Threshold conditions for curbing COVID-19 with a dynamic zero-case policy derived from 101 outbreaks in China.

By 31 May 2022, original/Alpha, Delta and Omicron strains induced 101 outbreaks of COVID-19 in mainland China. Most outbreaks were cleared by combining non-pharmaceutical interventions (NPIs) with vaccines, but continuous virus variations challenged the dynamic zero-case policy (DZCP), posing questions of what are the prerequisites and threshold levels for success? And what are the independent effects of vaccination in each outbreak? Using a modified classic infectious disease dynamic model and an iterative relationship for new infections per day, the effectiveness of vaccines and NPIs was deduced, from which the independent effectiveness of vaccines was derived. There was a negative correlation between vaccination coverage rates and virus transmission. For the Delta strain, a 61.8% increase in the vaccination rate (VR) reduced the control reproduction number (CRN) by about 27%. For the Omicron strain, a 20.43% increase in VR, including booster shots, reduced the CRN by 42.16%. The implementation speed of NPIs against the original/Alpha strain was faster than the virus's transmission speed, and vaccines significantly accelerated the DZCP against the Delta strain. The CRN ([Formula: see text]) during the exponential growth phase and the peak time and intensity of NPIs were key factors affecting a comprehensive theoretical threshold condition for DZCP success, illustrated by contour diagrams for the CRN under different conditions. The DZCP maintained the [Formula: see text] of 101 outbreaks below the safe threshold level, but the strength of NPIs was close to saturation especially for Omicron, and there was little room for improvement. Only by curbing the rise in the early stage and shortening the exponential growth period could clearing be achieved quickly. Strengthening China's vaccine immune barrier can improve China's ability to prevent and control epidemics and provide greater scope for the selection and adjustment of NPIs. Otherwise, there will be rapid rises in infection rates and an extremely high peak and huge pressure on the healthcare system, and a potential increase in excess mortality.

Lessons drawn from Shanghai for controlling highly transmissible SARS-CoV-2 variants: insights from a modelling study.

BACKGROUND: The continuous emergence of novel SARS-CoV-2 variants with markedly increased transmissibility presents major challenges to the zero-COVID policy in China. It is critical to adjust aspects of the policy about non-pharmaceutical interventions (NPIs) by searching for and implementing more effective ways. We use a mathematical model to mimic the epidemic pattern of the Omicron variant in Shanghai to quantitatively show the control challenges and investigate the feasibility of different control patterns in avoiding other epidemic waves. METHODS: We initially construct a dynamic model with a core step-by-step release strategy to reveal its role in controlling the spread of COVID-19, including the city-based pattern and the district-based pattern. We used the least squares method and real reported case data to fit the model for Shanghai and its 16 districts, respectively. Optimal control theory was utilized to explore the quantitative and optimal solutions of the time-varying control strength (i.e., contact rate) to suppress the highly transmissible SARS-CoV-2 variants. RESULTS: The necessary period for reaching the zero-COVID goal can be nearly 4 months, and the final epidemic size was 629,625 (95%CI: [608,049, 651,201]). By adopting the city-based pattern, 7 out of 16 strategies released the NPIs more or earlier than the baseline and ensured a zero-resurgence risk at the average cost of 10 to 129 more cases in June. By adopting the district-based pattern, a regional linked release can allow resumption of social activity to ~ 100% in the boundary-region group about 14 days earlier and allow people to flow between different districts without causing infection resurgence. Optimal solutions of the contact rate were obtained with various testing intensities, and higher diagnosis rate correlated with higher optimal contact rate while the number of daily reported cases remained almost unchanged. CONCLUSIONS: Shanghai could have been bolder and more flexible in unleashing social activity than they did. The boundary-region group should be relaxed earlier and more attention should be paid to the centre-region group. With a more intensive testing strategy, people could return to normal life as much as possible but still ensure the epidemic was maintained at a relatively low level.

Home quarantine or centralized quarantine? A mathematical modelling study on the COVID-19 epidemic in Guangzhou in 2021.

