The coronavirus disease (COVID-19) worldwide outbreak has led to a dramatic challenge for all healthcare systems, including inflammatory bowel disease (IBD) centres. Here, we describe the fast changes and clinical issues that IBD specialists could face during this SARS-CoV-2 infection pandemic, highlighting the potential rearrangements of care and resetting of clinical priorities.
Since December 2019 when the 2019 novel coronavirus (2019-nCoV as it was then termed, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the WHO) outbreak had been described in Wuhan, Hubei, China, the situation has dramatically evolved1. The pandemic, as declared by the WHO, has led to >300,000 cases worldwide reported as of March 2020, in all continents, excluding Antarctica, spreading on a logarithmic scale in Europe. Italy is currently the second most affected country after China and, as of 13 March 2020, Europe was declared the centre of the pandemic2. Because of the very high transmission capacity, the WHO declared the outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection a public health emergency of international concern.
As the need for hospitalization is very high among symptomatic cases (~10%), with an increased need to have access to intensive care units and mortality in the order of 3% globally2,3, European hospitals have started to intensively reduce elective activities, including surgery, to prepare for the high numbers of admissions. In addition, action by governments to contain the outbreak and slow the spread of COVID-19 has restricted regions and nations (the entire country of Italy, for example) by reducing their mobility within countries and across borders.
Patients with IBD
But what are the implications of COVID-19 for patients with inflammatory bowel disease (IBD)? With >5,000 patients with Crohn’s disease and ulcerative colitis, our IBD center in Milan, Italy, has been flooded by requests from the patients themselves inquiring about the risk of infection in patients with IBD, and asking what precautions to take, particularly regarding, but not limited to, their immunosuppressive treatment. The COVID-19 outbreak is a fast and evolving situation, and information on the incidence and/or risk of infection in patients with IBD is not yet available. However, it is important to counsel patients to inform them that >80% of reported cases of COVID-19 have been mild in published studies, and the proportion of fatal cases might be an overestimate as many asymptomatic cases are not identified3.
In our opinion, the best advice for patients with IBD is to try to minimize the risk of infection by following good hand hygiene (frequent washing with soap and water), covering the mouth and nose with a tissue or your sleeve (not hands) when coughing or sneezing, avoiding close contact with anyone with influenza-like and/or upper respiratory symptoms, and staying home or isolated if possible. In addition to these measures, emerging reports state that patients might have viral RNA present in their faeces and live virus has been isolated from faecal samples4,5,6. Thus, caution should be taken when using public toilets given the implications for the potential route of faecal–oral transmission.
An increasing number of patients with IBD treated with immunomodulators or biologic agents in our centre have asked whether a pause in their immunosuppressive therapy would be justified during the COVID-19 outbreak. At the moment, there are no formal evidence-based recommendations from clinical societies or governments for patients on immunosuppression, such as those with IBD. However, a study in a tertiary care population of 2,600 patients with IBD followed for >15,000 patient-years described an exhaustive characterization and validation (hospitalization reports) of all serious viral infections (for example, all that required hospitalization) including varicella zoster virus (VZV), herpes simplex virus (HSV), cytomegalovirus (CMV) and Epstein–Barr virus (EBV) but not SARS-CoV-2 (ref.7). The follow-up included >3,800 patient-years of exposure to anti-TNF agents, >4,800 patient-years of exposure to immunosuppressants, and >1,200 patient-years of follow-up in those >65 years. The researchers identified 31 cases of serious viral infections related to EBV, CMV, VZV and HSV infection. The two independent drivers of the risk were clinically active IBD and exposure to thiopurines. No cases of severe seasonal flu and no deaths by seasonal flu were observed. Although many of our patients have been vaccinated against seasonal flu, as recommended by European Crohn’s and Colitis Organisation (ECCO) guidelines, vaccination strategy adoption is very low and the protective effect of the vaccine is moderate, particularly in patients with an immunosuppression status. Thus, at the moment, it does not seem appropriate to recommend the pause of immunosuppressive treatment in patients with IBD, as stated by International Organization of IBD8 (Fig. 1), Crohn’s & Colitis UK and Crohn’s & Colitis Foundation in their guidance for patients. Moreover, although thiopurines have been associated with risk of serious viral infection in IBD7, the IOIBD recommends they continue to be taken as these agents take months to leave the body and so stopping these medications will not help in the short term. In addition, a survey from the European Federation of Crohn’s and Colitis association and ECCO is ongoing to explore the need for education about COVID-19.
