologists, psychiatrists,
nutritionists, rheumatologists, dermatologists, gynecologists, abdominal and pelvic
surgeons, infectious disease specialists, and other specialists. Furthermore, the
center directly provides highly specialized diagnostic exams including endoscopy,
surveillance endoscopy for cancer and chromoendoscopy, enteroscopy, capsule endoscopy,
and intestinal ultrasound. It manages scheduling of examinations performed by other
departments in the hospital, including computed tomography, magnetic resonance imaging
(MRI), enterography, pelvic MRI, perianal ultrasonography, and surgical evaluation
under anesthesia.
In this scenario, the COVID-19 pandemic shifted the prioritization of planning for
IBD management. In our center, we considered that all visits for stable patients with
IBD non-essential and could be postponed, so they were rescheduled in 8 to 12 weeks
(“delayed for clinical reasons”). Conversely, all visits for IBD therapy (administration
of biologic therapies and experimental therapies) or for patients who were unstable
or had a relapse were judged as not eligible to be postponed. The majority of patients
receiving biologic or experimental therapies were maintained on the same schedules,
as were those receiving therapy as part of clinical trials (“confirmed”). However,
up to 10 % of followed patients decided independently to post-one their treatment
(“delayed for patient choice”) and up to 10 % asked to be referred to a local center
(“rescheduled at a local IBD center”). This resulted in an overall minimal reduction
in total planned procedures.
No treatment was stopped for medical reasons. There was a reduction in clinical trial
enrollment, mainly for international indications from the central study team management.
Moreover, we significantly increased remote follow-up of patients (200 % increase)
by email, and by telephone. New treatments with biologics were still initiated for
patients with moderate to severe IBD. Scheduled visits for unstable patients needing
surgery or consultation with other specialists were also maintained.
Endoscopic setting for IBD patients during pre-COVID-19 era
Prior to the pandemic, several standards existed for high-quality endoscopy for IBD
endoscopy [16 ]. In our center, access to high-definition endoscopy, particularly for colon cancer
surveillance, was routinely provided to patients with UC or colonic CD, as well as
deep sedation during endoscopy for selected patients. Furthermore, endoscopy for IBD
was mainly performed by dedicated IBD specialists experienced in use of endoscopic
scores, such as the Mayo score, Rutgeerts’ score for patients with CD undergoing surgery
and SES-CD for patients with CD who have not undergone surgery, together with a detailed
description of lesions and support of a dedicated pathologist. Finally, patients treated
surgically for CD usually undergo colonoscopy to evaluate disease recurrence within
6 to 12 months. These standards are usually maintained thanks to a well-organized
group that starts at the IBD outpatient clinic with a recall service for selected
patients, which includes dedicated IBD nurses, an IBD endoscopic agenda, and dedicated
physicians.
Rearrangement of the endoscopy unit: specific implications for patients with IBD
After the COVID-19 pandemic, our endoscopy unit, including procedures and personnel
for IBD-related endoscopy, had to be reorganized quickly, for several reasons.
First, as recommended at the national and local level, only endoscopic exams forh
specific indications – colorectal cancer screening, endoscopies in cancer patients,
interventional endoscopies in at-risk adenomatous lesions, gastrointestinal bleedings
and other emergency exams, fecal microbiota transplants for recurrent Clostridium difficile infection – and exams determined to be clinically urgent, based on physician evaluation,
were performed. Accordingly, the volume of IBD-related endoscopies was decreased as
well, going from 30 exams per week to approximately eight exams per week (73 % decrease,
“delayed for clinical reasons”). Specifically, five main types of indications were
kept (“confirmed”), including endoscopic dilations of CD strictures in symptomatic
patients; push and pull enteroscopies and videocapsule endoscopies for the study of
the small bowel in active and/or newly diagnosed CD; endoscopic assessment of clinically
moderate-to-severe IBD reactivation; screening and follow-up endoscopies within clinical
trials in active IBD patients; and fecal microbiota transplants for recurrent C. difficile superinfection in patients with IBD ([Fig. 1 ]).
Fig. 1 Flowchart for endoscopic procedures for IBD in a high-volume IBD unit in Italy during
the COVID-19 pandemic.
Each week, procedures to be prioritized in the endoscopic list were discussed among
physicians in a multidisciplinary fashion, based on patient referrals to the clinical
IBD center.
Once in the endoscopy waiting room area, all patients received instructions for hand
hygiene, social distancing, and disclosure of fever, cough or flu0like symptoms using
a COVID checklist form. Finally, all patients and individuals accompanying them (maximum
one person per patient) were asked to wear surgical masks [9 ]. The waiting area was reorganized with all administrative procedures located close
to the endoscopy waiting area in order to avoid crowd formation and to limit movements
of patients through the hospital ([Fig. 2 ]).
