INTRODUCTION
The COVID-19 pandemic has disproportionately affected patients with inborn errors of immunity (IEIs) and other forms of immune compromise and dysregulation, with higher mortality,1,2 rare presentations such as multisystem inflammatory syndrome in children (MIS-C),3 and delayed viral clearance reported.4 Inborn errors of type I interferon pathway and autoantibody phenocopies have also been found to cause a substantial proportion of previously healthy patients with life-threatening COVID-19 pneumonia.5,6
mRNA and inactivated COVID-19 vaccines protect strongly against severe outcomes of COVID-19 at the population level.7,8Patients with IEIs or immune dysregulation likely have variable levels of vaccine efficacy, especially for those with defects in adaptive immunity. The initial licensing COVID-19 vaccine trials excluded patients with immunocompromise, driving the need for post-licensure studies to study the immunogenicity of COVID-19 vaccines in IEI patients.
Several studies have reported the immunogenicity of COVID-19 vaccines in IEI patients, but most only focused on 2 doses of COVID-19 mRNA vaccines in adult patients with IEI, mainly common variable immunodeficiency (CVID).9-14 Inactivated vaccines against COVID-19 such as CoronaVac are extensively used worldwide with more than 4 billion doses distributed, and differ in their ability to induce antibody and T cell responses compared to mRNA vaccines.15 Moreover, children and adolescents respond to SARS-CoV-2 infection and vaccination differently than adults,16,17 and we previously reported that adolescents elicit higher antibody response to BNT162b2 and CoronaVac compared with adults.15 Currently in Hong Kong, immunocompromised patients above the age of 5 are recommended to receive a 3-dose mRNA or inactivated vaccine primary series; or, for those aged 3-4, a 3-dose inactivated vaccine primary series, based on poorer immunogenicity and clinical vulnerability.18However, the immunogenicity of three doses of vaccine in patients with heterogeneous IEI remain unclear. In addition, intradermal vaccination of some vaccines such as seasonal flu vaccine has been trialed in immunocompromised patients or older adults, to enhance immunogenicity.19 This represents a potential option for enhanced immunogenicity of COVID-19 vaccination in patients of IEI as well.
The Omicron BA lineage poses a public health threat with enhanced transmissibility and escape from virus neutralization,20,21 reducing the effectiveness of COVID-19 vaccines against symptomatic disease but less so for severe outcomes.7 While T cell epitopes are believed to be preserved,22 how the neutralizing antibody response in IEI patients is affected by Omicron remains unknown.
To address these questions, we initiated a 3-year nonrandomized study (NCT04800133) to study the safety and immunogenicity of COVID-19 vaccines in children and adults receiving mRNA COVID-19 vaccine BNT162b2 or inactivated whole-virion vaccine CoronaVac in Hong Kong. In the present interim analysis, we focus on patients with IEI who received 3-doses of BNT162b2 (aged 12 and above) or CoronaVac (aged 3 and above). Adverse reactions (ARs) and adverse events (AEs) were monitored after each dose, and humoral and cellular immunogenicity against the wild-type (WT) SARS-CoV-2, as well as neutralization capacity against Omicron BA.1 in IEI patients were studied. Cases of Omicron BA.2 breakthrough infections were also described.