As priorities and resources increasingly shift towards the COVID-19 pandemic, will it be possible to maintain the high standard and quality of care for patients with IBD? Multiple layers of complexity are faced during this challenging scenario. The interruption of any elective or routine follow-up clinic has caused anxiety among patients and clinicians. However, patients should be reminded that this interruption is temporary, and a shift towards virtual clinics can help patients and healthcare providers to avoid any potential loss of follow-up in case of clinical issues. This approach has also been initiated by IBD specialists in China during the COVID-19 outbreak9.
The running of biologic agent clinics and drug administration during travel restrictions in tandem with recommendations by health authorities to stay at home have been of major concern. So far, IBD biologic agent clinics have been maintained in our centre following rigorous actions to avoid infection outbreaks (Fig. 1), such as: checkpoints at the hospital entrance to screen and ask if there has been any cough or fever in the previous 2 weeks; verification of patient contact information with people with similar symptoms such as cough and fever; respecting 1–2 m distance between chairs where patients sit for their infusions and during clinics; use of surgical masks for clinical staff and patients, and latex gloves for clinical staff.
A topic of discussion is whether wearing surgical masks is a requirement, which is still a matter of debate. The WHO does not recommend wearing masks in the community as evidence is lacking10. However, facing such a novel situation with limited options, the use of masks could lead to benefit. Indeed, for influenza it has long been recommended that affected patients should wear masks to limit droplet spread and, therefore, the very same action could be used for immunosuppressed patients to reduce the risk of spread of infection. We have chosen to use surgical masks for both the clinical staff and the patients, but a global shortage of disposable surgical masks is creating challenges and this issue continues.
As timely surgery is the other mainstay of IBD care, it is of deep concern that stopping scheduled surgery completely for several weeks for patients with IBD (allowing only oncological cases to undergo surgery) will soon result in increased numbers of emergency presentations and more complications from treatment delay. In the region of Milan, Italy, where elective surgery for every benign indication (including IBD) has been substantially slowed or stopped over the past 3 weeks, with the prospect of further weeks of delays or cancellations, notable concerns have been raised for possible disease progression and poor outcomes of IBD surgery once performed.
The COVID-19 pandemic will continue to spread worldwide with increasing burden on our health-care systems and care of all patients with disease, not just those affected by COVID-19. To face these challenging circumstances, as clinicians we need to support political decision-making to rapidly adapt priorities, to reset temporarily the standards of quality of care and to help to communicate relevant information to patients.
COVID-19 will likely be with us forever. Here’s how we’ll live with it.
As COVID-19 continues to run its course, the likeliest long-term outcome is that the virus SARS-CoV-2 becomes endemic in large swaths of the world, constantly circulating among the human population but causing fewer cases of severe disease. Eventually—years or even decades in the future—COVID-19 could transition into a mild childhood illness, like the four endemic human coronaviruses that contribute to the common cold.
“My guess is, enough people will get it and enough people will get the vaccine to reduce person-to-person transmission,” says Paul Duplex, director of the University of Pittsburgh’s Center for Vaccine Research. “There will be pockets of people who won’t take [the vaccines], there will be localized outbreaks, but it will become one of the ‘regular’ coronaviruses.”
But this transition won’t happen overnight. Experts say that SARS-CoV-2’s exact post-pandemic trajectory will depend on three major factors: how long humans retain immunity to the virus, how quickly the virus evolves, and how widely older populations become immune during the pandemic itself.
Depending on how these three factors shake out, the world could be facing several years of a halting post-pandemic transition—one marked by continued viral evolution, localized outbreaks, and possibly multiple rounds of updated vaccinations.
