Predictors of prolonged hospitalization of COVID-19 patients.

PURPOSE: Despite the importance of hospital bed network during the pandemic, there are scarce data available regarding factors predictive of prolonged length of hospitalization of COVID-19 patients. METHODS: We retrospectively analyzed a total of 5959 consecutive hospitalized COVID-19 patients in period 3/2020-6/2021 from a single tertiary-level institution. Prolonged hospitalization was defined as hospital stay > 21 days to account for mandatory isolation period in immunocompromised patients. RESULTS: Median length of hospital stay was 10 days. A total of 799 (13.4%) patients required prolonged hospitalization. Factors that remained independently associated with prolonged hospitalization in multivariate analysis were severe or critical COVID-19 and worse functional status at the time of hospital admission, referral from other institutions, acute neurological, acute surgical and social indications for admission vs admission indication of COVID-19 pneumonia, obesity, chronic liver disease, hematological malignancy, transplanted organ, occurrence of venous thromboembolism, occurrence of bacterial sepsis and occurrence of Clostridioides difficile infection during hospitalization. Patients requiring prolonged hospitalization experienced higher post-hospital discharge mortality (HR = 2.87, P < 0.001). CONCLUSIONS: Not only severity of COVID-19 clinical presentation but also worse functional status, referral from other hospitals, certain indications for admission, certain chronic comorbidities, and complications that arise during hospital stay independently reflect on the need of prolonged hospitalization. Development of specific measures aimed at improvement of functional status and prevention of complications might reduce the length of hospitalization.

Investigating the role of obstructive pulmonary diseases and eosinophil count at admission on all-cause mortality in SARS-CoV-2 patients : A single center registry-based retrospective cohort study.

INTRODUCTION: The impact of asthma and chronic obstructive pulmonary disease (COPD) in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2) infection is not clearly defined. Blood eosinophil count is a standard diagnostic test which, according to the previously published literature, might have a potential prognostic role on mortality in patients with SARS-CoV­2 infection. AIM: To investigate the potential prognostic value of peripheral blood eosinophil count on all-cause mortality of patients hospitalized with SARS-CoV­2 infection, as well as to assess the impact of asthma or COPD premorbidity on all-cause mortality. MATERIAL AND METHODS: We conducted a retrospective registry-based cohort study. Survival analysis was performed by employing the Cox proportional hazards regression model at 30 days of follow-up. Prognostic value of eosinophil count on all-cause mortality was assessed using receiver-operating characteristic (ROC) curve analysis. RESULTS: A total of 5653 participants were included in the study. Our model did not reveal that pre-existing asthma or COPD is a statistically significant covariate for all-cause mortality but, indicated that higher eosinophil count at admission might have a protective effect (hazard ratio, HR 0.13 (95% confidence interval, CI 0.06-0.27), p = 0.0001). ROC curve analysis indicates cut-off value of 20 cells/mm3 (81% specificity; 30.9% sensitivity). CONCLUSION: Our results indicate that eosinophil count at hospital admission might have a potential prognostic role for all-cause mortality at 30 days of follow-up; however this was not demonstrated for pre-existing obstructive lung diseases.

Real-life experience with remdesivir for treatment of hospitalized coronavirus disease 2019 patients: matched case-control study from a large tertiary hospital registry.

AIM: To evaluate the association of remdesivir use and the survival of hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: We retrospectively reviewed the medical records of 5959 COVID-19 patients admitted to our tertiary-level hospital from March 2020 to June 2021. A total of 876 remdesivir-treated patients were matched with 876 control patients in terms of age, sex, Charlson comorbidity index (CCI), WHO-defined COVID-19 severity on admission, and oxygen requirement at the time of remdesivir use. RESULTS: Among 1752 COVID-19 patients (median age 66 years, 61.8% men), 1405 (80.2%) had severe and 311 (17.8%) had critically severe COVID-19 on admission. Remdesivir was given at a median of one day after hospital admission and at a median of eight days from the onset of symptoms. Overall, 645 (73.6%) patients received remdesivir before high-flow oxygen therapy (HFOT) or mechanical ventilation (MV), 198 (22.6%) after HFOT institution, and 83 (9.5%) after MV institution. Remdesivir use was associated with improved survival in the entire cohort (hazard ratio 0.79, P=0.006). Survival benefit was evident among patients receiving remdesivir during low-flow oxygen requirement (hazard ratio 0.61, P<0.001) but not among patients who received it after starting HFOT (P=0.499) or MV (P=0.380). CONCLUSION: Remdesivir, if given during low-flow oxygen therapy, might be associated with survival benefit in hospitalized COVID-19 patients.

