Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. COVID-19 affected more than 6 million persons worldwide in fewer than 4 months after the report of the first cases in China in December 2019. In March 2020, the first cases in the United States were reported,1 and almost simultaneously the first imported case in Mexico City was reported. Since then, the number of cases on the continent have exponentially multiplied and are responsible for approximately 45% of all cases across the globe.

Seventy to eighty percent of cases have a mild disease course, but patients over 65 years of age and/or with comorbidities, such as diabetes, obesity, and high blood pressure, are considered risk groups for severe progression. Due to the speed at which the number of infections has increased and because we are dealing with a new pathogen, the effect COVID-19 may have on different chronic pathologies, including gastrointestinal ones, is unknown. In that regard, a preliminary multinational report on 103 patients with cirrhosis of the liver found that 23.3% of the cirrhotic patients needed to be admitted to intensive care, and invasive mechanical ventilation was required in 17.5%. In that same report, the mortality rate was 39.8%, greatly exceeding the rate in the general population with COVID-19 pneumonia.2

Equally important and uncertain is the relation of the disease caused by SARS-Cov-2 to immunosuppressive treatment utilized in different gastrointestinal disorders. That has resulted in a debate about suspending immunosuppressive treatment to improve infection outcome. Said suspension implies the inherent risk for graft rejection and autoimmune disease exacerbation that could potentially worsen the course of the infection.

Scientific activity is directed toward the search for a specific treatment and the development of vaccines, whereas clinical practice and health system priorities have been modified, directing a large part of the medical resources (human and technologic) toward the care of patients with COVID-19. Those actions, together with the physical distancing measures that have been implemented, have changed and limited the type of care and surveillance of patients with chronic illnesses, including those with gastrointestinal pathologies that require immunosuppressive treatment. Fortunately, there are few such pathologies and they are associated with low levels of incidence and prevalence (e.g., liver transplantation, autoimmune hepatopathy, autoimmune pancreatitis, inflammatory bowel disease). The risk for infection with COVID-19 does not appear to be greater in those patients than in the general population, but it is not known if its progression will be the same or if there will be an increased probability in the need for intrahospital care. Based on reports from China and other Asian countries, infected patients can present with elevated transaminases, diarrhea, or abdominal pain. In an acute case of COVID-19, it is difficult to differentiate whether those symptoms are directly caused by the viral infection, drug toxicity, systemic inflammatory response, or activity of the underlying disease.3

Other questions arise about the management of those diseases in the group of patients receiving some type of immunosuppression. Due to the scarcity and low quality of evidence available, the liver, pancreas, and liver transplantation clinics of the Instituto Nacional de ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) decided to document and report their positioning and issue recommendations on the management of autoimmune liver diseases, liver transplantation, and autoimmune pancreatitis in patients infected with SARS-Cov-2.

In regard to potential therapeutic modifications, the lack of knowledge about the effect SARS-CoV-2 can have on those chronic diseases and how, together with immunosuppressive drug use, they can contribute to a severe disease course, must be considered.

The group of patients with autoimmune liver diseases includes those diagnosed with autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. However, immunosuppressant use is only indicated in autoimmune hepatitis. Those patients may be at greater risk for infection or severe disease due to chronic immunosuppressant use and the presence of advanced liver disease. Therefore, maximizing general precautions and physical distancing is recommended in that group of patients.

Infection due to SARS-CoV-2 is associated with alterations in liver function tests and it is not known if that increases the risk for causing acute decompensation of the chronic liver disease.

The most commonly used medications in those pathologies include corticosteroids, antiproliferative drugs (e.g., azathioprine, mycophenolate mofetil), and calcineurin inhibitors (e.g., tacrolimus and cyclosporine) for both remission induction and maintenance therapy.4

In the INCMNSZ we have adhered to the previously mentioned recommendations. So far, the patients with autoimmune liver disease and COVID-19 infection that we have received at the institution have presented with mild disease, which we have been able to manage solely with support treatment and immunosuppressive treatment readjustment, as established in the recommendations. We have not found signs of reactivation or decompensation of the underlying disease.

