Immunological considerations for laboratory staff and COVID-19 biosafety

The vulnerability of healthcare and laboratory to potential infection by the SARS-CoV-2 virus has thus far been analysed through the lens of the acute phase of the pandemic, including remote-based work, as well as emergency settings that are different from routine healthcare operations. However, as lockdowns ease and activities return to an identifiable pre-pandemic routine, the safety considerations also require to shift accordingly. As laboratory workers are likely to continue being exposed to unidentified SARS-CoV-2 positive samples through routine blood collection and processing operations, COVID-19 might have to be re-considered as an occupational disease within this context. Additionally, as per many such occupational diseases, a surveillance system is implemented for the medium- and longer-term. This manuscript presents the views on the possible surveillance scenarios for laboratory staff, viewed from an immunological and biosafety perspective.

Immunological considerations for laboratory staff and COVID-19 biosafety.

The vulnerability of healthcare and laboratory to potential infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has thus far been analyzed through the lens of the acute phase of the pandemic, including remote-based work, as well as emergency settings that are different from routine healthcare operations. However, as lockdowns ease and activities return to an identifiable pre-pandemic routine, the safety considerations also require to shift accordingly. As laboratory workers are likely to continue being exposed to unidentified SARS-CoV-2 positive samples through routine blood collection and processing operations, coronavirus disease 2019 (COVID-19) might have to be re-considered as an occupational disease within this context. Additionally, as per many such occupational diseases, a surveillance system is implemented for the medium- and long-term. This manuscript presents the views on the possible surveillance scenarios for laboratory staff, viewed from an immunological and biosafety perspective.

Digital public health leadership in the global fight for health security.

The COVID-19 pandemic highlighted the need to prioritise mature digital health and data governance at both national and supranational levels to guarantee future health security. The Riyadh Declaration on Digital Health was a call to action to create the infrastructure needed to share effective digital health evidence-based practices and high-quality, real-time data locally and globally to provide actionable information to more health systems and countries. The declaration proposed nine key recommendations for data and digital health that need to be adopted by the global health community to address future pandemics and health threats. Here, we expand on each recommendation and provide an evidence-based roadmap for their implementation. This policy document serves as a resource and toolkit that all stakeholders in digital health and disaster preparedness can follow to develop digital infrastructure and protocols in readiness for future health threats through robust digital public health leadership.

Microbiota-derived psychedelics: Lessons from COVID-19.

Emil Kraepelin believed that dementia praecox, the disorder we now call schizophrenia, was caused by the brain being poisoned with toxins generated in other parts of the body, especially the mouth, intestine or genitals. In this regard, Kraepelin hinted at the microbiome and conceptualized microbial molecules as drivers of severe psychiatric illness. However, it was not until the coronavirus disease (COVID-19) pandemic that Kraepelin's paradigm gained traction, particularly because this virus was associated with both gut barrier disruption and new-onset psychosis.Likewise, despite numerous studies linking severe psychiatric illness to genomic damage and dysfunctional DNA repair, this pathogenetic mechanism was underappreciated before the COVID-19 pandemic. The use of the psychotomimetic anesthetic, ketamine, for treatment-resistant depression has reawakened the interest in endogenous serotonergic hallucinogens, especially tryptamine and N,N-dimethyltryptamine (DMT), which are beneficial for depression but associated with psychosis.In this editorial, we take a closer look at the role of the microbiome in psychopathology, attempting to answer 2 questions:1. Why may psychosis-predisposing serotonergic hallucinogens alleviate depression?2. Are microbiota-derived psychedelics part of an inbuilt antidepressant system similar to endogenous opioids?

The Use of Digital Technology for COVID-19 Detection and Response Management in Indonesia: Mixed Methods Study.

