Influenza vaccine uptake among children and older adults in China: A secondary analysis of a quasi-experimental study (preprint)

Background: Influenza vaccination is the key to reducing the influenza-related disease burden, especially among high-risk populations. However, influenza vaccine uptake is low in China. This secondary analysis of a quasi-experimental trial in Guangdong Province aimed to understand factors associated with influenza vaccine uptake among children and older people stratified by funding context. Methods: : A total of 225 children (aged 0.5-8 years) and 225 older people (aged 60 years or above) were recruited from three clinics (rural, suburban, urban). Participants were allocated into two groups based on different funding contexts: self-paid group (N=150, including 75 children and 75 older adults) in which participants paid full market price for their vaccination; and subsidized group (N=300, including 150 children and 150 older adults) in which varying levels of financial support was provided. Univariable and multivariable logistic regressions were conducted stratified by funding contexts. Results: : Overall, 75.0% (225/300) of participants in the subsidized group and 36.7% (55/150) in the self-paid group got vaccinated. Older adults had lower vaccination rates than children in both funding groups, while both age groups showed much higher uptake in the subsidized group than in the self-paid group (86.7% vs 53.3% among children; 63.3% vs 20.0% among older people). In the self-paid group, participants living with children (aOR:2.61, 95%CI: 1.06-6.42) or older people (aOR:4.76, 95%CI: 1.08-20.90) having prior influenza vaccination in the same household were more likely to be vaccinated; trust in providers’ advice (aOR=4.95, 95%CI:1.99, 12.43) or effectiveness of the vaccine (aOR: 12.18, 95%CI: 5.21-28.50), and experienced influenza-like illnesses in the family (aOR=46.52, 4.10, 533.78) were associated with higher vaccine uptake in the subsidized group. Conclusions: Older people had suboptimal vaccine uptake compared to children in both contexts and need more attention in future efforts to enhance influenza vaccination. Tailoring interventions to different vaccine funding contexts may help improve influenza vaccine uptake: In self-paid context, measures to motivate people to accept their first ever influenza vaccination may be a promising strategy. In subsidized context, strategies to improve public confidence in vaccine effectiveness and providers’ advice would be useful. Trial registration: ChiCTR2000040048. Registered on November 19, 2020.

Modelling the impact of rapid tests, tracing and distancing in lower-income countries suggest optimal policies varies with rural-urban settings (preprint)

Background Non-pharmaceutical intervention (NPI) remains the most reliable COVID-19 containment tool for low- and middle-income countries (LMICs) given the inequality of vaccine distribution and their vulnerable healthcare systems. We aimed to develop mathematical models that capture LMIC demographic characteristics such as young population and large household size and assess NPI effectiveness in rural and urban communities. Methods We constructed synthetic populations for rural, non-slum urban and slum settings to capture LMIC demographic characteristics that vary across communities. We integrated age mixing and household structure into contact networks for each community setting and simulated COVID-19 outbreaks within the networks. Using this agent-based model, we evaluate NPIs including testing and isolation, tracing and quarantine, and physical distancing. We explored the optimal containment strategies for rural and urban communities by designing and simulating setting-specific strategies that deploy rapid diagnostic test, symptom screening, contact tracing and physical distancing. We performed extensive simulations to capture the uncertainty of outbreak trajectories and the impact of varying model parameters. Findings We found the impact of testing, tracing and distancing varies with rural-urban settings. In rural communities, we found implementing either high quality (sensitivity > 50%) antigen rapid diagnostic tests or moderate physical distancing could contain the transmission. Additionally, antibody rapid diagnostic tests and symptom-based diagnosis could be useful for mitigating the transmission. In non-slum urban communities, we demonstrated that both physical distancing and case finding are essential for containing COVID-19 (average infection rate < 10%). In slum communities, we found physical distancing is less effective compared to rural and non-slum urban communities. Lastly, for all communities considered, we demonstrated contact quarantine is essential for effective containment and is effective at a low compliance rate (30%). Interpretation Our findings could guide setting-specific strategy design for different communities in LMICs. Our assessments also have implications on applying rapid diagnostic tests and symptom-based diagnosis for case finding, tracing and distancing in lower-income communities.

