Predictive value of immunoglobulin G, activated partial thromboplastin time, platelet, and indirect bilirubin for delayed viral clearance in patients infected with the Omicron variant.

Background: Omicron is the recently emerged highly transmissible severe acute respiratory syndrome coronavirus 2 variant that has caused a dramatic increase in coronavirus disease-2019 infection cases worldwide. This study was to investigate the association between demographic and laboratory findings, and the duration of Omicron viral clearance. Methods: Approximately 278 Omicron cases at the Ruijin Hospital Luwan Branch, Shanghai Jiaotong University School of Medicine were retrospectively analyzed between August 11 and August 31, 2022. Demographic and laboratory data were also collected. The association between demographics, laboratory findings, and duration of Omicron viral clearance was analyzed using Pearson correlation analysis and univariate and multivariate logistic regression. Results: Univariate logistic regression analyses showed that a prolonged viral clearance time was significantly associated with older age and lower immunoglobulin (Ig) G and platelet (PLT) levels. Using multinomial logistic regression analyses, direct bilirubin, IgG, activated partial thromboplastin time (APTT), and PLT were independent factors for longer viral shedding duration. The model combining direct bilirubin, IgG, APTT, and PLT identifies patients infected with Omicron whose viral clearance time was ≥7 days with 62.7% sensitivity and 83.4% specificity. Conclusion: These findings suggest that direct bilirubin, IgG, PLT, and APTT are significant risk factors for a longer viral shedding duration in patients infected with Omicron. Measuring levels of direct bilirubin, IgG, PLT, and APTT is advantageous to identify patients infected with Omicron with longer viral shedding duration.

Blood unconjugated bilirubin and tacrolimus are negative predictors of specific cellular immunity in kidney transplant recipients after SAR-CoV-2 inactivated vaccination.

The immunogenicity of SARS-CoV-2 vaccines is poor in kidney transplant recipients (KTRs). The factors related to poor immunogenicity to vaccination in KTRs are not well defined. Here, observational study demonstrated no severe adverse effects were observed in KTRs and healthy participants (HPs) after first or second dose of SARS-CoV-2 inactivated vaccine. Different from HPs with excellent immunity against SARS-CoV-2, IgG antibodies against S1 subunit of spike protein, receptor-binding domain, and nucleocapsid protein were not effectively induced in a majority of KTRs after the second dose of inactivated vaccine. Specific T cell immunity response was detectable in 40% KTRs after the second dose of inactivated vaccine. KTRs who developed specific T cell immunity were more likely to be female, and have lower levels of total bilirubin, unconjugated bilirubin, and blood tacrolimus concentrations. Multivariate logistic regression analysis found that blood unconjugated bilirubin and tacrolimus concentration were significantly negatively associated with SARS-CoV-2 specific T cell immunity response in KTRs. Altogether, these data suggest compared to humoral immunity, SARS-CoV-2 specific T cell immunity response are more likely to be induced in KTRs after administration of inactivated vaccine. Reduction of unconjugated bilirubin and tacrolimus concentration might benefit specific cellular immunity response in KTRs following vaccination.

Mortality rates of severe COVID-19-related respiratory failure with and without extracorporeal membrane oxygenation in the Middle Ruhr Region of Germany.

