Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. CONCLUSIONS: COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

Potential impact of annual vaccination with reformulated COVID-19 vaccines: lessons from the U.S. COVID-19 Scenario Modeling Hub.

Importance: COVID-19 continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Objective: To project COVID-19 hospitalizations and deaths from April 2023-April 2025 under two plausible assumptions about immune escape (20% per year and 50% per year) and three possible CDC recommendations for the use of annually reformulated vaccines (no vaccine recommendation, vaccination for those aged 65+, vaccination for all eligible groups). Design: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023-April 15, 2025 under six scenarios representing the intersection of considered levels of immune escape and vaccination. State and national projections from eight modeling teams were ensembled to produce projections for each scenario. Setting: The entire United States. Participants: None. Exposure: Annually reformulated vaccines assumed to be 65% effective against strains circulating on June 15 of each year and to become available on September 1. Age and state specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. Main outcomes and measures: Ensemble estimates of weekly and cumulative COVID-19 hospitalizations and deaths. Expected relative and absolute reductions in hospitalizations and deaths due to vaccination over the projection period. Results: From April 15, 2023-April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November-January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% PI: 1,438,000-4,270,000) hospitalizations and 209,000 (90% PI: 139,000-461,000) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% CI: 104,000-355,000) fewer hospitalizations and 33,000 (95% CI: 12,000-54,000) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI: 29,000-69,000) fewer deaths. Conclusion and Relevance: COVID-19 is projected to be a significant public health threat over the coming two years. Broad vaccination has the potential to substantially reduce the burden of this disease.

Role of immigration and emigration on the spread of COVID-19 in a multipatch environment: a case study of India.

Human mobility has played a critical role in the spread of COVID-19. The understanding of mobility helps in getting information on the acceleration or control of the spread of disease. The COVID-19 virus has been spreading among several locations despite all the best efforts related to its isolation. To comprehend this, a multi-patch mathematical model of COVID-19 is proposed and analysed in this work, where-in limited medical resources, quarantining, and inhibitory behaviour of healthy individuals are incorporated into the model. Furthermore, as an example, the impact of mobility in a three-patch model is studied considering the three worst-hit states of India, i.e. Kerala, Maharashtra and Tamil Nadu, as three patches. Key parameters and the basic reproduction number are estimated from the available data. Through results and analyses, it is seen that Kerala has a higher effective contact rate and has the highest prevalence. Moreover, if Kerala is isolated from Maharashtra or Tamil Nadu, the number of active cases will increase in Kerala but reduce in the other two states. Our findings indicate that the number of active cases will decrease in the high prevalence state and increase in the lower prevalence states if the emigration rate is higher than the immigration rate in the high prevalence state. Overall, proper travel restrictions are to be implemented to reduce or control the spread of disease from the high-prevalence state to other states with lower prevalence rates.

Comments on "Optimal control analysis of a COVID-19 and tuberculosis co-dynamics model".

Study of dynamics of COVID-19 and its co-infection with other diseases through mathematical models is the major focus of recent advancement in mathematical modeling of infectious diseases. There are numerous mathematical models on COVID-19 which describe its dynamics for different geographic regions. However, there are very few research papers dealing with co-infection of COVID-19 and TB. As both TB and COVID-19 are infectious diseases of same nature it becomes very difficult to predict the co-dynamics of these two diseases. The formulation of a correct mathematical model is very important in any kind of modeling and if the mathematical model is not proper then any prediction based on this may not be valid. This letter highlights the important limitations in the proposed mathematical model of co-dynamics of COVID-19 and TB by [1].

A co-infection model on TB - COVID-19 with optimal control and sensitivity analysis.

COVID-19 had been declared a public health emergency by the World Health Organization in the early 2020. Since then, this deadly virus has claimed millions of lives worldwide. Amidst its chaotic spread, several other diseases have faced negligence in terms of treatment and care, of which one such chronic disease is Tuberculosis. Due to huge rise in COVID-19 cases, there had been a drastic decrease in notification of TB cases which resulted in reversal of global TB target progress. Apart from these due to the earlier co-infections of TB with SARS and MERS-CoV viruses, the TB-COVID-19 co-infection posed a severe threat in the spread of the disease. All these factors backed to be major motivation factor in development of this model. Leading with this concern, a TB - COVID-19 co-infection model is developed in this study, considering possibility of waning immunity of both diseases. Considering different epidemiological traits, an epidemiological model with 11 compartments is developed and the co-dynamics is analysed. A detailed stability and bifurcation analysis is performed for the TB only sub-model, COVID-19 only sub-model and the complete TB - COVID-19 model. Impact of key parameters namely, infection rate, waning immunity, and face mask efficacy on disease prevalence is discussed in detail. Sensitivity analysis by means of normalized forward sensitivity index of the basic reproduction number and LHS-PRCC approach is carried to provide a thorough understanding of significance of various parameters in accelerating as well as controlling the disease spread. Optimal control analysis is presented extensively, incorporating controls related to timely and improved TB treatment, and enhanced COVID-19 tests and isolation facilities to curb the spread of these infectious diseases. The simulation results obtained from each of these analyses stress on the importance of different control measures in mitigation of the diseases and are illustrated accordingly. The study suggests that in the times of a pandemic, other disease treatment and care must not be neglected, and adequate care must be taken so that mortality due to co-infection and unavailability of timely treatment can be avoided.