“People have got to realize, this is not going to go away,” says Roy Anderson, an infectious disease epidemiologist at Imperial College London. “We’re going to be able to manage it because of modern medicine and vaccines, but it’s not something that will just vanish out of the window.”
The long road to another common cold
One of the essential factors governing the future of COVID-19 is our immunity to the illness. Immunity to any pathogen, including SARS-CoV-2, isn’t binary like a light switch. Instead, it’s more like a dimmer switch: The human immune system can confer varying degrees of partial protection from a pathogen, which can stave off severe illness without necessarily preventing infection or transmission.
In general, the partial protection effect is one of the reasons why the four known endemic human coronaviruses—the ones that cause a common cold—have such mild symptoms. A 2013 study in BMC Infectious Diseases shows that on average, humans are first exposed to all four of these coronaviruses between the ages of three and five-part of the first wave of infections that young children experience.
These initial infections lay the foundation for the body’s future immune response. As new variants of the endemic coronaviruses naturally evolve, the immune system has a head start in fighting them off—not enough to eradicate the virus instantly, but enough to ensure that symptoms don’t progress much beyond the sniffles.
“The virus is also its own enemy. Every time it infects you, it tops up your immunity,” says Marc Veldhoen, an immunologist at the Portugal’s University of Lisbon.
Past studies make clear that partial immunity can keep people from getting seriously ill, even as coronaviruses successfully enter their systems. Long-term, the same is likely to be true for the new coronavirus. Emory University postdoctoral fellow Jennie Lavine modeled SARS-CoV-2’s post-pandemic trajectory based on the 2013 study’s data, and her results—published in Science on January 12—suggest that if SARS-CoV-2 behaves like other coronaviruses, it will likely morph into mild nuisance years to decades from now.
This transition from pandemic to minor ailment, however, depends on how the immune response to SARS-CoV-2 holds up over time. Researchers are actively examining the body’s “immunological memory” of the virus. A study published in Science on January 6 tracked the immune response of 188 COVID-19 patients for five to eight months post-infection, and while individuals are varied, about 95 percent of patients had measurable levels of immunity.
“Immunity is waning, but certainly not gone, and I think this is key,” says Lavine, who wasn’t involved with the study.
In fact, it’s even possible that one of the cold-causing coronaviruses sparked a serious outbreak in the 1800s before fading into the litany of mild, commonplace human pathogens. Based on the spread of its family tree, researchers estimated in 2005 that the endemic coronavirus OC43 entered humans sometime in the late 19th century, likely the early 1890s. The timing has led some researchers to speculate that the original version of OC43 may have caused the “Russian flu” pandemic of 1890, which was noted for its unusually high rate of neurological symptoms—a noted effect of COVID-19.
“There’s no hard proof, but there are a lot of indications that this wasn’t an influenza pandemic but a corona-pandemic,” Veldhoen says.
The crucible of evolution
Though the carnage of past coronaviruses has faded over time, the road to a relatively painless coexistence between humans and SARS-CoV-2 will likely be bumpy. In the medium-term future, the impact of the virus will depend largely on its evolution.
SARS-CoV-2 is spreading uncontrollably around the world, and with every new replication, there’s a chance for mutations that could help the virus more effectively infect human hosts.
The human immune system, while protecting many of us from a serious illness, is also acting as an evolutionary crucible, putting pressure on the virus that selects for mutations that make it bind more effectively to human cells. The coming months and years will reveal how well our immune systems can keep up with these changes.
New SARS-CoV-2 variants also make widespread vaccination and other transmission-blocking measures, such as face masks and distancing, more crucial than ever. The less the virus spreads, the fewer opportunities it has to evolve.
We’re going to be able to manage it because of modern medicine and vaccines, but it’s not something that will just vanish out of the window.
