Safety and effectiveness of control measures for mitigating the burden of Influenza and COVID-19

Abstract

The substantial burden of influenza and COVID-19 underscores the need for effective interventions to mitigate their public health impact. This thesis explores the effectiveness and reactogenicity of vaccines, and the effectiveness of lateral flow tests and non-pharmaceutical interventions (NPIs) for mitigating the impact of influenza and SARS-CoV-2.

The test negative study is commonly used to estimate vaccine effectiveness. However, estimates may be biased if controls include other vaccine preventable diseases. With both COVID-19 and influenza vaccines recommended in Hong Kong, I evaluated the magnitude of bias in vaccine effectiveness estimates. The results demonstrated that both vaccines provided moderate protection against paediatric hospitalisations with minimal bias when including controls infected with other vaccine preventable diseases. However, the degree of bias varied in international settings, and data limitations precluded analysis of correlations between the receipt of influenza and COVID-19 vaccination, highlighting the need for further research.

Reactogenicity includes symptoms that are experienced shortly after vaccination. Reactogenicity after vaccination was assessed using data from a randomised controlled trial (influenza) and a cohort study (COVID-19). Enhanced influenza vaccines and theBNT162b2 mRNA vaccine were associated with higher frequencies of local reactions compared to standard influenza and inactivated COVID-19 vaccines. Younger individuals and women were found to experience more reactions, and severe reactions disrupting daily activities were more common with BNT162b2, particularly after the second and third doses. These findings emphasise the importance of considering reactogenicity profiles in vaccine recommendations. Using the same cohort study on COVID-19 vaccination I evaluated the impact of vaccine reactions on COVID-19 booster uptake. The results showed that systemic reactions, such as feverishness, chills, and fatigue, significantly reduced third-dose uptake, particularly among BNT162b2 recipients. Absenteeism due to adverse reactions also emerged as a key deterrent. However, no significant reduction in uptake was observed for the fourth dose, likely due to demographic differences between recipients.

The second part of the thesis evaluated other interventions to mitigate respiratory infections. Numerous brands of lateral flow tests were readily available with few studies evaluating their utility in clinical settings. I evaluated the performance of three lateral flow tests that each detect influenza, COVID-19, or RSV in outpatients. The results indicated lower sensitivity than the manufacturer-reported values, with performance improving at higher viral loads. Lastly, I conducted a systematic review to evaluate the effectiveness of community-wide NPIs to reduce SARS-CoV-2 transmission. The findings revealed that stringent measures, such as stay-at-home orders and mass gathering restrictions, were generally effective, although the results varied by context and study design. This review did not include the socioeconomic impact of NPIs.