Perceived risk of infection and death from COVID-19 among community members of low- and middle-income countries: A cross-sectional study [version 1; peer review: awaiting peer review]

Background: Risk perceptions of coronavirus disease 2019 (COVID-19) are considered important as they impact community health behaviors. The aim of this study was to determine the perceived risk of infection and death due to COVID-19 and to assess the factors associated with such risk perceptions among community members in low- and middle-income countries (LMICs) in Africa, Asia, and South America. Methods: An online cross-sectional study was conducted in 10 LMICs in Africa, Asia, and South America from February to May 2021. A questionnaire was utilized to assess the perceived risk of infection and death from COVID-19 and its plausible determinants. A logistic regression model was used to identify the factors associated with such risk perceptions. Results: A total of 1,646 responses were included in the analysis of the perceived risk of becoming infected and dying from COVID-19. Our data suggested that 36.4% of participants had a high perceived risk of COVID-19 infection, while only 22.4% had a perceived risk of dying from COVID-19. Being a woman, working in healthcare-related sectors, contracting pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, as well as seeing or reading about individuals infected with COVID-19 on social media or TV were all associated with a higher perceived risk of becoming infected with COVID-19. In addition, being a woman, elderly, having heart disease and pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, and seeing or reading about individuals infected with COVID-19 on social media or TV had a higher perceived risk of dying from COVID-19. Conclusions: The perceived risk of infection and death due to COVID-19 are relatively low among respondents; this suggests the need to conduct health campaigns to disseminate knowledge and information on the ongoing pandemic

Psychotherapy co-provision by peers and healthcare workers for substance use disorders in Indonesia

For many decades, the infringement of the autonomy of people who use drugs has permeated many levels in Indonesia. Drug use has been disparaged as a moral issue, marginalised by the public, and criminalised by authoritative governing bodies. For people who develop substance use disorders (SUD), healthcare services also commonly enact compulsory treatment that disregards clients' autonomy seeking help. However, in recent decades, there has been a growing movement of people who use drugs to regain autonomy in attaining health rights. In this chapter, we first describe the lack of autonomy experienced by people with SUD, particularly in regard to their health rights. We then outline roles of peer counsellors through direct observations of psychotherapy co-provision by both peer counsellors and healthcare workers (HCWs) in a novel SUD psychotherapy module we designed ourselves, termed Indonesia Drug Addiction Relapse Prevention Program (Indo-DARPP). We observed various peer counsellors' roles, including diversification of the knowledge taught in the sessions. We also report the preliminary results of the pilot study of Indo-DARPP, which showed that participants who received Indo-DARPP for three months reported good acceptability and usability. Finally, the design of a randomised controlled trial for Indo-DARPP evaluation is presented. Ultimately, we hope to present insights reinforcing peer involvement into formal SUD care, with the aim of helping people with SUD to regain their autonomy in healthcare

CRISPR-Cas9 as a curative drug for chronic viral infection

The innovation of CRISPR-Cas9 has single-handedly revolutionized biotechnology by enabling efficient and specific cutting of DNA. CRISPR-Cas9 approaches are promising not only to targetthe human genome but also DNA of pathogenic viruses, which coincidentally is the canonical function in its bacterial origin. Since 2014, a myriad of studies has proven the efficacy of CRISPR-Cas9 treatment to cleave viral DNA intermediates in vitro. One of the most widely targeted is theproviral genome of human immunodeficiency virus type-1 (HIV-1). The disease burden of HIV-1 is massive—the infection is incurable and has remained a pandemic for over four decades. Integrated HIV-1 provirus inside the human genome causes viral persistence inside latent cellular reservoirs, eluding antiretroviral therapy (ART) and sterilizing cure. Specific targeting anddisruption of HIV-1 proviral genome is necessary to achieve viral clearance, which can be achieved with CRISPR-Cas9. Here, we review the features and up to date evidence of CRISPRCas9 to target the HIV-1 proviral genome and suppress viral replication. We will also discuss potential CRISPR/Cas9 delivery methods in vivo, combination with other gene editing modalities and other therapeutic approaches, to bring gene editing-based HIV-1 cure closer into clinical use

Multiplexed tat-Targeting CRISPR-Cas9 Protects T Cells from Acute HIV-1 Infection with Inhibition of Viral Escape