Several outbreaks of COVID-19 caused by imported cases have occurred in China following the successful control of the outbreak in early 2020. In order to avoid recurrences of such local outbreaks, it is important to devise an efficient control and prevention strategy. In this paper, we developed a stochastic discrete model of the COVID-19 epidemic in Guangzhou in 2021 to compare the effectiveness of centralized quarantine and compulsory home quarantine measures. The model was calibrated by using the daily reported cases and newly centralized quarantined cases. The estimated results showed that the home quarantine measure increased the accuracy of contact tracing. The estimated basic reproduction number was lower than that in 2020, even with a much more transmissible variant, demonstrating the effectiveness of the vaccines and normalized control interventions. Sensitivity analysis indicated that a sufficiently implemented contact tracing and centralized quarantine strategy in the initial stage would contain the epidemic faster with less infections even with a weakly implemented compulsory home quarantine measure. However, if the accuracy of the contact tracing was insufficient, then early implementation of the compulsory home quarantine with strict contact tracing, screening and testing interventions on the key individuals would shorten the epidemic duration and reduce the total number of infected cases. Particularly, 94 infections would have been avoided if the home quarantine measure had been implemented 3 days earlier and an extra 190 infections would have arisen if the home quarantine measure was implemented 3 days later. The study suggested that more attention should be paid to the precise control strategy during the initial stage of the epidemic, otherwise the key group-based control measure should be implemented strictly.

Quantifying competitive advantages of mutant strains in a population involving importation and mass vaccination rollout.

The SARS-CoV-2 Delta variant, known as B.1.617.2 and first identified in India, is becoming a dominant strain in many countries due to its extreme infectiousness. Assessing and quantifying the transmissibility and competitive advantage of the Delta variant is of major significance for countries around the world so that appropriate measures to mitigate and even eliminate the epidemic can be introduced. Aiming at such problems, we proposed a method to model the invasion process of a novel strain and estimate the competitive advantage of the invading strain over the local strain. We applied this method to study the invasion and spread of the Delta variant into England. We have estimated the basic reproduction number of the Delta variant as being 49% higher than that of the Alpha variant (CI: 45-52%), assuming a mean generation interval of 5 days with a standard deviation of 3 days. In the period 11 April to 17 May 2021, the effective reproduction number of the Delta variant was 65% higher than that of the Alpha variant in England (CI: 61-70%). Our results show that the Delta variant has a significantly higher transmission capacity than other strains, which explains the rebound of the epidemic in many countries, even in those with relatively high vaccination coverages.

Effects of medical resource capacities and intensities of public mitigation measures on outcomes of COVID-19 outbreaks.

BACKGROUND: The COVID-19 pandemic is complex and is developing in different ways according to the country involved. METHODS: To identify the key parameters or processes that have the greatest effects on the pandemic and reveal the different progressions of epidemics in different countries, we quantified enhanced control measures and the dynamics of the production and provision of medical resources. We then nested these within a COVID-19 epidemic transmission model, which is parameterized by multi-source data. We obtained rate functions related to the intensity of mitigation measures, the effective reproduction numbers and the timings and durations of runs on medical resources, given differing control measures implemented in various countries. RESULTS: Increased detection rates may induce runs on medical resources and prolong their durations, depending on resource availability. Nevertheless, improving the detection rate can effectively and rapidly reduce the mortality rate, even after runs on medical resources. Combinations of multiple prevention and control strategies and timely improvement of abilities to supplement medical resources are key to effective control of the COVID-19 epidemic. A 50% reduction in comprehensive control measures would have led to the cumulative numbers of confirmed cases and deaths exceeding 590,000 and 60,000, respectively, by 27 March 2020 in mainland China. CONCLUSIONS: Multiple data sources and cross validation of a COVID-19 epidemic model, coupled with a medical resource logistic model, revealed the key factors that affect epidemic progressions and their outbreak patterns in different countries. These key factors are the type of emergency medical response to avoid runs on medical resources, especially improved detection rates, the ability to promote public health measures, and the synergistic effects of combinations of multiple prevention and control strategies. The proposed model can assist health authorities to predict when they will be most in need of hospital beds and equipment such as ventilators, personal protection equipment, drugs, and staff.

Impacts of varying strengths of intervention measures on secondary outbreaks of COVID-19 in two different regions.