ROY ANDERSONIMPERIAL COLLEGE LONDON
Current vaccines should still work well enough against emerging variants, such as the B.1.1.7 lineage first found in the United Kingdom, to prevent many cases of serious illness. Vaccines and natural infections create diverse swarms of antibodies that glom onto many different parts of SARS-CoV-2’s spike protein, which means that a single mutation can’t make the virus invisible to the human immune system.
Mutations may produce future variants of SARS-CoV-2 that partially resist current vaccines, however. In a preprint posted on November 19 and updated on January 19, Duplex and his colleagues show that mutations that delete parts of the SARS-CoV-2 genome’s spike protein region prevent certain human antibodies from binding.
“What I’ve learned from our own work is how deviously beautiful evolution is,” Duplex says.
Other labs have found that mutations in 501Y.V2, the variant first found in South Africa, are especially effective at helping the virus elude antibodies. Out of 44 recovered COVID-19 patients in South Africa, blood extracts from 21 of the patients didn’t effectively neutralize the 501Y.V2 variant, according to another preprint published on January 19. Those 21 people had mild to moderate cases of COVID-19, however, so their antibody levels were lower, to begin with, perhaps explaining why their blood did not neutralize the 501Y.V2 variant.
So far, currently authorized vaccines—which spur the production of high levels of antibodies—seem to be effective against the most concerning variants. In a third preprint published on January 19, researchers showed that antibodies from 20 people who had received the Pfizer-BioNTech or Moderna vaccines didn’t bind quite as well to viruses with the new mutations as they did to earlier variants—but they still bound, suggesting the vaccines will still protect against severe illness.
The new variants bring other threats as well. Some, such as B.1.1.7, appear to be more transmissible than earlier forms of SARS-CoV-2, and if left to spread uncontrollably, these variants could make many more people severely ill, which risks overwhelming healthcare systems around the world and even higher death tolls. Veldhoen adds that new variants also may pose a greater risk of reinfection to recovered COVID-19 patients.
Researchers are closely monitoring the new variants. If vaccines need to be updated in the future, Anderson says that it could be done quickly—in roughly six weeks for currently authorized mRNA vaccines, such as those made by Pfizer-BioNTech and Moderna. That timetable, though, doesn’t account for the regulatory approvals that updated vaccines would need to go through.
Anderson adds that depending on how the evolution of the virus progresses, lineages of SARS-CoV-2 may arise that are distinct enough that vaccines will need to be tailored to specific regions akin to vaccines for pneumococcus. To successfully guard against SARS-CoV-2 going forward, we will need a global monitoring network similar to the worldwide reference laboratories used to collect, sequence, and study variants of influenza.
“We’re going to have to live with it, we’re going to have to have constant vaccination, and we’re constantly going to have to have a very sophisticated molecular surveillance program to keep track of how the virus is evolving,” Anderson says.
The promise and challenge of widespread vaccination
Experts agree that transitioning beyond a pandemic depends on the prevalence of immunity, especially among older and more vulnerable populations. Younger people, especially children, will build up immunity to SARS-CoV-2 over a lifetime of exposure to the virus. Today’s adults have had no such luxury, leaving their immune systems naive and exposed.
The exact threshold for achieving population-wide immunity that slows down the virus’s spread will depend on how contagious future variants become. But so far, research of early variants of SARS-CoV-2 suggests at least 60 to 70 percent of the human population will need to become immune to end the pandemic phase.
This immunity can be achieved in one of two ways: large-scale vaccination, or recovery from natural infections. But achieving widespread immunity through uncontrolled spread comes at a terrible cost: hundreds of thousands more deaths and hospitalizations around the world. “If we don’t want to push forward vaccines and champion vaccines, we have to decide collectively how many old people we want to die—and I don’t want to be the one making that decision,” Duplex says.
Jeffrey Shaman, an infectious diseases expert at Columbia University, points out that the global push for vaccines also exposes existing inequities in global health. In a widely shared map from December, The Economist Intelligence Unit estimated that rich countries such as the U.S. will have widely accessible vaccines by early 2022, which may not happen for poorer countries in Africa and Asia until as late as 2023.