Lipidomics Revealed Plasma Phospholipid Profile Differences between Deceased and Recovered COVID-19 Patients.

Thorough understanding of metabolic changes, including lipidome alteration, associated with the development of COVID-19 appears to be crucial, as new types of coronaviruses are still reported. In this study, we analyzed the differences in the plasma phospholipid profiles of the deceased COVID-19 patients, those who recovered and healthy people. Due to identified abnormalities in plasma phospholipid profiles, deceased patients were further divided into two subgroups (D1 and D2). Increased levels of phosphatidylethanolamines (PE), phosphatidylcholines (PC) and phosphatidylserines (PS) were found in the plasma of recovered patients and the majority of deceased patients (first subgroup D1) compared to the control group. However, abundances of all relevant PE, PC and PS species decreased dramatically in the plasma of the second subgroup (D2) of five deceased patients. These patients also had significantly decreased plasma COX-2 activity when compared to the control, in contrast to unchanged and increased COX-2 activity in the plasma of the other deceased patients and recovered patients, respectively. Moreover, these five deceased patients were characterized by abnormally low CRP levels and tremendous increase in LDH levels, which may be the result of other pathophysiological disorders, including disorders of the immune system, liver damage and haemolytic anemia. In addition, an observed trend to decrease the autoantibodies against oxidative modifications of low-density lipoprotein (oLAb) titer in all, especially in deceased patients, indicate systemic oxidative stress and altered immune system that may have prognostic value in COVID-19.

Diversified Effects of COVID-19 as a Consequence of the Differential Metabolism of Phospholipids and Lipid Peroxidation Evaluated in the Plasma of Survivors and Deceased Patients upon Admission to the Hospital.

As a result of SARS-CoV-2 infection, inflammation develops, which promotes oxidative stress, leading to modification of phospholipid metabolism. Therefore, the aim of this study is to compare the effects of COVID-19 on the levels of phospholipid and free polyunsaturated fatty acids (PUFAs) and their metabolites produced in response to reactions with reactive oxygen species (ROS) and enzymes (cyclooxygenases-(COXs) and lipoxygenase-(LOX)) in the plasma of patients who either recovered or passed away within a week of hospitalization. In the plasma of COVID-19 patients, especially of the survivors, the actions of ROS and phospholipase A2 (PLA2) cause a decrease in phospholipid fatty acids level and an increase in free fatty acids (especially arachidonic acid) despite increased COXs and LOX activity. This is accompanied by an increased level in lipid peroxidation products (malondialdehyde and 8-isoprostaglandin F2α) and lipid mediators generated by enzymes. There is also an increase in eicosanoids, both pro-inflammatory as follows: thromboxane B2 and prostaglandin E2, and anti-inflammatory as follows: 15-deoxy-Δ-12,14-prostaglandin J2 and 12-hydroxyeicosatetraenoic acid, as well as endocannabinoids (anandamide-(AEA) and 2-arachidonylglycerol-(2-AG)) observed in the plasma of patients who recovered. Moreover, the expression of tumor necrosis factor α and interleukins (IL-6 and IL-10) is increased in patients who recovered. However, in the group of patients who died, elevated levels of N-oleoylethanolamine and N-palmitoylethanolamine are found. Since lipid mediators may have different functions depending on the onset of pathophysiological processes, a stronger pro-inflammatory response in patients who have recovered may be the result of the defensive response to SARS-CoV-2 in survivors associated with specific changes in the phospholipid metabolism, which could also be considered a prognostic factor.

Spontaneous spinal subdural hematoma in COVID-19 patient: Croatian national COVID hospital experience.