By March 2020, China and Singapore had achieved remarkable results in the prevention and control of COVID-19, but in April Singapore's outbreak began to deteriorate, while China's remained controlled. Using detailed data from Tianjin, China, and Singapore, a stochastic discrete COVID-19 epidemic model was constructed to depict the impact of the epidemic. Parameter estimation and sensitivity analysis were developed to study the probability of imported cases inducing an outbreak in relation to different prevention and control efforts. Results show that the resumption of work and the re-opening of schools will not lead to an outbreak if the effective reproduction number is lower than 1 and approaches 0 and tracking quarantine measures are strengthened. Once an outbreak occurs, if close contacts can be tracked and quarantined in time, the outbreak will be contained. If work is resumed and schools are re-opened with the effective reproduction number greater than 1, then it is more likely that a secondary outbreak will be generated. Also, the greater the number of undetected foreign imported cases and the weaker the prevention and control measures, the more serious the epidemic. Therefore, the key to prevention of a second outbreak is to return to work and to re-open schools only after the effective reproduction number is less than 1 for a period, and when tracking quarantine measures have been strengthened. Our model provides a qualitative and quantitative basis for decision-making for the prevention and control of COVID-19 epidemics and the prediction, early warning and risk assessment of secondary outbreaks.

Impact of Hospital Bed Shortages on the Containment of COVID-19 in Wuhan.

The global outbreak of COVID-19 has caused worrying concern amongst the public and health authorities. The first and foremost problem that many countries face during the outbreak is a shortage of medical resources. In order to investigate the impact of a shortage of hospital beds on the COVID-19 outbreak, we formulated a piecewise smooth model for describing the limitation of hospital beds. We parameterized the model while using data on the cumulative numbers of confirmed cases, recovered cases, and deaths in Wuhan city from 10 January to 12 April 2020. The results showed that, even with strong prevention and control measures in Wuhan, slowing down the supply rate, reducing the maximum capacity, and delaying the supply time of hospital beds all aggravated the outbreak severity by magnifying the cumulative numbers of confirmed cases and deaths, lengthening the end time of the pandemic, enlarging the value of the effective reproduction number during the outbreak, and postponing the time when the threshold value was reduced to 1. Our results demonstrated that establishment of the Huoshenshan, Leishenshan, and Fangcang shelter hospitals avoided 22,786 people from being infected and saved 6524 lives. Furthermore, the intervention of supplying hospital beds avoided infections in 362,360 people and saved the lives of 274,591 persons. This confirmed that the quick establishment of the Huoshenshan, Leishenshan Hospitals, and Fangcang shelter hospitals, and the designation of other hospitals for COVID-19 patients played important roles in containing the outbreak in Wuhan.

Differences in how interventions coupled with effective reproduction numbers account for marked variations in COVID-19 epidemic outcomes.

The COVID-19 outbreak, designated a "pandemic" by the World Health Organization (WHO) on 11 March 2020, has spread worldwide rapidly. Each country implemented prevention and control strategies, mainly classified as SARS LCS (SARS-like containment strategy) or PAIN LMS (pandemic influenza-like mitigation strategy). The reasons for variation in each strategy's efficacy in controlling COVID-19 epidemics were unclear and are investigated in this paper. On the basis of the daily number of confirmed local (imported) cases and onset-to-confirmation distributions for local cases, we initially estimated the daily number of local (imported) illness onsets by a deconvolution method for mainland China, South Korea, Japan and Spain, and then estimated the effective reproduction numbers Rt by using a Bayesian method for each of the four countries. China and South Korea adopted a strict SARS LCS, to completely block the spread via lockdown, strict travel restrictions and by detection and isolation of patients, which led to persistent declines in effective reproduction numbers. In contrast, Japan and Spain adopted a typical PAIN LMS to mitigate the spread via maintaining social distance, self-quarantine and isolation etc., which reduced the Rt values but with oscillations around 1. The finding suggests that governments may need to consider multiple factors such as quantities of medical resources, the likely extent of the public's compliance to different intensities of intervention measures, and the economic situation to design the most appropriate policies to fight COVID-19 epidemics.

Linking key intervention timing to rapid decline of the COVID-19 effective reproductive number to quantify lessons from mainland China.

Effective reproductive numbers (Rt) were calculated from data on the COVID-19 outbreak in China and linked to dates in 2020 when different interventions were enacted. From a maximum of 3.98 before the lockdown in Wuhan City, the values of Rt declined to below 1 by the second week of February, after the construction of hospitals dedicated to COVID-19 patients. The Rt continued to decline following additional measures in line with the policy of "early detection, early report, early quarantine, and early treatment." The results provide quantitative evaluations of how intervention measures and their timings succeeded, from which lessons can be learned by other countries dealing with future outbreaks.