Resilience of mental health services amidst Ebola disease outbreaks in Africa.

Introduction: Health systems including mental health (MH) systems are resilient if they protect human life and produce better health outcomes for all during disease outbreaks or epidemics like Ebola disease and their aftermaths. We explored the resilience of MH services amidst Ebola disease outbreaks in Africa; specifically, to (i) describe the pre-, during-, and post-Ebola disease outbreak MH systems in African countries that have experienced Ebola disease outbreaks, (ii) determine the prevalence of three high burden MH disorders and how those prevalences interact with Ebola disease outbreaks, and, (iii) describe the resilience of MH systems in the context of these outbreaks. Methods: This was a scoping review employing an adapted PRISMA statement. We conducted a five-step Boolean strategy with both free text and Medical Subject Headings (MeSH) to search 9 electronic databases and also searched WHO MINDbank and MH Atlas. Results: The literature search yielded 1,230 publications. Twenty-five studies were included involving 13,449 participants. By 2023, 13 African nations had encountered a total of 35 Ebola outbreak events. None of these countries had a metric recorded in MH Atlas to assess the inclusion of MH in emergency plans. The three highest-burden outbreak-associated MH disorders under the MH and Psychosocial Support (MHPSS) framework were depression, post-traumatic stress disorder (PTSD), and anxiety with prevalence ranges of 1.4-7%, 2-90%, and 1.3-88%, respectively. Furthermore, our analysis revealed a concerning lack of resilience within the MH systems, as evidenced by the absence of pre-existing metrics to gauge MH preparedness in emergency plans. Additionally, none of the studies evaluated the resilience of MH services for individuals with pre-existing needs or examined potential post-outbreak degradation in core MH services. Discussion: Our findings revealed an insufficiency of resilience, with no evaluation of services for individuals with pre-existing needs or post-outbreak degradation in core MH services. Strengthening MH resilience guided by evidence-based frameworks must be a priority to mitigate the long-term impacts of epidemics on mental well-being.

Evaluating the Performance of FlukeCatcher at Detecting Urogenital Schistosomiasis.

Urine filtration microscopy (UFM) lacks sensitivity in detecting low-intensity Schistosoma haematobium infections. In pursuit of a superior alternative, this study evaluated the performance of FlukeCatcher microscopy (FCM) at detecting S. haematobium eggs in human urine samples. Urine samples were collected from 572 school-age children in Afar, Ethiopia in July 2023 and examined using UFM and FCM approaches. Using the combined UFM and FCM results as a reference, the sensitivity, negative predictive value, and agreement levels for the two testing methods in detecting S. haematobium eggs in urine samples were calculated. The sensitivity and negative predictive value of detecting S. haematobium eggs in urine samples for FCM was 84% and 97%, respectively, compared to 65% and 93% for UFM. The FCM test results had an agreement of 61% with the UFM results, compared to 90% with the combined results of FCM and UFM. However, the average egg count estimates were lower when using FCM (6.6 eggs per 10 mL) compared to UFM (14.7 eggs per 10 mL) (p < 0.0001). Incorporating FCM into specimen processing could improve the diagnosis of S. haematobium infection but may underperform in characterizing the intensity of infection.

Antibiotic prophylaxis for leptospirosis.

