Controversies regarding shielding and susceptibility to COVID‐19 disease in liver transplant recipients in the United Kingdom

Abstract

December 2019 saw the emergence of a novel coronavirus, SARS-CoV-2, which rapidly escalated to a global pandemic,1 with an unprecedented impact on healthcare systems worldwide. The objective of this case series was to report on SARS-CoV-2 infection in liver transplant recipients and discuss the role of immunosuppression, comorbidities, and shielding. In the UK, transplant recipients were classified as individuals vulnerable to SARS-CoV-2 infection due to immunosuppression. They were advised in late March 2020 (Figure 1) by Public Health England to take additional social distancing precautions, a process referred to as "shielding".2 This is a more rigorous form of isolation that requires the individual to not leave their place of residence or come into contact with others. In essence, completely isolate to minimize the risk of being exposed to SARS-CoV-2. Age, male gender, obesity, hypertension, diabetes, heart disease, and lung or kidney disease have been established as risk factors for severe SARS-CoV-2 infection;3-5 however, immunosuppression is debated as a risk factor. A report from a high incidence area of northern Italy did not see fatalities in SARS-CoV-2-infected liver transplant patients, unless they were elderly and comorbid.6 Therefore, these authors suggest that immunosuppression alone is not a risk factor for development of severe SARS-CoV-2 disease. Previous literature from a previous coronavirus outbreak in 2013, MERS-CoV, reports an immunocompromised state as a risk factor for increased severity and death.7 We highlight three contrasting cases of SARS-CoV-2 infection in liver transplant recipients from the early stages of the pandemic in the UK (Table 1). All patients had similar comorbidities, previously highlighted as risk factors, and were shielded as soon as the government response advised. However, they exhibited a spectrum of COVID-19, with a clinical course ranging from mild-to-severe disease resulting in death in one case. Our patient with a high-level of immunosuppression (Case 1) experienced a severe course of illness, rapidly deteriorated, and died. The other cases described, despite a similar comorbidity profile, had a less severe clinical course. With the clarity of hindsight, it is our opinion that the advice for vulnerable individuals to strictly "shield" came too late for many. 47 y Male 7 mo (1st) (09/2019) 4 mo (2nd)(12/2019) Autoimmune Hepatitis Graft Failure (Vasculitis—fibrotic changes) IDDM Perioperative C. Diff Perioperative AKI BMI 27 HTN PRED. 7.5 mg TAC 8 mg AZA 50 mg Fever SOB GP Visit 10th March 24th March 69 y Male Ulcerative Colitis Ischemic Cholangiopathy Stage 3 CKD 2ry Adrenal suppression Recent NIDDM BMI 33 HCT 20 mg TAC 5 mg AZA 125mg Cough SOB Fever HCV-related Liver disease HCC IDDM HTN Stage 3 CKD BMI 26 PRED 5mg TAC 1mg AZA 50mg Fever SOB Vomiting Diarrhea Myalgia Husband had clinically suspected SARS-CoV-2 The rapid progression of respiratory failure, leading to the death of one of our patients on immunosuppression, served as a wake-up call after the previous reports that there were no additional risks. We suggest that liver transplant recipients are at high risk for severe SARS-CoV-2 infection and should continue to undergo strict isolation until the pandemic has passed, or robust evidence proves a lack of risk. Shielding, however, is not without a potentially negative impact, with a considerable risk of social isolation and psychological deterioration. It is therefore a priority to develop a robust evidence base to support or refute the risk of immunosuppression and severe COVID-19 and assess the risk/benefit profile of shielding for the wider transplant community. Ms Tamara Ramirez MD for independent review of radiological images. All authors declare no financial or other conflicts to declare. This study was approved by the Information Governance Department at Queen Elizabeth Hospital Birmingham (Clinical Research and Audit Management System approval number 16022) to assess the impact of SARS-CoV-2 on our transplant population via telephone interview and data access.

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