Mathematical modeling of COVID-19 in India and its states with optimal control.

A pandemic is an epidemic spread over a huge geographical area. COVID-19 is 5 th such pandemic documented after 1918 flu pandemic. In this work, we frame a mathematical epidemic model taking inspiration from the classic SIR model and develop a compartmental model with ten compartments to study the coronavirus dynamics in India and three of its most affected states, namely, Maharashtra, Karnataka, and Tamil Nadu, with inclusion of factors related to face mask efficacy, contact tracing, and testing along with quarantine and isolation. We fit the developed model and estimate optimum values of disease transmission rate, detection rate of undetected asymptomatic, and the same of undetected symptomatic. A sensitivity analysis is presented stressing on the importance of higher face mask usage, rapid testing, and contact tracing for curbing the disease spread. An optimal control analysis is performed with two control parameters to study the increase and decrease of the infected population with and without control. This study suggests that improved and rapid testing will help in identifying more infectives, thereby contributing in the decline of disease transmission rate. Optimal control analysis results on stressing on the importance of abiding by strict usage of face mask and social distancing for drastic decrease in number of infections. Time series behaviour of the symptomatic, asymptomatic, and hospitalized population is studied for a range of parameters, resulting in thorough understanding of significance of different parameters.

Mathematical modeling of COVID-19 in India and Nepal with optimal control and sensitivity analysis.

The pandemic started in the late 2019 and is still waving in claiming millions of lives with virus being mutated to deadlier form. This pandemic has caught attention toward interventions like improved detection of the infected, better quarantine facilities and adequate medical facilities in terms of hospital beds and other medical aid. In this study, we developed a 7-compartment epidemiological model, with inclusion of identified and unidentified infected population along with media factor associated with the aware identified infected population. This is included by using Holling function in the nonlinear incidence, that is responsible for reduction in infection rate via identified infected. The model is fitted to the observed active COVID-19 cases data, collected for a period of 11 months between July 2020 to May 2021 of Nepal and India, and the infection rate as well as the basic reproduction number is obtained for the first wave and second wave of the pandemic in both countries. A comparative analysis on the effect of different parameters on the disease prevalence for both the countries is presented in this work. Sensitivity analysis, time series behavior and optimal control analysis with control parameters equating with reduced infection rate, enhanced detection rate, improved quarantine and hospitalization rate are presented in detail. By means of PRCC, sensitivity analysis is performed and the key parameters influencing the disease prevalence are identified. A detailed study on impact of several parameters in the COVID-19 prevalence, thereby suggesting the interventions to be implemented is discussed in the work. Predictions till June 30, 2021, are obtained using the second wave data for both the countries, and a declining trend is observed for both the countries for the next 30 to 40 days. The estimated values of the infection rates and the hospitalization rates obtained are higher for India compared to Nepal. An optimal control analysis for both the countries is described in detail providing the difference in infectives and recoveries with and without any controls or interventions. The study suggests that improved treatment facilities, testing drives and other non-pharmaceutical interventions would bring down the infected cases to a major extent.

Modeling of COVID-19 with limited public health resources: a comparative study of three most affected countries.

COVID-19 has become a deadly pandemic in the recent times claiming millions of lives worldwide in a grievous manner. Most of the countries in the world have limited number of medical resources (hospitals, beds, ventilators, etc.), and in the case of large outbreak, it becomes very difficult to provide treatment to every infected individual. In this study, we propound a mathematical model where we classify the infected into two subcategories-asymptomatic and symptomatic. This model further accounts for the effect of limited medical resource for infected people and using face masks in combating the pandemic. Focusing on these aspects, we analyze the model and exploit the available data for assessing the pattern in three most affected countries, namely USA, India and Brazil. The developed model is calibrated to fit data for these three countries and estimate the transmission rate of symptomatic, asymptomatic individuals. The rate at which the individuals who are quarantined recover is estimated as well. Along with these estimations, a comparative study based on the basic reproduction number estimated for the three countries is presented. Standard methods of sensitivity analysis are performed to analyze the ways in which basic reproduction number is impacted upon due to changes in different parameters of the model. Further, we obtain disease-free equilibrium and endemic equilibrium of the model. It is observed that backward bifurcation occurs if the capacity of treatment is small and bistable equilibria are shown that makes the system more sensitive to the initial conditions. Sufficient conditions for the local asymptomatic stability of the endemic equilibrium and disease-free equilibrium of the system are obtained. The results of this study imply that to curb the severity of the increasing cases of the disease in these countries, effective strategies to control disease spread should be implemented so that the basic reproduction number can be decreased below the threshold value which is certainly less than unity. The use of protective masks in public is shown to be an important preventive measure to lower disease transmission rate. Also, the quantity of medical resources should increase so that every infected person can get better treatment.