BACKGROUND: Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in particular in travellers and high-risk groups. However, the clinical benefits are unknown, especially when considering possible treatment-associated adverse effects. This review assesses the use of antibiotic prophylaxis in leptospirosis and is an update of a previously published review in the Cochrane Library (2009, Issue 3). OBJECTIVES: To evaluate the benefits and harms of antibiotic prophylaxis for human leptospirosis. SEARCH METHODS: We identified randomised clinical trials through electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and other resources. We searched online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The last date of search was 17 April 2023. SELECTION CRITERIA: We included ⁠⁠randomised clinical trials of any trial design, assessing antibiotics for prevention of leptospirosis, and with no restrictions on age, sex, occupation, or comorbidity of trial participants. We looked for trials assessing antibiotics irrespective of route of administration, dosage, and schedule versus placebo or no intervention. We also included trials assessing antibiotics versus other antibiotics using these criteria, or the same antibiotic but with another dose or schedule. DATA COLLECTION AND ANALYSIS: We followed Cochrane methodology. The primary outcomes were all-cause mortality, laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases), clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation, clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases), and serious adverse events. The secondary outcomes were quality of life and the proportion of people with non-serious adverse events. We assessed the risk of bias of the included trials using the RoB 2 tool and the certainty of evidence using GRADE. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD), with their 95% confidence intervals (CI). We used a random-effects model for our main analyses and the fixed-effect model for sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up. MAIN RESULTS: We identified five randomised clinical trials comprising 2593 participants that compared antibiotics (doxycycline, azithromycin, or penicillin) with placebo, or one antibiotic compared with another. Four trials assessed doxycycline with different durations, one trial assessed azithromycin, and one trial assessed penicillin. One trial had three intervention groups: doxycycline, azithromycin, and placebo. Three trials assessed pre-exposure prophylaxis, one trial assessed postexposure prophylaxis, and one did not report this clearly. Four trials recruited residents in endemic areas, and one trial recruited soldiers who experienced limited time exposure. The participants' ages in the included trials were 10 to 80 years. Follow-up ranged from one to three months. Antibiotics versus placebo Doxycycline compared with placebo may result in little to no difference in all-cause mortality (RR 0.15, 95% CI 0.01 to 2.83; 1 trial, 782 participants; low-certainty evidence). Prophylactic antibiotics may have little to no effect on laboratory-confirmed leptospirosis, but the evidence is very uncertain (RR 0.56, 95% CI 0.25 to 1.26; 5 trials, 2593 participants; very low-certainty evidence). Antibiotics may result in little to no difference in the clinical diagnosis of leptospirosis regardless of laboratory confirmation (RR 0.76, 95% CI 0.53 to 1.08; 4 trials, 1653 participants; low-certainty evidence) and the clinical diagnosis of leptospirosis with laboratory confirmation (RR 0.57, 95% CI 0.26 to 1.26; 4 trials, 1653 participants; low-certainty evidence). Antibiotics compared with placebo may increase non-serious adverse events, but the evidence is very uncertain (RR 10.13, 95% CI 2.40 to 42.71; 3 trials, 1909 participants; very low-certainty evidence). One antibiotic versus another antibiotic One trial assessed doxycycline versus azithromycin but did not report mortality. Compared to azithromycin, doxycycline may have little to no effect on laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (RR 1.49, 95% CI 0.51 to 4.32; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), and on non-serious adverse events (RR 1.12, 95% CI 0.36 to 3.48; 1 trial, 137 participants), but the evidence is very uncertain. The certainty of evidence for all the outcomes was very low. None of the five included trials reported serious adverse events or assessed quality of life. One study is awaiting classification. Funding Four of the five trials included statements disclosing their funding/supporting sources, and the remaining trial did not include this. Three of the four trials that disclosed their supporting sources received the supply of trial drugs directly from the same pharmaceutical company, and the remaining trial received financial support from a governmental source. AUTHORS' CONCLUSIONS: We do not know if antibiotics versus placebo or another antibiotic has little or have no effect on all-cause mortality or leptospirosis infection because the certainty of evidence is low or very low. We do not know if antibiotics versus placebo may increase the overall risk of non-serious adverse events because of very low-certainty evidence. We lack definitive rigorous data from randomised trials to support the use of antibiotics for the prophylaxis of leptospirosis infection. We lack trials reporting data on clinically relevant outcomes.

Antibiotics for treatment of leptospirosis.

BACKGROUND: Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review. OBJECTIVES: To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis. SEARCH METHODS: We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023. SELECTION CRITERIA: We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported. DATA COLLECTION AND ANALYSIS: During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period. MAIN RESULTS: We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I2 = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I2 = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I2 = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies. AUTHORS' CONCLUSIONS: As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation.

Correction: Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines.

[This corrects the article DOI: 10.1371/journal.pmed.1003793.].

Modeling the Lassa fever outbreak synchronously occurring with cholera and COVID-19 outbreaks in Nigeria 2021: A threat to Global Health Security.

