The importance of non-pharmaceutical interventions during the COVID-19 vaccine rollout

The promise of efficacious vaccines against SARS-CoV-2 is fulfilled and vaccination campaigns have started worldwide. However, the fight against the pandemic is far from over. Here, we propose an age-structured compartmental model to study the interplay of disease transmission, vaccines rollout, and behavioural dynamics. We investigate, via in-silico simulations, individual and societal behavioural changes, possibly induced by the start of the vaccination campaigns, and manifested as a relaxation in the adoption of non-pharmaceutical interventions. We explore different vaccination rollout speeds, prioritization strategies, vaccine efficacy, as well as multiple behavioural responses. We apply our model to six countries worldwide (Egypt, Peru, Serbia, Ukraine, Canada, and Italy), selected to sample diverse socio-demographic and socio-economic contexts. To isolate the effects of age-structures and contacts patterns from the particular pandemic history of each location, we first study the model considering the same hypothetical initial epidemic scenario in all countries. We then calibrate the model using real epidemiological and mobility data for the different countries. Our findings suggest that early relaxation of safe behaviours can jeopardize the benefits brought by the vaccine in the short term: a fast vaccine distribution and policies aimed at keeping high compliance of individual safe behaviours are key to mitigate disease resurgence.

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Optimizing the spatio-temporal allocation of COVID-19 vaccines: Italy as a case study

10.1101/2021.05.06.21256732 ◽

2021 ◽

Author(s):

Joseph Chadi Lemaitre ◽

Damiano Pasetto ◽

Mario Zanon ◽

Enrico Bertuzzo ◽

Lorenzo Mari ◽

...

Keyword(s):

Optimal Control ◽

Disease Transmission ◽

Population Distribution ◽

Transmission Rate ◽

Supply And Distribution ◽

Simple Alternative ◽

Spatio Temporal ◽

Vaccine Distribution ◽

Vaccination Campaigns ◽

Allocation Strategies

While SARS-CoV-2 vaccine distribution campaigns are underway across the world, communities face the challenge of a fair and effective distribution of limited supplies. We wonder whether suitable spatial allocation strategies might significantly improve a campaign's efficacy in averting damaging outcomes. To that end, we address the problem of optimal control of COVID-19 vaccinations in a country-wide geographic and epidemiological context characterized by strong spatial heterogeneities in transmission rate and disease history. We seek the vaccine allocation strategies in space and time that minimize the number of infections in a prescribed time horizon. We examine scenarios of unfolding disease transmission across the 107 provinces of Italy, from January to April 2021, generated by a spatially explicit compartmental COVID-19 model tailored to the Italian geographic and epidemiological context. We develop a novel optimal control framework to derive optimal vaccination strategies given the epidemiological projections and constraints on vaccine supply and distribution logistic. Optimal schemes significantly outperform simple alternative allocation strategies based on incidence, population distribution, or prevalence of susceptibles in each province. Our results suggest that the complex interplay between the mobility network and the spatial heterogeneities imply highly non-trivial prioritization of local vaccination campaigns. The extent of the overall improvements in the objectives grants further inquiry aimed at refining other possibly relevant factors so far neglected. Our work thus provides a proof-of-concept of the potential of optimal control for complex and heterogeneous epidemiological contexts at country, and possibly global, scales.

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Early Phase of the COVID-19 Outbreak in Hungary and Post-Lockdown Scenarios

Viruses ◽

10.3390/v12070708 ◽

2020 ◽

Vol 12 (7) ◽

pp. 708 ◽

Cited By ~ 4

Author(s):

Gergely Röst ◽

Ferenc A. Bartha ◽

Norbert Bogya ◽

Péter Boldog ◽

Attila Dénes ◽

...

Keyword(s):

Statistical Analysis ◽

Spatial Heterogeneity ◽

Early Phase ◽

Disease Burden ◽

Compartmental Model ◽

Seasonal Effects ◽

Low Levels ◽

Age Structured ◽

Epidemic Wave ◽

Pharmaceutical Interventions

COVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a considerable reduction in the number of contacts and transmission of the virus. This strategy was effective in preventing epidemic growth and reducing the incidence of COVID-19 to low levels. In this report, we present the first epidemiological and statistical analysis of the early phase of the COVID-19 outbreak in Hungary. Then, we establish an age-structured compartmental model to explore alternative post-lockdown scenarios. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed.