BACKGROUND: The COVID-19 pandemic has triggered a greater use of digital technologies as part of the health care response in many countries, including Indonesia. It is the world's fourth-most populous nation and Southeast Asia's most populous country, with considerable public health pressures. OBJECTIVE: The aim of our study is to identify and review the use of digital health technologies in COVID-19 detection and response management in Indonesia. METHODS: We conducted a literature review of publicly accessible information in technical and scientific journals, as well as news articles from September 2020 to August 2022 to identify the use case examples of digital technologies in COVID-19 detection and response management in Indonesia. RESULTS: The results are presented in 3 groups, namely (1) big data, artificial intelligence, and machine learning (technologies for the collection or processing of data); (2) health care system technologies (acting at the public health level); and (3) COVID-19 screening, population treatment, and prevention population treatment (acting at the individual patient level). Some of these technologies are the result of government-academia-private sector collaborations during the pandemic, which represent a novel, multisectoral practice in Indonesia within the public health care ecosystem. A small number of the identified technologies pre-existed the pandemic but were upgraded and adapted for current needs. CONCLUSIONS: Digital technologies were developed in Indonesia during the pandemic, with a direct impact on supporting COVID-19 management, detection, response, and treatment. They addressed different areas of the technological spectrum and with different levels of adoption, ranging from local to regional to national. The indirect impact of this wave of technological creation and use is a strong foundation for fostering future multisectoral collaboration within the national health care system of Indonesia.

Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies

Similar to previous pandemics, COVID-19 has been succeeded by well-documented post-infectious sequelae, including chronic fatigue, cough, shortness of breath, myalgia, and concentration difficulties, which may last 5 to 12 weeks or longer after the acute phase of illness. Both the psychological stress of SARS-CoV-2 infection and being diagnosed with COVID-19 can upregulate cortisol, a stress hormone that disrupts the efferocytosis effectors, macrophages, and natural killer cells, leading to the excessive accumulation of senescent cells and disruption of biological barriers. This has been well-established in cancer patients who often experience unrelenting fatigue as well as gut and blood–brain barrier dysfunction upon treatment with senescence-inducing radiation or chemotherapy. In our previous research from 2020 and 2021, we linked COVID-19 to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) via angiotensin II upregulation, premature endothelial senescence, intestinal barrier dysfunction, and microbial translocation from the gastrointestinal tract into the systemic circulation. In 2021 and 2022, these hypotheses were validated and SARS-CoV-2-induced cellular senescence as well as microbial translocation were documented in both acute SARS-CoV-2 infection, long COVID, and ME/CFS, connecting intestinal barrier dysfunction to disabling fatigue and specific infectious events. The purpose of this narrative review is to summarize what is currently known about host immune responses to translocated gut microbes and how these responses relate to fatiguing illnesses, including long COVID. To accomplish this goal, we examine the role of intestinal and blood–brain barriers in long COVID and other illnesses typified by chronic fatigue, with a special emphasis on commensal microbes functioning as viral reservoirs. Furthermore, we discuss the role of SARS-CoV-2/Mycoplasma coinfection in dysfunctional efferocytosis, emphasizing some potential novel treatment strategies, including the use of senotherapeutic drugs, HMGB1 inhibitors, Toll-like receptor 4 (TLR4) blockers, and membrane lipid replacement.

The Use of a Health Compliance Monitoring System During the COVID-19 Pandemic in Indonesia: Evaluation Study.

BACKGROUND: COVID-19 cases are soaring in Asia. Indonesia, Southeast Asia's most populous country, is now ranked second in the number of cases and deaths in Asia, after India. The compliance toward mask wearing, social distancing, and hand washing needs to be monitored to assess public behavioral changes that can reduce transmission. OBJECTIVE: This study aimed to evaluate this compliance in Indonesia between October 2020 and May 2021 and demonstrate the use of the Bersatu Lawan COVID-19 (BLC) mobile app in monitoring this compliance. METHODS: Data were collected in real time by the BLC app from reports submitted by personnel of military services, police officers, and behavioral change ambassadors. Subsequently, the data were analyzed automatically by the system managed by the Indonesia National Task Force for the Acceleration of COVID-19 Mitigation. RESULTS: Between October 1, 2020, and May 2, 2021, the BLC app generated more than 165 million reports, with 469 million people monitored and 124,315,568 locations under observation in 514 districts/cities in 34 provinces in Indonesia. This paper grouped them into 4 colored zones, based on the degree of compliance, and analyzed variations among regions and locations. CONCLUSIONS: Compliance rates vary among the 34 provinces and among the districts and cities of those provinces. However, compliance to mask wearing seems slightly higher than social distancing. This finding suggests that policy makers need to promote higher compliance in other measures, including social distancing and hand washing, whose efficacies have been proven to break the chain of transmission when combined with masks wearing.

