Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases.

The twenty-first century has already recorded more than ten major epidemic or pandemic virus emergence events, including the ongoing and devastating coronavirus disease 2019 (COVID-19) pandemic. As viral disease emergence is expected to accelerate, these data dictate a need for proactive approaches to develop broadly active family-specific and cross-family therapeutics for use in future disease outbreaks. Emphasis should focus not only on the development of broad-spectrum small-molecule and antibody direct-acting antivirals, but also on host-factor therapeutics, including repurposing previously approved or in-pipeline drugs. Another new class of therapeutics with great antiviral therapeutic potential is RNA-based therapeutics. Rather than only focusing on known risks, dedicated efforts must be made toward pre-emptive research focused on outbreak-prone virus families, ultimately offering a strategy to shorten the gap between outbreak and response. Emphasis should also focus on orally available drugs for outpatient use, if possible, and on identifying combination therapies that combat viral and immune-mediated pathologies, extend the effectiveness of therapeutic windows and reduce drug resistance. While such an undertaking will require new vision, dedicated funding and private, federal and academic partnerships, this approach offers hope that global populations need never experience future pandemics such as COVID-19.

Requirement of Fc-Fc Gamma Receptor Interaction for Antibody-Based Protection against Emerging Virus Infections.

Identification of therapeutics against emerging and re-emerging viruses remains a continued priority that is only reinforced by the recent SARS-CoV-2 pandemic. Advances in monoclonal antibody (mAb) isolation, characterization, and production make it a viable option for rapid treatment development. While mAbs are traditionally screened and selected based on potency of neutralization in vitro, it is clear that additional factors contribute to the in vivo efficacy of a mAb beyond viral neutralization. These factors include interactions with Fc receptors (FcRs) and complement that can enhance neutralization, clearance of infected cells, opsonization of virions, and modulation of the innate and adaptive immune response. In this review, we discuss recent studies, primarily using mouse models, that identified a role for Fc-FcγR interactions for optimal antibody-based protection against emerging and re-emerging virus infections.

Ethics of emerging infectious disease outbreak responses: Using Ebola virus disease as a case study of limited resource allocation.

Emerging infectious diseases such as Ebola Virus Disease (EVD), Nipah Virus Encephalitis and Lassa fever pose significant epidemic threats. Responses to emerging infectious disease outbreaks frequently occur in resource-constrained regions and under high pressure to quickly contain the outbreak prior to potential spread. As seen in the 2020 EVD outbreaks in the Democratic Republic of Congo and the current COVID-19 pandemic, there is a continued need to evaluate and address the ethical challenges that arise in the high stakes environment of an emerging infectious disease outbreak response. The research presented here provides analysis of the ethical challenges with regard to allocation of limited resources, particularly experimental therapeutics, using the 2013-2016 EVD outbreak in West Africa as a case study. In-depth semi-structured interviews were conducted with senior healthcare personnel (n = 16) from international humanitarian aid organizations intimately engaged in the 2013-2016 EVD outbreak response in West Africa. Interviews were recorded in private setting, transcribed, and iteratively coded using grounded theory methodology. A majority of respondents indicated a clear propensity to adopt an ethical framework of guiding principles for international responses to emerging infectious disease outbreaks. Respondents agreed that prioritization of frontline workers' access to experimental therapeutics was warranted based on a principle of reciprocity. There was widespread acceptance of adaptive trial designs and greater trial transparency in providing access to experimental therapeutics. Many respondents also emphasized the importance of community engagement in limited resource allocation scheme design and culturally appropriate informed consent procedures. The study results inform a potential ethical framework of guiding principles based on the interview participants' insights to be adopted by international response organizations and their healthcare workers in the face of allocating limited resources such as experimental therapeutics in future emerging infectious disease outbreaks to ease the moral burden of individual healthcare providers.

Utility of Proteomics in Emerging and Re-Emerging Infectious Diseases Caused by RNA Viruses.

