key: cord-0847783-j12r4jjd authors: Vujaklija Brajković, Ana; Zlopaša, Ozrenka; Gubarev Vrdoljak, Nina; Goran, Tešović; Lovrić, Daniel; Radonic, Radovan title: Acute liver and cardiac failure in multisystem inflammatory syndrome in adults after COVID-19 date: 2021-03-11 journal: Clin Res Hepatol Gastroenterol DOI: 10.1016/j.clinre.2021.101678 sha: 63a9abed79b54ea4ec3405379c2ded6a4b0eddb2 doc_id: 847783 cord_uid: j12r4jjd nan A rapid spread of a novel coronavirus began at the end of 2019 in China. The World Health Organization named the disease COVID-19 [1] and the causative virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the early course of the epidemic, it seemed that children do not develop a severe acute illness. However, in the late spring a new multisystem inflammatory syndrome in children (MIS-C) associated with the SARS-CoV-2 infection was described. Most reported cases included characteristics of shock, cardiac dysfunction, gastrointestinal symptoms, substantially elevated inflammatory markers (C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (IL-6)), and positive tests for SARS-CoV-2 infection [2] . Possible mechanisms of injury in MIS-C include direct viral tissue damage, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways [3] . Nowadays MIS-C is considered as a post-infectious complication rather than an active infection. The clinical presentation of COVID-19 in adults varies extremely. It ranges from asymptomatic cases and mild disease to severe and critical illness. Rare cases of multisystem inflammatory syndrome were also described in adults, forming a so-called multisystem inflammatory syndrome in adults (MIS-A). The current criteria for MIS-A includes: 1) a severe illness requiring hospitalization in a person aged ≥21 years; 2) a positive test result for current or previous SARS-CoV-2 infection (nucleic acid, antigen, or antibody) during admission or in the previous 12 weeks; 3) severe dysfunction of one or more extrapulmonary organ systems (e.g., hypotension or shock, cardiac dysfunction, arterial or venous thrombosis or thromboembolism, or acute liver injury); 4) laboratory evidence of severe inflammation (e.g., elevated CRP, ferritin, D-dimer, or IL -6); and J o u r n a l P r e -p r o o f 5) absence of severe respiratory illness (to exclude patients in which inflammation and organ dysfunction might be attributable simply to tissue hypoxia) [4] . We describe a case of a 22-year-old previously healthy Caucasian male who was admitted to the intensive care unit due to an acute liver and cardiac dysfunction, presenting approximately four weeks after uncomplicated COVID-19 disease. A few days before the hospitalization the patient had fever with chills, headache, sore throat followed by cough due to which the general care physician prescribed azithromycin and amoxicillin. He did not use alcohol, tobacco, or illicit substances. On examination, the patient was alert and oriented. The temperature was 39°C, the heart rate 130 beats per minute, the blood pressure RR 95/70 mmHg, the respiratory rate 24 breaths per minute, and the oxygen saturation 90% while the patient was breathing ambient air. Heart examination revealed tachycardia and normal heart sounds. Lung auscultation revealed vesicular breathing. Tenderness in the right upper quadrant of the abdomen was observed accompanied by the enlarged liver. Polymerase chain reaction SARS-CoV-2 (E gene) was negative and the anti-SARS-CoV-2 antibody test was positive. During initial observation and treatment in the emergency department, the patient received 1 liter of 0.9% saline. Initial laboratory tests showed increased inflammatory markers, liver and myocardial injury (Table 1 ). Respiratory insufficiency was present, but of minor relevance. Anti HCV was negative. A multidisciplinary team including intensivists, infectious disease specialists, and cardiologists jointly treated the patient. Laboratory tests on the seventh hospital day indicated improvement of myocardial and liver function and a decrease of the inflammatory markers ( Table 1 ). The patient was afebrile, hemodynamically stable, and was discharged from the hospital. Medication at discharge included ASA, ramipril, bisoprolol, pantoprazole, and methylprednisolone tablets. An initial follow-up performed 7 days after the hospital discharge indicated complete normalization of inflammatory and cardiac biomarkers and still elevated liver function tests. LVEF was 60%. The final followup was performed 30 days after hospital discharge (Table 1) . We described a case of MIS-A that developed approximately one month after an uncomplicated COVID-19 infection. The most pronounced symptoms at the admission were cardiac dysfunction and acute liver injury. A degree of liver and cardiac dysfunction and ethnicity differentiate our patient from previously described cases of MIS-A. The patient had acute liver injury marked by a thirtyfold increase of ALT, tenfold increase of AST, and a moderate decrease of prothrombin time (PT). During the hospital stay the PT normalized, the concentration of both ALT and AST decreased but remained elevated even at the first followup. Such a degree of liver injury was not yet associated with MIS-A. On the other hand, acute liver injury presenting with elevated AST or ALT was described during the COVID-19 [5, 6] . The origin of liver injury during COVID-19 remains unresolved and could be related to systemic inflammation, SARS-CoV-2 infection (SARS-CoV-2 might directly bind to ACE2-expressing cholangiocytes [7] ), or drug administration. Previous research found that systemic release of proinflammatory cytokines seems to cause a progression of disease in COVID-19 [6, 8] , including liver injury as well. Effenberger et al found an interesting correlation between AST level at the J o u r n a l P r e -p r o o f hospital admission and markers of systemic inflammation, including IL-6, CRP, ferritin, and LDH concentration [9] . It is possible that liver injury in our patient could be at least partially explained by cytokine release syndrome or dysregulation of the immune response. Another interesting feature is significantly and globally reduced ventricular function that rapidly improved which might be at least partially explained by furosemide application and resolution of volume overload. Further improvement of cardiac function is probably due to immune modifying therapy. As to our knowledge only two other cases with severely compromised cardiac function were described, LVEF <30%. One of those patients was initially treated with ECMO following LVAD and RVAD [6, 10] . Recovery in those two patients took longer than in our patient. Another difference between the described patient and previously reported patients is ethnicity. The presented patient is Caucasian, while the majority of previously reported were of African or Hispanic origin [4] . This report adds to the literature on MIS-A presenting the young patient with no comorbidities, living in a good social environment who presented with severe cardiac and liver dysfunction. The improvement of cardiac dysfunction was prompt and complete, while the resolution of liver injury was slower. The successful treatment of the patient could be considered a result of joint work of experts gathered in multidisciplinary team. WHO Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020 n.d COVID-19-Associated Multisystem Inflammatory Syndrome in Children -United States Extrapulmonary manifestations of COVID-19 Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection -United Kingdom and United States Clinical Characteristics of Coronavirus Disease 2019 in China Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection COVID-19: consider cytokine storm syndromes and immunosuppression Systemic inflammation as fuel for acute liver injury in COVID-19 Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ESR-erythrocyte sedimentation rate; BUNblood urea nitrogen; CRP -C-reactive protein; PCT procalcitonin; IL-6ilnterleukin 6; ALT -alanine aminotransferase; AST -aspartate aminotransferase; INR -international normalized ratio; CK -creatine kinase; LDH -lactate dehydrogenase; NT-proBNP -N-terminal prohormone of brain natriuretic peptide; GGTgamma-glutamyl transferase, AP -alkaline phosphatase; PT -prothrombin time