Year: 2023
Type: dissertation
Study design: Observational Study
Abstract: Care homes were disproportionately affected by the COVID-19 pandemic, with outbreaks resulting in high mortality rates in elderly residents. Understanding the ability of older individuals to mount robust and durable responses to SARS-CoV-2 providing protection from reinfection is vital to inform vaccination strategies. Antibodies, in particular the neutralising fraction (nAbs), can provide sterilising immunity against viruses, but they may wane or fail to provide sufficient functional flexibility to cross-recognise viral variants. Antigen-specific memory B cells (MBCs) have the potential to compensate for antibody responses of inadequate titre or cross-reactivity upon pathogen re-encounter. The SARS-CoV-2 specific humoral immune response of staff and residents from 13 care homes with varying experiences of COVID-19 during the first wave of the pandemic in London, UK were characterised. High rates of asymptomatic infection and transmission were observed, even in care homes with no reported COVID-19 cases. Over 95% of SARS-CoV-2 PCR-positive staff and residents developed antibodies irrespective of symptom status, and nearly 90% of seropositive individuals developed nAbs irrespective of age. Longitudinal monitoring identified significant waning of nAbs in the five months following infection, which was more pronounced in older residents. In spite of this, protective effectiveness of prior SARS-CoV-2 infection was over 90% over nine months, including to the more genetically diverse emerging alpha variant. The presence and functional ability of SARS-CoV-2 MBCs was investigated in a subgroup of care home residents and staff, a high proportion of whom had lost nAbs five months after primary infection. Class-switched SARS-CoV-2 spike and receptor binding domain (RBD)-specific MBCs with a classical phenotype persisted irrespective of age and in the majority who had lost nAbs. SARS-CoV-2 spike/S1/RBD-specific recall was detectable by ELISpot in some who had lost nAbs, but was significantly impaired in the elderly, highlighting the potential impact of functional defects in B cell immunity on susceptibility to reinfection and disease in the elderly. The findings presented in this thesis have important implications for the development of vaccine strategies for the elderly and for pandemic preparedness in the vulnerable setting of care homes.
Author: Jeffery-Smith, A
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Public Health England
OpenAlex ID: W6982288541