Emerging and re-emerging infectious diseases due to RNA viruses cause major negative consequences for the quality of life, public health, and overall economic development. Most of the RNA viruses causing illnesses in humans are of zoonotic origin. Zoonotic viruses can directly be transferred from animals to humans through adaptation, followed by human-to-human transmission, such as in human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and, more recently, SARS coronavirus 2 (SARS-CoV-2), or they can be transferred through insects or vectors, as in the case of Crimean-Congo hemorrhagic fever virus (CCHFV), Zika virus (ZIKV), and dengue virus (DENV). At the present, there are no vaccines or antiviral compounds against most of these viruses. Because proteins possess a vast array of functions in all known biological systems, proteomics-based strategies can provide important insights into the investigation of disease pathogenesis and the identification of promising antiviral drug targets during an epidemic or pandemic. Mass spectrometry technology has provided the capacity required for the precise identification and the sensitive and high-throughput analysis of proteins on a large scale and has contributed greatly to unravelling key protein-protein interactions, discovering signaling networks, and understanding disease mechanisms. In this Review, we present an account of quantitative proteomics and its application in some prominent recent examples of emerging and re-emerging RNA virus diseases like HIV-1, CCHFV, ZIKV, and DENV, with more detail with respect to coronaviruses (MERS-CoV and SARS-CoV) as well as the recent SARS-CoV-2 pandemic.

China's practice to prevent and control COVID-19 in the context of large population movement.

BACKGROUND: The emerging infectious disease, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a serious threat in China and worldwide. Challenged by this serious situation, China has taken many measures to contain its transmission. This study aims to systematically review and record these special and effective practices, in hope of benefiting for fighting against the ongoing worldwide pandemic. METHODS: The measures taken by the governments was tracked and sorted on a daily basis from the websites of governmental authorities (e.g. National Health Commission of the People's Republic of China). And the measures were reviewed and summarized by categorizations, figures and tables, showing an ever-changing process of combating with an emerging infectious disease. The population shift levels, daily local new diagnosed cases, daily mortality and daily local new cured cases were used for measuring the effect of the measures. RESULTS: The practices could be categorized into active case surveillance, rapid case diagnosis and management, strict follow-up and quarantine of persons with close contacts, and issuance of guidance to help the public understand and adhere to control measures, plus prompt and effective high-level policy decision, complete activation of the public health system, and full involvement of the society. Along with the measures, the population shift levels, daily local new diagnosed cases, and mortality were decreased, and the daily local new cured cases were increased in China. CONCLUSIONS: China's practices are effective in controlling transmission of SARS-CoV-2. Considering newly occurred situations (e.g. imported cases, work resumption), the control measures may be adjusted.

Policy Recommendations Regarding Skilled Nursing Facility Management of Coronavirus 19 (COVID-19): Lessons from New York State.

To provide policy recommendations for managing Coronavirus 19 (COVID-19) in skilled nursing facilities, a group of certified medical directors from several facilities in New York state with experience managing the disease used e-mail, phone, and video conferencing to develop consensus recommendations. The resulting document provides recommendations on screening, protection of staff, screening of residents, management of Coronavirus 19 positive and presumed positive cases, communication during an outbreak, management of admissions and readmissions, and providing emotional support for staff. These consensus guidelines have been endorsed by the Executive Board of the New York Medical Directors Association and the Board of the Metropolitan Area Geriatrics Society.

Coping With Trauma, Celebrating Life: Reinventing Patient And Staff Support During The COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic presented unprecedented challenges to the New York City Health + Hospitals system. In addition to ramping up capacity and adapting operations quickly to handle the patient surge, NYC Health + Hospitals had to find new ways to provide emotional and psychological support for patients, families, and staff. To help families keep in touch, dedicated staff members provided daily updates by telephone and used tablets for virtual visits. An expanded palliative care team held virtual consultations with families to discuss advance care planning and end-of-life decisions. Bereavement hotlines were set up for families who lost loved ones. Enhanced staff support included one-on-one and group sessions with behavioral health specialists, a behavioral health hotline, a webinar series, and respite rooms, as well as complimentary lodging and child care. NYC Health + Hospitals created new rituals to celebrate recoveries and mourn losses. As regular operations resume, NYC Health + Hospitals plans to sustain and build on emotional and psychological support initiatives developed during the surge.

