Background Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk irrespective of conventional risk factors. The role of gut-liver interaction is implicated in its development. We investigated the effects of VSL#3® probiotic supplementation on biomarkers of cardiovascular risk and liver injury in patients with NAFLD. Methods A randomised, double-blinded, placebo-controlled, proof-of-concept study was undertaken. Patients with NAFLD were randomly allocated to take 2 sachets VSL#3® probiotic or placebo twice daily for 10 weeks. Measurements of endothelial function (digital photoplethysmography, sVCAM-1 and cGMP), oxidative stress (glutathione ratio and LHP), inflammation (hsCRP), insulin resistance (HOMA-IR) and liver injury [transaminases, fibrosis risk score and acoustic structure quantification (ASQ)] were undertaken before and after intervention. Difference in baseline characteristics between the treatment groups was analysed using independent t-test or Mann Whitney U test for non-parametric data. Independent t-test was used to compare the outcomes at the end of the study between the two treatment groups. Wilcoxon Signed Rank test was used to determine the difference in fibrosis risk scores before and after treatment. Spearman’s correlation was used to determine any association between cardiovascular and hepatic markers at baseline. Results Thirty-five patients completed the study (28 males and 7 females) with a mean age of 57 ± 8 years, body mass index of 32.6 ± 5.0 kg/m2 and a relatively short duration of NAFLD (median duration 0.3 IQR 2.0 years). No significant difference was observed in biomarkers of cardiovascular risk and liver injury following VSL#3® supplementation. Significant correlations were noted between sVCAM-1 and hsCRP (rho = 0.392, p = 0.01), and HOMA-IR and AST (rho = 0.489, p < 0.01) at baseline. Conclusions This is the first study to evaluate the effect of VSL#3® on ASQ in patients with NAFLD. VSL#3® did not significantly improve markers of cardiovascular risk and liver injury in patients with NAFLD. However, the study supports an association between endothelial dysfunction and inflammation in patients with NAFLD and suggests that NAFLD is linked with insulin resistance. Trial registration: ISRCTN05474560 (https://doi.org/10.1186/ISRCTN05474560) Registered 9 August 2012 (retrospectively registered).

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We read with interest the article by Morrison et al. on acute hypertriglyceridemia secondary to tocilizumab in patients with severe coronavirus disease . 1 One patient also had pancreatitis, a dreaded complication of hypertriglyceridemia.Both patients were already on lopinavir/ritonavir before tocilizumab (added day 9 and 13) was added. Propofol was briefly used.We recently had two out of 47 patients with moderate/severe COVID-19 who were treated with lopinavir/ritonavir and developed significant hypertriglyceridemia resulting in lipemic serum. The first patient (51-year-old man) with undiagnosed stage II chronic kidney disease (estimated glomerular filtration rate 61.12 mL/min) and no history of lipid disorder or diabetes mellitus was started on lopinavir/ritonavir (400 and 100 mg twice daily for 14 days) on the 10th day of admission. Blood serum became lipemic on the 10th day of treatment (Figure 1). Serum triglyceride levels ranged between 921.2 and 1071.7 mg/dL (normal range <150 mg/dL). His serum amylase was normal. He was started on bezafibrate and the lipemic serum settled. The second patient (45-year-old man) with hypertension, dyslipidemia and uncontrolled diabetes mellitus was started lopinavir/ritonavir monotherapy on the 4th day of admission. His blood was reported to be lipemic on the 11th day of treatment despite being on atorvastatin. Fortunately he completed treatment without any complications. Follow-up showed no recurrence of lipemic serum in both patients. The second patient had risk factors for hypertriglyceridemia.Lopinavir/ritonavir is known to be associated with lipid abnormality, 2,3 more so than tocilizumab. One study showed that at 12 weeks of treatment of lopinavir/ritonavir in patients with human immunodefieciency virus, small but significant increase from baseline in the fasting total cholesterol and triglyceride was observed. 2 Our patients developed lipemic serum within 2 weeks of treatment. In Morrison's cases, it is possible that the lopinavir/ ritonavir had contributed to or even caused the hypertriglyceridemia. Therefore it is important for clinicians to be aware and monitor for complications given that the COVID-19 pandemic will continue and these two medications continue to be used until better treatment options become available.

Objective: Bacterial co-infections in cases of coronavirus disease 2019 (COVID-19) can lead to less favourable outcomes. The aim of this study was to determine the prevalence of primary bacterial co-infections among patients with COVID-19 in Brunei Darussalam. Methods: Seventy-one of 180 patients admitted to the National Isolation Centre between 9 March 2020 and 4 February 2021 were screened for primary bacterial co-infection (infection occurring <48 h from admission). We compared patients with a primary bacterial co-infection to those without. Results: Of the 71 screened patients, 8 (11.2%) had a primary bacterial co-infection (sputum 37.5% [6/16], blood 2.8% [1/36], urine 1.7% [1/60]), for a period prevalence rate of 4.4% (respiratory tract infection 3.3% [6/180], bloodstream 0.6% [1/180], urine 0.6% [1/180]) among all COVID-19 patients. Older age, presence of comorbidity, symptoms at admission (fever, dyspnoea, nausea/vomiting), abnormal chest X-ray (CXR) and more severe COVID-19 (P < 0.05) were associated with primary bacterial co-infection. Primary bacterial co-infection was also associated with development of secondary infection and death (all P < 0.05). Only one patient with primary bacterial co-infection died (methicillin-sensitive Staphylococcus aureus septicaemia and multiorgan failure). Conclusions: Our study showed that primary bacterial co-infection affected 4.4% of patients with COVID-19 in Brunei Darussalam. Older age, presence of comorbidity, symptoms and abnormal CXR at admission and more severe disease were associated with a primary bacterial co-infection. Lower respiratory tract infection was the most common co-infection.