Short-term outcomes of patients with chronic liver disease hospitalised with COVID-19.

BACKGROUND: Patients with chronic liver disease (CLD) might have an aggravated course after acquisition of coronavirus disease 2019 (COVID-19). AIMS: To analyse the outcomes of patients with CLD who were hospitalised due to COVID-19. METHODS: The medical records of 4014 patients hospitalised because of COVID-19 in a regional referral hospital over a 12-month period were analysed. Patients with CLD were identified based on discharge diagnoses according to the International Classification of Diseases-10th Revision. Patients were followed for 30 days from admission and their outcomes (intensive care unit (ICU) admission, mechanical ventilation (MV) or death) were analysed. RESULTS: Of the 4014 patients, 110 (2.7%) had CLD and 49 (1.2%) had cirrhosis. The median age of CLD patients was 67.5 years, 79 (71.8%) were males, 224 (23.5%) were obese, 56 (50.9%) reported alcohol abuse, 24 (21.8%) had non-alcoholic fatty liver disease, 11 (10%) had viral hepatitis and 98 (89.1%) had pneumonia. The median length of hospitalisation was 12 days; 32 (29.1%) patients required ICU admission and 23 (20.9%) patients required MV, while 43 (39.1%) died. In univariate analysis, patients with cirrhosis (45% vs 73%, hazard ratio (HR) = 2.95; P < 0.001), but not those with non-cirrhotic CLD (74% vs 73%; P > 0.05), experienced worse 30-day survival when compared with age, sex and COVID-19 duration-matched cohorts. In a logistic regression analysis conducted on the overall and matched cohorts, liver cirrhosis, but not CLD, predicted inferior survival independently of age, comorbidities and severity of COVID-19, with a fourfold higher adjusted risk of 30-day mortality. CONCLUSION: Cirrhosis is independently associated with higher 30-day mortality of hospitalised patients with COVID-19.

SARS-CoV-2 Spike and Nucleocapsid Antibody Response in Vaccinated Croatian Healthcare Workers and Infected Hospitalized Patients: A Single Center Cohort Study.

Studies assessing the dynamics and duration of antibody responses following SARS-CoV-2 infection or vaccination are an invaluable tool for vaccination schedule planning, assessment of risk groups and management of pandemics. In this study, we developed and employed ELISA assays to analyze the humoral responses to Nucleocapsid and Spike proteins in vaccinated health-care workers (HCW) and critically ill COVID-19 patients. Sera of more than 1000 HCWs and critically ill patients from the Clinical Hospital Center Rijeka were tested across a one-year period, encompassing the spread of major SARS-CoV-2 variants of concern (VOCs). We observed 97% of seroconversion in HCW cohort as well as sustained anti-Spike antibody response in vaccinees for more than 6 months. In contrast, the infection-induced anti-Nucleocapsid response was waning significantly in a six-month period. Furthermore, a substantial decrease in vaccinees' anti-Spike antibodies binding to Spike protein of Omicron VOC was also observed. Critically ill COVID-19 patients had higher levels of anti-Spike and anti-Nucleocapsid antibodies compared to HCWs. No significant differences in anti-Spike and anti-Nucleocapsid antibody levels between the critically ill COVID-19 patients that were on non-invasive oxygen supplementation and those on invasive ventilation support were observed. However, stronger anti-Spike, but not anti-Nucleocapsid, antibody response correlated with a better disease outcome in the cohort of patients on invasive ventilation support. Altogether, our results contribute to the growing pool of data on humoral responses to SARS-CoV-2 infection and vaccination.

SARS-CoV-2 Viral Load in the Pulmonary Compartment of Critically Ill COVID-19 Patients Correlates with Viral Serum Load and Fatal Outcomes.

