Impact of directly acting-antivirals and behavior change due to the COVID 19 pandemic on HCV micro-elimination in MSM in Germany (preprint)

Introduction Directly-acting antivirals (DAA) are the cornerstone to reach HCV elimination. In men who have sex with men (MSM) with HIV coinfection, recently acquired HCV infection (RAHCV) is common. Sexual practices and reinfection rates may hamper micro-elimination despite high treatment rates. Methods The cohort included MSM with RAHCV from 2014 to 2021. The patients’ demographic, clinical, behavioral, and laboratory data were documented, as well as treatment and reinfection outcomes.  Results 237 men with RAHCV were included, 216 (91%) were PLWH. Median age was 46 years (IQR: 39–52), median CD4 count was 660/mm3 (IQR: 527–835). The annual incidence of RAHCV remained between 0.28% and 0.43%, but dropped to 0.02% in 2021 during the onset of the COVID-pandemic almost reaching micro-elimination. The reinfection incidence was 15.5 per 100 patient-years (95%-CI: 12.6-18.8), reinfection was associated with use of crystal methamphetamine (p=0.032) and ketamine (p=0.042). 31.3% had multiple reinfections, four reinfections occurred in PrEP users. Conclusions High treatment and cure rates did not lead to HCV elimination. A change in sexual behavior, potentially imposed by COVID-19 restrictions, led to micro-elimination in the NoCo cohort. As RAHCV is prevalent in HIV-positive and -negative MSM, surveillance is necessary to consolidate elimination goals.

Efficacy and Safety of Dapagliflozin versus Liraglutide in Patients with Overweight or Obesity and Type 2 Diabetes Mellitus: A Randomised Controlled Clinical Trial in Tianjin, China

Objective We aimed to clarify the efficacy of dapagliflozin versus liraglutide in patients with overweight or obesity and type 2 diabetes mellitus (T2DM) at the beginning of the coronavirus disease 2019 (COVID-19) pandemic. Methods T2DM patients with overweight or obesity who visited the Metabolic Disease Management Center at Tianjin Fourth Central Hospital from October 2019 to January 2020 were recruited and randomised to receive dapagliflozin or liraglutide for 24 weeks. Changes in blood glucose and lipid levels, blood pressure, and body weight, as well as the occurrence of hypoglycaemia and other adverse events, were compared. Results 309 patients completed the study (143 in liraglutide group and 166 in dapagliflozin group). After 24 weeks, HbA1c, fasting blood glucose (FPG), and 2 h postprandial blood glucose (2hPG) levels significantly decreased from 8.80% ± 1.41% to 7.02% ± 1.05%, 10.41 ± 3.13 to 7.59 ± 2.16 mmol/L, and 17.90 ± 4.39 to 10.12 ± 2.47 mmol/L, respectively, in the dapagliflozin group, and from 8.92% ± 1.49% to 6.78% ± 1.00%, 10.04 ± 2.99 to 7.20 ± 1.63 mmol/L, and 17.30 ± 4.39 to 10.13 ± 4.15 mmol/L, respectively, in the liraglutide group. Changes in HbA1c, FPG, and 2hPG levels between groups were not significantly different. Systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) level significantly decreased from 144.1 ± 19.1 to 139.7 ± 16.2 mmHg (p = 0.001) and from 3.21 ± 0.94 to 2.98 ± 0.89 mmol/L (p = 0.014), respectively, in the dapagliflozin group. After COVID-19 outbreak, the number of patients taking sleep-promoting drugs increased from 4.9% to 9.4% (p = 0.029). Conclusions Liraglutide and dapagliflozin had strong hypoglycaemic effects in patients with overweight or obesity and T2DM at the beginning of the COVID-19 pandemic. Dapagliflozin may be beneficial in improving SBP and LDL-C levels;however, further research is warranted.

Perceptions, Barriers and Enablers on Salt Reduction in Malaysia Out of Home Sectors (MyOH): From Point of View of the Policy Makers and Food Industries (preprint)

