key: cord-256351-q8lkhklw authors: Di Giorgio, Angelo; Nicastro, Emanuele; Speziani, Camilla; De Giorgio, Massimo; Pasulo, Luisa; Magro, Bianca; Fagiuoli, Stefano; Antiga, Lorenzo D' title: Health status of patients with Autoimmune Liver Disease during SARS-CoV-2 outbreak in northern Italy date: 2020-05-12 journal: J Hepatol DOI: 10.1016/j.jhep.2020.05.008 sha: doc_id: 256351 cord_uid: q8lkhklw nan There is a mounting evidence that severe COVID-19 is characterized by an imbalanced multi-system immune-inflammatory response to the pathogen by the host, and acknowledged risk factors for poorer outcome are older age and preexisting non-respiratory chronic pro-inflammatory conditions such as obesity, hypertension, diabetes and cardiovascular disease (1) . Hypertransaminasemia, low platelet count and hypoalbuminemia have been associated with high mortality in COVID-19 pneumonia, but whether preexisting chronic liver disease is an additional risk factor for a severe course is still matter of debate (2) . Our preliminary experience suggested that patients with cirrhosis, liver transplantation, autoimmune liver disease, inflammatory bowel disease, have a benign course during the pandemic (3, 4) . Nonetheless there are no granular figures on patients with autoimmune liver disease (AILD) (5) . Northern Italy has been the earliest and most extensively hit European area during COVID-19 epidemic in early 2020, and our centre is located at the epicentre of the Italian outbreak, and hosts a large hepatology and transplantation unit. Thus, our setting represents a reliable opportunity to explore the health status and possible challenges presented by AILD patients during this outbreak. We therefore decided to carry out a phone-based survey using a 26-queries questionnaire to explore the clinical features of SARS-CoV-2 infection in patients with AILD under IS. The infection was confirmed in case of positive nasal-pharyngeal swab (NPS) for SARS-CoV-2 nucleic acid using real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) assay. The severity of illness was classified as mild, moderate, severe or critical according to previously reported classifications (1, 6) . At the time of the study 153 patients were followed at our centre; 148 patients [F= 91 (61%), median age 47.4 years, range 2.8-81.9] were considered eligible; 5 patients (all < 18 years) were excluded: 4 because they were off-therapy, one because he moved to Canada. Of 148 patients, 47 (32%) were children (aged from 2.8 to 17.8 years) diagnosed with autoimmune hepatitis (AIH)(n=37/47, 76%) and autoimmune sclerosing cholangitis (ASC)(n=11/47, 23%); 101/148 (68%) were adults (aged from 18.4 to 81.9 years) diagnosed with AIH (n=97/101 patients, 96%), PSC/AIH overlap syndrome (n= 2 patients, 2%), and CBP/AIH (n= 2 patients, 2%). The questionnaire was successfully filled in by all eligible patients, and the survey completeness was 100%. Suspected COVID-19 was the presence of at least one among: 1) Acute respiratory tract infection; 2) Close contact with a confirmed or highly probable COVID-19 case. Confirmed COVID-19 was a patient having a positive NPS (1). The observed incidence was weighted to expected cases using previously published models (7). Thirty-nine of 148 (26%) were suspected COVID-19 cases. All had symptoms: fever (26/39), cough (23/39), dyspnoea (3/39). None required admission to hospital, oxygen therapy or discontinuation of IS; 33/39 (85%, 6 children) had a close contact with a highly probable case. A 23 year-old female with AIH and Trisomy 21 died from septic shock unrelated to COVID-19. The estimated incidence of SARS-CoV-2 infection in the general population was 38 cases (26,935 cases/100,000 inhabitants), versus 43 observed in AILD (p= ns). Overall, 146 patients survived (n=104 asymptomatic, n=39 suspected COVID-19; n=3 confirmed COVID-19); 2 patients died (n=1 due to COVID-19, n= 1 due to septic shock). Discontinuation of IS therapy was carried in only 1 patient (3%)( Table 1 ). The sudden appearance of SARS-CoV-2 pandemic has challenged health care systems worldwide, and lead to a re-thinking of management of patients with any sort of acute or chronic illness. In this respect, It has been suggested that COVID-19 could accelerate the onset of complications in patients with compensated cirrhosis. This remains to be determined for SARS-CoV-2. Liver cells can be infected by this virus, since its receptor, angiotensin-converting enzyme 2 (ACE2), is expressed on cholangiocytes (2). However, indirect signs of biliary injury have not been recorded in patients with severe COVID-19 (9). Nonetheless, since in general the comorbidities are risk factors for severe COVID-19, it is likely that cirrhotic patients in a labile compensation status are more vulnerable than the general population. For this reason, the EASL/ESCMID position paper suggests to adopt several protective measures in patients with any chronic liver disease, hepatocellular carcinoma, listed for transplantation or who received a transplant recently (8) . For AILD patients this expert panel advises against reducing immunosuppressive treatment. In this survey we found that a total of 25% of our patients had a close contact with a suspected or confirmed case of COVID-19. The majority of our patients, though, remained asymptomatic (70%, n=104). Twenty-six per cent (n= 39) developed mild/moderate respiratory symptoms likely due to an underlying SARS-CoV-2 infection; however, since the NPS was not carried out, they were classified as suspected cases of COVID-19. Only four patients (3%, all female older than 18 years) were diagnosed as confirmed COVID-19 cases; the majority of them (3/4 patients, 75%) presented with a mild or moderate clinical phenotype (1 was asymptomatic) whilst 1 patient died ; this patient had risk factors for complicated COVID-19 described in the general population, including old age and associated comorbidities. Interestingly, we found that the observed incidence of cases in our cohort of patients was not different from the estimated incidence in the general population, suggesting that AILD patients are not more susceptible to COVID-19 than the general population (7). We previously reported our review of past outbreaks of coronavirus infections and our preliminary experience with these patients followed in our center, and we suggested that immunocompromised patients (adults and children) are not at increased risk of COVID-19 complicated course compared to the general population (3). There is growing evidence confirming this finding, including some reports suggesting that immunosuppression may even provide some protection from lung damage in patients with COVID-19. However different immunosuppressive drugs have a different effector pathway, therefore a generalization of this concept seems unwise. Immunosuppressive medications have effects on humoral immunity, cellmediated immunity and neutrophil function, potentially increasing the risk of severe infections caused by many viral agents. Nonetheless, in previous Coronaviruses epidemics, IS have not been shown to favour a complicate course, and this study confirms it. Patients with AILD are mainly treated with steroids and antimetabolites. The National Institute of Health (NIH) COVID-19 treatment guidelines reports that oral corticosteroid therapy, used prior to COVID-19 diagnosis for another underlying condition, should not be discontinued, but the recommend against the routine use of systemic corticosteroids in hospitalized patients with COVID-19 (10) . However it should be reminded that patients with autoimmune disorders under chronic steroid treatment are at risk of developing adrenal crises under any physical stress, due to secondary adrenal insufficiency. Therefore AILD patients developing severe COVID-19 should be administered steroids for adrenal replacement. The experience with antimetabolites (such as azathioprine or mycophenolate mofetil) is scarce. However we recently reported the uneventful course of patients with inflammatory bowel disease who were under IS or immunomodulating drugs, including antimetabolites, during the SARS-CoV-2 epidemic (4). In conclusion, during SARS-CoV-2 outbreak in northern Italy, children and adults with AILD maintained a good health status. COVID-19 was diagnosed in a percentage of patients that is similar to the general population, and the outcome was favorable in the majority of cases. 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