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Ranking the Effectiveness of Non-Pharmaceutical Interventions to Counter COVID-19 in UK Universities with Vaccinated Population

10.1101/2021.11.07.21266028 ◽

2021 ◽

Author(s):

Zirui Niu ◽

Giordano Scarciotti

Keyword(s):

Optimal Control ◽

Compartmental Model ◽

Optimal Control Problems ◽

Control Problems ◽

Minimum Number ◽

Input Variables ◽

Campus Activities ◽

Vaccination Campaigns ◽

Pharmaceutical Interventions ◽

Environmental Disinfection

Several universities around the world have resumed in-person teaching after successful vaccination campaigns have covered 70/80% of the population. In this study, we combine a new compartmental model with an optimal control formulation to discover, among different non-pharmaceutical interventions, the best prevention strategy to maximize on-campus activities while keeping spread under control. Composed of two interconnected Susceptible-Exposed-Infected-Quarantined-Recovered (SEIQR) structures, the model enables staff-to-staff infections, student-to-staff cross infections, student-to-student infections, and environment-to-individual infections. Then, we model input variables representing the implementation of different non-pharmaceutical interventions and formulate and solve optimal control problems for four desired scenarios: minimum number of cases, minimum intervention, minimum non-quarantine intervention, and minimum quarantine intervention. Our results reveal the particular significance of mask wearing and social distancing in universities with vaccinated population (with proportions according to UK data). The study also reveals that quarantining infected students has a higher importance than quarantining staff. In contrast, other measures such as environmental disinfection seems to be less important.

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Early phase of the COVID-19 outbreak in Hungary and post-lockdown scenarios

10.1101/2020.06.02.20119313 ◽

2020 ◽

Cited By ~ 2

Author(s):

Gergely Röst ◽

Ferenc A. Bartha ◽

Norbert Bogya ◽

Péter Boldog ◽

Attila Dénes ◽

...

Keyword(s):

Statistical Analysis ◽

Spatial Heterogeneity ◽

Early Phase ◽

Disease Burden ◽

Compartmental Model ◽

Seasonal Effects ◽

Low Levels ◽

Age Structured ◽

Epidemic Wave ◽

Pharmaceutical Interventions

AbstractCOVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a huge reduction in the number of contacts and transmission of the virus. This strategy was effective in preventing epidemic growth and reducing the incidence of COVID-19 to low levels. In this report, we present the first epidemiological and statistical analysis of the early phase of the COVID-19 outbreak in Hungary. Then, we establish an age-structured compartmental model to explore alternative post-lockdown scenarios. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed.

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Modeling layered non-pharmaceutical interventions against SARS-CoV-2 in the United States with Corvid

10.1101/2020.04.08.20058487 ◽

2020 ◽

Cited By ~ 7

Author(s):

Dennis L. Chao ◽

Assaf P. Oron ◽

Devabhaktuni Srikrishna ◽

Michael Famulare

Keyword(s):

United States ◽

Disease Transmission ◽

Family Members ◽

The United States ◽

School Closures ◽

Work From Home ◽

Effective Option ◽

History Of ◽

Novel Coronavirus ◽

Pharmaceutical Interventions

AbstractBackgroundThe novel coronavirus SARS-CoV-2 has rapidly spread across the globe and is poised to cause millions of deaths worldwide. There are currently no proven pharmaceutical treatments, and vaccines are likely over a year away. At present, non-pharmaceutical interventions (NPIs) are the only effective option to reduce transmission of the virus, but it is not clear how to deploy these potentially expensive and disruptive measures. Modeling can be used to understand the potential effectiveness of NPIs for both suppression and mitigation efforts.Methods and FindingsWe developed Corvid, an adaptation of the agent-based influenza model called FluTE to SARS-CoV-2 transmission. To demonstrate features of the model relevant for studying the effects of NPIs, we simulated transmission of SARS-CoV-2 in a synthetic population representing a metropolitan area in the United States. Transmission in the model occurs in several settings, including at home, at work, and in schools. We simulated several combinations of NPIs that targeted transmission in these settings, such as school closures and work-from-home policies. We also simulated three strategies for testing and isolating symptomatic cases. For our demonstration parameters, we show that testing followed by home isolation of ascertained cases reduced transmission by a modest amount. We also show how further reductions may follow by isolating cases in safe facilities away from susceptible family members or by quarantining all family members to prevent transmission from likely infections that have yet to manifest.ConclusionsModels that explicitly include settings where individuals interact such as the home, work, and school are useful for studying the effectiveness of NPIs, as these are more dependent on community structure than pharmaceutical interventions such as vaccination. Corvid can be used to help evaluate complex combinations of interventions, although there is no substitute for real-world observations. Our results on NPI effectiveness summarize the behavior of the model for an assumed set of parameters for demonstration purposes. Model results can be sensitive to the assumptions made about disease transmission and the natural history of the disease, both of which are not yet sufficiently characterized for SARS-CoV-2 for quantitative modeling. Models of SARS-CoV-2 transmission will need to be updated as the pathogen becomes better-understood.

