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Nosocomial transmission and immunocompromise as risk factors for exposure and adverse outcomes associated with novel pandemic coronavirus SARS-CoV-2 disease (COVID-19).

Ponsford, Mark 2023. Nosocomial transmission and immunocompromise as risk factors for exposure and adverse outcomes associated with novel pandemic coronavirus SARS-CoV-2 disease (COVID-19). PhD Thesis, Cardiff University.
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Background: In the first year since its emergence, the novel coronavirus SARS-CoV-2 caused over 79 million infections and 1.7 million deaths. Understanding risk factors for exposure and severe disease remain crucial for our pandemic exit. Aims: This thesis explores the potential for nosocomial amplification of SARS-CoV-2 transmission and the significance of immunocompromised states to COVID-19 outcome and immunisation. Methods: Evaluation of 2,508 adults hospitalised with molecularly-confirmed COVID19 across 18 hospitals during the first wave, supported by systematic review and metaanalysis (PROSPERO: CRD42021249023). Establishment of COVID-19 ENLIST study (REC: 20/YH/0309), including determination of anti-SARS-CoV-2-Spike-IgG response in up to 1077 kidney transplant recipients, 156 individuals with predominant-antibody deficiency, 134 haemodialysis-recipients, and 33 healthy volunteers following receipt of up to 4 COVID-19 immunisations. Results: The risk of all-cause inpatient mortality was 1.24 times greater in individuals with nosocomial SARS-CoV-2, relative to community-acquired admissions (95% CI: 1.06 to 1.42) in Wales. Internationally, mortality risk was twice as high amongst immunocompromised individuals with nosocomial infection, compared to communityacquired COVID-19 (RR: 2.14, 95% CI: 1.76 to 2.61). Despite high vaccine uptake (≥90%) amongst immunocompromised individuals, failure to mount a detectable humoral response following two COVID-19 vaccines occurred in approximately one-third of individuals with predominant-antibody deficiency. After four vaccines, one-fifth of kidney transplant recipients failed to mount a detectable humoral response, compared to 1.7% of haemodialysis recipients. Pilot testing of 20 persistently seronegative individuals identified one previously undiagnosed hypogammaglobulinaemia case (IgG 3.2g/L). Discussion: Nosocomial transmission of respiratory infections, including SARS-CoV-2, remains a barrier to safe and efficient healthcare delivery. Immunocompromised individuals demonstrated vaccine hypo-responsiveness, suggesting ongoing vulnerability. Risk mitigation strategies, including pre-exposure measures such as inpatient vaccination, and early post-exposure therapeutics guided by serosurveillance are suggested. Failure to mount a detectable anti-SARS-CoV-2-Spike-IgG response despite serial COVID-19 vaccination may indicate wider humoral immunodeficiency.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 19 June 2023
Last Modified: 16 Jun 2024 01:30

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