Background: High salt intake is a major cause of hypertension and cardiovascular diseases. The out-of-home sectors have been identified as one of the contributors of high salt intake in the population. The National Salt Reduction Policy of Malaysia was initiated in 2015; however, out-of-home sectors are yet to be emphasized and perception by policy makers and the food industries towards salt reduction are yet unknown. This study aimed to determine the perceptions, barriers and enablers towards salt reduction in the out-of-home sector in Malaysia, as well as among the policy makers and the food industries. Methods: : This is a qualitative study via semi-structured in-depth interview (IDI) and focus group discussion (FGD) involving several stakeholders consisting of policy makers from five ministries, five non-government organizations (NGOs), food science/food technology researchers from five regions (West, North, East, South of Peninsular and East Malaysia/ Borneo) as well as the food industries. The IDI and FGD sessions were recorded, transcribed verbatim and analyzed thematically using Nvivo software version 12. Result: All participants agreed that salt intake in Malaysia is high and leads to hypertension and cardiovascular diseases. Lack of awareness, poor eating culture and behavior, and frequent eating out were among the causes of high salt intake. Awareness campaign and education, sodium content labelling and product reformulation were strategies that have been implemented by the government; whilst for the food industries, some of them have tried to reduce salt and labelled the sodium content on their food products. However, there were several barriers including perceived poor consumer acceptance, lack of knowledge and resources, challenges in reformulation, as well as unavailability of guidelines and salt targets. Hence, several enablers have been suggested, which include prioritizing salt reduction strategy, creating more awareness, collaboration and engagement, research and technology particularly for reformulation and shelf-life stability, incentives, and salt tax. Conclusion: Salt reduction efforts of out-of-home sector in Malaysia could be achieved through several measures or enablers that can overcome the barriers currently faced by the stakeholders, especially the policy makers, food industries and the consumers themselves. This study will benefit the policy makers to improve the salt reduction policy of out-of-home sectors and highlight the concerns among the food industries on the policy.

Systems and Longitudinal Analysis Reveals Early-Stage and Highly Coordinated Immune Responses in Mild COVID-19 Patients (preprint)

While immunopathology has been widely studied in severe COVID-19 patients, immunoprotective factors in non-hospitalized patients have remained largely elusive. We systematically analyzed 484 peripheral immune cell signatures, various serological parameters and TCR repertoire in a longitudinal cohort of 63 mild and 15 hospitalized patients versus 14 asymptomatic and 26 control individuals. Within three days following PCR diagnosis, we observed coordinated responses of CD4 and CD8 T cells, various antigen presenting cells and antibody-secreting cells in mild, but not hospitalized COVID-19 patients. This early-stage SARS-CoV-2-specific response was predominantly characterized by substantially expanded clonotypes of CD4 and less of CD8 T cells. The early-stage responses of T cells and dendritic cells were highly predictive for later seroconversion and protective antibody levels after three weeks in mild non-hospitalized, but not in hospitalized patients. Our systemic analysis reveals the first full picture and early-stage trajectory of highly-coordinated immune responses in mild COVID-19 patients.Funding: The Predi-COVID study is supported by the Luxembourg National Research Fund (FNR) (Predi-COVID, 14716273) and the André Losch Fondation. We also highly appreciate the expert support of the IBBL processing and biorepository teams. F.Q.H. was partially supported by FNR CORE programme grant (CORE/14/BM/8231540/GeDES), FNR AFR- RIKEN bilateral programme (TregBAR, 11228353, F.Q.H. and M.O.) and PRIDE programme grants (PRIDE/11012546/NEXTIMMUNE and PRIDE/10907093/CRITICS). C.H. was partially supported by the FNR fast-track call COVID-19/2020-1/14703957/COV-Immun.Declaration of Interests: The authors declare that they have no conflict of interest.Ethics Approval Statement: All collections were performed with approval from relevant ethic organizations. Informed consent was obtained from each participant prior to collection. The blood sampling was performed by nurses from Clinical and Epidemiological Investigation Centre (CIEC) of LIH.

SARS-CoV-2 Infection Causes Dopaminergic Neuron Senescence (preprint)

COVID-19 patients commonly present with neurological signs of central nervous system (CNS) and/or peripheral nervous system dysfunction. However, which neural cells are permissive to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been controversial. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively permissive to SARS-CoV-2 infection both in vitro and upon transplantation in vivo, and that SARS-CoV-2 infection triggers a DA neuron inflammatory and cellular senescence response. A high-throughput screen in hPSC-derived DA neurons identified several FDA approved drugs, including riluzole, metformin, and imatinib, that can rescue the cellular senescence phenotype and prevent SARS-CoV-2 infection. RNA-seq analysis of human ventral midbrain tissue from COVID-19 patients, using formalin-fixed paraffin-embedded autopsy samples, confirmed the induction of an inflammatory and cellular senescence signature and identified low levels of SARS-CoV-2 transcripts. Our findings demonstrate that hPSC-derived DA neurons can serve as a disease model to study neuronal susceptibility to SARS-CoV-2 and to identify candidate neuroprotective drugs for COVID-19 patients. The susceptibility of hPSC-derived DA neurons to SARS-CoV-2 and the observed inflammatory and senescence transcriptional responses suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.