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Estimating the relationship between mobility, non-pharmaceutical interventions, and COVID-19 transmission in Ghana

10.1101/2021.11.01.21265660 ◽

2021 ◽

Author(s):

Hamish Gibbs ◽

Yang Liu ◽

Sam Abbott ◽

Isaac Baffoe-Nyarko ◽

Dennis O. Laryea ◽

...

Keyword(s):

Disease Transmission ◽

Disease Surveillance ◽

Large Scale ◽

Mixed Model ◽

Linear Mixed Model ◽

Human Mobility ◽

Mobility Data ◽

Generalised Linear Mixed Model ◽

The Relationship ◽

Pharmaceutical Interventions

Governments around the world have implemented non-pharmaceutical interventions (NPIs), e.g. physical distancing and travel restrictions, to limit the transmission of COVID-19. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of the degree to which these interventions impact disease transmission, and how they are reflected in measures of human behaviour. Further, there is a lack of understanding about how new sources of data can be used to monitor NPIs, where these data have the potential to augment existing disease surveillance and modelling efforts. In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of Rt, a real-time measure of the intensity of COVID-19 transmission in subnational districts of Ghana using a multilevel generalised linear mixed model. We demonstrate a relationship between reductions in human mobility and decreases in Rt during the early stages of the COVID-19 epidemic in Ghana, and show how reductions in human mobility relate to increasing stringency of NPIs. We demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity to estimate and monitor the effect of NPI policies.

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Nanomedicine Reformulation of Chloroquine and Hydroxychloroquine

Molecules ◽

10.3390/molecules26010175 ◽

2020 ◽

Vol 26 (1) ◽

pp. 175

Author(s):

David M. Stevens ◽

Rachael M. Crist ◽

Stephan T. Stern

Keyword(s):

Safety Evaluation ◽

Therapeutic Index ◽

Short Term ◽

Tissue Concentrations ◽

History Of ◽

History Of Use ◽

Novel Applications ◽

Therapeutic Doses ◽

Extensive Clinical Experience ◽

Higher Doses

The chloroquine family of antimalarials has a long history of use, spanning many decades. Despite this extensive clinical experience, novel applications, including use in autoimmune disorders, infectious disease, and cancer, have only recently been identified. While short term use of chloroquine or hydroxychloroquine is safe at traditional therapeutic doses in patients without predisposing conditions, administration of higher doses and for longer durations are associated with toxicity, including retinotoxicity. Additional liabilities of these medications include pharmacokinetic profiles that require extended dosing to achieve therapeutic tissue concentrations. To improve chloroquine therapy, researchers have turned toward nanomedicine reformulation of chloroquine and hydroxychloroquine to increase exposure of target tissues relative to off-target tissues, thereby improving the therapeutic index. This review highlights these reformulation efforts to date, identifying issues in experimental designs leading to ambiguity regarding the nanoformulation improvements and lack of thorough pharmacokinetics and safety evaluation. Gaps in our current understanding of these formulations, as well as recommendations for future formulation efforts, are presented.

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Predictors for clinical effectiveness of baricitinib in rheumatoid arthritis patients in routine clinical practice: data from a Japanese multicenter registry

Scientific Reports ◽

10.1038/s41598-020-78925-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Nobunori Takahashi ◽

Shuji Asai ◽

Tomonori Kobayakawa ◽

Atsushi Kaneko ◽

Tatsuo Watanabe ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Disease Activity ◽

Retention Rate ◽

Oral Prednisone ◽

Multivariate Logistic Regression Analysis ◽

Jak Inhibitors ◽

Short Term ◽

History Of ◽

Multicenter Registry

AbstractThis study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan–Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.

