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.