Endemic and Emerging Coronavirus Pulmonary Infections.

Coronaviruses are a well-known cause of upper and lower respiratory disease, and since 2002 have been a recognized source of potential pandemic spread. Over the past two decades, since the Severe Acute Respiratory Syndrome (SARS) outbreak, a large body of research has accumulated on the virology, clinical symptoms and signs, and experimental treatments of Coronaviruses. In 2020, a new form of Coronaviruses (SARS-CoV-2) emerged and spread rapidly throughout the globe. Given the wide-ranging clinical presentations of those infected with SARS-CoV-2, other viruses might be overlooked when evaluating at-risk patients. Furthermore, due to suboptimal testing capabilities, an early clinical diagnosis is not always possible. Here, we present a case of a patient with pneumonia thought to be caused by SARS-CoV-2 only to be found to have another Coronavirus. This emphasizes the need to be vigilant when evaluating patients with viral-like respiratory infections.

Logic in the time of coronavirus.

Much has happened here since the local news media trumpeted the first Australian COVID-19 fatality, and stirred up a medieval fear of contagion. We now need to take a step back to examine the logic underlying the use of our limited COVID-19 countermeasures. Emerging infectious diseases by their nature, pose new challenges to the diagnostic-treatment-control nexus, and push our concepts of causality beyond the limits of the conventional Koch-Henle approach to aetiology. We need to use contemporary methods of assessing causality to ensure that clinical, laboratory and public health measures draw on a rational, evidence-based approach to argumentation. The purpose of any aetiological hypothesis is to derive actionable insights into this latest emerging infectious disease. This review is an introduction to a conversation with medical microbiologists, which will be supported by a moderated blog.

Treatment for emerging viruses: Convalescent plasma and COVID-19.

Use of convalescent plasma transfusions could be of great value in the current pandemic of coronavirus disease (COVID-19), given the lack of specific preventative and therapeutic options. This convalescent plasma therapy is of particular interest when a vaccine or specific therapy is not yet available for emerging viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. This report summarizes existing literature around convalescent plasma as a therapeutic option for COVID-19. It also includes recommendations for establishing a convalescent plasma program, enhancement considerations for convalescent plasma, and considerations around pathogen reduction treatment of convalescent plasma. Time is of the essence to set up protocols for collection, preparation, and administration of apheresis-collected convalescent plasma in response to the current pandemic. The immediate use of convalescent plasma provides prompt availability of a promising treatment while specific vaccines and treatments are evaluated and brought to scale. Further development of improved convalescent plasma, vaccines and other therapeutics depends on quick generation of additional data on pathogenesis and immune response. Additionally, given the lack of information around the natural history of this disease, PRT should be considered to add a layer of safety to protect recipients of convalescent plasma.

Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases.

WHO interim guidelines recommend offering extracorporeal membrane oxygenation (ECMO) to eligible patients with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The number of patients with COVID-19 infection who might develop severe ARDS that is refractory to maximal medical management and require this level of support is currently unknown. Available evidence from similar patient populations suggests that carefully selected patients with severe ARDS who do not benefit from conventional treatment might be successfully supported with venovenous ECMO. The need for ECMO is relatively low and its use is mostly restricted to specialised centres globally. Providing complex therapies such as ECMO during outbreaks of emerging infectious diseases has unique challenges. Careful planning, judicious resource allocation, and training of personnel to provide complex therapeutic interventions while adhering to strict infection control measures are all crucial components of an ECMO action plan. ECMO can be initiated in specialist centres, or patients can receive ECMO during transportation from a centre that is not specialised for this procedure to an expert ECMO centre. Ensuring that systems enable safe and coordinated movement of critically ill patients, staff, and equipment is important to improve ECMO access. ECMO preparedness for the COVID-19 pandemic is important in view of the high transmission rate of the virus and respiratory-related mortality.