The use of extracorporeal membrane oxygenation (ECMO) is discussed to improve patients' outcome in severe COVID-19 with respiratory failure, but data on ECMO remains controversial. The aim of the study was to determine the characteristics of patients under invasive mechanical ventilation (IMV) with or without veno-venous ECMO support and to evaluate outcome parameters. Ventilated patients with COVID-19 with and without additional ECMO support were analyzed in a retrospective multicenter study regarding clinical characteristics, respiratory and laboratory parameters in day-to-day follow-up. Recruitment of patients was conducted during the first three COVID-19 waves at four German university hospitals of the Ruhr University Bochum, located in the Middle Ruhr Region. From March 1, 2020 to August 31, 2021, the charts of 149 patients who were ventilated for COVID-19 infection, were included (63.8% male, median age 67 years). Fifty patients (33.6%) received additional ECMO support. On average, ECMO therapy was initiated 15.6 ± 9.4 days after symptom onset, 10.6 ± 7.1 days after hospital admission, and 4.8 ± 6.4 days after the start of IMV. Male sex and higher SOFA and RESP scores were observed significantly more often in the high-volume ECMO center. Pre-medication with antidepressants was more often detected in survivors (22.0% vs. 6.5%; p = 0.006). ECMO patients were 14 years younger and presented a lower rate of concomitant cardiovascular diseases (18.0% vs. 47.5%; p = 0.0004). Additionally, cytokine-adsorption (46.0% vs. 13.1%; p < 0.0001) and renal replacement therapy (76.0% vs. 43.4%; p = 0.0001) were carried out more frequently; in ECMO patients thrombocytes were transfused 12-fold more often related to more than fourfold higher bleeding complications. Undulating C-reactive protein (CRP) and massive increase in bilirubin levels (at terminal stage) could be observed in deceased ECMO patients. In-hospital mortality was high (Overall: 72.5%, ECMO: 80.0%, ns). Regardless of ECMO therapy half of the study population deceased within 30 days after hospital admission. Despite being younger and with less comorbidities ECMO therapy did not improve survival in severely ill COVID-19 patients. Undulating CRP levels, a massive increase of bilirubin level and a high use of cytokine-adsorption were associated with worse outcomes. In conclusion, ECMO support might be helpful in selected severe cases of COVID-19.

Liver Injury in Patients with COVID-19: A Retrospective Study.

Objectives: The objective of this study is to explore the incidence, characteristics, risk factors, and prognosis of liver injury in patients with COVID-19. Methods: We collected clinical data of 384 cases of COVID-19 and retrospectively analyzed the incidence, characteristics, and risk factors of liver injury of the patients. In addition, we followed the patient two months after discharge. Results: A total of 23.7% of the patients with COVID-19 had liver injury, with higher serum AST (P < 0.001), ALT (P < 0.001), ALP (P = 0.004), GGT (P < 0.001), total bilirubin (P = 0.002), indirect bilirubin (P = 0.025) and direct bilirubin (P < 0.001) than the control group. The median serum AST and ALT of COVID-19 patients with liver injury were mildly elevated. Risk factors of liver injury in COVID-19 patients were age (P = 0.001), history of liver diseases (P = 0.002), alcoholic abuse (P = 0.036), body mass index (P = 0.037), severity of COVID-19 (P < 0.001), C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.001), Qing-Fei-Pai-Du-Tang treatment (P = 0.032), mechanical ventilation (P < 0.001), and ICU admission (P < 0.001). Most of the patients (92.3%) with liver injury were treated with hepatoprotective drugs. 95.6% of the patients returned to normal liver function tests at 2 months after discharge. Conclusions: Liver injury was commen in COVID-19 patients with risk factors, most of them have mild elevations in transaminases, and conservative treatment has a good short-term prognosis.

Favipiravir Efficacy And Safety For The Treatment Of Severe Coronavirus Disease 2019: A Retrospective Study.

BACKGROUND: Corona virus disease is caused by the enveloped, single stranded RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becoming the deadliest disease of the century. Its global outbreak has led researchers to develop drugs or vaccines to prevent the spread of the disease. Favipiravir is an approved orally administered antiviral drug that selectively inhibits RNA-dependent RNA polymerase, used off-label to treat COVID-19. Objectives: The purpose of this study was to assess the efficacy and safety of this drug for severe COVID-19 infection. METHODS: This was an observational retrospective study, carried out at the ICU of King Saud Medical City (KSMC) from June 2020 to August 2020. Including a total of one thousand six hundred and ninety-nine patients (n=1699). Categorized into a treatment group (193 patients) who received Favipiravir along with standard care, and non-treatment group (1506 patients) who received standard care only. RESULTS: ICU all-cause mortality was similar in both groups i.e., (Treated group 38.3% Vs Untreated group 39.4%, 95% CI of difference: -6.6% to +8.4%; p = 0.8). The subgroup analysis of survivors as compared to deceased in the treatment group showed that survivors had significantly lower age, international normalising ratio (INR), blood urea nitrogen (BUN), and creatinine. The mean ICU length of stay (LOS) was shorter for survivors compared to deceased (11.2± 8.03 Vs 16.7±9.8 days respectively), while hospital LOS was almost similar between the two groups. Advanced age (OR 1.03 [95% CI: 1.01-1.06]; p=0.004), higher INR and BUN were significantly associated with increased odds of mortality. Comparison of lab investigations at day 1 and day 10 in the treatment group (regardless of outcome) showed that there was a significant increase in Alanine transaminase (ALT), alkaline phosphatase (ALK), and Bilirubin, while an insignificant trend of increase in Aspartate transaminase (AST) and creatinine was recorded. CONCLUSIONS: In this study, Favipiravir showed better therapeutic responses in patients with severe COVID-19 infection, in terms of average duration of stay in the intensive care unit and was well tolerated in the younger age, but showed no mortality benefit. However, elevated levels of inflammatory markers, including increased ALT, AST, BUN, bilirubin, and creatinine, needs to be carefully examined.