Nigeria struggles with seasonal outbreaks of Lassa fever (LF), with 70 to 100% of its states affected annually. Since 2018, the seasonal dynamics have changed with a stark increase in infections, though the pattern in 2021 differed from the other years. Nigeria had three outbreaks of Lassa Fever in 2021. In that year, Nigeria also experienced substantial burdens from COVID-19 and Cholera. There is potential that these three outbreak events interacted with each other. This may have been from community disruption and so changes in how people access the health system, how the health system responds, or overlapping biological interactions, misclassification, social factors, misinformation, and pre-existing disparities and vulnerabilities. We assessed the syndemic potential of Lassa Fever, COVID-19, and Cholera through modeling their interactions across the 2021 calendar year employing a Poisson regression model. We included the number of states affected and the month of the year. We used these predictors to forecast the progression of the outbreak using a Seasonal Autoregressive Integrated Moving Average (SARIMA) model. The Poisson model prediction for the confirmed number of Lassa fever cases was significantly dependent on the number of confirmed COVID-19 cases, the number of states affected, and the month of the year (p-value < 0.001), and the SARIMA model was a good fit, accounting for 48% of the change in the number of cases of Lassa fever (p-value < 0.001) with parameters ARIMA (6, 1, 3) (5, 0, 3). Lassa Fever, COVID-19, and Cholera 2021 case curves have mirrored dynamics and likely interact. Further research into common, intervenable aspects of those interactions should be performed.

An epidemiological synthesis of emerging and re-emerging zoonotic disease threats in Cameroon, 2000-2022: a systematic review.

Introduction: Population factors such as urbanization, socio-economic, and environmental factors are driving forces for emerging/re-emerging zoonotic diseases in Cameroon. To inform preparedness and prioritization efforts, this study mapped out epidemiological data (including prevalence) of zoonotic diseases occurring in Cameroon between 2000 and 2022 by demographic factors. Methods: Following the PRISMA guidelines, a protocol was registered in the PROSPERO database (CRD42022333059). Independent reviewers searched the PubMed, Embase, CINAHL, Cochrane, and Scopus databases on May 30, 2022 for relevant articles; duplicates were removed, and the titles, abstracts, and full texts were screened to identify eligible articles. Results: Out of 4142 articles identified, 64 eligible articles were retrieved in the database search and an additional 12 from the cited literature (N = 76). Thirty-five unique zoonoses (viral, bacterial, and parasitic) were indexed, including Cameroon priority zoonoses: anthrax, bovine tuberculosis, Ebola and Marburg virus disease, highly pathogenic avian influenza, and rabies. The number of studies varied by region, ranging from 12 in the Far North to 32 in the Centre Region. The most reported were as follows: brucellosis (random-effects pooled estimate proportion (effect size), ES 0.05%, 95% confidence interval (CI) 0.03-0.07; n = 6), dengue (ES 0.13%, 95% CI 0.06-0.22; n = 12), avian and swine influenza virus (ES 0.10%, 95% CI 0.04-0.20; n = 8), and toxoplasmosis (ES 0.49%, 95% CI 0.35-0.63; n = 11), although I 2 values were greater than 75%, thus there was high inter-study heterogeneity (P < 0.01). Conclusions: This understanding of the distribution of emerging and re-emerging zoonotic threats in Cameroon is vital to effective preventive and resource prioritization measures.

Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% ( sd , 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.

Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity.

Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES: Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS: Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log2 increase, 1.53; 95% CI, 1.17-2.00; p = 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors (p for interaction = 8.1 × 10-5). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19. ANGPTL4 single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls. CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.

Outbreak of SARS-CoV-2 B.1.617.2 (Delta Variant) in a Youth Camp Associated With Community Spread, Nebraska, June-July 2021.

OBJECTIVES: During June-July 2021, an outbreak of SARS-CoV-2 occurred among attendees of a summer youth camp in Nebraska. We assessed the factors that contributed to onward transmission of disease. METHODS: The Four Corners Health Department conducted an outbreak investigation and recorded both laboratory-confirmed and self-reported cases of SARS-CoV-2 and mitigation measures employed. We generated sequences on positive specimens, created an epidemic curve to assist with outbreak visualization, and examined epidemiologic, genomic, and laboratory outcomes. RESULTS: Evaluation of 3 index cases led to the identification of 25 people with COVID-19 who interacted directly with the camp. Contact tracing revealed an additional 18 cases consistent with onward community transmission. Most (24 of 35, 68.5%) vaccine-eligible community cases were not vaccinated. We sequenced 8 positive specimens; all were identified as the Delta variant. Precamp planning incorporated local health officials who recommended wearing face masks, practicing social distancing, and using attendee cohorts to limit mixing of people involved in various activities. CONCLUSION: Low vaccination levels and poor face mask-wearing habits among attendees resulted in secondary and tertiary spread of SARS-CoV-2 and severe outcomes among young adults. This outbreak of COVID-19 at a youth camp highlights the importance of vaccination and use of other measures to interrupt opportunities for SARS-CoV-2 spread in the community and shows that vaccinated people remain vulnerable to infection when in an environment of high exposure to SARS-CoV-2. Proactive case identification and interruption of chains of transmission can help decrease the number of cases and avoid further severe outcomes.