Background: Spontaneous spinal subdural hematoma (SSDH) is a rare condition and causes of acute spinal cord compression, with symptoms varying from mild to severe neurological deficit. SSDH could occur as a consequence of posttraumatic, iatrogenic, or spontaneous causes, including underlying arteriovenous malformations, tumors, or coagulation disorder. Due to its rarity, it is difficult to establish standardized treatment. We present a rare case of SSDH in COVID-19 patient and course of treatment in COVID hospital. Case Description: A 71-year-old female patient was admitted due to instability, weakness of the left leg, and intensive pain in the upper part of thoracic spine as well as mild respiratory symptoms of COVID-19. She was not on pronounced anticoagulant therapy and her coagulogram at admission was within normal range. MRI revealed acute subdural hematoma at the level C VII to Th III compressing the spinal cord. The patient underwent a decompressive Th I and Th II laminectomy and hematoma evacuation. Post-operative MRI revealed a satisfactory decompression and re-expansion of the spinal cord. COVID-19 symptoms remained mild. Conclusion: SSDH represents a neurological emergency, possibly leading to significant deficit and requires urgent recognition and treatment. One of the main difficulties when diagnosing is to consider such condition when there is no history of anticoagulant treatment or previous trauma. Since high incidence of coagulation abnormalities and thromboembolic events was described COVID-19 patients, when considering the pathology of the central nervous system, the bleeding within it due to COVID-19 should be taken into account, in both brain and spine.

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.

Differences in Immunoglobulin G Glycosylation Between Influenza and COVID-19 Patients.

The essential role of immunoglobulin G (IgG) in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine 297 of the Fc domain that occur under such circumstances. These glycans impact the antibody stability, half-life, secretion, immunogenicity, and effector functions. Therefore, in this study, we analyzed and compared the total IgG glycome-at the level of individual glycan structures and derived glycosylation traits (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc))-of 64 patients with influenza, 77 patients with coronavirus disease 2019 (COVID-19), and 56 healthy controls. Our study revealed a significant decrease in IgG galactosylation, sialylation, and bisecting GlcNAc (where the latter shows the most significant decrease) in deceased COVID-19 patients, whereas IgG fucosylation was increased. On the other hand, IgG galactosylation remained stable in influenza patients and COVID-19 survivors. IgG glycosylation in influenza patients was more time-dependent: In the first seven days of the disease, sialylation increased and fucosylation and bisecting GlcNAc decreased; in the next 21 days, sialylation decreased and fucosylation increased (while bisecting GlcNAc remained stable). The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses, while the observed changes in deceased COVID-19 patients may indicate its deviation.

Survival after hospital discharge in patients hospitalized for acute coronavirus disease 2019: data on 2586 patients from a tertiary center registry.

AIM: To assess the long-term survival after hospital discharge of patients hospitalized due to coronavirus disease 2019 (COVID-19). METHODS: We retrospectively reviewed data on post-discharge survival of 2586 COVID-19 patients hospitalized in our tertiary hospital from March 2020 to March 2021. RESULTS: Among 2586 patients, 1446 (55.9%) were men. The median age was 70 years, interquartile range (IQR, 60-80). The median Charlson comorbidity index was 4 points, IQR (2-5). The median length of hospital stay was 10 days, IQR (7-16). During a median follow-up of 4 months, 192 (7.4%) patients died. The median survival time after hospital discharge was not reached, and 3-month, 6-month, and 12-month survival rates were 93%, 92%, and 91%, respectively. In a multivariate analysis, mutually independent predictors of worse mortality after hospital discharge were age >75 years, Eastern Cooperative Oncology Group status 4, white blood cell count >7 ×109/L, red cell distribution width >14%, urea on admission >10.5 mmol/L, mechanical ventilation during hospital stay, readmission after discharge, absence of obesity, presence of chronic obstructive pulmonary disease, dementia, and metastatic malignancy (P<0.05 for all). CONCLUSION: Substantial risk of death persists after hospital admission due to COVID-19. Factors related to an increased risk are older age, higher functional impairment, need for mechanical ventilation during hospital admission, parameters indicating more pronounced inflammation, impaired renal function, and particular comorbidities. Interventions aimed at improving patients' functional capacity may be needed.

Distribution of Pathogens and Predictive Values of Biomarkers of Inflammatory Response at ICU Admission on Outcomes of Critically Ill COVID-19 Patients with Bacterial Superinfections-Observations from National COVID-19 Hospital in Croatia.

