No abstract

Background and Aims Coronavirus disease 2019 (COVID‐19) has been associated with acute liver injury (ALI) manifested by increased liver enzymes in reports worldwide. Prevalence of liver injury and associated clinical characteristics are not well defined. We aim to identify the prevalence of and risk factors for development of COVID‐19‐associated ALI in a large cohort in the United States. Approach and Results In this retrospective cohort study, all patients who underwent SARS‐CoV‐2 testing at three hospitals in the NewYork‐Presbyterian network were assessed. Of 3,381 patients, 2,273 tested positive and had higher initial and peak alanine aminotransferase (ALT) than those who tested negative. ALI was categorized as mild if ALT was greater than the upper limit of normal (ULN) but <2 times ULN, moderate if ALT was between 2 and 5 times the ULN, and severe if ALT was >5 times the ULN. Among patients who tested positive, 45% had mild, 21% moderate, and 6.4% severe liver injury (SLI). In multivariable analysis, severe ALI was significantly associated with elevated inflammatory markers, including ferritin (odds ratio [OR], 2.40; P < 0.001) and interleukin‐6 (OR, 1.45; P = 0.009). Patients with SLI had a more severe clinical course, including higher rates of intensive care unit admission (69%), intubation (65%), renal replacement therapy (RRT; 33%), and mortality (42%). In multivariable analysis, peak ALT was significantly associated with death or discharge to hospice (OR, 1.14; P = 0.044), controlling for age, body mass index, diabetes, hypertension, intubation, and RRT. Conclusions ALI is common in patients who test positive for SARS‐CoV‐2, but is most often mild. However, among the 6.4% of patients with SLI, a severe disease course should be anticipated.

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS‐CoV‐2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS‐CoV‐2 infection who underwent antibody testing with a single commercially available anti‐nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. 70 SOT recipients were studied (56% kidney, 19% lung, 14% liver +/‐ kidney, and 11% heart +/‐ kidney recipients). 36 (51%) had positive anti‐nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared those who did not receive a kidney (p=0.04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p=0.002) and baseline immunosuppression with more than 2 agents (OR 0.26, p=0.03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51 % of patients had detectable anti‐nucleocapsid antibodies, and transplant‐related variables including the level and nature of immunosuppression are important predictors. These findings raise the concern that SOT recipients with COVID‐19 may be less likely to form SARS‐CoV‐2 antibodies.

The safety and efficacy of tocilizumab for the treatment of severe respiratory symptoms due to COVID‐19 remain uncertain, in particular among solid organ transplant (SOT) recipients. Thus, we evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID‐19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID‐19, 29 (24.8%) received tocilizumab. The 90‐day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, P = .03). When compared to control patients matched by age, hypertension, chronic kidney disease, and administration of high dose corticosteroids, there was no significant difference in mortality (41% vs 28%, P = .27), hospital discharge (52% vs 72%, P = .26), or secondary infections (34% vs 24%, P = .55). Among patients who received tocilizumab, there was also no difference in mortality based on the level of oxygen support (intubated vs not intubated) at the time of tocilizumab initiation. In this matched cohort study, tocilizumab appeared to be safe but was not associated with decreased 90‐day mortality. Larger randomized studies are needed to identify whether there are subsets of SOT recipients who may benefit from tocilizumab for treatment of COVID‐19.

Whether solid organ transplant (SOT) recipients are at increased risk of poor outcomes due to COVID‐19 in comparison to the general population remains uncertain. In this study, we compared outcomes of SOT recipients and non‐SOT patients hospitalized with COVID‐19 in a propensity score matched analysis based on age, race, ethnicity, BMI, diabetes, and hypertension. After propensity matching, 117 SOT recipients and 350 non‐SOT patients were evaluated. The median age of SOT recipients was 61 years, with a median time from transplant of 5.68 years. The most common transplanted organs were kidney (48%), followed by lung (21%), heart (19%), and liver (10%). Overall, SOT recipients were more likely to receive COVID‐19 specific therapies and to require ICU admission. However, mortality (23.08% in SOT recipients vs. 23.14% in controls, P = .21) and highest level of supplemental oxygen ( P = .32) required during hospitalization did not significantly differ between groups. In this propensity matched cohort study, SOT recipients hospitalized with COVID‐19 had similar overall outcomes as non‐SOT recipients, suggesting that chronic immunosuppression may not be an independent risk factor for poor outcomes in COVID‐19.