Engaging communities in therapeutics clinical research during pandemics: Experiences and lessons from the ACTIV COVID-19 therapeutics research initiative.

This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVID-19 trials.

Host response to influenza infections in human blood: association of influenza severity with host genetics and transcriptomic response.

Introduction: Influenza virus infections are a major global health problem. Influenza can result in mild/moderate disease or progress to more severe disease, leading to high morbidity and mortality. Severity is thought to be primarily driven by immunopathology, but predicting which individuals are at a higher risk of being hospitalized warrants investigation into host genetics and the molecular signatures of the host response during influenza infections.

Building Clinical Care Capacity for Patients With Special Pathogens in Advance of the Next Outbreak.

In response to the growing number of outbreaks of emerging infectious diseases, the US Administration for Strategic Preparedness and Response (ASPR) has embarked on a plan to improve and expand special pathogen patient care capabilities. To achieve this, ASPR is developing a coordinated network of Regional Emerging Special Pathogen Treatment Centers (RESPTCs) to serve as state-of-the-art facilities staffed by a highly trained workforce to care for and manage special pathogen patients across the lifespan. The RESPTC network represents the operational arm of a broader US National Special Pathogen System of care to prevent and prepare for the next infectious disease outbreak.

Health and economic impacts of Lassa vaccination campaigns in West Africa.

Lassa fever is a zoonotic disease identified by the World Health Organization (WHO) as having pandemic potential. This study estimates the health-economic burden of Lassa fever throughout West Africa and projects impacts of a series of vaccination campaigns. We also model the emergence of "Lassa-X" - a hypothetical pandemic Lassa virus variant - and project impacts of achieving 100 Days Mission vaccination targets.

Ebola Virus-Specific Neutralizing Antibody Persists at High Levels in Survivors 2 Years After Resolution of Disease in a Sierra Leonean Cohort.

Ebola virus (EBOV) infection results in Ebola virus disease (EVD), an often severe disease with a nonspecific presentation. Since its recognition, periodic outbreaks of EVD continue to occur in sub-Saharan Africa. The 2013-2016 West African EVD outbreak was the largest recorded, resulting in a substantial cohort of EVD survivors with persistent health complaints and variable immune responses.

ZMapp reduces diffusion of Ebola viral particles in fresh human cervicovaginal mucus.

Vaginal transmission from semen of male Ebola virus (EBOV) survivors has been implicated as a potential origin of Ebola virus disease (EVD) outbreaks. While EBOV in semen must traverse cervicovaginal mucus (CVM) to reach target cells, the behaviour of EBOV in CVM is poorly understood. CVM contains substantial quantities of IgG, and arrays of IgG bound to a virion can develop multiple Fc-mucin bonds, immobilizing the IgG/virion complex in mucus.

COVID-19 hospitalization risk after outpatient nirmatrelvir/ritonavir use, January to August 2022, North Carolina.

Background: In the USA, nirmatrelvir/ritonavir is authorized for the treatment of mild-to-moderate COVID-19 in patients at least 12 years of age, at high risk for progression to severe COVID-19.

Objectives: To estimate the impact of outpatient nirmatrelvir/ritonavir on COVID-19 hospitalization risk in a US healthcare system.

Methods: We conducted a cohort study using electronic health records among outpatients with a positive SARS-CoV-2 PCR test between January and August 2022.

Association Between Anterior Nasal and Plasma SARS-CoV-2 RNA Levels and Hospitalization or Death in Nonhospitalized Adults With Mild-to-Moderate COVID-19.

Background: There is little information regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA as a predictor for clinical outcomes in outpatients with mild-to-moderate coronavirus disease 2019 (COVID-19).

Methods: Anterior nasal (AN) and plasma SARS-CoV-2 RNA data from 2115 nonhospitalized adults who received monoclonal antibodies (mAbs) or placebo in the ACTIV-2/A5401 trial were analyzed for associations with hospitalization or death.

Results: One hundred two participants were hospitalized or died through 28 days of follow-up.

A prospective, multi-site, cohort study to estimate incidence of infection and disease due to Lassa fever virus in West African countries (the Enable Lassa research programme)-Study protocol.

Background: Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries.

Evaluation of a COVID-19 convalescent plasma program at a U.S. academic medical center.

Amidst the therapeutic void at the onset of the COVID-19 pandemic, a critical mass of scientific and clinical interest coalesced around COVID-19 convalescent plasma (CCP). To date, the CCP literature has focused largely on safety and efficacy outcomes, but little on implementation outcomes or experience. Expert opinion suggests that if CCP has a role in COVID-19 treatment, it is early in the disease course, and it must deliver a sufficiently high titer of neutralizing antibodies (nAb).

