Multi-cell type deconvolution using a probabilistic model for single-molecule DNA methylation haplotypes (preprint)

Background: Deconvolution is used to estimate the proportion of mixed cell types from tissue or blood samples based on genomic profiling. DNA methylation is commonly used because specific CpG positions reflect cell type identity and can be accurately measured at either the population or single-molecule level. Methylation sequencing techniques can profile multiple individual CpGs on a single DNA molecule, but few deconvolution models have been developed to exploit these single-molecule methylation haplotypes for cell type deconvolution. Results and Conclusions: We used simulated whole-genome methylation data and in silico mixtures of real data to compare existing deconvolution tools with two new models developed here. We found that adapting an existing model CelFiE to incorporate methylation haplotype information improved deconvolution accuracy by ~30% over other tools, including the original CelFiE. In addition to overall higher accuracy, our new tool CelFiE Integrated Single-molecule Haplotypes (or CelFiE-ISH) outperformed others in detecting rare cell types present at 0.1% and below. Detection of rare cell types is important for the analysis of circulating DNA, which we demonstrate using a patient-derived plasma sequencing dataset.Finally,we show that marker selection strategy has a strong effect on deconvolution accuracy, concluding that haplotype-aware deconvolution can take advantage of markers tailored for that purpose.

Taking hospital pathogen surveillance to the next level.

High-throughput bacterial genomic sequencing and subsequent analyses can produce large volumes of high-quality data rapidly. Advances in sequencing technology, with commensurate developments in bioinformatics, have increased the speed and efficiency with which it is possible to apply genomics to outbreak analysis and broader public health surveillance. This approach has been focused on targeted pathogenic taxa, such as Mycobacteria, and diseases corresponding to different modes of transmission, including food-and-water-borne diseases (FWDs) and sexually transmitted infections (STIs). In addition, major healthcare-associated pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and carbapenemase-producing Klebsiella pneumoniae are the focus of research projects and initiatives to understand transmission dynamics and temporal trends on both local and global scales. Here, we discuss current and future public health priorities relating to genome-based surveillance of major healthcare-associated pathogens. We highlight the specific challenges for the surveillance of healthcare-associated infections (HAIs), and how recent technical advances might be deployed most effectively to mitigate the increasing public health burden they cause.

Challenges of COVID-19 Case Forecasting in the US, 2020-2021 (preprint)

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naive baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making. Author SummaryAs SARS-CoV-2 began to spread throughout the world in early 2020, modelers played a critical role in predicting how the epidemic could take shape. Short-term forecasts of epidemic outcomes (for example, infections, cases, hospitalizations, or deaths) provided useful information to support pandemic planning, resource allocation, and intervention. Yet, infectious disease forecasting is still a nascent science, and the reliability of different types of forecasts is unclear. We retrospectively evaluated COVID-19 case forecasts, which were often unreliable. For example, forecasts did not anticipate the speed of increase in cases in early winter 2020. This analysis provides insights on specific problems that could be addressed in future research to improve forecasts and their use. Identifying the strengths and weaknesses of forecasts is critical to improving forecasting for current and future public health responses.

Key challenges for the surveillance of respiratory viruses: transitioning out of the acute phase of the SARS-CoV-2 pandemic (preprint)

To support the ongoing management of viral respiratory diseases, many countries are moving towards an integrated model of surveillance for SARS-CoV-2, influenza, and other respiratory pathogens. While many surveillance approaches catalysed by the COVID-19 pandemic provide novel epidemiological insight, continuing them as implemented during the pandemic is unlikely to be feasible for non-emergency surveillance, and many have already been scaled back. Furthermore, given anticipated co-circulation of SARS-CoV-2 and influenza, surveillance activities in place prior to the pandemic require review and adjustment to ensure their ongoing value for public health. In this perspective, we highlight key challenges for the development of integrated models of surveillance. We discuss the relative strengths and limitations of different surveillance practices and studies, their contribution to epidemiological assessment, forecasting, and public health decision making.

At the intersection of trust and mistrust: A qualitative analysis of motivators and barriers to research participation at a safety-net hospital.