HIV-1 cure strategy by means of proviral knock-out using CRISPR-Cas9 has been hampered by the emergence of viral resistance against the targeting guide RNA (gRNA). Here, we proposed multiple, concentrated gRNA attacks against HIV-1 regulatory genes to block viral escape. The T cell line were transduced with single and multiple gRNAs targeting HIV-1 tat and rev using lentiviral-based CRISPR-Cas9, followed by replicative HIV-1NL4-3 challenge in vitro. Viral p24 rebound was observed for almost all gRNAs, but multiplexing three tat-targeting gRNAs maintained p24 suppression and cell viability, indicating the inhibition of viral escape. Multiplexed tat gRNAs inhibited acute viral replication in the 2nd round of infection, abolished cell-associated transmission to unprotected T cells, and maintained protection through 45 days, post-infection (dpi) after a higher dose of HIV-1 infection. Finally, we describe here for the first time the assembly of all-in-one lentiviral vectors containing three and six gRNAs targeting tat and rev. A single-vector tat-targeting construct shows non-inferiority to the tat-targeting multi-vector in low-dose HIV-1 infection. We conclude that Cas9-induced, DNA repair-mediated mutations in tat are sufficiently deleterious and deplete HIV-1 fitness, and multiplexed disruption of tat further limits the possibility of an escape mutant arising, thus elevating the potential of CRISPR-Cas9 to achieve a long-term HIV-1 cure

Relapse prevention group therapy via video-conferencing for substance use disorder: protocol for a multicentre randomised controlled trial in Indonesia

[Background] Substance use disorder (SUD) is a leading contributor to the global burden of disease. In Indonesia, the availability of formal treatment for SUD falls short of the targeted coverage. A standardised therapeutic option for SUD with potential for widespread implementation is required, yet evidence-based data in the country are scarce. In this study, we developed a cognitive behavioural therapy (CBT)-based group telemedicine model and will investigate effectiveness and implementability in a multicentre randomised controlled trial. [Methods] A total of 220 participants will be recruited from the social networks of eight sites in Indonesia: three hospitals, two primary healthcare centres and three rehabilitation centres. The intervention arm will participate in a relapse prevention programme called the Indonesia Drug Addiction Relapse Prevention Programme (Indo-DARPP), a newly developed 12-week module based on CBT and motivational interviewing constructed in the Indonesian context. The programme will be delivered by a healthcare provider and a peer counsellor in a group therapy setting via video-conferencing, as a supplement to participants’ usual treatments. The control arm will continue treatment as usual. The primary outcome will be the percentage increase in days of abstinence from the primarily used substance in the past 28 days. Secondary outcomes will include addiction severity, quality of life, motivation to change, psychiatric symptoms, cognitive function, coping, and internalised stigma. Assessments will be performed at baseline (week 0), post-treatment (week 13), and 3 and 12 months post-treatment completion (weeks 24 and 60). Retention, participant satisfaction, and cost-effectiveness will be assessed as the implementation outcomes. [Ethics and dissemination] The study protocol was reviewed and approved by the Ethics Committees of Universitas Indonesia and Kyoto University. The results will be disseminated via academic journals and international conferences. Depending on trial outcomes, the treatment programme will be advocated for adoption as a formal healthcare-based approach for SUD

COVID-19 Vaccines: Current Status and Implication for Use in Indonesia

The coronavirus disease 2019 (COVID-19) has inflicted catastrophic damages in public health, economic and social stability—putting life globally on hold in 2020 and presumably a year more. Indonesia bears a heavy burden of the pandemic, counting the highest case prevalence and fatality rate in all of Southeast Asia. One hope remains in the groundbreaking universal effort in search of a vaccine against the causative virus SARS-CoV-2, which has shown success unparalleled in human vaccine development thus far. An array of modalities including novel techniques are being utilized as vaccine platforms, with the closest to phase III clinical trial completion being mRNA (manufactured by Moderna and BioNTech/Pfizer), inactivated virus (Sinovac, Sinopharm), viral vector (Oxford/AstraZeneca, Gamaleya, Janssen/Johnson&Johnson, CanSino), and protein subunit (Novavax). The vaccine produced by BioNTech/Pfizer has been deployed to the public as the first ever licensed COVID-19 vaccine. In this review, we will review all of these modalities on their safety and immunogenicity, phase II/III trial results of the nine vaccine candidates and current situation as of 29 December 2020, as well as the implication for use and distribution in Indonesia. COVID-19 vaccine progress, however, is moving exceedingly fast and new advances are unfolding on a daily basis, to which we hope an update to this review can be published in early 2021

Persistence of long COVID symptoms in COVID-19 survivors worldwide and its potential pathogenesis - A systematic review and meta-analysis

