COV-AD: COVID infection in patients with antibody deficiency

Our previous study found that individuals with immunodeficiency are more likely to develop severe COVID-19. We also know that our patients with immune deficiency respond less well to vaccination than the general public and may be less well protected against future infection. Furthermore, concern has also been raised that the SARS-CoV-2 virus can mutate more rapidly in individuals with immune deficiency, potentially posing a public health risk. Therefore, understanding the immune response following COVID-19 infection and vaccination is therefore of the upmost importance for individual with immune deficiency and the general public.

By recruiting 1050 patients with antibody deficiency, this multicentre study involving Clinical Immunology centres across the United Kingdom, will aim to answer important questions about the immune response to COVID-19 infection in individuals with immune deficiency and provide insight into whether vaccination will offer effective protection from the disease in the future. We will do this through antibody and T cell testing. In partnership with the Saving Lives charity, who have pioneered remote virus and antibody testing for patients who are shielding, the study also hopes to estimate how many patients with antibody deficiency have been asymptomatically infected with the virus, how many are unable to clear the virus and also what factors make patients with immune deficiency so susceptible to COVID-19. In doing so, we hope to understand what individual and public health measures are most likely to protect our patients from COVID-19 in the future.

Our national case series has found that individuals with primary and secondary immunodeficiencies are more likely to develop severe COVID-19. Individuals with immune deficiency respond poorly to some vaccinations and concern has been raised suboptimal immune responses may allow viral persistence, accelerated viral evolution and the emergence of viral escape variants that may potentially pose a public health risk. Understanding the immune response to the SARS-CoV-2 virus following natural infection or following vaccination is, therefore, of the upmost importance in individuals with immune deficiency.

This multicentre study, involving a network of Clinical Immunology centres across the United Kingdom, will recruit 1050 individuals with antibody deficiency to study the magnitude and quality of their immunological responses following natural infection with SARS-CoV-2 and/or their response to vaccination. In partnership with the SavingLIVES charity, individuals will be invited to submit swabs and dried blood spots which will be tested for the presence of the virus and the presence of antibodies against the SARS-CoV-2 spike glycoprotein respectively. Serial swabs will be used to understand the prevalence of persistent viral infection in individuals with antibody deficiency and this information will be correlated with symptom diaries the spectrum of disease in patients with antibody deficiency. PCR positive samples will be submitted to the UK COG consortium for sequencing and phylogenetic analysis. Separate study arms will examine whether patients with immune deficiency make antigen specific antibody and cellular responses to the virus following natural infection or vaccination. This study will provide valuable insight into how SARS-CoV-2 infection manifests in immunologically vulnerable individuals and inform on whether public health countermeasures including vaccination are likely to be successful in preventing infection and disease in this population.