Patients with primary or secondary immunodeficiency are at higher risk of severe disease and death following SARS-CoV-2 infection compared with the general population, according to a new study published in the journal Clinical & Experimental Immunology and led by researchers from the University of Birmingham.
The pandemic has disproportionately affected individuals with primary and secondary immunodeficiencies, for whom SARS-CoV-2, the virus that causes COVID-19, poses a higher risk as their immune system does not function optimally to protect against serious disease.
In a study led by the University of Birmingham, immunology researchers around the UK set out to better understand how seriously COVID-19 affected patients with primary immunodeficiency (PID) and secondary immunodeficiency (SID). These conditions arise when the immune system’s ability to fight infectious disease is compromised or entirely absent as a result of genetic mutations (PID) or other factors such as immunosuppressive drugs, blood cancers or cancer treatment (SID).
The UK Primary Immunodeficiency Network (UK PIN) collated the health outcomes of 310 individuals with PID or SID between March 2020 and July 2021 following SARS-CoV-2 infection. The cases included 218 individuals with PID and 92 individuals with SID.
What data did they collect?
Researchers collected data from each patient including demographic factors such as age, sex and ethnicity. They also recorded information on the health status and treatment that each patient had been receiving before their COVID-19 infection, including their levels of white blood cells called lymphocytes. When targeted COVID-19 treatments became available later in the pandemic, the treatments received by individuals who were hospitalised with COVID-19 were also recorded.
What were the results of this study?
Of the 310 individuals recorded, 45.8% of patients with PID and SID were hospitalised with COVID-19 and unfortunately, 17.7% died. These results were compared with national statistics and show that, on average, patients with PID or SID died up to 26 years younger than the average age of death from COVID-19 of the general population in the UK.
The risk of dying in these patients varied between subgroups of these conditions as seen in the following mortality rates:
- 18.3% of 93 patients with common variable immunodeficiency disorder
- 16.3% of 159 patients with PID receiving immunoglobulin replacement therapy
- 7.7% of 26 patients with X-linked agammaglobulinemia
- 31.6% of 92 patients with SID
- 0% of 13 patients with C1 inhibitor deficiency (only one patient was hospitalised)
Risk factors and targeted COVID-19 treatments
In patients with PID, additional risk factors for developing serious COVID-19 disease were similar to those in the general population, such as older age and cardiovascular disease. These conditions were not identified as risk factors for patients with SID, but these individuals faced a much higher risk of death overall from COVID-19.
The researchers identified that patients with PID or SID were more likely to develop serious disease if they had lymphopenia, an abnormally low level of lymphocytes.
Over the course of this study, 33 patients with PID or SID received a targeted COVID-19 treatment as part of ongoing clinical trials. Due to the small number of patients studied, the results must be interpreted cautiously, however the survival rates of patients treated with dexamethasone and/or remdesivir and/or antibody-based treatments exceeded 75%.
What can we conclude from this study?
Compared with the general population, individuals with PID or SID are at a higher risk becoming very ill if they contract SARS-CoV-2. Older age, low lymphocyte levels and the presence of co-existing health conditions further increase the risk of becoming seriously ill from COVID-19.
This study highlights the severe risk that COVID-19 poses for individuals with PID or SID and the urgent need to continue to protect these people as COVID-19 restrictions ease. It is important to note that this study did not consider the COVID-19 vaccination status of these individuals, however a study on COVID-19 vaccine responses in patients with antibody deficiency is ongoing. It will be important to consider the level of protection that COVID-19 vaccination provides in these individuals, as well as the results of ongoing studies on the effectiveness of COVID-19 treatments, when developing public health policies to protect our communities as the pandemic evolves.
For media enquiries, please read our press release for this paper.
For more information, details of the full paper are as follows: Shields et al. 2022. Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the United Kingdom. Clinical & Experimental Immunology DOI: 10.1093/cei/uxac008