Fig. 2 Structural and organizational changes in a high-volume IBD unit in Italy during the
COVID-19 pandemic.
Another relevant change introduced was the methodology of precautions and the dress
code for staff and patients. After a pre-endoscopic triage, during which nurses assessed
the clinical status of a patient and presence of symptoms suggestive of COVID-19,
all patients coming into the endoscopy rooms had to wear surgical masks and plastic,
single-use gloves. Physicians and nurses working in the endoscopy unit had to wash
their hands with soap or an alcoholic solution prior to and after interacting with
patients, and wear at least an FFP1 mask and a disposable coat as personal protective
equipment. There were no specific methods for dealing with patients with IBD in the
endoscopy unit, so the general rules described above were followed ([Fig. 2 ]).
Finally, the endoscopy unit had to be reorganized because of shortage staff, as several
physicians were moved to COVID wards. Specifically, three endoscopists expert in IBD
were temporarily redeployed to COVID wards, temporarily eliminating the clinic dedicated
to endoscopy for IBD. However, that did not impact our ability to offer endoscopy
to patients with IBD, the logistics of which were adjusted mainly for security reasons,
to reduce risk of spreading COVID-19.
Discussion
The critical involvement of our hospital in facing this dramatic outbreak has led
to massive organizational changes, with many doctors reassigned to dedicated treatment
of SARS-CoV-2-positive inpatients. Social restrictions enacted by Italian national
authorities beginning on March 4, 2020, consequent rules for travel limitations and
social distancing, and the burden of hospitalizations and relocation of clinicians
and nurses have produced resulted in drastic changes in the clinical organization
of our IBD unit, and consequently, in our procedures for endoscopy in patients with
IBD. This paper is the first observational detailed report about short-term impact
of COVID pandemic in this field. What was observed directly regarding staff organization
reflected decisions made by the risk management team, which was largely responsible
for guiding the hospital during these historic conditions. On the other hand, we also
tried to organize our work plans in keeping with the necessity for endoscopy. Furthermore,
our work focused on patients with active IBD who were coming to the center for treatment
with biological therapy and/or innovative clinical trial drugs. Overall, our patients
were worried about COVID-19 and the impact of biological therapy on SARS-CoV-2 infection.
Accordingly, the volume of IBD-related endoscopic procedures registered a decrease
of 73 %, with maintenance of specific examinations that were necessary and could not
be postponed.
These measures are undoubtedly guaranteeing a higher level of safety for both patients
with IBD and healthcare personnel. Indeed, endoscopy should be considered a risky
procedure [17 ]. Risk of infection of endoscopy staff and patients is linked to presence of individuals
with respiratory disease spread through an airborne route. Short physical distance
from patients to healthcare staff is required for endoscopic exams, but droplets from
infected individuals can easily be infective with COVID-19 [17 ]
[18 ]
[19 ]. Furthermore, recent findings from SARS-CoV-2 in biopsy and stool samples support
potential fecal-oral transmission [12 ]
[13 ]. SARS-CoV-2 is able to enter cells through the ACE2 receptor, which is expressed
more in cells from the lung and kidney, as well as in enterocytes of the ileum and
colon [6 ]. Considering the virus’s ability to spread during the incubation period in asymptomatic
individuals, methods of transmission are even more important. On the other hand, in
patients for whom an endoscopic procedure could be postponed, that delay allowed them
to remain at home, further reducing their likelihood of infection with COVID-19.
Current evidence does not support SARS-CoV-2 infection as a potential cause of IBD
flares, but the possibility exists that they may occur. Indeed, despite the absence
of gastrointestinal infection, H1N1 virus was linked to mild flares during the first
week of infection, especially in UC [20 ]. Because the risk of SARS-CoV-2 infection is the same in the general population
and as in patients with IBD, potential IBD flares may be more challenging to manage
in this situation. Therefore, there was a significant need to reduce endoscopic procedures
for IBD and patients were advised to continue their therapies, especially if their
IBD was in remission. We believe that establishing preventive measures in an endoscopic
unit dedicated to IBD is critical for guaranteeing high-quality care in a very safe
setting and could help to avoid further unrecognized spread of COVID-19.
Conclusion
Optimization of endoscopy for IBD will be essential when the COVID-19 pandemic is
over and an overload of postponed procedures will have to be faced. In that scenario,
when the light at the end of this dramatic tunnel comes, it will be appropriate to
revisit measures for infection prevention and control. The fundamental changes in
physical and functional settings that we are experiencing in organization of facilities
and personnel for performance of endoscopy for IBD will need to be further refined
to deal not only with the prevalent risk of SARS-CoV-2 infection, but also with other
new pathogens that may emerge. In this field, solid data are needed on the incidence
and prognosis of COVID-19 in patients with IBD.