The effect of Favipiravir on liver enzyme among patients with mild to moderate COVID-19 infection: A prospective cohort study.

Teratogenicity and hyperuricemia are considered as the major adverse effects of favipiravir, but less is known about other possible side effects which includes drug-induced liver damage and renal injury. In the current research, assessment of favipiravir-induced liver injury was performed by evaluating liver enzymes among patients with mild to moderate COVID-19 infection. A prospective cohort study was conducted on 66 patients diagnosed with mild to moderate COVID-19 infection who were treated with favipiravir for 5 days. During this period, a baseline assessment of liver enzymes (aspartate aminotransferase - AST, alanine transaminase - ALT and alkaline phosphatase - ALP) in addition to bilirubin before initiation of therapy and after 1 day of completion of therapy were carried out. The comparison of all measured parameters among all patients before and after receiving the treatment showed that non-significant differences were obtained in their levels. It was noticed that COVID-19 patients demonstrated high AST levels in which only 16 patients out of the all-subjected cases (66 patients) had AST levels of less than 45 U/L whereas the majority of patients showed normal ALT, ALP, and bilirubin levels. It was concluded that 5 days administration of favipiravir in mild to moderate COVID-19 patients who had no previous liver diseases did not affect the liver enzymes significantly and only transient elevations were occurred.

Lymphocyte-C-reactive protein ratio can differentiate disease severity of COVID-19 patients and serve as an assistant screening tool for hospital and ICU admission.

In this study, we aimed to explore whether lymphocyte-C-reactive protein ratio (LCR) can differentiate disease severity of coronavirus disease 2019 (COVID-19) patients and its value as an assistant screening tool for admission to hospital and intensive care unit (ICU). A total of 184 adult COVID-19 patients from the COVID-19 Treatment Center in Heilongjiang Province at the First Affiliated Hospital of Harbin Medical University between January 2020 and March 2021 were included in this study. Patients were divided into asymptomatic infection group, mild group, moderate group, severe group, and critical group according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data including gender, age, comorbidities, severity of COVID-19, white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), red blood cell distribution width (RDW), platelet (PLT), C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr), albumin (ALB), total bilirubin (TB), direct bilirubin (DBIL), indirect bilirubin (IBIL), and D-dimer were obtained and collated from medical records at admission, from which sequential organ failure assessment (SOFA) score and LCR were calculated, and all the above indicators were compared among the groups. Multiple clinical parameters, including LYMPH, CRP, and LCR, showed significant differences among the groups. The related factors to classify COVID-19 patients into moderate, severe, and critical groups included age, number of comorbidities, WBC, LCR, and AST. Among these factors, the number of comorbidities showed the greatest effect, and only WBC and LCR were protective factors. The area under the receiver operating characteristic (ROC) curve of LCR to classify COVID-19 patients into moderate, severe, and critical groups was 0.176. The cutoff value of LCR and the sensitivity and specificity of the ROC curve were 1,780.7050 and 84.6% and 66.2%, respectively. The related factors to classify COVID-19 patients into severe and critical groups included the number of comorbidities, PLT, LCR, and SOFA score. Among these factors, SOFA score showed the greatest effect, and LCR was the only protective factor. The area under the ROC curve of LCR to classify COVID-19 patients into severe and critical groups was 0.106. The cutoff value of LCR and the sensitivity and specificity of the ROC curve were 571.2200 and 81.3% and 90.0%, respectively. In summary, LCR can differentiate disease severity of COVID-19 patients and serve as a simple and objective assistant screening tool for hospital and ICU admission.

Blood phenotype O and indirect bilirubin are associated with lower, early COVID-19-related mortality: A retrospective study.

