Did the risk of severe COVID-19 in the immunodeficient population of the UK change following vaccination deployment?

In a recent study published in Frontiers in Immunology¸ researchers evaluated the changing risk of severe coronavirus disease 2019 (COVID-19) outcomes in individuals with primary and secondary immunodeficiencies in the context of COVID-19 vaccinations.

Background

Although COVID-19 vaccinations have dramatically altered the risk of mortality and morbidity due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, a large percentage of the population with primary and secondary immunodeficiencies is still vulnerable.

Studies have shown that the immunodeficient population has experienced higher morbidity and mortality from SARS-CoV-2 infections. The vaccine responses have been observed to be impaired in this group, and there is a dearth of information on the immunogenicity of the vaccine and its efficacy against severe COVID-19 outcomes in immunocompromised populations. Furthermore, the change in severe COVID-9 outcomes in the context of vaccines, monoclonal antibody therapies, and the emerging SARS-CoV-2 variants also remains unexplored.

About the study

The present research recruited patients from two studies in the United Kingdom (UK) examining SARS-CoV-2 infection and vaccination-related immune responses in primary and secondary immunodeficiency patients — the COVID-19 in Antibody Deficiency (COV-AD) study and the UK Primary Immunodeficiency Network (UK PIN) national COVID-19 case series.

The COV-AD study recruited participants with primary and secondary antibody deficiencies who were older than 18 years and were undergoing immunoglobulin replacement therapy or had lower than 4g/L serum immunoglobulin G concentration and were on regular antibiotic prophylaxis treatment against infections. Participants were followed-up and serological analyzes were conducted after vaccinations or SARS-CoV-2 infections.

The UK PIN COVID-19 data consisted of anonymized, routinely collected SARS-CoV-2 infection outcome information from primary and secondary immunodeficiency patients being treated in the UK.

The study was based on two cohorts. Cohort A used the data from the UK PIN COVID-19 study on patients infected between March and July 2020, before vaccinations and widespread antiviral treatments were available. Cohort B consisted of patients enrolled in the COV-AD study and participants of the UK PIN COVID-19 study who were infected between January 2021 and April 2022, when vaccines and interventions were easily available.

Additionally, demographic factors, COVID-19 outcomes, hospitalization rates, and comorbidities were compared across the two cohorts. Comorbidities included pulmonary, cardiovascular, rheumatological, hepatic, renal, and gastrointestinal diseases, diabetes mellitus, and organ-specific autoimmune disease. Due to the unavailability of uniform information, ethnicity and body mass index data were not included in the analysis.

Results

The results reported a significant decrease in mortality (20% vs. 3.4%) and hospitalization rates (53.5% vs. 17.9%) due to SARS-CoV-2 infections among patients with primary immunodeficiency between cohort A and cohort B, albeit still high compared to the general population. Furthermore, while almost 70% of the general population had been infected with SARS-CoV-2 at least once, the percentage was much lower among immunodeficient individuals (22.7%).

According to the authors, this reduction in mortality and morbidity rates could be the combined result of vaccines, antiviral therapies, precautionary measures such as social distancing and mask-wearing, and the emergence of SARS-CoV-2 variants that are less virulent.

Given the fact that asymptomatic SARS-CoV-2 infections are highly unlikely among immunodeficient individuals, the authors concluded that over 75% of the immunodeficient individuals in the UK have not been infected by SARS-CoV-2. The adherence to non-pharmacological interventions such as social distancing and wearing face masks is believed to have reduced the frequency of COVID-19 among the immunodeficient population.

Additionally, the stringent following of non-pharmacological measures is thought to have delayed SARS-CoV-2 infections among individuals with primary and secondary immunodeficiencies since most infections among the immunodeficient population were during the predominance of the SARS-CoV-2 Omicron variant.

SARS-CoV-2 viral ribonucleic acid (RNA) carriage in the nasopharynx of immunodeficient COVID-19 patients was for shorter durations, which was attributed to the serological response to vaccination, but it did not result in a significant difference in the mortality or hospitalization rates.

Findings

To summarize, the study explored the change in severity and mortality rates associated with SARS-CoV-2 infections among immunodeficient individuals, given the advancement and availability of vaccines and anti-viral therapies.

Overall, the results indicated a decrease in hospitalization and mortality rates among immunodeficient COVID-19 patients with the widespread availability of vaccinations and antiviral treatment options in the UK. However, compared to the general population, immunodeficient individuals continue to be at a greater risk of poor COVID-19 outcomes. The authors believe that infection mitigation strategies, vaccination, and therapeutic options must be optimized for the immunocompromised population.