Psychotropic drugs interaction with the lipid nanoparticle of COVID-19 mRNA therapeutics.

The messenger RNA (mRNA) vaccines for COVID-19, Pfizer-BioNTech and Moderna, were authorized in the US on an emergency basis in December of 2020. The rapid distribution of these therapeutics around the country and the world led to millions of people being vaccinated in a short time span, an action that decreased hospitalization and death but also heightened the concerns about adverse effects and drug-vaccine interactions. The COVID-19 mRNA vaccines are of particular interest as they form the vanguard of a range of other mRNA therapeutics that are currently in the development pipeline, focusing both on infectious diseases as well as oncological applications. The Vaccine Adverse Event Reporting System (VAERS) has gained additional attention during the COVID-19 pandemic, specifically regarding the rollout of mRNA therapeutics. However, for VAERS, absence of a reporting platform for drug-vaccine interactions left these events poorly defined. For example, chemotherapy, anticonvulsants, and antimalarials were documented to interfere with the mRNA vaccines, but much less is known about the other drugs that could interact with these therapeutics, causing adverse events or decreased efficacy. In addition, SARS-CoV-2 exploitation of host cytochrome P450 enzymes, reported in COVID-19 critical illness, highlights viral interference with drug metabolism. For example, patients with severe psychiatric illness (SPI) in treatment with clozapine often displayed elevated drug levels, emphasizing drug-vaccine interaction.

Harmonizing the COVID-19 sample biobanks: Barriers and opportunities for standards, best practices and networks.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the practice of infectious diseases biobanking, as well as existing challenges and opportunities. Thus, the future of infectious diseases biobanking in the post-pandemic era, shall not be an "entry-level version" of its counterpart in non-communicable diseases and large population cohorts, but incorporate the lessons learned. Biobanks constitute a critical research infrastructure supported by harmonized practices through the implementation of international standards, and perceived within the broader scope of healthcare's intersection with research. This perspective paper considers the barriers in biobanking and standardization of practices, as well as the emerging opportunities in the field.

Biobanking in LMIC settings for infectious diseases: Challenges and enablers.

Biobanking facilities are well established in high-income settings, where substantial funding has been invested in infrastructure. In contrast, such facilities are much less developed in resource-restricted settings. However, low-and middle-income countries (LMICs) still face a disproportionately high infectious diseases burden. Thus, the further development of infrastructure facilities, including biobanks is warranted as an important component of this unfolding clinical research environment. This perspective manuscript summarises the challenges and enablers for biobanking in LMICs, with a particular focus on infectious diseases, incorporating some of the lessons learned from the recent coronavirus disease 2019 (COVID-19) pandemic.

Neuronal and Non-Neuronal GABA in COVID-19: Relevance for Psychiatry

Infection with SARS-CoV-2, the causative agent of the COVID-19 pandemic, originated in China and quickly spread across the globe. Despite tremendous economic and healthcare devastation, research on this virus has contributed to a better understanding of numerous molecular pathways, including those involving γ-aminobutyric acid (GABA), that will positively impact medical science, including neuropsychiatry, in the post-pandemic era. SARS-CoV-2 primarily enters the host cells through the renin–angiotensin system's component named angiotensin-converting enzyme-2 (ACE-2). Among its many functions, this protein upregulates GABA, protecting not only the central nervous system but also the endothelia, the pancreas, and the gut microbiota. SARS-CoV-2 binding to ACE-2 usurps the neuronal and non-neuronal GABAergic systems, contributing to the high comorbidity of neuropsychiatric illness with gut dysbiosis and endothelial and metabolic dysfunctions. In this perspective article, we take a closer look at the pathology emerging from the viral hijacking of non-neuronal GABA and summarize potential interventions for restoring these systems.

Building on health security capacities in Indonesia: Lessons learned from the COVID-19 pandemic responses and challenges.