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The effects of non-pharmaceutical interventions on SARS-CoV-2 transmission in different socioeconomic populations in Kuwait: a modeling study

BMC Public Health ◽

10.1186/s12889-021-10984-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fatima Khadadah ◽

Abdullah A. Al-Shammari ◽

Ahmad Alhashemi ◽

Dari Alhuwail ◽

Bader Al-Saif ◽

...

Keyword(s):

Disease Transmission ◽

Reproduction Number ◽

Transmission Model ◽

Socioeconomic Groups ◽

Before And After ◽

Cross Transmission ◽

Community Transmission ◽

The Impact ◽

Pharmaceutical Interventions ◽

The Basic Reproduction Number

Abstract Background Aggressive non-pharmaceutical interventions (NPIs) may reduce transmission of SARS-CoV-2. The extent to which these interventions are successful in stopping the spread have not been characterized in countries with distinct socioeconomic groups. We compared the effects of a partial lockdown on disease transmission among Kuwaitis (P1) and non-Kuwaitis (P2) living in Kuwait. Methods We fit a modified metapopulation SEIR transmission model to reported cases stratified by two groups to estimate the impact of a partial lockdown on the effective reproduction number ($$ {\mathcal{R}}_e $$ R e ). We estimated the basic reproduction number ($$ {\mathcal{R}}_0 $$ R 0 ) for the transmission in each group and simulated the potential trajectories of an outbreak from the first recorded case of community transmission until 12 days after the partial lockdown. We estimated $$ {\mathcal{R}}_e $$ R e values of both groups before and after the partial curfew, simulated the effect of these values on the epidemic curves and explored a range of cross-transmission scenarios. Results We estimate $$ {\mathcal{R}}_e $$ R e at 1·08 (95% CI: 1·00–1·26) for P1 and 2·36 (2·03–2·71) for P2. On March 22nd, $$ {\mathcal{R}}_e $$ R e for P1 and P2 are estimated at 1·19 (1·04–1·34) and 1·75 (1·26–2·11) respectively. After the partial curfew had taken effect, $$ {\mathcal{R}}_e $$ R e for P1 dropped modestly to 1·05 (0·82–1·26) but almost doubled for P2 to 2·89 (2·30–3·70). Our simulated epidemic trajectories show that the partial curfew measure greatly reduced and delayed the height of the peak in P1, yet significantly elevated and hastened the peak in P2. Modest cross-transmission between P1 and P2 greatly elevated the height of the peak in P1 and brought it forward in time closer to the peak of P2. Conclusion Our results indicate and quantify how the same lockdown intervention can accentuate disease transmission in some subpopulations while potentially controlling it in others. Any such control may further become compromised in the presence of cross-transmission between subpopulations. Future interventions and policies need to be sensitive to socioeconomic and health disparities.

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Age-dependent intra-specific competition in pre-adult life stages and its effects on adult population dynamics

European Journal of Applied Mathematics ◽

10.1017/s0956792515000418 ◽

2015 ◽

Vol 27 (1) ◽

pp. 131-156

Author(s):

RONGSONG LIU ◽

GERGELY RÖST ◽

STEPHEN A. GOURLEY

Keyword(s):

Disease Transmission ◽

Adult Population ◽

Adult Life ◽

Life Stages ◽

Larval Competition ◽

Amphibian Species ◽

Age Dependent ◽

Age Structured ◽

Delay Differential ◽

Boundedness And Persistence

Intra-specific competition in insect and amphibian species is often experienced in completely different ways in their distinct life stages. Competition among larvae is important because it can impact on adult traits that affect disease transmission, yet mathematical models often ignore larval competition. We present two models of larval competition in the form of delay differential equations for the adult population derived from age-structured models that include larval competition. We present a simple prototype equation that models larval competition in a simplistic way. Recognising that individual larvae experience competition from other larvae at various stages of development, we then derive a more complex equation containing an integral with a kernel that quantifies the competitive effect of larvae of ageāon larvae of agea. In some parameter regimes, this model and the famous spruce budworm model have similar dynamics, with the possibility of multiple co-existing equilibria. Results on boundedness and persistence are also proved.

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