Impact of vaccination on hospitalization and mortality from COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience

Background: 

Individuals with primary and secondary immunodeficiency (PID/SID) were shown to be at risk of poor outcomes during the early stages of the SARS-CoV-2 pandemic. SARS-CoV-2 vaccines demonstrate reduced immunogenicity in these patients.

Objectives: 

To understand whether the risk of severe COVID-19 in individuals with PID or SID has changed following the deployment of vaccination and therapeutics in the context of the emergence of novel viral variants of concern.

Methods: 

The outcomes of two cohorts of patients with PID and SID were compared: the first, infected between March and July 2020, prior to vaccination and treatments, the second after these intervention became available between January 2021 and April 2022.

Results: 

22.7% of immunodeficient patients have been infected at least once with SARS-CoV-2 since the start of the pandemic, compared to over 70% of the general population. Immunodeficient patients were typically infected later in the pandemic when the B.1.1.529 (Omicron) variant was dominant. This delay was associated with receipt of more vaccine doses and higher pre-infection seroprevalence. Compared to March-July 2020, hospitalization rates (53.3% vs 17.9%, p<0.0001) and mortality (Infection fatality rate 20.0% vs 3.4%, p=0.0003) have significantly reduced for patients with PID but remain elevated compared to the general population. The presence of a serological response to vaccination was associated with a reduced duration of viral detection by PCR in the nasopharynx. Early outpatient treatment with antivirals or monoclonal antibodies reduced hospitalization during the Omicron wave.

Conclusions: 

Most individuals with immunodeficiency in the United Kingdom remain SARS-CoV-2 infection naïve. Vaccination, widespread availability of outpatient treatments and, possibly, the emergence of the B.1.1.529 variant have led to significant improvements in morbidity and mortality followings SARS-CoV-2 infection since the start of the pandemic. However, individuals with PID and SID remain at significantly increased risk of poor outcomes compared to the general population; mitigation, vaccination and treatment strategies must be optimized to minimize the ongoing burden of the pandemic in these vulnerable cohorts.

Author list

 

Affiliations:

  1. Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
  2. Department of Clinical Immunology, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
  3. Department of Immunology, Royal Free London National Health Service (NHS) Foundation Trust, London, United Kingdom
  4. Department of Allergy and Clinical Immunology, Leeds Teaching Hospitals National Health Service (NHS) Trust, Leeds, United Kingdom
  5. Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
  6. Department of Clinical Immunology, University Hospitals North Midlands, Stoke-on-Trent, United Kingdom
  7. Department of Clinical Immunology, University College London Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
  8. National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC) Oxford Biomedical Centre, University of Oxford, Oxford, United Kingdom
  9. Department of Clinical Immunology, Oxford University Hospitals National Health Service (NHS) Foundation Trust, Oxford, United Kingdom
  10. Department of Immunology, Salford Royal National Health Service (NHS) Foundation Trust, Salford, United Kingdom
  11. Department of Clinical Immunology, Hull University Teaching Hospitals National Health Service (NHS) Trust, Hull, United Kingdom
  12. Department of Allergy and Clinical Immunology, University Hospitals Plymouth National Health Service (NHS) Trust, Plymouth, United Kingdom
  13. Department of Allergy and Clinical Immunology, Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle upon Tyne, Newcastle, United Kingdom
  14. Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, United Kingdom
  15. Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
  16. Institute of Immunity and Transplantation, University College London, London, United Kingdom

Authors:

Adrian M. Shields1,2*, Susan Tadros3, Adam Al-Hakim4, Jeremy M. Nell5, Me Me Nay Lin3, Michele Chan3, Sarah Goddard6, John Dempster7, Magdalena Dziadzio7, Smita Y. Patel8,9, Shuayb Elkalifa10, Aarnoud Huissoon2, Christopher J. A. Duncan5, Archana Herwadkar10, Sujoy Khan11, Claire Bethune12, Suzanne Elcombe13, James Thaventhiran14, Paul Klenerman15, David M. Lowe3,16, Sinisa Savic4, Siobhan O. Burns3,16*† and Alex G. Richter1,2*† on behalf of the COV-AD consortium

Novel Coronavirus SARS-CoV-2

10.3389/fimmu.2022.984376

Frontiers in Immunology