Characterising respiratory viral infections and cross-reactive immunity among hospitalised and community cohorts during and post-COVID-19 pandemic

Vink, Elen Hannah (2025) Characterising respiratory viral infections and cross-reactive immunity among hospitalised and community cohorts during and post-COVID-19 pandemic. PhD thesis, University of Glasgow.

Abstract

Acute respiratory tract infections carry a high burden of morbidity and mortality across the world. A significant proportion of these infections are caused by respiratory viruses, however the aetiology and epidemiology of respiratory viral infections are poorly characterised. The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) in 2019 and the subsequent COVID-19 (Coronavirus disease 2019) pandemic, has further changed the landscape of viral respiratory tract infections and highlighted the importance of understanding the contribution of respiratory viruses to respiratory infections.

Methods:
Multiplex respiratory PCR (polymerase chain reaction) was performed on upper respiratory tract (URT) samples from 1002 hospitalised SARS-CoV-2 positive patients recruited to the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) study between February 2020 and June 2021 in the UK to investigate the prevalence and impact of viral co-infection on disease severity.

Within a prospective longitudinal cohort of randomly selected households, in an urban and rural site in Malawi, adult participants provided URT samples at four timepoints between February 2021 – April 2022. Comprehensive clinical, exposure risk, and socio-economic data were combined with results of multiplex respiratory PCR to investigate endemic respiratory virus circulation patterns in a country that implemented less restrictive non-pharmaceutical interventions (NPIs) than the UK.

An enhanced surveillance study of severe acute respiratory infection (SARI) patients admitted to a large hospital in Glasgow, UK, was carried out between January 2023 and March 2024. Clinical and routine NHS data was collected for 780 participants, and URT samples were tested by PCR for a wide range of respiratory viruses, to investigate the epidemiology of SARI in the post-pandemic era.

Phage immunoprecipitation and sequencing (PhIPSeq) technology was used to screen serum samples from 160 SARS-CoV-2 vaccinated or infected participants, plus pre-pandemic controls, for epitope level immune responses to SARS-CoV-2, and potential cross-reactive responses to other human and animal coronaviruses.

Results:
Viral co-infections in hospitalised UK COVID-19 patients in the early waves of the pandemic were rare. In Malawi, during the pandemic, respiratory viruses continued to circulate in the community with SARS-CoV-2 and rhinovirus detected most frequently. Influenza, RSV (respiratory syncytial virus), and viral co-infections were rarely detected. Distinct differences in respiratory virus epidemiology and population demographics were seen between the rural and urban sites.

In our post-pandemic enhanced surveillance study in a single busy UK centre, almost half of SARI cases tested positive for a respiratory virus; SARS-CoV-2, rhinovirus, and influenza viruses were most frequently detected. Routine testing would have missed over half of these diagnoses. A diagnosis of viral SARI, particularly made at the hospital front door, was associated with significantly lower antibiotic prescribing rates and a shorter hospital admission, compared to those that tested respiratory virus-negative. Viral co-infection prevalence was low and detected in younger, less comorbid/frail participants. In-hospital mortality was 2.5%. Charlson Comorbidity Index (CCI) score ≥ 5, respiratory rate >20 breaths per minute at admission, and an oxygen requirement at admission were all independent predictors of death whilst SARS-Cov-2/influenza virus mono-infection and chronic lung disease were predictive of survival.

PhIPSeq analysis of serum samples detected higher magnitude immune responses to spike epitopes following vaccination with mRNA vaccines compared to the AstraZeneca vaccine or SARS-CoV-2 infection. Immunoreactivity differed by individual epitopes; strong antibody responses targeting the spike fusion peptide were restricted to SARS-CoV-2-convalescent individuals. Evidence of cross-reactive responses directed against human coronavirus (HCoV) OC43, SARS-CoV, and bat/pangolin coronaviruses was demonstrated.

Conclusion:
Respiratory virus epidemiology has evolved over the course of the COVID-19 pandemic across the world and will continue to change in the future. Ongoing enhanced surveillance to map this evolution, and to detect emerging pathogens, is essential for healthcare planning and pandemic preparedness. New technologies such as PhIPSeq have potential to aid in high throughput pathogen screening, epitope level immune response analysis, and vaccine design.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology; Q Science > QR Microbiology > QR180 Immunology; Q Science > QR Microbiology > QR355 Virology; R Medicine > RA Public aspects of medicine
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Supervisor's Name: Ho, Professor Antonia and Thomson, Professor Emma
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85515
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 20 Oct 2025 08:22
• Last Modified: 20 Oct 2025 08:23
• Thesis DOI: 10.5525/gla.thesis.85515
• URI: https://theses.gla.ac.uk/id/eprint/85515

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