INTRODUCTION: The underrepresentation of Black, Indigenous, and People of Color (BIPOC) individuals in healthcare research limits generalizability and contributes to healthcare inequities. Existing barriers and attitudes toward research participation must be addressed to increase the representation of safety net and other underserved populations. METHODS: We conducted semi-structured qualitative interviews with patients at an urban safety net hospital, focusing on facilitators, barriers, motivators, and preferences for research participation. We conducted direct content analysis guided by an implementation framework and used rapid analysis methods to generate final themes. RESULTS: We completed 38 interviews and identified six major themes related to preferences for engagement in research participation: (1) wide variation in research recruitment preferences; (2) logistical complexity negatively impacts willingness to participate; (3) risk contributes to hesitation toward research participation; (4) personal/community benefit, interest in study topic, and compensation serve as motivators for research participation; (5) continued participation despite reported shortcomings of informed consent process; and (6) mistrust could be overcome by relationship or credibility of information sources. CONCLUSION: Despite barriers to participation in research studies among safety-net populations, there are also facilitators that can be implemented to increase knowledge and comprehension, ease of participation, and willingness to join research studies. Study teams should vary recruitment and participation methods to ensure equal access to research opportunities. PATIENT/PUBLIC CONTRIBUTION: Our analysis methods and study progress were presented to individuals within the Boston Medical Center healthcare system. Through this process community engagement specialists, clinical experts, research directors, and others with significant experience working with safety-net populations supported data interpretation and provided recommendations for action following the dissemination of data.

Rapid SARS-CoV-2 testing with duplexed recombinase polymerase amplification and a bacteriophage internal control

OBJECTIVES/GOALS: Current COVID-19 rapid molecular tests require cartridge-reader detection, expensive circuitry, and complex microfluidics making the most accurate tests unavailable to the masses. Here we present a rapid molecular diagnostic leveraging isothermal amplification and paper-based microfluidics for a low-cost ultra-sensitive COVID-19 assay. METHODS/STUDY POPULATION: We designed a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of SARS-CoV-2 and bacteriophage MS2 RNA. RT-RPA is a sequence specific, ultrasensitive, rapid isothermal DNA amplification technique that is well suited to home based testing due to its rapid assay time, robustness, ease of use, and readout options. RT-RPA reagents are added to a tube and incubated at 39°C in a fluorometer. Realtime fluorometer data gives results in under 15 minutes. This assay also provides visual detection via lateral flow readout with results in 23 minutes. RESULTS/ANTICIPATED RESULTS: We have developed a rapid multiplexed nucleic acid amplification assay with an internal process control for SARS-CoV-2 using single-pot RT-RPA. We screened 21 primer combinations to select primers that demonstrated excellent performance and target specificity against common respiratory viruses. We demonstrate the ability to multiplex SARS-CoV-2 and MS2 detection, utilizing MS2 as an internal process control for lysis, reverse transcription, amplification, and readout. We show duplexed detection using both fluorescence readout and visual readout using lateral flow strips. Duplexed fluorescence detection shows a limit of detection of 25 copies per reaction. Duplexed lateral flow readout shows a limit of detection of 50 copies per reaction DISCUSSION/SIGNIFICANCE: We developed a duplexed RT-RPA assay for SARS-CoV-2 with fluorescence or lateral flow readout. Our assay does not re-quire expensive reader, circuity, or fluid handling. The low material cost, temperature, and robustness make it ideal for a more accurate home-based COVID-19 diagnostic.

Effect of COVID-19 pandemic on outcomes in intracerebral hemorrhage.

OBJECTIVES: Patients with severe intracerebral hemorrhage (ICH) often suffer from impaired capacity and rely on surrogates for decision-making. Restrictions on visitors within healthcare facilities during the pandemic may have impacted care and disposition for patient with ICH. We investigated outcomes of ICH patients during the COVID-19 pandemic compared to a pre-pandemic period. MATERIALS AND METHODS: We conducted a retrospective review of ICH patients from two sources: (1) University of Rochester Get With the Guidelines database and (2) the California State Inpatient Database (SID). Patients were divided into 2019-2020 pre-pandemic and 2020 pandemic groups. We compared mortality, discharge, and comfort care/hospice. Using single-center data, we compared 30-day readmissions and follow-up functional status. RESULTS: The single-center cohort included 230 patients (n = 122 pre-pandemic, n = 108 pandemic group), and the California SID included 17,534 patients (n = 10,537 pre-pandemic, n = 6,997 pandemic group). Inpatient mortality was no different before or during the pandemic in either cohort. Length of stay was unchanged. During the pandemic, more patients were discharged to hospice in the California SID (8.4% vs. 5.9%, p<0.001). Use of comfort care was similar before and during the pandemic in the single center data. Survivors in both datasets were more likely to be discharged home vs. facility during the pandemic. Thirty-day readmissions and follow-up functional status in the single-center cohort were similar between groups. CONCLUSIONS: Using a large database, we identified more ICH patients discharged to hospice during the COVID-19 pandemic and, among survivors, more patients were discharged home rather than healthcare facility discharge during the pandemic.