Efforts to vaccinate the developing world hinge, in part, on vaccines that can be stored with standard refrigeration, such as the vaccines under development by Oxford/AstraZeneca and Johnson & Johnson. (See the latest on COVID-19 vaccine development around the world.)
As of the week of January 18, according to a World Health Organization estimate, some 40 million COVID-19 vaccine doses have been administered around the world, mostly in high-income countries. In Africa, only two countries, Seychelles and Guinea, have started providing vaccines. And in Guinea, a low-income country, only 25 people have received doses.
Patients with IBD should receive COVID-19 vaccine, despite concerns
“For patients with IBD we would advocate, based on [International Organization for the Study of Inflammatory Bowel Disease (IOIBD)], that patients get vaccinated, acknowledging that there is a lack of data specifically in IBD patients,” Ryan C. Ungaro, MD, MS, gastroenterologist with Mount Sinai Hospital’s Feinstein IBD Center, told Healio Gastroenterology. “But we think the benefits outweigh the risks and based on prior experience with vaccinations in IBD patients.”
CDC and IOIBD recommend patients with IBD should receive the COVID-19 vaccine.
According to Ungaro, the CDC recommended immunocompromised patients should get the COVID-19 vaccine. Patients should be counseled that it is not yet known whether the safety and effectiveness of the vaccine in immunocompromised patients are the same compared with the general population.
“The major concern would be certain medications could lead to decreased response to the vaccine,” he said. “That is something that is going to need to be studied but right now the expert consensus is that IBD patients should get vaccinated against COVID-19.”
According to IOIBD recommendations, patients with IBD should receive the COVID-19 vaccine as soon as possible. Messenger RNA vaccines, replication vector vaccines, inactivated vaccines, and recombinant vaccines are safe to be administered in IBD patients, Ungaro said.
Additionally, the IOIBD said vaccines should not be deferred if an IBD patient is receiving immune-modifying therapies.
According to Ungaro, patients with IBD who take corticosteroids and get the vaccine should receive counseling that there may be a decreased systemic response. He said this needs to be studied further.
“Prospective studies are being planned to look at the real-world effectiveness and side effects of the COVID-19 vaccine in IBD patients,” Ungaro said. “This would require cohorts that are vaccinated and followed. Some studies are ongoing for that both in the United States and internationally. [Surveillance Epidemiology of Coronavirus Under Research Exclusion-IBD (SECURE-IBD)] is going to help support some of these efforts as well.”
Ungaro and his team at Mount Sinai in collaboration with the University of North Carolina developed the SECURE-IBD registry early in 2020 to monitor and report outcomes of COVID-19 in patients with IBD.
He said, “Physicians can encourage IBD patients to enroll in the Crohn’s and Colitis Foundation’s IBD Partners, they will be one of the sources for the prospective COVID-19 vaccine studies.”
Udo’s Choice® Super 8 Microbiotic
People liveing with crohns sisease can have a altered “microbiome” which means that the digestive bacteria thats in ther gut can be unbalanced ,that were takeing
Some experts maintain that using probiotics to restore the microbiome can allow a person with Crohn’s disease to reduce irregular immune responses and experience fewer symptoms.
They believe that adding healthful bacteria to the digestive tract, potentially by incorporating natural probiotic food sources to the diet, can reduce both intestinal inflammation and anomalies of the immune system. This could minimize symptoms of Crohn’s disease, such as gastrointestinal irritation, diarrhea, and stomach upset.
To see whether or not probiotics work for them, people with Crohn’s disease can keep a food diary and slowly incorporate some of these foods into their diet, noting any changes in their symptoms.
Probiotic foods include:
A person may also incorporate prebiotic foods into their diet. These are food sources that feed bacteria in the digestive tract and can promote their growth. These foods include onions, leeks, and asparagus.
Research has not proven that the probiotics in food can help reduce Crohn’s disease symptoms, so some people may wish to try taking a supplement first.
However, as long as someone does not have an allergy to foods that contain probiotics, incorporating them into the diet is a relatively risk-free method to try to improve overall health and help manage the disease.
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