While SARS-CoV-2 detection in sputum and swabs from the upper respiratory tract has been used as a diagnostic tool, virus quantification showed poor correlation to disease outcome and thus, poor prognostic value. Although the pulmonary compartment represents a relevant site for viral load analysis, limited data exploring the lower respiratory tract is available, and its association to clinical outcomes is relatively unknown. Using bronchoalveolar lavage (BAL) and serum samples, we quantified SARS-CoV-2 copy numbers in the pulmonary and systemic compartments of critically ill patients admitted to the intensive care unit of a COVID-19 referral hospital in Croatia during the second and third pandemic waves. Clinical data, including 30-day survival after ICU admission, were included. We found that elevated SARS-CoV-2 copy numbers in both BAL and serum samples were associated with fatal outcomes. Remarkably, the highest and earliest viral loads after initiation of mechanical ventilation support were increased in the non-survival group. Our results imply that viral loads in the lungs contribute to COVID-19 disease severity, while blood titers correlate with lung virus titers, albeit at a lower level. Moreover, they suggest that BAL SARS-CoV-2 copy number quantification at ICU admission may provide a predictive parameter of clinical COVID-19 outcomes.

Human serum from SARS-CoV-2-vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant.

BACKGROUND: The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and immediately classified as a variant of concern (VOC), since it shows substantially more mutations in the spike protein than any previous variant, especially in the receptor-binding domain (RBD). We analyzed the binding of the Omicron RBD to the human angiotensin-converting enzyme-2 receptor (ACE2) and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta, or Delta RBD variants. METHODS: All RBDs were produced in insect cells. RBD binding to ACE2 was analyzed by ELISA and microscale thermophoresis (MST). Similarly, sera from 27 COVID-19 patients, 81 vaccinated individuals, and 34 booster recipients were titrated by ELISA on RBDs from the original Wuhan strain, Beta, Delta, and Omicron VOCs. In addition, the neutralization efficacy of authentic SARS-CoV-2 wild type (D614G), Delta, and Omicron by sera from 2× or 3× BNT162b2-vaccinated persons was analyzed. RESULTS: Surprisingly, the Omicron RBD showed a somewhat weaker binding to ACE2 compared to Beta and Delta, arguing that improved ACE2 binding is not a likely driver of Omicron evolution. Serum antibody titers were significantly lower against Omicron RBD compared to the original Wuhan strain. A 2.6× reduction in Omicron RBD binding was observed for serum of 2× BNT162b2-vaccinated persons. Neutralization of Omicron SARS-CoV-2 was completely diminished in our setup. CONCLUSION: These results indicate an immune escape focused on neutralizing antibodies. Nevertheless, a boost vaccination increased the level of anti-RBD antibodies against Omicron, and neutralization of authentic Omicron SARS-CoV-2 was at least partially restored. This study adds evidence that current vaccination protocols may be less efficient against the Omicron variant.

Prevalence and Prognostic Impact of Deranged Liver Blood Tests in COVID-19: Experience from the Regional COVID-19 Center over the Cohort of 3812 Hospitalized Patients.

BACKGROUND: Derangement of liver blood tests (LBT) is frequent in patients with Coronavirus disease 2019 (COVID-19). We aimed to evaluate (a) the prevalence of deranged LBT as well as their association with (b) clinical severity at admission and (c) 30-day outcomes among the hospitalized patients with COVID-19. METHODS: Consecutive patients with COVID-19 hospitalized in the regional referral center over the 12-month period were included. Clinical severity of COVID-19 at hospital admission and 30-day outcomes (need for intensive care, mechanical ventilation, or death) were analyzed. RESULTS: Derangement of LBT occurred in 2854/3812 (74.9%) of patients, most frequently due to elevation of AST (61.6%), GGT (46.1%) and ALT (33.4%). Elevated AST, ALT, GGT and low albumin were associated with more severe disease at admission. However, in multivariate Cox regression analysis, when adjusted for age, sex, obesity and presence of chronic liver disease, only AST remained associated with the risk of dying (HR 1.5081 and 2.1315, for elevations 1-3 × ULN and >3 × ULN, respectively) independently of comorbidity burden and COVID-19 severity at admission. Patients with more severe liver injury more frequently experienced defined adverse outcomes. CONCLUSIONS: Deranged LBTs are common among patients hospitalized with COVID-19 and might be used as predictors of adverse clinical outcomes.