The impact of COVID-19 on the motivations of women seeking a uterus transplant.

Aim: The aim of this study was to investigate the change if any, in the motivations of women seeking a UTx and determine the impact of the COVID-19 pandemic. Methods: A cross-sectional survey. Results: 59% of women answered they were more motivated in achieving a pregnancy following the COVID-19 pandemic. 80% strongly agreed or agreed the pandemic had no impact on their motivation for a UTx, and 75% strongly agreed or agreed their desire for a baby strongly outweighs the risks of undergoing a UTx during a pandemic. Conclusion: Women continue to express a high level of motivation and desire for a UTx despite the risks imposed by the COVID-19 pandemic.

"Community members have more impact on their neighbors than celebrities": leveraging community partnerships to build COVID-19 vaccine confidence.

BACKGROUND: Vaccines are a strong public health tool to protect against severe disease, hospitalization, and death from COVID-19. Still, inequities in COVID-19 vaccination rates and health outcomes continue to exist among Black and Latino populations. Boston Medical Center (BMC) has played a significant role in vaccinating medically underserved populations, and organized a series of community-engaged conversations to better understand community concerns regarding the COVID-19 vaccine. This paper describes the themes which resulted from these community-engaged conversations and proposes next steps for healthcare leaders. METHODS: We accessed nine publicly available recordings of the community-engaged conversations which were held between March 2021 and September 2021 and ranged from 8 to 122 attendees. Six conversations prioritized specific groups: the Haitian-Creole community, the Cape Verdean community, the Latino community, the Black Christian Faith community, guardians who care for children living with disabilities, and individuals affected by systemic lupus erythematosus. Remaining conversations targeted the general public of the Greater Boston Area. We employed a Consolidated Framework for Implementation Research-driven codebook to code our data. Our analysis utilized a modified version of qualitative rapid analysis methods. RESULTS: Five main themes emerged from these community-engaged conversations: (1) Structural factors are important barriers to COVID-19 vaccination; (2) Mistrust exists due to the negative impact of systemic oppression and perceived motivation of the government; (3) There is a desire to learn more about biological and clinical characteristics of the COVID-19 vaccine as well as the practical implications of being vaccinated; (4) Community leaders emphasize community engagement for delivering COVID-19 information and education and; (5) Community leaders believe that the COVID-19 vaccine is a solution to address the pandemic. CONCLUSION: This study illustrates a need for community-engaged COVID-19 vaccine messaging which reflects the nuances of the COVID-19 vaccine and pandemic without oversimplifying information. In highlighting common concerns of the Greater Boston Area which contribute to a lack of confidence in the COVID-19 vaccine, we underscore important considerations for public health and healthcare leadership in the development of initiatives which work to advance health equity.

Keep It Up! 3.0: Study protocol for a type III hybrid implementation-effectiveness cluster-randomized trial.

BACKGROUND: Despite evidence that eHealth approaches can be effective in reducing HIV risk, their implementation requirements for public health scale up are not well established, and effective strategies to bring these programs into practice are still unknown. Keep It Up! (KIU!) is an online program proven to reduce HIV risk among young men who have sex with men (YMSM) and ideal candidate to develop and evaluate novel strategies for implementing eHealth HIV prevention programs. KIU! 3.0 is a Type III Hybrid Effectiveness-Implementation cluster randomized trial designed to 1) compare two strategies for implementing KIU!: community-based organizations (CBO) versus centralized direct-to-consumer (DTC) recruitment; 2) examine the effect of strategies and determinants on variability in implementation success; and 3) develop materials for sustainment of KIU! after the trial concludes. In this article, we describe the approaches used to achieve these aims. METHODS: Using county-level population estimates of YMSM, 66 counties were selected and randomized 2:1 to the CBO and DTC approaches. The RE-AIM model was used to drive outcome measurements, which were collected from CBO staff, YMSM, and technology providers. Mixed-methods research mapped onto the domains of the Consolidated Framework for Implementation Research will examine determinants and their relationship with implementation outcomes. DISCUSSION: In comparing our implementation recruitment models, we are examining two strategies which have shown effectiveness in delivering health technology interventions in the past, yet little is known about their comparative advantages and disadvantages in implementation. The results of the trial will further the understanding of eHealth prevention intervention implementation.