OBJECTIVES: To evaluate the ABO blood type and indirect bilirubin to predict early mortality in adults with severe COVID-19. METHODS: This retrospective observational study was conducted on 268 adult patients with laboratory-confirmed COVID-19 who had attended the intensive care unit (ICU), Quena general hospital and Luxor International Hospital, and other hospitals or centers for the treatment of COVID-19, during the period from January 2021 till December 2021. RESULTS: Relation between mortality and ABO group were highly significant, as we found non-O blood group with more risk of early mortality and intensive care unit admission ICU. There were significant differences between dead and alive cases as regards platelets, white blood cells WBCs (neutrophil, lymphocyte), albumin, liver enzymes aspartate transeferase (AST), alanine transferase (ALT), total direct and indirect bilirubin, creatinine, and urea. CONCLUSION: There was a highly significant relation between dead cases and ABO blood group as between the O and non-O groups; also, group O was associated with less severe manifestations and or ventilation and less mortality in patients with severe COVID-19 infection. Direct bilirubin >0.5 was found to be the best predictor for mortality in cases with COVID-19 so indirect bilirubin may be considered a good protector against complications of the infection.

Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid.

BACKGROUND & AIMS: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. METHODS: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). RESULTS: One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. CONCLUSIONS: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use.

Severe refractory warm autoimmune haemolytic anaemia after the SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA) managed with emergency splenectomy and complement inhibition with eculizumab.

A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and autoimmune haemolytic anaemia (AIHA, aged 6 years) presented with jaundice, dark urine, fatigue and chest discomfort that began 48 hours after the first dose of SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed a warm AIHA picture. Over 4 weeks the patient developed life-threatening anaemia culminating in haemoglobin of 35 g/L (after transfusion), lactate dehydrogenase of 1293 units/L and bilirubin of 228 µmol/L, refractory to standard treatment with corticosteroids and rituximab. An emergency splenectomy was performed that slowed haemolysis but did not completely ameliorate it. Eculizumab, a terminal complement pathway inhibitor, was initiated to arrest intravascular haemolysis and showed a favourable response. AIHA is rare but described after the SARS-CoV-2 Pfizer-BioNTech vaccine. This case highlights the rare complication of AIHA, the use of emergency splenectomy for disease control, and the use of eculizumab.

Real-World Evidence for COVID-19 Delta Variant's Effects on the Digestive System and Protection of Inactivated Vaccines from a Medical Center in Yangzhou, China: A Retrospective Observational Study.

Background: Coronavirus disease 2019 (COVID-19) is rapidly disseminated worldwide, and it continues to threaten global public health. Recently, the Delta variant has emerged as the most dreaded variant worldwide. COVID-19 predominantly affects the respiratory tract, and studies have reported the transient effects of COVID-19 on digestive system function. However, the relationship between the severity of the Delta variant and digestive system function remains to be investigated. Additionally, data on the ability of the inactive Chinese vaccines (Sinovac or Sinopharm) to protect against the Delta variant or COVID-19-induced gastrointestinal symptoms in the real world are insufficient. Thus, the present retrospective observational study first attempted to use the total gastrointestinal symptom rating scale scores (GSRS) to quantify the possible changes in digestive system functions following the Delta variant infection in the early stage. In addition, the study discusses the potential of inactivated vaccines in preventing severe or critical symptoms or Delta variant-induced digestive system dysfunction. Methods: To evaluate the difference between mild illness group, moderate illness group, and severe or critical illness group, analysis of variance (ANOVA) was employed to compare the three groups' total gastrointestinal symptom rating scale scores (GSRS). A chi-squared test was used to compare the differences in the ratio of the abnormal biochemical measurements among the three groups first. Then, the percentage of the vaccinated population was compared among the three groups. Additionally, the ratio of the abnormal serum markers between the vaccinated and nonvaccinated cohorts was compared. A P value < 0.05 was considered statistically significant. Results: Significant differences were observed in the abnormal ratio of alanine aminotransferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), lactate dehydrogenase (LDH), and Interleukin 6 (IL-6) ratio among the three groups (P < 0.05). Additionally, no significant difference was observed in the abnormal serum markers ratio between day 14 and day 21 after treatment (P > 0.05). A significant difference was observed in the total GSRS scores among the three groups and the ratio of the vaccinated population among the three groups (P < 0.05). A significant difference was observed in the ratio of the abnormal serum ALT and AST levels between the vaccinated and nonvaccinated cohorts (P < 0.05). Conclusions: In summary, serum AST, DBIL, LDH, and IL-6 levels are potential markers for distinguishing severe or critical patients in the early stage of the Delta variant infection. Additionally, changes in the levels of these serum makers are transient, and the levels can return to normal after treatment. Furthermore, severe gastrointestinal discomfort was significantly more prevalent in patients with severe or critical diseases and should thus be considered in patients diagnosed with Delta variant infection. Finally, inactivated vaccines may prevent severe or critical symptoms and Delta variant-induced liver dysfunction. Vaccination programs must be promoted to protect public health.