BACKGROUND: Superinfections contribute to mortality and length of stay in critically ill COVID-19 patients. The aim of this study was to determine the incidence and pathogen distribution of bacterial and fungal superinfections of the lower respiratory tract (LRTI), urinary tract (UTI) and bloodstream (BSI) and to determine the predictive value of biomarkers of inflammatory response on their ICU survival rates. METHODS: A retrospective observational study that included critically ill COVID-19 patients treated during an 11-month period in a Croatian national COVID-19 hospital was performed. Clinical and diagnostic data were analyzed according to the origin of superinfection, and multivariate regression analysis was performed to determine the predictive values of biomarkers of inflammation on their survival rates. RESULTS: 55.3% critically ill COVID-19 patients developed bacterial or fungal superinfections, and LRTI were most common, followed by BSI and UTI. Multidrug-resistant pathogens were the most common causes of LRTI and BSI, while Enterococcus faecalis was the most common pathogen causing UTI. Serum ferritin and neutrophil count were associated with decreased chances of survival in patients with LRTI, and patients with multidrug-resistant isolates had significantly higher mortality rates, coupled with longer ICU stays. CONCLUSION: The incidence of superinfections in critically ill COVID-19 patients was 55.3%, and multidrug-resistant pathogens were dominant. Elevated ferritin levels and neutrophilia at ICU admission were associated with increased ICU mortality in patients with positive LRTI.

The Impact of Severe COVID-19 on Plasma Antioxidants.

Several studies suggested the association of COVID-19 with systemic oxidative stress, in particular with lipid peroxidation and vascular stress. Therefore, this study aimed to evaluate the antioxidant signaling in the plasma of eighty-eight patients upon admission to the Clinical Hospital Dubrava in Zagreb, of which twenty-two died within a week, while the other recovered. The differences between the deceased and the survivors were found, especially in the reduction of superoxide dismutases (SOD-1 and SOD-2) activity, which was accompanied by the alteration in glutathione-dependent system and the intensification of the thioredoxin-dependent system. Reduced levels of non-enzymatic antioxidants, especially tocopherol, were also observed, which correlated with enhanced lipid peroxidation (determined by 4-hydroxynonenal (4-HNE) and neuroprostane levels) and oxidative modifications of proteins assessed as 4-HNE-protein adducts and carbonyl groups. These findings confirm the onset of systemic oxidative stress in patients with severe SARS-CoV-2, especially those who died from COVID-19, as manifested by strongly reduced tocopherol level and SOD activity associated with lipid peroxidation. Therefore, we propose that preventive and/or supplementary use of antioxidants, especially of lipophilic nature, could be beneficial for the treatment of COVID-19 patients.

IgG N-glycome changes during the course of severe COVID-19: An observational study.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory illness named coronavirus disease 2019 (COVID-19), which is one of the main global health problems since 2019. Glycans attached to the Fc portion of immunoglobulin G (IgG) are important modulators of IgG effector functions. Fc region binds to different receptors on the surface of various immune cells, dictating the type of immune response. Here, we performed a large longitudinal study to determine whether the severity and duration of COVID-19 are associated with altered IgG glycosylation. METHODS: Using ultra-high-performance liquid chromatography analysis of released glycans, we analysed the composition of the total IgG N-glycome longitudinally during COVID-19 from four independent cohorts. We analysed 77 severe COVID-19 cases from the HR1 cohort (74% males, median age 72, age IQR 25-80); 31 severe cases in the HR2 cohort (77% males, median age 64, age IQR 41-86), 18 mild COVID-19 cases from the UK cohort (17% males, median age 50, age IQR 26-71) and 28 mild cases from the BiH cohort (71% males, median age 60, age IQR 12-78). FINDINGS: Multiple statistically significant changes in IgG glycome composition were observed during severe COVID-19. The most statistically significant changes included increased agalactosylation of IgG (meta-analysis 95% CI [0.03, 0.07], adjusted meta-analysis P= <0.0001), which regulates proinflammatory actions of IgG via complement system activation and indirectly as a lack of sialylation and decreased presence of bisecting N-acetylglucosamine on IgG (meta-analysis 95% CI [-0.11, -0.08], adjusted meta-analysis P= <0.0001), which indirectly affects antibody-dependent cell-mediated cytotoxicity. On the contrary, no statistically significant changes in IgG glycome composition were observed in patients with mild COVID-19. INTERPRETATION: The IgG glycome in severe COVID-19 patients is statistically significantly altered in a way that it indicates decreased immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the severity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in COVID-19. FUNDING: This work has been supported in part by Croatian Science Foundation under the project IP-CORONA-2020-04-2052 and Croatian National Centre of Competence in Molecular Diagnostics (The European Structural and Investment Funds grant #KK.01.2.2.03.0006), by the UKRI/MRC (Cov-0331 - MR/V027883/1) and by the National Institutes for Health Research Nottingham Biomedical Research Centre and by Ministry Of Science, Higher Education and Youth Of Canton Sarajevo, grant number 27-02-11-4375-10/21.

