Public health and epidemiological considerations in the control of epidemic and pandemic respiratory infections

Abstract

Despite the collective pandemic preparedness efforts from last decades, the evolving COVID-19 pandemic, caused by an emerging SARS-CoV-2 infection, has posed devasting impact to the population health and socio-economy. This thesis examined a number of novel applications of public health and epidemiological methods to inform various key control strategies, specifically in the areas of scalable diagnostic testing, community surveillance, and vaccination.

The first study comprehensively investigated the comparative diagnostic performance of different respiratory sampling methods for SARS-CoV-2 RT-PCR testing in ambulatory care. Pooled nasal and throat swabs offered the best diagnostic performance of SARS-CoV-2 infection, and represent the optimal alternative sampling approach. Saliva and nasal swabs are clinically acceptable alternative methods. Throat swabs gave a much lower sensitivity and should not be recommended. Self-collection of specimen was not associated with any significant impairment of diagnostic accuracy. This study has rectified the existing reporting inadequacy without examining the positive and negative predictive values, identified a more appropriate way for gold standard comparison in study design, and provided a framework for evidence-based assessment.

The second study examined the testing performance of the latter introduced gargling as an additional sampling approach. Self-collection of gargle achieved a high performance and represented a reliable specimen for both the purposes of diagnosing SARS-CoV-2 infection and monitoring viral shedding. A potential dependency of testing performance on the nature and sterility of gargle media was highlighted. This study informed the practical implementation of gargling, in terms of duration of gargling and volume of solution. These findings have informed health authorities in guidelines for testing practice and scalable testing for pandemic control.

In the third study, a daily antigen rapid testing surveillance (DARTS) system was established with a representative cohort of more than 10000 individuals. The system’s daily point prevalence data monitored the changing SARS-CoV-2 activity over the fifth and sixth waves of omicron BA.2, BA.5, XBB variants. The DARTS system filled an important surveillance gap resulted from overloaded laboratory testing capacity, and demonstrated the feasibility of building a large-scale participatory community surveillance system.

The fourth study assessed the effectiveness of mRNA and inactivated COVID-19 vaccines against SARS-CoV-2 infection. Weekly rapid antigen testing regardless of symptom and exposure status provided an unique platform for ascertaining both asymptomatic and symptomatic SARS-CoV-2 infections. Two doses of either BNT162b2 and CoronaVac did not provide significant protection against SARS-CoV-2 infection; and a booster dose with either BNT162b2 or CoronaVac was needed for a significant protection against omicron infection and symptomatic infection.

The fifth study examined the impact of lottery-based incentivization on COVID-19 vaccine uptake behavior in the community-wide vaccination programme. The vaccine lottery was associated with a significant increase in vaccine uptake among the overall population. Provision of vaccine lottery shall thoroughly consider its ethical implication on informed consent process.

Overall, this thesis highlighted the importance of timely identification of important knowledge gaps, exploration of novel public health strategies, and adoption of robust research designs to control the pandemic in an evidence-based manner.