Association of COVID-19 vaccination before conception with maternal liver function during early pregnancy: a cohort study of 7745 Chinese pregnant women.

ABSTRACTMulticenter case series has reported patients with hepatic injury following COVID-19 vaccination, which raised concern for the possibility of vaccine-induced liver dysfunction. We aimed to assess the impact of COVID-19 vaccination on liver function of pregnant women, who may be uniquely susceptible to vaccine-induced liver dysfunction. We conducted a retrospective cohort study at a tertiary hospital in Shanghai, China. Vaccine administration was obtained from the electronic vaccination record. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bile acid (TBA) and total bilirubin (TBIL) in early pregnancy were determined by enzymatic methods. Among the 7745 included pregnant women, 3832 (49.5%) received at least two doses of an inactivated vaccine. COVID-19 vaccination was significantly associated with higher levels of maternal serum TBA. Compared with unvaccinated pregnant women, the mean TBA levels increased by 0.17 µmol/L (ß = 0.17, 95% CI, 0.04, 0.31) for women who had been vaccinated within 3 months before the date of conception. Moreover, COVID-19 vaccination was significantly associated with an increased risk of maternal hyperbileacidemia. The risk of hyperbileacidemia increased by 113% (RR = 2.13; 95% CI, 1.17-3.87) for pregnant women who had been vaccinated within 3 months before conception compared with unvaccinated pregnant women. However, when the interval from complete vaccination to conception was prolonged to more than 3 months, COVID-19 vaccination was not associated with serum TBA levels or maternal hyperbileacidemia. Our findings suggest that vaccination with inactivated COVID-19 vaccines more than 3 months before conception have no detrimental effects on maternal liver function in early pregnancy.

Pilot study of home phototherapy for neonatal jaundice monitored in maternity ward during the enforced Italy-wide COVID-19 national lockdown.

In Italy, where neonatal jaundice treatment is required, it is largely carried out in hospitals. However, it is possible to safely administer home phototherapy (HPT). We report our pilot center's experience of HPT and its potential benefits during the COVID-19-enforced national lockdown. This is an observational study performed at the Policlinic Abano Terme, a suburban hospital that covers a large catchment area near the Euganean Hills in Northeast Italy with around 1000 deliveries per year. HPT was started after regular nursery discharge, and the mothers brought the neonates back to the hospital maternity ward each day to check infants' bilirubin levels, weight, and general state of health, until it was deemed safe to stop. The efficacy of HPT in bilirubin reduction, hospital readmission rates, and parental satisfaction were evaluated. Thirty infants received HPT. In 4 of these infants, HPT was associated with total serum bilirubin (TSB) between 75 and 95th percentile (high-intermediate-risk zone) and in 26 infants HPT was associated with TSB > 95th percentile (high-risk zone) of the Bhutani nomogram. Among these 30 infants, 27 (90%) completed the HPT with a progressive decrease of TSB levels with 4 neonates requiring a second course and 3 infants requiring a third course of 24-h HPT. Three (10%) neonates failed HPT and were readmitted after one 24-h phototherapy course. No abnormalities of breastfeeding, body weight (defined as > 10% decrease), temperature, nor COVID infections were detected following HPT consultation in the neonatal ward. Home treatment efficacy with varying degrees of parental satisfaction occurred in all but 3 cases that involved difficulties with the equipment and inconsistent lamp manipulation practices. CONCLUSION: Our pilot study suggests that HPT for neonatal jaundice can be carried out effectively and with parental satisfaction as supported by daily back bilirubin monitoring in the maternity ward during the enforced COVID-19 national lockdown in Italy. WHAT IS KNOWN: • No high-quality evidence is currently available to support or refute the practice of phototherapy in patients' own homes. WHAT IS NEW: • Phototherapy can be delivered at home in a select group of infants and could be an ideal option if parents are able to return with their infants to the hospital maternity ward for daily follow-up. • It can be as effective as inpatient phototherapy and potentially helps in delivering family-centered care.