Social egg freezing: Motivations, treatment experiences and the impact of Covid-19 - a single-center experience.

INTRODUCTION: This study aims to assess the motivations and treatment experiences of women undergoing social egg freezing and to understand the impact of the Covid-19 pandemic. MATERIAL AND METHODS: Between January 2011 to December 2021, 191 social egg freezing patients were recruited from the Lister Fertility Clinic, London UK. Participants completed a validated questionnaire investigating patients' perspectives of social egg freezing. A response rate of 46.6% was achieved. RESULTS: In all, 93.9% of women expressed concern regarding age-related fertility decline which influenced their decision to undergo social egg freezing. The majority (89.5%) of women were not in a relationship at the time of social egg freezing and considered this a motivating factor. Also, 39.0% of participants had side effects related to treatment which affected work and social life. Participants were significantly more likely to experience side effects if they underwent multiple egg freezing cycles (χ2 , p < 0.01) or if they cryopreserved oocytes during the COVID-19 pandemic (χ2 , p < 0.05). Of the women, 64.0% wished to have cryopreserved oocytes at a younger age, a view significantly more likely if older than 37 years at first social egg freezing cycle (χ2 , p < 0.001). Also, 82.3% of women reported their decision to undergo social egg freezing was not delayed due to concerns regarding COVID-19 exposure during treatment; 44.1% considered the pandemic made them more willing to undergo social egg freezing. CONCLUSIONS: Most participants did not regret their decision to undergo social egg freezing but the majority wished they had cryopreserved oocytes at a younger age. This highlights the importance of early education to optimize outcomes and patient choice. The egg freezing process can be stressful, women may have concerns around social egg freezing and unprecedented situations such as the COVID-19 pandemic may alter treatment experience.

Evaluating disparities by social determinants in hospital admission decisions for patients with COVID-19 quaternary hospital early in the pandemic.

The COVID-19 pandemic has highlighted significant disparities in hospital outcomes when focusing on social determinants of health. Better understanding the drivers of these disparities is not only critical for COVID-19 care but also to ensure equitable treatment more generally. In this paper, we look at how hospital admission patterns, both to the medical ward and the intensive care unit (ICU), may have differed by race, ethnicity, and social determinants of health. We conducted a retrospective chart review of all patients who presented to the Emergency Department of a large quaternary hospital between March 8 and June 3, 2020. We built logistic regression models to analyze how race, ethnicity, area deprivation index, English as a primary language, homelessness, and illicit substance use impacted the likelihood of admission while controlling for disease severity and timing of admission in relation to the start of data collection. We had 1302 recorded Emergency Department visits of patients diagnosed with SARS-CoV-2. White, Hispanic, and African American patients made up 39.2%, 37.5%, and 10.4% of the population respectively. Primary language was recorded as English for 41.2% and non-English for 30% of patients. Among the social determinants of health assessed, we found that illicit drug use significantly increased the likelihood for admission to the medical ward (odds ratio 4.4, confidence interval 1.1-17.1, P = .04), and that having a language other than English as a primary language significantly increased the likelihood of ICU admission (odds ratio 2.6, confidence interval 1.2-5.7, P = .02). Illicit drug use was associated with an increased likelihood of medical ward admission, potentially due to clinician concerns for complicated withdrawal or blood-stream infections from intravenous drug use. The increased likelihood of ICU admission associated with a primary language other than English may have been driven by communication difficulties or differences in disease severity that our model did not detect. Further work is required to better understand drivers of disparities in hospital COVID-19 care.

Towards Equitable Access to Public Health Pathogen Genomics in the Western Pacific.