Tracheomegaly as a Potential Predictor of Severe Tracheal Damage in COVID-19 Patients on Long-Term Mechanical Ventilation

Tracheomegaly (TM) is a rare appearance that is radiologically defined as an excessive enlargement of the tracheal diameter. We present a comprehensive analysis of tracheal diameter measurements and TM incidence in patients admitted and treated due to COVID-19 pneumonitis and its association with possible respiratory complications. In this retrospective study, we included 1015 patients divided into three groups: 383 patients treated using mechanical ventilation (MV), 132 patients treated using high-flow ventilation (HFV), and 500 randomly selected patients using nasal catheter (NC) oxygenation. The tracheal lumen diameter was measured continuously using a chest X-ray, and the cuff/trachea (C/T) diameter ratio was calculated. We detected TM in 71 patients (18.54%). Regression analysis showed statistical significance in MV patients for the trachea diameter at the level of the cuff, maximal trachea diameter and C/T diameter ratio, and days on MV. Respiratory complications showed a significant association with the C/T diameter ratio. The C/T diameter ratio was shown to be a reliable potential predictor of the occurrence of respiratory complications. The results of the study highlight the importance of the early detection and prevention of TM in COVID-19 patients on MV using a chest X-ray and measurement of the C/T diameter ratio.

Asymptomatic deep vein thromboses in prolonged hospitalized COVID-19 patients.

High incidence of venous thromboembolic (VTE) events in coronavirus disease 2019 (COVID-19) patients has been reported despite pharmacologic thromboprophylaxis. We performed prospective bilateral lower extremity ultrasound evaluation of prolonged hospitalized COVID-19 ward patients from our institution without clinical suspicion of deep vein thrombosis (DVT).A total of 102 patient were included in the study. All patients were receiving pharmacologic thromboprophylaxis, the majority in intermediate or therapeutic doses. Asymptomatic DVT was detected in 26/102 (25.5%) patients: 22 had distal and four had proximal DVT, six had bilateral leg involvement. Pulmonary embolism was highly prevalent (17/70, 24.3%) but similarly grouped among patients with and without asymptomatic DVT. In total 37.2% of patients included in the study were recognized as having VTE.Asymptomatic DVT events were more common in intensive care unit (ICU) survivors (60% in postmechanically ventilated ICU survivors, 21.2% in ward patients, 22% in high-flow oxygen treated patients; P = 0.031), in patients with higher modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk-score (median 3 vs. 2 points with and without DVT; P = 0.021) and higher body temperature on admission (median 38.7 °C vs. 37.7 °C with and without DVT; P = 0.001). No clear associations with Padua VTE risk score, demographic and other clinical characteristics, intensity of thromboprophylaxis, severity of other COVID-19 symptoms, degree of systemic inflammation or D­dimers on admission were found (P > 0.05 for all analyses).Systematic ultrasound assessment in prolonged hospitalized severe COVID-19 patients prior to hospital discharge is needed, especially in ICU survivors, to timely recognize and appropriately treat patients with asymptomatic DVT.

Vaccination provides protection from respiratory deterioration and death among hospitalized COVID-19 patients: Differences between vector and mRNA vaccines.