The Relationship of Liver and Pancreas Density With Chest Computed Tomography Score Progression and Laboratory Findings in Patients With COVID-19.

OBJECTIVE: Abdominal involvement of COVID-19 is a current issue. We aimed to evaluate hepatic and pancreatic density alterations on computed tomography (CT) and to analyze whether these alterations had a relationship with chest CT score and laboratory findings. METHODS: Patients with reverse transcription-polymerase chain reaction-confirmed COVID-19 from March 11, 2020, to February 6, 2021, were retrospectively analyzed. Patients were divided into nonprogressive and progressive groups according to their chest CT scores. Liver and pancreas density, and liver-to-spleen (L/S) ratio were calculated. Laboratory findings, medication, intensive care unit stay, and survival were noted. RESULTS: There were 51 patients in the nonprogressive group and 123 patients in the progressive group. The median (minimum to maximum) L/S value of the nonprogressive group was 1 (0.28-1.53) at admission and 1.06 (0.33-1.83) at follow-up ( P < 0.001). In the progressive group, the median L/S value was 1.08 (0.35-1.51) at admission and 0.92 (0.33-1.75) at follow-up ( P < 0.001). A significant difference was found between the 2 groups at admission and follow-up ( P = 0.010 and P < 0.001, respectively). Pancreatic density measured at follow-up was significantly lower in the progressive group ( P = 0.045). In the progressive group, aspartate aminotransferase, total bilirubin, creatinine, urea, C-reactive protein, D-dimer, and white blood cell values were higher; albumin and lymphocyte values were lower ( P < 0.05). CONCLUSIONS: Patients with COVID-19 with progressive CT scores may have a decrease in L/S values, and their pancreatic density is lower than nonprogressives. Aspartate aminotransferase, total bilirubin, creatinine, urea, C-reactive protein, D-dimer, and white blood cell values tend to be higher in patients with a high chest CT score.

[Characteristics of liver function changes in 111 elderly patients with COVID-19 pneumonia].

Objective: To retrospectively analyze the characteristics and influencing factors of liver function changes in 111 elderly patients with COVID-19 pneumonia. Methods: 111 elderly patients with COVID-19 admitted to the Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 5 to March 3, 2020 were enrolled. According to the severity of disease and liver function condition, they were divided into severe group (n=40), normal group (n=71), abnormal liver function group (n=86) and normal liver function group (n=25). The indexes related to liver function changes [total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT)] and related influencing factors were analyzed. Results: Among 111 cases, 86 (77.5%) had abnormal liver function of varying degrees, and 28 (25.2%) had liver injury. The abnormal rates of TBil, AST, ALP and GGT were significantly higher in the severe group than normal group (P<0.05). There were no significant differences in age, ribavirin, glucocorticoid and the application of lopinavir-ritonavir tablets between the abnormal liver function and the normal group (P>0.05). The proportion of male was significantly higher in the abnormal liver function than normal liver function group (P<0.05). Conclusion: Elderly COVID-19 patients have a higher proportion of abnormal liver function, and patients in the severe group are more likely to have higher level of TB, AST, ALP and GGT. The abnormal liver function may be related to the direct viral infection of the liver and the inflammatory immune response of the body after infection in elderly patients.

Surface plasmon-enhanced fluorescence and surface-enhanced Raman scattering dual-readout chip constructed with silver nanowires: Label-free clinical detection of direct-bilirubin.

It has been found that the direct/total bilirubin ratio (D/T-BIL) is related to the survival rate of COVID-19 pneumonia. The presence of an excessive amount of bilirubin in human blood also causes liver and neurological damage, leading to death. Therefore, upon considering the adverse impact of the presence of excessive bilirubin in human blood, it has become highly imperative to detect bilirubin in a fast and label-free manner. Herein, we designed and constructed a random-crossed-woodpile nanostructure from silver nanowires to form a 3-dimensional plasmonic hotspot-rich (3D-PHS) nanostructure and successfully used it to detect direct bilirubin (D-BIL) in human blood in a label-free manner. The 3D-PHS nanochip provides rich spatial hot spots that are simultaneously responsive to SERS and SPEF effects and consequently, successfully used to measure and characterize D-BIL with a detection limit of ∼10 nM, requiring only 10µL of human serum for rapid screening, which is the first time D-BIL has been detected in a clinically relevant range. This demonstrates a simple, label-free, pretreatment-free potential biosensing technology that can be used in health care units, and further, in the efficient detection of point-of-care testing with a portable spectrometer.

Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: A higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose-response relationship between ketamine and bilirubin levels. METHODS: Post hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure-effect relationship between ketamine infusion and total bilirubin levels. RESULTS: Two-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9-2.0] mg/kg/h for 9 [4-18] days. The mixed-effects model revealed a positively correlated infusion duration-effect as well as dose-effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3-7.8] (p = 0.01). CONCLUSIONS: A causally plausible, dose-effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients.

Age-adjusted mortality and predictive value of liver chemistries in a Viennese cohort of COVID-19 patients.

BACKGROUND AND AIMS: The coronavirus disease of 2019 (COVID-19) causes considerable mortality worldwide. We aimed to investigate the frequency and predictive role of abnormal liver chemistries in different age groups. METHODS: Patients with positive severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) test between 03/2020-07/2021 at the Vienna General Hospital were included. Patients were stratified for age: 18-39 vs. 40-69 vs. ≥70 years (y). Aspartate aminotransferase (AST), alanine-aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) were recorded. RESULTS: 900 patients (18-39 years: 32.2%, 40-69 years: 39.7%, ≥70 years: 28.1%) were included. Number of comorbidities, median D-dimer and C-reactive protein increased with age. During COVID-19, AST/ALT and ALP/GGT levels significantly increased. Elevated hepatocellular transaminases (AST/ALT) and cholestasis parameters (ALP/GGT/BIL) were observed in 40.3% (n  = 262/650) and 45.0% (n  = 287/638) of patients respectively. Liver-related mortality was highest among patients with pre-existing decompensated liver disease (28.6%, p < .001). 1.7% of patients without pre-existing liver disease died of liver-related causes, that is consequences of hepatic dysfunction or acute liver failure. Importantly, COVID-19-associated liver injury (16.0%, p < .001), abnormal liver chemistries and liver-related mortality (6.5%, p < .001) were most frequent among 40-69 years old patients. Elevated AST and BIL after the first positive SARS-CoV-2 PCR independently predicted mortality in the overall cohort and in 40-69 years old patients. CONCLUSIONS: Almost half of the COVID-19 patients exhibit abnormal hepatocellular and cholestasis-related liver chemistries with 40-69 years old patients being at particularly high risk for COVID-19-related liver injury and liver-related mortality. Elevated AST and BIL after SARS-CoV-2 infection are independent predictors of mortality, especially in patients aged 40-69 years.

Update on Phototherapy and Childhood Cancer in a Northern California Cohort.

OBJECTIVES: We aimed to reassess the relationship between phototherapy and cancer in an extended version of a previous cohort and to replicate a report from Quebec of increased cancer risk after phototherapy beginning at age 4 years. METHODS: This cohort study included 139 100 children born at ≥35 weeks' gestation from 1995 to 2017, followed through March 16, 2019, in Kaiser Permanente Northern California hospitals who had a qualifying bilirubin level from -3 mg/dL to +4.9 mg/dL from the American Academy of Pediatrics phototherapy threshold; an additional 40 780 children and 5 years of follow-up from our previous report. The exposure was inpatient phototherapy (yes or no), and the outcomes were various types of childhood cancer. We used Cox proportional hazard models, controlling for propensity-score quintiles, and allowed for time-dependent exposure effects to assess for the risk of cancer after a latent period. RESULTS: Over a mean (SD) follow-up of 8.2 (5.7) years, the crude incidence of cancer per 100 000 person-years was 25.1 among those exposed to phototherapy and 19.2 among those not exposed (233 cases of cancer). After propensity adjustment, phototherapy was not associated with any cancer (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 0.83-1.54), hematopoietic cancer (HR: 1.17, 95% CI: 0.74-1.83), or solid tumors (HR: 1.01, 95% CI: 0.65-1.58). We also found no association with cancer diagnoses at age ≥4 years. CONCLUSIONS: We did not confirm previous, concerning associations between phototherapy and adjusted risk of any cancer, nonlymphocytic leukemia, or brain and/or central nervous systems tumors in later childhood.