Insights into the practical effectiveness of RT-PCR testing for SARS-CoV-2 from serologic data, a cohort study (preprint)

Background: Virologic detection of SARS-CoV-2 through Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) has limitations for surveillance. Serologic tests can be an important complementary approach. Objective: Assess the practical performance of RT-PCR based surveillance protocols, and the extent of undetected SARS-CoV-2 transmission in Shenzhen, China. Design: Cohort study nested in a public health response. Setting: Shenzhen, China; January-May 2020. Participants: 880 PCR-negative close-contacts of confirmed COVID-19 cases and 400 residents without known exposure (main analysis). Fifty-seven PCR-positive case contacts (timing analysis). Measurements: Virological testing by RT-PCR. Measurement of anti-SARS-CoV-2 antibodies in PCR-negative contacts 2-15 weeks after initial testing using total Ab ELISA. Rates of undetected infection, performance of RT-PCR over the course of infection, and characteristics of seropositive but PCR-negative individuals were assessed. Results: The adjusted seropositivity rate for total Ab among 880 PCR-negative close-contacts was 4.1% (95%CI, 2.9% to 5.7%), significantly higher than among residents without known exposure to cases (0.0%, 95%CI, 0.0% to 1.0%). PCR-positive cases were 8.0 times (RR; 95% CI, 5.3 to 12.7) more likely to report symptoms than the PCR-negative individuals who were seropositive, but otherwise similar. RT-PCR missed 36% (95%CI, 28% to 44%) of infected close-contacts, and false negative rates appear to be highly dependent on stage of infection. Limitations: No serological data were available on PCR-positive cases. Sample size was limited, and only 20% of PCR-negative contacts met inclusion criteria. Conclusion: Even rigorous RT-PCR testing protocols may miss a significant proportion of infections, perhaps in part due to difficulties timing testing of asymptomatics for optimal sensitivity. Surveillance and control protocols relying on RT-PCR were, nevertheless, able to contain community spread in Shenzhen.

A Modelling Study for Designing a Multi-layered Surveillance Approach to Detect the Potential Resurgence of SARS-CoV-2 (preprint)

Background: Countries achieving control of COVID-19 after an initial outbreak will continue to face the risk of SARS-CoV-2 resurgence. This study explores surveillance strategies for COVID-19 containment based on polymerase chain reaction tests. Methods: Using a dynamic SEIR-type model to simulate the initial dynamics of a COVID-19 introduction, we investigate COVID-19 surveillance strategies among healthcare workers, hospital patients, and community members. We estimate surveillance sensitivity as the probability of COVID-19 detection using a hypergeometric sampling process. We identify test allocation strategies that maximise the probability of COVID-19 detection across different testing capacities. We use Beijing, China as a case study. Findings: Surveillance subgroups are more sensitive in detecting COVID-19 transmission when they are defined by more COVID-19 specific symptoms. In this study, fever clinics have the highest surveillance sensitivity, followed by respiratory departments. With a daily testing rate of 0.07/1000 residents, via exclusively testing at fever clinic and respiratory departments, there would have been 598 [95% eCI: 35, 2154] and 1373 [95% eCI: 47, 5230] cases in the population by the time of first case detection, respectively. Outbreak detection can occur earlier by including non-syndromic subgroups, such as younger adults in the community, as more testing capacity becomes available. Interpretation: A multi-layer approach that considers both the surveillance sensitivity and administrative constraints can help identify the optimal allocation of testing resources and thus inform COVID-19 surveillance strategies. Funding: Bill & Melinda Gates Foundation, National Institute of Health Research (UK), National Institute of Health (US), the Royal Society, and Wellcome Trust.

What is required to prevent a second major outbreak of the novel coronavirus SARS-CoV-2 upon lifting the metropolitan-wide quarantine of Wuhan city, China (preprint)

Background: The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted. Method: We constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic. Results: We estimated that at the end of the epidemic, a total of 65,572 (46,156-95,264) individuals would be infected by the virus, among which 16,144 (14,422-23,447, 24.6%) would be infected through public contacts, 45,795 (32,390-66,395, 69.7%) through household contact, 3,633 (2,344-5,865, 5.5%) through hospital contacts (including 783 (553-1,134) non-COVID-19 patients and 2,850 (1,801-4,981) medical staff members). A total of 3,262 (1,592-6,470) would die of COVID-19 related pneumonia in Wuhan. For an early lifting date (21st March), facial mask needed to be sustained at a relatively high rate ([≥]85%) if public contacts were to recover to 100% of the pre-quarantine level. In contrast, lifting the quarantine on 18th April allowed public person-to-person contact adjusted back to the pre-quarantine level with a substantially lower level of facial mask usage (75%). However, a low facial mask usage (<50%) combined with an increased public contact (>100%) would always lead a significant second outbreak in most quarantine lifting scenarios. Lifting the quarantine on 25th April would ensure a smooth decline of the epidemics regardless of the combinations of public contact rates and facial mask usage. Conclusion: The prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate.