Serum glucose, lactate dehydrogenase and hypertension are mediators of the effect of body mass index on severity of COVID-19.

Background: COVID-19 has a broad clinical spectrum. We investigated the role of serum markers measured on admission on severity as assessed at discharge and investigated those which relate to the effect of BMI on severity. Methods: Clinical and laboratory data from 610 COVID-19 cases hospitalized in the province of Zheijang, China were investigated as risk factors for severe COVID-19 (assessed by respiratory distress) compared to mild or common forms using logistic regression methods. Biochemical markers were correlated with severity using spearman correlations, and a ROC analysis was used to determine the individual contribution of each of the biochemical markers on severity. We carried out formal mediation analyses to investigate the extent of the effect of body mass index (BMI) on COVID-19 severity mediated by hypertension, glycemia, Lactose Dehydrogenase (LDH) at the time of hospitalization and C-Reactive Protein levels (CRP), in units of standard deviations. Results: The individual markers measured on admission contributing most strongly to prediction of COVID-19 severity as assessed at discharge were LDH, CRP and glucose. The proportion of the effect of BMI on severity of COVID-19 mediated by CRP, glycemia or hypertension, we find that glucose mediated 79% (p < .0001), LDH mediated 78% (p < .0001), hypertension mediated 66% (p < .0001); however, only 44% (p < .005) was mediated by systemic inflammation (CRP). Conclusion: Our data indicate that a larger proportion of the effect of BMI on severity of COVID-19 is mediated by glycemia and LDH levels whereas less than half of it is mediated by systemic inflammation.

Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients.

BACKGROUND AND AIMS: Anti-tuberculosis drugs remain as an important cause of drug-induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti-tuberculosis DILI (ATDILI). METHODS: Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis. RESULTS: In the derivation cohort (n = 3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3 months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR = 1.014, 95% CI: 1.005-1.023), baseline ALT (HR = 1.014, 95% CI: 1.003-1.024), haemoglobin (HR = 1.011, 95% CI: 1.002-1.020) and HBsAg positivity (HR = 1.516, 95% CI: 1.004-2.290) were independent risk factors for DILI. In the second cohort (n = 1497) of which 85 (5.7%) developed ATDILI. Age (HR = 1.029, 95% CI: 1.003-1.056), baseline AST (HR = 1.036, 95% CI: 1.010-1.062), previous TB treatment (HR = 3.894, 95% CI: 1.304-11.625) and active drinking (HR = 3.624, 95% CI: 1.147-11.454) were risk factors for developing jaundice. CONCLUSION: Elevation of ALT of ≥3 × ULN during anti-TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients.

Role of Drugs Used for Chronic Disease Management on Susceptibility and Severity of COVID-19: A Large Case-Control Study.

This study aimed to investigate whether specific medications used in the treatment chronic diseases affected either the development and/ or severity of coronavirus disease 2019 (COVID-19) in a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zhejiang, China. Using a cohort of 578 COVID-19 cases and 48,667 population-based controls from Zhejiang, China, we tested the role of usage of cardiovascular, antidiabetic, and other medications on risk and severity of COVID-19. Analyses were adjusted for age, sex, and body mass index and for presence of relevant comorbidities. Individuals with hypertension taking calcium channel blockers had significantly increased risk (odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.2-2.3) of manifesting symptoms of COVID-19, whereas those taking angiotensin receptor blockers and diuretics had significantly lower disease risk (OR = 0.22, 95% CI 0.15-0.30 and OR = 0.30, 95% CI 0.19-0.58, respectively). Among those with type 2 diabetes, dipeptidyl peptidase-4 inhibitors (OR = 6.02, 95% CI 2.3-15.5) and insulin (OR = 2.71, 95% CI 1.6-5.5) were more and glucosidase inhibitors were less prevalent (OR = 0.11, 95% CI 0.1-0.3) among with patients with COVID-19. Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but, not its severity.

[Liver histopathological features influencing HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B responding to Peg-IFN treatment].

OBJECTIVE: To investigate the therapeutic efficiency of antiviral treatment with pegylated-interferon (Peg-IFN) for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) and to explore whether liver histopathological features or other factors influence the HBeAg seroconversion treatment response. METHODS: Eighty HBeAg-positive CHB patients with diagnosis confirmed by liver puncture were treated with Peg-IFN(2a or 2b)body weight dose, once weekly). At treatment week 48, the rate of HBeAg seroconversion was determined and used to analyze the influence of liver histopathological features (liver biopsy assessment of: inflammation, graded G0 to G4; fibrosis stage, graded S0 to S4), sex, age, differential levels (pre-treatment baseline vs. week 48 post-treatment) of serum alanine transferase (ALT), and HBV DNA, by binary logistic analysis. RESULTS: At week 48, the overall rate of HBeAg seroconversion was 30.0%. The rate of HBeAg seroconversion gradually advanced with increased liver inflammation (X2 = 8.435, P = 0.015): 9.09% of the 22 patients with G1; 31.58% of the 38 patients with G2; 47.30% of the 19 patients with G3; the one patient with G4. In contrast, the rate of HBeAg seroconversion showed a much weaker association with liver fibrosis (X2 = 5.917, P = 0.116). Only baseline HBeAg level, and no other baseline index, was significantly different between the patients who achieved HBeAg seroconversion and those who did not. Liver inflammation and baseline HBeAg level were identified as influencing factors of HbeAg seroconversion in response to Peg-IFN treatment. CONCLUSION: Peg-IFN therapy induces a higher rate of HBeAg seroconversion in HBeAg-positive CHB patients with severe liver inflammation; histological analysis of pre-treatment liver biopsies may help to identify patients most likely to benefit from the antiviral regimen.