At present, the liver transplantation program has been suspended at the national level, eliminating the need for evaluating or listing patients considered priorities. The majority of patient care has been carried out by telephone or telemedicine, reducing the risk of exposure for patients that results from hospital visits. Patients with hepatocellular carcinoma waiting for treatment have been referred to other healthcare institutions, to not postpone their treatment, or they have been treated with radiotherapy, which continues to be functioning at our hospital.

Up to the time the present article was written, there has been no information on the risk for infections in patients with immunosuppression and autoimmune pancreatitis (AIP), much less in the context of the new SARS-CoV-2 coronavirus. However, theoretically, that risk should not be higher than the risk seen with other types of infections. As in other pathologies, whether immunosuppression conditions a higher risk for severe cases of COVID-19 is not known.

Patients with AIP can present with acute pancreatitis (< 20%) but the majority have changes associated with chronic pancreatitis. In our experience, close to 50% present with bile duct strictures or increased pancreatic volume, which are the main indicators for immunosuppression. Similar to other immunologic disorders, initial treatment (induced remission) focuses on rapidly decreasing the inflammatory process and bringing about its remission, which is generally achieved through steroid use. Regarding AIP, the large majority of cases have treatment response and remain in remission after a 12-week course of steroids. A percentage of cases, especially those with extra-pancreatic manifestations, require maintenance treatment based on other immunosuppressants, such as azathioprine, 6-mercaptopurine, and in exceptional cases, rituximab.

It is well-known that the risk for infections with the use of systemic steroids is dependent on the time of administration and the intensity of the dosage.21,22 For inducing remission, adequate selection is required, along with the differentiation of patients that need emergency treatment (obstructive jaundice, abdominal pain) from patients with non-emergency indications (asymptomatic extra-pancreatic lesions, asymptomatic patients with a persistent pancreatic mass in imaging studies).23 Treatment delay, even in asymptomatic pancreatic lesions associated with the gradual development of chronic pancreatitis and exocrine and endocrine insufficiencies, should be considered and discussed with the patient.

Shortened induction regimens with 2 weeks of prednisone administration at a dose of 0.6 mg/kg/day, with later weekly dose reduction, should be preferable options.23 The risk-benefit should always be evaluated upon starting high doses. It is uncertain whether the use of steroids can be useful or harmful. A cytokine storm has been described in severe COVID-19 cases whose intensity could hypothetically be reduced with that type of drug. However, the effect in relation to viral load and replication is also uncertain.24

We believe patients that are in maintenance therapy should continue their treatment with no modifications, given that suspension could cause reactivation of the disease and add to comorbidity for the patient. Changes in therapy regarding the type of drug or dosage should be individualized and preferably postponed.

The severity of SARS-CoV-2 infection and the risk involved in maintaining immunosuppression should always be considered. Nevertheless, in the particular case of AIP, in which maintenance is usually carried out with azathioprine, drug depuration and its immunosuppressive effects tend to occur 3 to 6 months after its suspension and so its effects on immune response are not immediate. However, the dose should be reduced if there is lymphopenia, which is a datum associated with COVID-19 and confers a potentially poor outcome.25

Patients with mild disease on maintenance treatment with a low dose of prednisone (2.5-10 mg/day), azathioprine, or rituximab, could continue with no change to treatment, given that there is no evidence that their use increases the risk for severe infections.22,26–28 Immunoglobulin measurement in patients on maintenance therapy with rituximab is advisable and if levels are found to be reduced, mainly those of immunoglobulin G, intravenous immunoglobulin replacement could be beneficial in reducing mortality.29

Immunosuppressive therapy should be suspended in severe cases, critically ill patients, or if the physicians in charge of the patient consider it pertinent. Systemic steroids should be considered to prevent adrenal insufficiency.

The articles cited herein meet the international regulations on bioethics research and have been authorized by the ethics committees where they were carried out. Likewise, the case series and case reports contain no personal information that can identify the patients.

No financial support was received in relation to this article.

The authors declare that there is no conflict of interest.