COV-AD: COVID infection in patients with antibody deficiency

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.