As an active member country of the WHO's International Health Regulation and Global Health Security Agenda, Indonesia, the world's fourth-most populous and largest archipelagic country has recorded the second-highest COVID-19 cases in Asia with over 1.8 million cases in early June 2021. This geographically and socially diverse country has a dynamic national and sub-national government coordination with decentralized authorities that can complicate a pandemic response which often requires nationally harmonized policies, adaptability to sub-national contexts and global interconnectedness. This paper analyses and reviews COVID-19 public data, regulations, guidance documents, statements and other related official documents to present a narrative that summarizes the government's COVID-19 response strategies. It further analyses the challenges and achievements of the country's zoonotic diseases preparedness and responses and lastly provides relevant recommendations. Findings are presented in four sections according to the Global Health Security Agenda capacities, namely epidemiological surveillance (detect capacity); laboratory diagnostic testing (respond capacity); data management and analysis (enable capacity); and the role of sub-national governments. The COVID-19 pandemic has been a catalyst for the rapid transformation of existing surveillance systems, inter-related stakeholder coordination and agile development from the pre-pandemic health security capacities. This paper offers several recommendations on surveillance, laboratory capacity and data management, which might be useful for Indonesia and other countries with similar characteristics beyond the COVID-19 response, such as achieving long-term health security, zoonoses and pandemic prevention, as well as a digital transformation of their governmental capacities.

Virus-Induced Membrane Fusion in Neurodegenerative Disorders.

A growing body of epidemiological and research data has associated neurotropic viruses with accelerated brain aging and increased risk of neurodegenerative disorders. Many viruses replicate optimally in senescent cells, as they offer a hospitable microenvironment with persistently elevated cytosolic calcium, abundant intracellular iron, and low interferon type I. As cell-cell fusion is a major driver of cellular senescence, many viruses have developed the ability to promote this phenotype by forming syncytia. Cell-cell fusion is associated with immunosuppression mediated by phosphatidylserine externalization that enable viruses to evade host defenses. In hosts, virus-induced immune dysfunction and premature cellular senescence may predispose to neurodegenerative disorders. This concept is supported by novel studies that found postinfectious cognitive dysfunction in several viral illnesses, including human immunodeficiency virus-1, herpes simplex virus-1, and SARS-CoV-2. Virus-induced pathological syncytia may provide a unified framework for conceptualizing neuronal cell cycle reentry, aneuploidy, somatic mosaicism, viral spreading of pathological Tau and elimination of viable synapses and neurons by neurotoxic astrocytes and microglia. In this narrative review, we take a closer look at cell-cell fusion and vesicular merger in the pathogenesis of neurodegenerative disorders. We present a "decentralized" information processing model that conceptualizes neurodegeneration as a systemic illness, triggered by cytoskeletal pathology. We also discuss strategies for reversing cell-cell fusion, including, TMEM16F inhibitors, calcium channel blockers, senolytics, and tubulin stabilizing agents. Finally, going beyond neurodegeneration, we examine the potential benefit of harnessing fusion as a therapeutic strategy in regenerative medicine.

Successfully Implementing Digital Health to Ensure Future Global Health Security During Pandemics: A Consensus Statement.

Importance: COVID-19 has highlighted widespread chronic underinvestment in digital health that hampered public health responses to the pandemic. Recognizing this, the Riyadh Declaration on Digital Health, formulated by an international interdisciplinary team of medical, academic, and industry experts at the Riyadh Global Digital Health Summit in August 2020, provided a set of digital health recommendations for the global health community to address the challenges of current and future pandemics. However, guidance is needed on how to implement these recommendations in practice. Objective: To develop guidance for stakeholders on how best to deploy digital health and data and support public health in an integrated manner to overcome the COVID-19 pandemic and future pandemics. Evidence Review: Themes were determined by first reviewing the literature and Riyadh Global Digital Health Summit conference proceedings, with experts independently contributing ideas. Then, 2 rounds of review were conducted until all experts agreed on the themes and main issues arising using a nominal group technique to reach consensus. Prioritization was based on how useful the consensus recommendation might be to a policy maker. Findings: A diverse stakeholder group of 13 leaders in the fields of public health, digital health, and health care were engaged to reach a consensus on how to implement digital health recommendations to address the challenges of current and future pandemics. Participants reached a consensus on high-priority issues identified within 5 themes: team, transparency and trust, technology, techquity (the strategic development and deployment of technology in health care and health to achieve health equity), and transformation. Each theme contains concrete points of consensus to guide the local, national, and international adoption of digital health to address challenges of current and future pandemics. Conclusions and Relevance: The consensus points described for these themes provide a roadmap for the implementation of digital health policy by all stakeholders, including governments. Implementation of these recommendations could have a significant impact by reducing fatalities and uniting countries on current and future battles against pandemics.