The COVID-19 pandemic has increased interest and understanding of the utility of pathogen genomics across the Western Pacific region. Access to genomic data enhances surveillance and response to COVID-19, and will also support surveillance of other infectious diseases and antimicrobial resistant pathogens. Models of access can be determined based on intended purpose, use and sustainability. Achieving equitable access to genomics across the Western Pacific will contribute to the development of a regional public health genomics network to respond to major disease threats in the future.

The dental triage method at Rothschild Hospital during the first lockdown due to the COVID-19 pandemic.

OBJECTIVE: This study aims to (1) assess the efficacy of a face-to-face emergency protocol in children and adults and (2) measure the efficacies of prediagnosis at the triage level and clinical diagnosis at the emergency department level during the COVID-19 pandemic. METHODS: A triage protocol was applied for patients at the entry of the Rothschild Hospital (AP-HP) between March 18th and May 11th, 2020. First, patients underwent a triage based on self-reported symptoms. If their condition was deemed urgent, they were oriented toward dental professionals, who performed an intraoral examination leading to a clinical diagnosis. Triage and diagnoses were categorized into four emergency groups: infectious, prosthetic, traumatic, and others. The agreement between triage and clinical diagnosis was tested (χ2 test). Positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity for each diagnostic category were assessed to evaluate the performance and efficacy of the triage. RESULTS: Out of 1562 dental visits, 1064 were included in this analysis. The most frequently reported symptoms by children at triage were pain (31.5%) and trauma (22%). Adults mainly complained of abscesses (45.1%) and pulpitis (20.5%). The most frequent clinical diagnoses were abscesses (29.2%) and pulpitis (20.5%) among children and adults, respectively. Tooth extraction was the most frequent treatment modality. Systemic antibiotics were prescribed for 49.2% of patients. Regardless of the age class, the PPV was high for groups 1 to 3, ranging from 78.9% to 100%. The NPV was high in all groups, ranging from 68.8% to 99.1%. CONCLUSION: This study demonstrates that the triage implanted during the first COVID-19 lockdown was effective and is an appropriate tool for the referral of adults and children before clinical examination.

Evolutionary rate of SARS-CoV-2 increases during zoonotic infection of farmed mink.

To investigate genetic signatures of adaptation to the mink host, we characterised the evolutionary rate heterogeneity in mink-associated severe acute respiratory syndrome coronaviruses (SARS-CoV-2). In 2020, the first detected anthropozoonotic spillover event of SARS-CoV-2 occurred in mink farms throughout Europe and North America. Both spill-back of mink-associated lineages into the human population and the spread into the surrounding wildlife were reported, highlighting the potential formation of a zoonotic reservoir. Our findings suggest that the evolutionary rate of SARS-CoV-2 underwent an episodic increase upon introduction into the mink host before returning to the normal range observed in humans. Furthermore, SARS-CoV-2 lineages could have circulated in the mink population for a month before detection, and during this period, evolutionary rate estimates were between 3 × 10-3 and 1.05 × 10-2 (95 per cent HPD, with a mean rate of 6.59 × 10-3) a four- to thirteen-fold increase compared to that in humans. As there is evidence for unique mutational patterns within mink-associated lineages, we explored the emergence of four mink-specific Spike protein amino acid substitutions Y453F, S1147L, F486L, and Q314K. We found that mutation Y453F emerged early in multiple mink outbreaks and that mutations F486L and Q314K may co-occur. We suggest that SARS-CoV-2 undergoes a brief, but considerable, increase in evolutionary rate in response to greater selective pressures during species jumps, which may lead to the occurrence of mink-specific mutations. These findings emphasise the necessity of ongoing surveillance of zoonotic SARS-CoV-2 infections in the future.

Bioinformatic investigation of discordant sequence data for SARS-CoV-2: insights for robust genomic analysis during pandemic surveillance (preprint)

The capacity to undertake whole genome sequencing (WGS) in public health laboratories (PHLs) has grown rapidly in response to COVID-19, and SARS-CoV-2 genomic data has been invaluable for managing the pandemic. The public health response has been further supported by the rapid upgrade and implementation of laboratory and bioinformatic resources. However, there remains a high degree of variability in methods and capabilities between laboratories. In addition to evolving methodology and improved understanding of SARS-CoV-2, public health laboratories have become strained during surges in case numbers, adding to the difficulty of ensuring the highest data accuracy. Here, we formed a national working group comprised of laboratory scientists and bioinformaticians from Australia and New Zealand to improve data concordance across PHLs. Through investigating discordant sequence data from Australia's first external SARS-CoV-2 WGS proficiency testing program (PTP), we show that most discrepancies in genome assessment arose from intrahost variation. While others could be remedied using reasonable, parsimonious bioinformatic quality control. Furthermore, we demonstrate how multidisciplinary national working groups can inform guidelines in real time for bioinformatic quality acceptance criteria. Provision of technical feedback allows laboratory improvement during a pandemic in real time, enhancing public health responses.

