The Liver Can Deliver: Utility of Hepatic Function Tests as Predictors of Outcome in COVID-19, Influenza and RSV Infections.

BACKGROUND: liver test abnormalities have been described in patients with Coronavirus-2019 (COVID-19), and hepatic involvement may correlate with disease severity. With the relaxing of COVID-19 restrictions, seasonal respiratory viruses now circulate alongside SARS-CoV-2. AIMS: we aimed to compare patterns of abnormal liver function tests in patients suffering from COVID-19 infection and seasonal respiratory viruses: respiratory syncytial virus (RSV) and influenza (A and B). METHODS: a retrospective cohort study was performed including 4140 patients admitted to a tertiary medical center between 2010-2020. Liver test abnormalities were classified as hepatocellular, cholestatic or mixed type. Clinical outcomes were defined as 30-day mortality and mechanical ventilation. RESULTS: liver function abnormalities were mild to moderate in most patients, and mainly cholestatic. Hepatocellular injury was far less frequent but had a strong association with adverse clinical outcome in RSV, COVID-19 and influenza (odds ratio 5.29 (CI 1.2-22), 3.45 (CI 1.7-7), 3.1 (CI 1.7-6), respectively) COVID-19 and influenza patients whose liver functions did not improve or alternatively worsened after 48 h had a significantly higher risk of death or ventilation. CONCLUSION: liver function test abnormalities are frequent among patients with COVID-19 and seasonal respiratory viruses, and are associated with poor clinical outcome. The late liver tests' peak had a twofold risk for adverse outcome. Though cholestatic injury was more common, hepatocellular injury had the greatest prognostic significance 48 h after admission. Our study may provide a viral specific auxiliary prognostic tool for clinicians facing patients with a respiratory virus.

Risk factors, clinical characteristics and prognostic value of acute kidney injury in COVID-19 compared with influenza virus and respiratory syncytial virus.

BACKGROUND: Acute Kidney Injury (AKI) complicates a substantial part of patients with COVID-19. Direct viral penetration of renal cells through the Angiotensin Converting Enzyme 2 receptor, and indirect damage by the aberrant inflammatory response characteristic of COVID-19 are likely mechanisms. Nevertheless, other common respiratory viruses such as Influenza and Respiratory Syncytial Virus (RSV) are also associated with AKI. METHODS: We retrospectively compared the incidence, risk factors and outcomes of AKI among patients who were admitted to a tertiary hospital because of infection with COVID-19, influenza (A + B) or RSV. RESULTS: We collected data of 2593 patients hospitalized with COVID-19, 2041 patients with influenza and 429 with RSV. Patients affected by RSV were older, had more comorbidities and presented with higher rates of AKI at admission and within 7 days (11.7% vs. 13.3% vs. 18% for COVID-19, influenza and RSV, respectively p = 0.001). Nevertheless, patients hospitalized with COVID-19 had higher mortality (18% with COVID-19 vs. 8.6% and 13.5% for influenza and RSV, respectively P < 0.001) and higher need of mechanical ventilation (12.4% vs. 6.5% vs.8.2% for COVID-19, influenza and RSV, respectively, P = 0.002). High ferritin levels and low oxygen saturation were independent risk factors for severe AKI only in the COVID-19 group. AKI in the first 48 h of admission and in the first 7 days of hospitalization were strong independent risk factors for adverse outcome in all groups. CONCLUSION: Despite many reports of direct kidney injury by SARS-COV-2, AKI was less in patients with COVID-19 compared to influenza and RSV patients. AKI was a prognostic marker for adverse outcome across all viruses.

Elevated Serum Amyloid A Levels Contribute to Increased Platelet Adhesion in COVID-19 Patients.

Coronavirus disease-19 (COVID-19) patients are prone to thrombotic complications that may increase morbidity and mortality. These complications are thought to be driven by endothelial activation and tissue damage promoted by the systemic hyperinflammation associated with COVID-19. However, the exact mechanisms contributing to these complications are still unknown. To identify additional mechanisms contributing to the aberrant clotting observed in COVID-19 patients, we analyzed platelets from COVID-19 patients compared to those from controls using mass spectrometry. We identified increased serum amyloid A (SAA) levels, an acute-phase protein, on COVID-19 patients' platelets. In addition, using an in vitro adhesion assay, we showed that healthy platelets adhered more strongly to wells coated with COVID-19 patient serum than to wells coated with control serum. Furthermore, inhibitors of integrin aIIbß3 receptors, a mediator of platelet-SAA binding, reduced platelet adhesion to recombinant SAA and to wells coated with COVID-19 patient serum. Our results suggest that SAA may contribute to the increased platelet adhesion observed in serum from COVID-19 patients. Thus, reducing SAA levels by decreasing inflammation or inhibiting SAA platelet-binding activity might be a valid approach to abrogate COVID-19-associated thrombotic complications.

Prognostic value of neutrophil-to-lymphocyte ratio in COVID-19 compared with Influenza and respiratory syncytial virus infection.

A high neutrophil to lymphocyte ratio (NLR) is considered an unfavorable prognostic factor in various diseases, including COVID-19. The prognostic value of NLR in other respiratory viral infections, such as Influenza, has not hitherto been extensively studied. We aimed to compare the prognostic value of NLR in COVID-19, Influenza and Respiratory Syncytial Virus infection (RSV). A retrospective cohort of COVID-19, Influenza and RSV patients admitted to the Tel Aviv Medical Center from January 2010 to October 2020 was analyzed. Laboratory, demographic, and clinical parameters were collected. Two way analyses of variance (ANOVA) was used to compare the association between NLR values and poor outcomes among the three groups. ROC curve analyses for each virus was applied to test the discrimination ability of NLR. 722 COVID-19, 2213 influenza and 482 RSV patients were included. Above the age of 50, NLR at admission was significantly lower among COVID-19 patients (P < 0.001). NLR was associated with poor clinical outcome only in the COVID-19 group. ROC curve analysis was performed; the area under curve of poor outcomes for COVID-19 was 0.68, compared with 0.57 and 0.58 for Influenza and RSV respectively. In the COVID-19 group, multivariate logistic regression identified a high NLR (defined as a value above 6.82) to be a prognostic factor for poor clinical outcome, after adjusting for age, sex and Charlson comorbidity score (odds ratio of 2.9, P < 0.001). NLR at admission is lower and has more prognostic value in COVID-19 patients, when compared to Influenza and RSV.