Pandemic Response Requires Research Samples: A U.S. Safety-Net Hospital's Experience and Call for National Action.

Biorepositories provide a critical resource for gaining knowledge of emerging infectious diseases and offer a mechanism to rapidly respond to outbreaks; the emergence of the novel coronavirus, SARS-CoV-2, has proved their importance. During the COVID-19 pandemic, the absence of centralized, national biorepository efforts meant that the onus fell on individual institutions to establish sample repositories. As a safety-net hospital, Boston Medical Center (BMC) recognized the importance of creating a COVID-19 biorepository to both support critical science at BMC and ensure representation in research for its urban patient population, most of whom are from underserved communities. This article offers a realistic overview of the authors' experience in establishing this biorepository at the onset of the COVID-19 pandemic during the height of the first surge of cases in Boston, Massachusetts, with the hope that the challenges and solutions described are useful to other institutions. Going forward, funders, policymakers, and infectious disease and public health communities must support biorepository implementation as an essential element of future pandemic preparedness.

CDC Safety Training Course for Ebola Virus Disease Healthcare Workers.

Response to sudden epidemic infectious disease emergencies can demand intensive and specialized training, as demonstrated in 2014 when Ebola virus disease (EVD) rapidly spread throughout West Africa. The medical community quickly became overwhelmed because of limited staff, supplies, and Ebola treatment units (ETUs). Because a mechanism to rapidly increase trained healthcare workers was needed, the US Centers for Disease Control and Prevention developed and implemented an introductory EVD safety training course to prepare US healthcare workers to work in West Africa ETUs. The goal was to teach principles and practices of safely providing patient care and was delivered through lectures, small-group breakout sessions, and practical exercises. During September 2014-March 2015, a total of 570 participants were trained during 16 course sessions. This course quickly increased the number of clinicians who could provide care in West Africa ETUs, showing the feasibility of rapidly developing and implementing training in response to a public health emergency.

Strengthening Health Systems While Responding to a Health Crisis: Lessons Learned by a Nongovernmental Organization During the Ebola Virus Disease Epidemic in Sierra Leone.

An epidemic of Ebola virus disease (EVD) beginning in 2013 has claimed an estimated 11 310 lives in West Africa. As the EVD epidemic subsides, it is important for all who participated in the emergency Ebola response to reflect on strengths and weaknesses of the response. Such reflections should take into account perspectives not usually included in peer-reviewed publications and after-action reports, including those from the public sector, nongovernmental organizations (NGOs), survivors of Ebola, and Ebola-affected households and communities. In this article, we first describe how the international NGO Partners In Health (PIH) partnered with the Government of Sierra Leone and Wellbody Alliance (a local NGO) to respond to the EVD epidemic in 4 of the country's most Ebola-affected districts. We then describe how, in the aftermath of the epidemic, PIH is partnering with the public sector to strengthen the health system and resume delivery of regular health services. PIH's experience in Sierra Leone is one of multiple partnerships with different stakeholders. It is also one of rapid deployment of expatriate clinicians and logistics personnel in health facilities largely deprived of health professionals, medical supplies, and physical infrastructure required to deliver health services effectively and safely. Lessons learned by PIH and its partners in Sierra Leone can contribute to the ongoing discussion within the international community on how to ensure emergency preparedness and build resilient health systems in settings without either.

Automating biomedical literature review for rapid drug discovery: Leveraging GPT-4 to expedite pandemic response.

OBJECTIVE: The rapid expansion of the biomedical literature challenges traditional review methods, especially during outbreaks of emerging infectious diseases when quick action is critical. Our study aims to explore the potential of ChatGPT to automate the biomedical literature review for rapid drug discovery. MATERIALS AND METHODS: We introduce a novel automated pipeline helping to identify drugs for a given virus in response to a potential future global health threat. Our approach can be used to select PubMed articles identifying a drug target for the given virus. We tested our approach on two known pathogens: SARS-CoV-2, where the literature is vast, and Nipah, where the literature is sparse. Specifically, a panel of three experts reviewed a set of PubMed articles and labeled them as either describing a drug target for the given virus or not. The same task was given to the automated pipeline and its performance was based on whether it labeled the articles similarly to the human experts. We applied a number of prompt engineering techniques to improve the performance of ChatGPT. RESULTS: Our best configuration used GPT-4 by OpenAI and achieved an out-of-sample validation performance with accuracy/F1-score/sensitivity/specificity of 92.87%/88.43%/83.38%/97.82% for SARS-CoV-2 and 87.40%/73.90%/74.72%/91.36% for Nipah. CONCLUSION: These results highlight the utility of ChatGPT in drug discovery and development and reveal their potential to enable rapid drug target identification during a pandemic-level health emergency.

Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024.

Liberia adherence and loss-to-follow-up in HIV and AIDS care and treatment: A retrospective cohort of adolescents and adults from 2016-2019.

Antiretroviral therapy (ART) is a lifesaving intervention for people living with HIV infection, reducing morbidity and mortality; it is likewise essential to reducing transmission. The "Treat all" strategy recommended by the World Health Organization has dramatically increased ART eligibility and improved access. However, retaining patients on ART has been a major challenge for many national programs in low- and middle-income settings, despite actionable local policies and ambitious targets. To estimate retention of patients along the HIV care cascade in Liberia, and identify factors associated with loss-to-follow-up (LTFU), death, and suboptimal treatment adherence, we conducted a nationwide retrospective cohort study utilizing facility and patient-level records. Patients aged ≥15 years, from 28 facilities who were first registered in HIV care from January 2016 -December 2017 were included. We used Cox proportional hazard models to explore associations between demographic and clinical factors and the outcomes of LTFU and death, and a multinomial logistic regression model to investigate factors associated with suboptimal treatment adherence. Among the 4185 records assessed, 27.4% (n = 1145) were males and the median age of the cohort was 37 (IQR: 30-45) years. At 24 months of follow-up, 41.8% (n = 1751) of patients were LTFU, 6.6% (n = 278) died, 0.5% (n = 21) stopped treatment, 3% (n = 127) transferred to another facility and 47.9% (n = 2008) were retained in care and treatment. The incidence of LTFU was 46.0 (95% CI: 40.8-51.6) per 100 person-years. Relative to patients at WHO clinical stage I at first treatment visit, patients at WHO clinical stage III [adjusted hazard ratio (aHR) 1.59, 95%CI: 1.21-2.09; p <0.001] or IV (aHR 2.41, 95%CI: 1.51-3.84; p <0.001) had increased risk of LTFU; whereas at registration, age category 35-44 (aHR 0.65, 95%CI: 0.44-0.98, p = 0.038) and 45 years and older (aHR 0.60, 95%CI: 0.39-0.93, p = 0.021) had a decreased risk. For death, patients assessed with WHO clinical stage II (aHR 2.35, 95%CI: 1.53-3.61, p<0.001), III (aHR 2.55, 95%CI: 1.75-3.71, p<0.001), and IV (aHR 4.21, 95%CI: 2.57-6.89, p<0.001) had an increased risk, while non-pregnant females (aHR 0.68, 95%CI: 0.51-0.92, p = 0.011) and pregnant females (aHR 0.42, 95%CI: 0.20-0.90, p = 0.026) had a decreased risk when compared to males. Suboptimal adherence was strongly associated with the experience of drug side effects-average adherence [adjusted odds ratio (aOR) 1.45, 95% CI: 1.06-1.99, p = 0.02) and poor adherence (aOR 1.75, 95%CI: 1.11-2.76, p = 0.016), and attending rural facility decreased the odds of average adherence (aOR 0.01, 95%CI: 0.01-0.03, p<0.001) and poor adherence (aOR 0.001, 95%CI: 0.0004-0.003, p<0.001). Loss-to-follow-up and poor adherence remain major challenges to achieving viral suppression targets in Liberia. Over two-fifths of patients engaged with the national HIV program are being lost to follow-up within 2 years of beginning care and treatment. WHO clinical stage III and IV were associated with LTFU while WHO clinical stage II, III and IV were associated with death. Suboptimal adherence was further associated with experience of drug side effects. Active support and close monitoring of patients who have signs of clinical progression and/or drug side effects could improve patient outcomes.

Global COVID-19 vaccine inequity: The scope, the impact, and the challenges.

