The interaction of disease transmission, mortality, and economic output over the first 2 years of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has caused over 7.02 million deaths as of January 2024 and profoundly affected most countries' Gross Domestic Product (GDP). Here, we study the interaction of SARS-CoV-2 transmission, mortality, and economic output between January 2020 and December 2022 across 25 European countries. METHODS: We use a Bayesian mixed effects model with auto-regressive terms to estimate the temporal relationships between disease transmission, excess deaths, changes in economic output, transit mobility and non-pharmaceutical interventions (NPIs) across countries. RESULTS: Disease transmission intensity (logRt) decreases GDP and increases excess deaths, where the latter association is longer-lasting. Changes in GDP as well as prior week transmission intensity are both negatively associated with each other (-0.241, 95% CrI: -0.295 - -0.189). We find evidence of risk-averse behaviour, as changes in transit and prior week transmission intensity are negatively associated (-0.055, 95% CrI: -0.074 to -0.036). Our results highlight a complex cost-benefit trade-off from individual NPIs. For example, banning international travel is associated with both increases in GDP (0.014, 0.002-0.025) and decreases in excess deaths (-0.014, 95% CrI: -0.028 - -0.001). Country-specific random effects, such as the poverty rate, are positively associated with excess deaths while the UN government effectiveness index is negatively associated with excess deaths. INTERPRETATION: The interplay between transmission intensity, excess deaths, population mobility and economic output is highly complex, and none of these factors can be considered in isolation. Our results reinforce the intuitive idea that significant economic activity arises from diverse person-to-person interactions. Our analysis quantifies and highlights that the impact of disease on a given country is complex and multifaceted. Long-term economic impairments are not fully captured by our model, as well as long-term disease effects (Long COVID).

Spatiotemporal dynamics and recurrence of chikungunya virus in Brazil: an epidemiological study.

BACKGROUND: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013. METHODS: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses. FINDINGS: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins. INTERPRETATION: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings. FUNDING: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Assessment of COVID-19 as the Underlying Cause of Death Among Children and Young People Aged 0 to 19 Years in the US.

Importance: COVID-19 was the underlying cause of death for more than 940 000 individuals in the US, including at least 1289 children and young people (CYP) aged 0 to 19 years, with at least 821 CYP deaths occurring in the 1-year period from August 1, 2021, to July 31, 2022. Because deaths among US CYP are rare, the mortality burden of COVID-19 in CYP is best understood in the context of all other causes of CYP death. Objective: To determine whether COVID-19 is a leading (top 10) cause of death in CYP in the US. Design, Setting, and Participants: This national population-level cross-sectional epidemiological analysis for the years 2019 to 2022 used data from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying cause of death in the US to identify the ranking of COVID-19 relative to other causes of death among individuals aged 0 to 19 years. COVID-19 deaths were considered in 12-month periods between April 1, 2020, and August 31, 2022, compared with deaths from leading non-COVID-19 causes in 2019, 2020, and 2021. Main Outcomes and Measures: Cause of death rankings by total number of deaths, crude rates per 100 000 population, and percentage of all causes of death, using the National Center for Health Statistics 113 Selected Causes of Death, for ages 0 to 19 and by age groupings (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years). Results: There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the US, ranking eighth among all causes of deaths, fifth in disease-related causes of deaths (excluding unintentional injuries, assault, and suicide), and first in deaths caused by infectious or respiratory diseases when compared with 2019. COVID-19 deaths constituted 2% of all causes of death in this age group. Conclusions and Relevance: The findings of this study suggest that COVID-19 was a leading cause of death in CYP. It caused substantially more deaths in CYP annually than any vaccine-preventable disease historically in the recent period before vaccines became available. Various factors, including underreporting and not accounting for COVID-19's role as a contributing cause of death from other diseases, mean that these estimates may understate the true mortality burden of COVID-19. The findings of this study underscore the public health relevance of COVID-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, appropriate pharmaceutical and nonpharmaceutical interventions (eg, vaccines, ventilation, air cleaning) will continue to play an important role in limiting transmission of the virus and mitigating severe disease in CYP.

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Report 46: Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals.

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma's spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma's detection, and were largely transient after Gamma's detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil's COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. NOTE: The following manuscript has appeared as 'Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals' at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875 . ONE SENTENCE SUMMARY: COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice.

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples. Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2. Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

Global disparities in SARS-CoV-2 genomic surveillance.

Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness.

Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study.

BACKGROUND: COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. METHODS: Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. FINDINGS: In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. INTERPRETATION: Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.