The impact of the COVID-19 pandemic on perinatal services and maternal mental health in the UK.

BACKGROUND: COVID-19 has created many challenges for women in the perinatal phase. This stems from prolonged periods of lockdowns, restricted support networks and media panic, alongside altered healthcare provision. AIMS: We aimed to review the evidence regarding the psychological impact on new and expecting mothers following changes to antenatal and postnatal service provision within the UK throughout the pandemic. METHOD: We conducted a narrative literature search of major databases (PubMed, Medline, Google Scholar). The literature was critically reviewed by experts within the field of antenatal and perinatal mental health. RESULTS: Changes to service provision, including the introduction of telemedicine services, attendance of antenatal appointments without partners or loved ones, and lack of support during the intrapartum period, are associated with increased stress, depression and anxiety. Encouraging women and their partners to engage with aspects of positive psychology through newly introduced digital platforms and virtual service provision has the potential to improve access to holistic care and increase mental well-being. An online course, designed by Imperial College Healthcare NHS Trust in response to changes to service provision, focuses on postnatal recovery inspiration and support for motherhood (PRISM) through a 5-week programme. So far, the course has received positive feedback. CONCLUSIONS: The pandemic has contributed to increased rates of mental illness among pregnant and new mothers in the UK. Although the long-term implications are largely unpredictable, it is important to anticipate increased prevalence and complexity of symptoms, which could be hugely detrimental to an already overburdened National Health Service.

Laboratory test trends within 72 hours of hospital admission associated with death among COVID-19 patients.

Early identification of patients at risk for severe coronavirus disease 2019 (COVID-19) is crucial for appropriate triage and determination of need for closer monitoring. Few studies have examined laboratory trends in COVID-19 infection and sought to quantify the degree to which laboratory values affect mortality. We conducted a retrospective cohort (n = 407) study of hospitalized patients with COVID-19 early in the course of the pandemic, from March 16th to April 8th, 2020 and compared baseline to repeat laboratory testing 72 hours into admission. The primary outcome was death. We found that rises of 25 mg/L C-reactive protein, 50 units/L lactate dehydrogenase, and 100 ng/mL ferritin were associated with 23%, 28%, and 1% increased odds of death, respectively. In contrast, changes in fibrinogen, D-dimer, white blood cell count, and creatinine in the first few days of hospital admission were not associated with mortality. These quantitative findings may assist clinicians in determining the risk of potential clinical decline in patients with COVID-19 and influence early management.

The epidemiology of the COVID-19 pandemic in the small, low-resource country of Timor-Leste, January 2020 - June 2022.

Abstract: Timor-Leste, a small, mountainous half-island nation which shares a land border with Indonesia and which is 550 km from Australia, has a population of 1.3 million and achieved independence for the second time in 2002. It is one of the poorest nations in Asia. In response to the global coronavirus disease 2019 (COVID-19) pandemic, the Timor-Leste Ministry of Health undertook surveillance and contact tracing activities on all notified COVID-19 cases. Between 1 January 2020 and 30 June 2022, there were 22,957 cases of COVID-19 notified which occurred in three waves, the first which was delayed until April 2021 (community transmission of B.1.466.2 variant following major flooding), followed by waves in August 2021 (B.1.617.2 Delta variant transmission) and February 2022 (B.1.1.529 Omicron variant transmission). There were 753 people hospitalised due to COVID-19 and 133 deaths. Of the 133 deaths, 122 (92%) were considered not fully vaccinated (< 2 COVID-19 vaccines) and none had received boosters. Timor-Leste implemented measures to control COVID-19, including: rapid closure of international borders; isolation of cases; quarantining of international arrivals and close contacts; restrictions on internal travel; social and physical distancing; and, finally, a country-wide vaccination program. The health system's capacity was never exceeded.