The COVID in patients with Antibody Deficiency (COV-AD) continues to provide valuable insight into the effects of the COVID-19 pandemic on individuals with primary and secondary immunodeficiency. COV-AD is a multicentre UK study, led by Professor Alex Richter and Dr Adrian Shields from the University of Birmingham and Professor Siobhan Burns at University College London, that has focussed on understanding the effects of SARS-CoV-2 infection and vaccinations amongst individuals with primary and secondary immune deficiencies. In collaboration with the UK Primary Immunodeficiency Network (UK PIN) , the team has also been considering outcomes following SARS-CoV-2 infection in vulnerable individuals.

At the start of the SARS-CoV-2 pandemic, the UK PIN and COV-AD study team documented the outcomes from COVID-19 in the first 100 individuals with primary and secondary immunodeficiency infected with the SARS-CoV-2 virus. Hospitalisation rates and death were exceptionally high during this first wave of the pandemic – as many as 1 in 4 individuals with immunodeficiency died of COVID-19 if they were unfortunate enough to contract it (1). Additional risk factors for poor outcome were defined in a subsequent study of over 300 individuals including increasing age and low white blood cell counts (2).

In their third paper, published in the medical journal Frontiers in Immunology in September 2022, the study team sought to re-examine hospitalisation and death rates amongst individuals with immunodeficiency after deployment of of primary and booster vaccinations and novel treatments. The study looked at those who developed COVID-19 between January 2021, the start of the vaccine rollout until April 2022, a period that captured the alpha, delta and early omicron (BA.1, BA.2) pandemic waves. The study had several important findings.

Firstly, compared to the general population, the proportion of individuals with immunodeficiency who had ever been infected with SARS-CoV-2 was significantly lower (Figure 1). By April 2022, only 23% of individuals with immunodeficiency had suffered one or more SARS-CoV-2 infections, compared to over 71% of the general population. This large discrepancy is likely due to the community continuing to shield from infection. Furthermore, compared to the general population, individuals with immunodeficiency were infected later in the pandemic. The peak of hospitalisations and deaths in the general population occurred in January 2021 during the alpha wave of the pandemic. In contrast, the majority of infection amongst individuals with immunodeficiency occurred over a year later during the Omicron wave. This delay meant that individuals with immunodeficiency received more vaccine doses by the time they were infected; the COV-AD study has previously shown that three doses of vaccine generate better immune responses than two doses in patients with antibody deficiency (3,4).

Figure 1: Comparison of cumulative SARS-CoV-2 infection rates between participants in the COV-AD study and the general population between April 2020 and April 2022.

Thankfully, SARS-CoV-2 vaccinations have significantly reduced hospitalisation and mortality from COVID-19 amongst patients with immunodeficiency. For example, in individuals with primary immunodeficiency, mortality has fallen from 1 in 5 at the start of the pandemic, prior to vaccination to around 1 in 33 following the deployment of vaccinations. In secondary immunodeficiency, the effect is similar, reducing mortality from 1 in 3 to approximately 1 in 12.

However, SARS-CoV-2 continues to pose immediate and significant risks to the immunodeficiency community. The Omicron variant, which has been dominant in the UK since mid-December 2021, has been mooted to cause less serious disease than previous variants of the SARS-CoV-2 virus. Yet amongst those with primary and secondary immunodeficiency, 10% of individuals infected with Omicron required hospitalisation and 2.7% of individual died compared to 2.2% of the general population requiring hospitalisation and 0.2% succumbing to COVID-19.

Concerningly, the study team found that individuals faced significant issues accessing early outpatient treatments for COVID-19. From December 2021, vulnerable individuals were eligible for assessment for antiviral or monoclonal antibody treatment from community based COVID medicine dispensing units (CMDU). However, only 61% of patients who were eligible for treatment, received treatment from these units, despite clear evidence that early community treatment reduced the rate of subsequent hospitalisation.

The COV-AD study formally concludes at the end of November 2022; the study team would like to take the opportunity, once again, to thank all those members of the UK immunodeficiency community who have participated in the COV-AD study. We recognise the pandemic is not over for individuals with immunodeficiency; COVID-19 continues to significantly impact our community and their remains great uncertainty about impact of further SARS-CoV-2 variants when they emerge. The study team are continuing to work with Immunodeficiency UK and other charities to petition the government to better support and protect vulnerable individuals from COVID-19 as we approach the winter period.

The paper entitled – Impact of vaccination on hospitalization and mortality from COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience – can be read at the following link –

This article was written by Dr Adrian Shields, Associate Professor – Clinical Immunology, Honorary Consultant Immunologist, Clinical Immunology Service, College of Medical and Dental Sciences, University of Birmingham.

November 2022


  1. Shields AM et al. COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience. J Allergy Clin Immunol 2021 Mar;147(3):870-875.e1. (doi: 10.1016/j.jaci.2020.12.620)
  2. Shields AM et al. Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK. Clin Exp Immunol. 2022 Sep 29;209(3):247-258. (doi: 10.1093/cei/uxac008)
  3. Shields AM et al. SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study. J Clin Immunol. 2022 Jul;42(5):923-934. (doi: 10.1007/s10875-022-01231-7.)
  4. Shields AM et al. Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study. Front Immunol. 2022 Jun 2;13:912571