Outcomes of 109 hospitalized COVID-19 patients who received at least one vaccine dose 14 or more days prior the disease onset were retrospectively compared to control cohort of 109 age, sex, and Charlson comorbidity index-matched patients chosen among 2990 total hospitalized patients in our tertiary-level institution in a period from January to June 2021. Among 109 vaccinated patients, 84 patients were partially and 25 fully vaccinated. Vaccinated patients experienced significantly lower 30 days mortality (30% vs. 49%; hazard ratio [HR]: 0.56 [0.37-0.85]; p = 0.008), less frequently required high flow oxygen therapy (17% vs. 34%; HR: 0.45 [0.26-0.76]; p = 0.005), and mechanical ventilation (8% vs. 18%; HR: 0.41 [0.20-0.88]; p = 0.027) in comparison to the matched cohort of unvaccinated patients. More favorable survival was observed in patients receiving vector in comparison to messenger RNA (mRNA) vaccine types in unadjusted analysis (30 days mortality 18% vs. 40%; HR: 0.45 [0.25-0.79]; p = 0.034). In the multivariable Cox regression analysis model both mRNA (HR: 0.59 [0.36-0.98]; p = 0.041) and vector vaccine types (HR: 0.30 [0.15-0.60]; p < 0.001) were associated with improved survival in comparison to unvaccinated patients, independently of age (HR: 1.03 [1.01-1.06]; p = 0.011), male sex (HR: 1.78 [1.14-2.76]; p = 0.010), severity of illness (HR: 2.06 [1.36-3.10]; p < 0.001) and functional status on admission (HR: 1.42 [1.07-1.85]; p = 0.013).

FibroScan-AST Score Predicts 30-Day Mortality or Need for Mechanical Ventilation among Patients Hospitalized with COVID-19.

BACKGROUND: Liver involvement in Coronavirus disease 2019 (COVID-19) has been recognised. We aimed to investigate the correlation of non-invasive surrogates of liver steatosis, fibrosis and inflammation using transient elastography (TE) and FibroScan-AST (FAST) score with (a) clinical severity and (b) 30-day composite outcome of mechanical ventilation (MV) or death among patients hospitalized due to COVID-19. METHOD: Patients with non-critical COVID-19 at admission were included. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed by TE. Clinical severity of COVID-19 was assessed by 4C Mortality Score (4CMS) and need for high-flow nasal cannula (HFNC) oxygen supplementation. RESULTS: 217 patients were included (66.5% males, median age 65 years, 4.6% with history of chronic liver disease). Twenty-four (11.1%) patients met the 30-day composite outcome. Median LSM, CAP and FAST score were 5.2 kPa, 274 dB/m and 0.31, respectively, and neither was associated with clinical severity of COVID-19 at admission. In multivariate analysis FAST > 0.36 (OR 3.19, p = 0.036), 4CMS (OR 1.68, p = 0.002) and HFNC (OR 7.03, p = 0.001) were independent predictors of adverse composite outcome. CONCLUSION: Whereas LSM and CAP failed to show correlation with COVID-19 severity and outcomes, FAST score was an independent risk factor for 30-day mortality or need for MV.

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.

Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19.

Major findings of the pilot study involving 21 critically ill patients during the week after admission to the critical care unit specialized for COVID-19 are presented. Fourteen patients have recovered, while seven passed away. There were no differences between them in respect to clinical or laboratory parameters monitored. However, protein adducts of the lipid peroxidation product 4-hydroxynonenal (HNE) were higher in the plasma of the deceased patients, while total antioxidant capacity was below the detection limit for the majority of sera samples in both groups. Moreover, levels of the HNE-protein adducts were constant in the plasma of the deceased patients, while in survivors, they have shown prominent and dynamic variations, suggesting that survivors had active oxidative stress response mechanisms reacting to COVID-19 aggression, which were not efficient in patients who died. Immunohistochemistry revealed the abundant presence of HNE-protein adducts in the lungs of deceased patients indicating that HNE is associated with the lethal outcome. It seems that HNE was spreading from the blood vessels more than being a consequence of pneumonia. Due to the limitations of the relatively small number of patients involved in this study, further research on HNE and antioxidants is needed. This might allow a better understanding of COVID-19 and options for utilizing antioxidants by personalized, integrative biomedicine approach to prevent the onset of HNE-mediated vitious circle of lipid peroxidation in patients with aggressive inflammatory diseases.

Effects of Environmental Factors on Severity and Mortality of COVID-19.

Background: Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. Methods: We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Findings: Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988, p < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773-0.944, p = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Interpretation: Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.