Access, socioeconomic environment, and death from COVID-19 in Nebraska.

Our study assesses whether factors related to healthcare access in the first year of the pandemic affect mortality and length of stay (LOS). Our cohort study examined hospitalized patients at Nebraska Medicine between April and October 2020 who were tested for SARS-CoV-2 and had a charted sepsis related diagnostic code. Multivariate logistic was used to analyze the odds of mortality and linear regression was used to calculate the parameter estimates of LOS associated with COVID-19 status, age, gender, race/ethnicity, median household income, admission month, and residential distance from definitive care. Among 475 admissions, the odds of mortality is greater among those with older age (OR: 1.04, 95% CI: 1.02-1.07) and residence in an area with low median household income (OR: 2.11, 95% CI: 0.52-8.57), however, the relationship between mortality and wealth was not statistically significant. Those with non-COVID-19 sepsis had longer LOS (Parameter Estimate: -5.11, adjusted 95% CI: -7.92 to -2.30). Distance from definitive care had trends toward worse outcomes (Parameter Estimate: 0.164, adjusted 95% CI: -1.39 to 1.97). Physical and social aspects of access to care are linked to poorer COVID-19 outcomes. Non-COVID-19 healthcare outcomes may be negatively impacted in the pandemic. Strategies to advance patient-centered outcomes in vulnerable populations should account for varied aspects (socioeconomic, residential setting, rural populations, racial, and ethnic factors). Indirect impacts of the pandemic on non-COVID-19 health outcomes require further study.

Severe Acute Respiratory Infection-Preparedness: Protocol for a Multicenter Prospective Cohort Study of Viral Respiratory Infections.

Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity. DESIGN: Prospective cohort study. SETTING: Multicenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States. PATIENTS: Patients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes. CONCLUSIONS: SARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI.

Fielding vaccines-challenges and opportunities in outbreaks, complex emergencies, and mass gatherings.

With the recent COVID-19 pandemic, the importance of vaccine development, distribution, and uptake has come to the forefront of the public eye. Effectively fielding vaccines during an emergency-whether that emergency is a result of an infectious disease or not-requires an understanding of usual vaccine-related processes; the impact of outbreak, complex emergencies, mass gatherings, and other events on patients, communities, and health systems; and ways in which diverse resources can be applied to successfully achieve needed vaccine uptake. In this review, both the emergency setting and briefly vaccine product design are discussed in these contexts in order to provide a concise source of general knowledge from experts in fielding vaccines that can aid in future vaccine ventures and increase general awareness of the process and barriers in various settings.

Heterogeneity and Risk of Bias in Studies Examining Risk Factors for Severe Illness and Death in COVID-19: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis synthesized the evidence on the impacts of demographics and comorbidities on the clinical outcomes of COVID-19, as well as the sources of the heterogeneity and publication bias of the relevant studies. Two authors independently searched the literature from PubMed, Embase, Cochrane library, and CINAHL on 18 May 2021; removed duplicates; screened the titles, abstracts, and full texts by using criteria; and extracted data from the eligible articles. The variations among the studies were examined by using Cochrane, Q.; I2, and meta-regression. Out of 11,975 articles that were obtained from the databases and screened, 559 studies were abstracted, and then, where appropriate, were analyzed by meta-analysis (n = 542). COVID-19-related severe illness, admission to the ICU, and death were significantly correlated with comorbidities, male sex, and an age older than 60 or 65 years, although high heterogeneity was present in the pooled estimates. The study design, the study country, the sample size, and the year of publication contributed to this. There was publication bias among the studies that compared the odds of COVID-19-related deaths, severe illness, and admission to the ICU on the basis of the comorbidity status. While an older age and chronic diseases were shown to increase the risk of developing severe illness, admission to the ICU, and death among the COVID-19 patients in our analysis, a marked heterogeneity was present when linking the specific risks with the outcomes.

Mumps to COVID-19: Vaccinated persons remain vulnerable when community uptake is low.