The study sought to determine the prevalence of persistent long COVID symptoms such as anxiety, depression, dizziness, chest pain, sleep difficulty, palpitations, weight loss, and hair loss among coronavirus disease 2019 (COVID-19) survivors worldwide and to discuss the potential pathogeneses. Potential studies were searched in three databases (PubMed, Scopus, and Web of Science) as of January 30, 2021. Data on study characteristics, patient characteristics during the follow-up, the number of patients with persistent long COVID symptoms and total COVID-19 survivors were collected according to PRISMA guidelines. To assess the quality of studies, the Newcastle-Ottawa scale was used. The estimated prevalence of each long COVID symptom and the association between COVID-19 severity and the occurrence of prolonged symptoms was assessed, if appropriate. The global prevalence of prolonged anxiety was 15.76% (95%CI: 6.36%, 25.15%). Chest pain persisted in 10.36% (239/3,224) of COVID-19 patients (95%CI: 4.92%, 15.80%). Prolonged depression was found in 24 of 548 COVID-19 survivors with an estimated prevalence of 4.32% (95%CI: 2.62%, 6.03%) and dizziness was presented in 4.83% (118/2,219, 95%CI: 1.50%, 8.16%) after recovery. Hair loss was complained by 527 of 2,251 recovered patients (cumulative prevalence of 24.76%, 95%CI: 19.60%, 29.91%), while weight loss was identified in 37 cases among 452 COVID-19 survivors (8.19%, 95%CI: 5.66%, 10.71%). Prolonged palpitation was experienced by 19.38% (211/1,926) survivors with 95%CI: 2.40%, 41.16%. Sleep difficulty was found in 541 of 2,622 COVID-19 survivors (17.87%, 95%CI: 7.55%, 28.20%). The association between COVID-19 severity and the occurrence of persistent long COVID symptoms was not analyzed due to the lack of data. In conclusion, persistent psychological symptoms are frequently reported among COVID-19 survivors. Follow-up studies with a longer duration and larger population are warranted to assess the extent of prolonged symptoms and the quality of life of COVID-19 survivors. Despite various potential pathogeneses that have been hypothesized, a definitive mechanism is yet to be addressed

Persistence of long COVID symptoms in COVID-19 survivors worldwide and its potential pathogenesis - A systematic review and meta-analysis

The study sought to determine the prevalence of persistent long COVID symptoms such as anxiety, depression, dizziness, chest pain, sleep difficulty, palpitations, weight loss, and hair loss among coronavirus disease 2019 (COVID-19) survivors worldwide and to discuss the potential pathogeneses. Potential studies were searched in three databases (PubMed, Scopus, and Web of Science) as of January 30, 2021. Data on study characteristics, patient characteristics during the follow-up, the number of patients with persistent long COVID symptoms and total COVID-19 survivors were collected according to PRISMA guidelines. To assess the quality of studies, the Newcastle-Ottawa scale was used. The estimated prevalence of each long COVID symptom and the association between COVID-19 severity and the occurrence of prolonged symptoms was assessed, if appropriate. The global prevalence of prolonged anxiety was 15.76% (95%CI: 6.36%, 25.15%). Chest pain persisted in 10.36% (239/3,224) of COVID-19 patients (95%CI: 4.92%, 15.80%). Prolonged depression was found in 24 of 548 COVID-19 survivors with an estimated prevalence of 4.32% (95%CI: 2.62%, 6.03%) and dizziness was presented in 4.83% (118/2,219, 95%CI: 1.50%, 8.16%) after recovery. Hair loss was complained by 527 of 2,251 recovered patients (cumulative prevalence of 24.76%, 95%CI: 19.60%, 29.91%), while weight loss was identified in 37 cases among 452 COVID-19 survivors (8.19%, 95%CI: 5.66%, 10.71%). Prolonged palpitation was experienced by 19.38% (211/1,926) survivors with 95%CI: 2.40%, 41.16%. Sleep difficulty was found in 541 of 2,622 COVID-19 survivors (17.87%, 95%CI: 7.55%, 28.20%). The association between COVID-19 severity and the occurrence of persistent long COVID symptoms was not analyzed due to the lack of data. In conclusion, persistent psychological symptoms are frequently reported among COVID-19 survivors. Follow-up studies with a longer duration and larger population are warranted to assess the extent of prolonged symptoms and the quality of life of COVID-19 survivors. Despite various potential pathogeneses that have been hypothesized, a definitive mechanism is yet to be addressed