Global vaccine inequity is prolonging the COVID-19 pandemic. Here, we outline the scope and impact of inequitable vaccine distribution and identify challenges in vaccine development, manufacturing, and distribution as well as potential solutions to address this crisis.

Neurologic Findings Among Inpatients With COVID-19 at a Safety-net US Hospital.

OBJECTIVE: To characterize the breadth of neurologic findings associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a diverse group of inpatients at an urban, safety-net US medical center. METHODS: Patients were identified through an electronic medical record review from April 15, 2020, until July 1, 2020, at a large safety-net hospital in Boston, MA, caring primarily for underserved, low-income, and elderly patients. All hospitalized adult patients with positive nasopharyngeal swab or respiratory PCR testing for SARS-CoV-2 during their hospitalization or in the 30 days before admission who received an inpatient neurologic or neurocritical care consultation or admission during the study period were enrolled. RESULTS: Seventy-four patients were identified (42/57% male, median age 64 years). The majority of patients self-identified as Black or African American (38, 51%). The most common neurologic symptoms at presentation to the hospital included altered mental status (39, 53%), fatigue (18, 24%), and headache (18, 18%). Fifteen patients had ischemic strokes (20%). There were 10 in-hospital mortalities, with moderately severe disability among survivors at discharge (14%, median modified Rankin Scale score of 4). CONCLUSIONS: Neurologic findings spanned inflammatory, vascular pathologies, sequelae of critical illness and metabolic derangements, possible direct involvement of the nervous system by SARS-CoV-2, and exacerbation of underlying neurologic conditions, highlighting a broad range of possible etiologies of neurologic complications in patients with coronavirus disease 2019 (COVID-19). Further studies are needed to characterize the infectious and postinfectious neurologic complications of COVID-19 in diverse patient populations.

Institutional policies and readiness in management of critical illness among patients with viral hemorrhagic fever.

OBJECTIVE: In response to the 2013-2016 Ebola virus disease outbreak, the US government designated certain healthcare institutions as Ebola treatment centers (ETCs) to better prepare for future emerging infectious disease outbreaks. This study investigated ETC experiences and critical care policies for patients with viral hemorrhagic fever (VHF). DESIGN: A 58-item questionnaire elicited information on policies for 9 critical care interventions, factors that limited care provision, and innovations developed to deliver care. SETTING AND PARTICIPANTS: The questionnaire was sent to 82 ETCs. METHODS: We analyzed ordinal and categorical data pertaining to the ETC characteristics and descriptive data about their policies and perceived challenges. Statistical analyses assessed whether ETCs with experience caring for VHF patients were more likely to have critical care policies than those that did not. RESULTS: Of the 27 ETCs who responded, 17 (63%) were included. Among them, 8 (47%) reported experience caring for persons under investigation or confirmed cases of VHF. Most felt ready to provide intubation, chest compressions, and renal replacement therapy to these patients. The factors most cited for limiting care were staff safety and clinical futility. Innovations developed to better provide care included increased simulation training and alternative technologies for procedures and communication. CONCLUSIONS: There were broad similarities in critical care policies and limitations among institutions. There were several interventions, namely ECMO and cricothyrotomy, which few institutions felt ready to provide. Future studies could identify obstacles to providing these interventions and explore policy changes after increased experience with novel infectious diseases, such as COVID-19.

A clinician's primer on epidemiology for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in a concomitant deluge of medical, biological, and epidemiologic research. Clinicians are interested in incorporating the best new evidence-based practices when treating individuals with COVID-19 and instituting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission prevention protocols. However, without sufficient background knowledge, evaluating epidemiologic studies can be challenging, and failure to identify sources of bias could lead to poor treatment decisions. Here we provide a brief primer on key concepts and terms related to COVID-19 epidemiology to provide clinicians with a starting point for evaluating the emerging COVID-19 literature.

Interruption of tuberculosis detection and care during the Ebola virus disease epidemic (2014-2015) in Liberia: time-series analyses for 2013-2017.

