Prevention of SARS-CoV-2 infection during the COVID-19 pandemic

Abstract

The emergence of SARS-CoV-2 in December 2019 led to the COVID-19 pandemic, causing the biggest global health crisis of a generation. The most effective means of reducing morbidity and mortality from infection is to prevent transmission of the virus. There are a variety of methods which can prevent or reduce the risk of transmission, each with specific strengths and limitations.

This thesis examines a number of different non-pharmaceutical and pharmaceutical interventions which can be deployed to prevent the transmission of SARS-CoV-2. Each chapter represents a different part of my research conducted in response to the COVID-19 pandemic across these themes. This includes a literature review which was conducted in real time during the early stages of the pandemic to inform clinicians, policy makers and the public on the evidence surrounding COVID-19 in children, performed with the support of the Royal College of Paediatrics and Child Health. This revealed the important and counter-intuitive finding that children played a lesser role in the transmission of SARS-CoV-2 than had been anticipated on the basis of other respiratory viruses.

This work informed my role on the National Institute for Health Research working group on the Transmission of COVID-19 in Schools (ToCS). The ToCS working group developed a protocol for studying the silent transmission of COVID-19 in these settings, which could serve as an “off the shelf” option for deploying a study in the event of a future pandemic.

Given the emergency in protecting healthcare workers and the initial shortage of effective personal protective equipment, the Personal Respirator Southampton (PeRSo) was developed and deployed at the University Hospital Southampton. Evaluation of its deployment found it to be the preferred personal protective equipment by healthcare workers due to it feeling safer, being more comfortable and more easy to use than standard airborne precautions.

Whilst non-pharmaceutical interventions are most readily deployed in the event of a disease outbreak, they often come with large social and economic costs. Pharmaceutical interventions, and vaccines in particular are the definitive management of large infectious disease outbreaks. Highly effective vaccines were produced for COVID-19, but due to waning immunity and theemergence of variants of concern with immune escape, booster vaccinations were required. The COV-BOOST randomised controlled trial of booster vaccines for COVID-19 found that several heterologous booster vaccines were safe and immunogenic, and that fourth doses were equally safe and well tolerated.

Given the emergence of variants of concern and the prospect of future pandemics occurring due to Sarbecoviruses, the development of a vaccine which can cover across a broad range of the Sarbecovirus family would provide more robust protection against SARS-CoV-2 as well as providing protection against future outbreaks. The phase 1, first in human study of pEVAC-PS which contains digitally synthesised antigens to create broad immunity against Sarbecoviruses, was found to be safe and well tolerated at the first three doses trialled. Further study will be needed to determine safety at the highest dose, and to determine immunogenicity.

These findings provide important lessons for future pandemics. Rapid evidence gathering and synthesis programmes specific to children should be ready to be deployed. Networks and working groups to coordinate emergency research necessary for children and research with educational environments should be established. Healthcare systems should consider investing in personal respirators for staff, as they can provide stocks which are robust to demand shock. They also provide the highest level of protection, best user experience and are most environmentally and economically efficient. Future vaccine development programmes for disease outbreaks should plan for the needs for booster doses at the outset, and protocols which are ready to be deployed in an emergency should be prepared. Finally, vaccine development needs to be proactive in determining the highest risk groups of pathogens, such as Sarbecoviruses, and trialling vaccines which stimulate more broad protection.

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Identifiers

ORCID for Saul Faust: orcid.org/0000-0003-3410-7642

ORCID for Chrissie Jones: orcid.org/0000-0003-1523-2368

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