Vaccines against coronavirus disease 2019 (COVID-19) first became available in the United States and Europe outside clinical trials in December 2020, when administration began in high-priority populations such as healthcare workers and long-term care residents. [1] Since that time, global rollout progresses with wide variation in vaccination rates by country. [2] Depending upon product and SARS-CoV-2 variant, vaccine efficacies against infection range from approximately 70 to well over 90%, higher against severe disease. Well-resourced settings are starting to focus on booster doses among high risk persons, and locations with higher vaccination rates appear to have less COVID-19 patient and community impact. Yet, in every setting, primary vaccination to as many persons as possible remains incredibly important to effective pandemic risk management. Why this is the case, why even in settings with comparatively high vaccination rates and boosting we still should make the case that more primary vaccination matters can be answered by remembering mumps, and applying those lessons to promoting vaccine access.

The size and culturability of patient-generated SARS-CoV-2 aerosol.

BACKGROUND: Aerosol transmission of COVID-19 is the subject of ongoing policy debate. Characterizing aerosol produced by people with COVID-19 is critical to understanding the role of aerosols in transmission. OBJECTIVE: We investigated the presence of virus in size-fractioned aerosols from six COVID-19 patients admitted into mixed acuity wards in April of 2020. METHODS: Size-fractionated aerosol samples and aerosol size distributions were collected from COVID-19 positive patients. Aerosol samples were analyzed for viral RNA, positive samples were cultured in Vero E6 cells. Serial RT-PCR of cells indicated samples where viral replication was likely occurring. Viral presence was also investigated by western blot and transmission electron microscopy (TEM). RESULTS: SARS-CoV-2 RNA was detected by rRT-PCR in all samples. Three samples confidently indicated the presence of viral replication, all of which were from collected sub-micron aerosol. Western blot indicated the presence of viral proteins in all but one of these samples, and intact virions were observed by TEM in one sample. SIGNIFICANCE: Observations of viral replication in the culture of submicron aerosol samples provides additional evidence that airborne transmission of COVID-19 is possible. These results support the use of efficient respiratory protection in both healthcare and by the public to limit transmission.

How are healthcare provider systems preparing for health emergency situations?

Natural disasters, disease outbreaks, famine, and human conflict have strained communities everywhere over the course of human existence. However, modern changes in climate, human mobility, and other factors have increased the global community's vulnerability to widespread emergencies. We are in the midst of a disruptive health event, with the COVID-19 pandemic testing our health provider systems globally. This study presents a qualitative analysis of published literature, obtained systematically, to examine approaches health providers are taking to prepare for and respond to mass casualty incidents around the globe. The research reveals emerging trends in the weaknesses of systems' disaster responses while highlighting proposed solutions, so that others may better prepare for future disasters. Additionally, the research examines gaps in the literature, to foster more targeted and actionable contributions to the literature.

Uncertainty, scarcity and transparency: Public health ethics and risk communication in a pandemic.

Communicating public health guidance is key to mitigating risk during disasters and outbreaks, and ethical guidance on communication emphasizes being fully transparent. Yet, communication during the pandemic has sometimes been fraught, due in part to practical and conceptual challenges around being transparent. A particular challenge has arisen when there was both evolving scientific knowledge on COVID-19 and reticence to acknowledge that resource scarcity concerns were influencing public health recommendations. This essay uses the example of communicating public health guidance on masking in the United States to illustrate ethical challenges of developing and conveying public health guidance under twin conditions of uncertainty and resource scarcity. Such situations require balancing two key principles in public health ethics: the precautionary principle and harm reduction. Transparency remains a bedrock value to guide risk communication, but optimizing transparency requires consideration of additional ethical values in developing and implementing risk communication strategies.

Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines.

BACKGROUND: The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research. METHODS AND FINDINGS: We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies. CONCLUSIONS: These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.

The future of zoonotic risk prediction.

In the light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programmes will identify hundreds of novel viruses that might someday pose a threat to humans. To support the extensive task of laboratory characterization, scientists may increasingly rely on data-driven rubrics or machine learning models that learn from known zoonoses to identify which animal pathogens could someday pose a threat to global health. We synthesize the findings of an interdisciplinary workshop on zoonotic risk technologies to answer the following questions. What are the prerequisites, in terms of open data, equity and interdisciplinary collaboration, to the development and application of those tools? What effect could the technology have on global health? Who would control that technology, who would have access to it and who would benefit from it? Would it improve pandemic prevention? Could it create new challenges? This article is part of the theme issue 'Infectious disease macroecology: parasite diversity and dynamics across the globe'.