Post-Ebola Symptoms 7 Years After Infection: The Natural History of Long Ebola.

Background: Lingering symptoms have been reported by survivors of Ebola virus disease (EVD). There are few data describing the persistence and severity of these symptoms over time.

Methods: Symptoms of headache, fatigue, joint pain, muscle pain, hearing loss, visual loss, numbness of hands or feet were longitudinally assessed among participants in the Liberian Ebola Survivors Cohort study.

The prevalence of Post-Ebola Syndrome hearing loss, Sierra Leone.

Background: Globally, hearing loss is the second leading cause of disability, affecting approximately 18.7% of the world's population. However, the burden of hearing loss is unequally distributed, with the majority of affected individuals located in Asia or Sub-Saharan Africa.

Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) are among the treatments recommended for high-risk ambulatory persons with coronavirus 2019 (COVID-19). Here, we study viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial (ClinicalTrials.gov: NCT04518410).

Creation and impact of containment units with high-risk zones during the coronavirus disease 2019 (COVID-19) pandemic.

Background: The rapid spread of coronavirus disease 2019 (COVID-19) required swift preparation to protect healthcare personnel (HCP) and patients, especially considering shortages of personal protective equipment (PPE). Due to the lack of a pre-existing biocontainment unit, we needed to develop a novel approach to placing patients in isolation cohorts while working with the pre-existing physical space.

Objectives: To prevent disease transmission to non-COVID-19 patients and HCP caring for COVID-19 patients, to optimize PPE usage, and to provide a comfortable and safe working environment.

Longitudinal SARS-CoV-2 Testing among the Unvaccinated Is Punctuated by Intermittent Positivity and Variable Rates of Increasing Cycle Threshold Values.

The coronavirus disease 2019 (COVID-19) pandemic is complicated by cases of vaccine breakthrough and reinfection and widespread transmission of variants of concern (VOCs). Consequently, the need to interpret longitudinal positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests is crucial in guiding clinical decisions regarding infection control precautions and treatment. Although diagnostic real-time reverse transcription (RT)-PCR tests yield values that are inversely correlated with RNA quantity, these tests are only approved for qualitative interpretation.

Major Bleeding and Thrombosis Events in COVID-19 Versus Influenza Patients Requiring Extracorporeal Membrane Oxygenation.

Initial reports described a hypercoagulable state and an increased risk of thrombosis in patients who tested positive for SARS-CoV-2. Infected patients with severe acute respiratory distress syndrome in the setting of coronavirus disease 2019 (COVID-19) may require extracorporeal membrane oxygenation (ECMO), leading to coagulopathies and further increasing the risk for bleeding and thrombosis. We conducted a single-center retrospective cohort study to compare the incidence of major bleeding and thrombosis in COVID-19 versus influenza-positive patients requiring ECMO.

Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Virus in Symptomatic Coronavirus Disease 2019 (COVID-19) Outpatients: Host, Disease, and Viral Correlates.

Background: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (COVID-19) has been associated with viral RNA levels and symptom duration, little is known about the host, disease, and viral determinants of infectious virus detection.

Methods: COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary.

Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection.

Monoclonal antibodies (mAbs) are the treatment of choice for high-risk ambulatory persons with mild to moderate COVID-19. We studied viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial. Viral load by qPCR and viral culture were performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7.

A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus.

There is an urgent need for an effective, oral, direct-acting therapeutic to block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent progression to severe coronavirus disease 2019 (COVID-19). In a phase 2a double-blind, placebo-controlled, randomized, multicenter clinical trial, we evaluated the safety, tolerability, and antiviral efficacy of the nucleoside analog molnupiravir in 202 unvaccinated participants with confirmed SARS-CoV-2 infection and symptom duration <7 days. Participants were randomized 1:1 to receive molnupiravir (200 mg) or placebo and then 3:1 to receive molnupiravir (400 or 800 mg) or placebo, orally twice daily for 5 days.

Rapid analysis of local data to inform off-label tocilizumab use early in the COVID-19 pandemic.

The interleukin-6 receptor antagonist tocilizumab became widely used early in the coronavirus disease 2019 (COVID-19) pandemic based on small observational studies that suggested clinical benefit in COVID-19 patients with a hyperinflammatory state. To inform our local treatment algorithms in the absence of randomized clinical trial results, we performed a rapid analysis of the first 11 hospitalized COVID-19 patients treated with tocilizumab at our academic medical center. We report their early clinical outcomes and describe the process by which we assembled a team of diverse trainees and stakeholders to extract, analyze, and disseminate data during a time of clinical uncertainty.