OBJECTIVE: Interrupted time-series analyses, using 5 years of routinely collected health information system data, were conducted to estimate the magnitude of impact of the 2014-2015 Ebola virus disease (EVD) epidemic and determine trends in tuberculosis (TB) care services in Liberia. METHODS: A segmented linear regression model was used to generate estimates and predictions for trends for three TB service indicators before, during, and after EVD, from January 2013 to December 2017. RESULTS: It was found that the number of presumptive TB cases declined significantly at the start of the EVD outbreak, with an estimated loss of 3222 cases (95% confidence interval (CI) -5691 to -752; P = 0.014). There was also an estimated loss of 709 cases per quarter post-EVD (95% CI -1346 to -71; P = 0.032). However, over the post-EVD period, quarterly increases were observed in the proportion of smear-positive to presumptive cases (1.45%, 95% CI 0.38% to 2.5%; P = 0.011) and the proportion of treatment success to TB cases evaluated (3.3%, 95% CI 0.82% to 5.79%; P = 0.013). CONCLUSIONS: These findings suggest that the EVD outbreak (2014-2015) negatively affected TB care services. Rigorous quantitative analyses can be used to assess the magnitude of interruption and advocate for preparedness in settings with limited healthcare capacity.

Optimizing Highly Infectious Disease Isolation Unit Management: Experiences From the Infectious Diseases Isolation and Research Unit, Fort Portal, Uganda.

Infectious disease outbreaks on the scale of the current coronavirus disease 2019 (COVID-19) pandemic are a new phenomenon in many parts of the world. Many isolation unit designs with corresponding workflow dynamics and personal protective equipment postures have been proposed for each emerging disease at the health facility level, depending on the mode of transmission. However, personnel and resource management at the isolation units for a resilient response will vary by human resource capacity, reporting requirements, and practice setting. This study describes an approach to isolation unit management at a rural Uganda Hospital and shares lessons from the Uganda experience for isolation unit managers in low- and middle-income settings.

Novel ELISA Protocol Links Pre-Existing SARS-CoV-2 Reactive Antibodies With Endemic Coronavirus Immunity and Age and Reveals Improved Serologic Identification of Acute COVID-19 via Multi-Parameter Detection.

The COVID-19 pandemic has drastically impacted work, economy, and way of life. Sensitive measurement of SARS-CoV-2 specific antibodies would provide new insight into pre-existing immunity, virus transmission dynamics, and the nuances of SARS-CoV-2 pathogenesis. To date, existing SARS-CoV-2 serology tests have limited utility due to insufficient reliable detection of antibody levels lower than what is typically present after several days of symptoms. To measure lower quantities of SARS-CoV-2 IgM, IgG, and IgA with higher resolution than existing assays, we developed a new ELISA protocol with a distinct plate washing procedure and timed plate development via use of a standard curve. Very low optical densities from samples added to buffer coated wells at as low as a 1:5 dilution are reported using this 'BU ELISA' method. Use of this method revealed circulating SARS-CoV-2 receptor binding domain (RBD) and nucleocapsid protein (N) reactive antibodies (IgG, IgM, and/or IgA) in 44 and 100 percent of pre-pandemic subjects, respectively, and the magnitude of these antibodies tracked with antibody levels of analogous viral proteins from endemic coronavirus (eCoV) strains. The disease status (HIV, SLE) of unexposed subjects was not linked with SARS-CoV-2 reactive antibody levels; however, quantities were significantly lower in subjects over 70 years of age compared with younger counterparts. Also, we measured SARS-CoV-2 RBD- and N- specific IgM, IgG, and IgA antibodies from 29 SARS-CoV-2 infected individuals at varying disease states, including 10 acute COVID-19 hospitalized subjects with negative serology results by the EUA approved Abbott IgG chemiluminescent microparticle immunoassay. Measurements of SARS-CoV-2 RBD- and N- specific IgM, IgG, IgA levels measured by the BU ELISA revealed higher signal from 9 of the 10 Abbott test negative COVID-19 subjects than all pre-pandemic samples for at least one antibody specificity/isotype, implicating improved serologic identification of SARS-CoV-2 infection via multi-parameter, high sensitive antibody detection. We propose that this improved ELISA protocol, which is straightforward to perform, low cost, and uses readily available commercial reagents, is a useful tool to elucidate new information about SARS-CoV-2 infection and immunity and has promising implications for improved detection of all analytes measurable by this platform.