New study sheds light on COVID-19 outcomes in patients with rare inborn immune disorders

An international consortium led by Isabelle Meyts (KU Leuven) and Stuart Tangye (Garvan Institute) has published its findings on COVID-19 outcomes in individuals with rare inherited immune disorders known as PIDs. Compared to the general population, these patients had similar disease outcomes, but they were more likely to need intensive care and their average age was lower.

"We wanted to find out the impact of SARS-CoV-2 infection one individuals with rare immune disorders known as primary immunodeficiencies (PIDs). This group of patients is assumed to be at risk of severe COVID-19 disease if infected with SARS-CoV-2. As PID patients are so rare, this study was only possible through a large global research collaboration across 50 centres," says Professor Stuart Tangye, Leader of the Immunity and Inflammation Research Theme at the Garvan Institute of Medical Research and senior author of the study.

"The findings show that pre-existing immune deficiencies were generally not found to be a significant risk factor as the rate of fatality from COVID-19 was no higher in this group than the general population. Some immune defects even appeared to be protective against the dramatic immune pathology that is frequently seen in severe disease. However, our study suggests younger male patients with PIDs are more likely to endure severe COVID-19 and require ICU admission," says Isabelle Meyts, Professor at KU Leuven, and clinical lead of the primary immunodeficiency care program at University Hospitals Leuven.

Inborn errors of immunity

The consequences of infection with the SARS-CoV-2 coronavirus are vastly different across individuals. Some infected people are more at risk than others, including older individuals and those with underlying health conditions. However, little is known about those with pre-existing rare inherited immune disorders.

"There has been substantial anxiety within the PID community that their immune condition would result in a more severe clinical outcome should they contract SARS-CoV-2 and develop COVID-19," says Professor Meyts.

The researchers invited clinical immunologists from around the world who manage patients with inborn errors of immunity to complete a questionnaire if their patients had contracted the SARS-CoV-2 virus. Data were collected from patients in the US, UK, France, Spain, Italy, Germany, the Netherlands, and Latin America.

Of the 94 reported patients, 25 had mild disease and were treated as outpatients, while 59 (63%) required hospitalisation. Of those hospitalised, 13 required non-invasive breathing assistance, and 15 were admitted to intensive care for invasive ventilation.

Sadly, nine of the 94 patients passed away from COVID-19 (9.6%), which is within the range of global data of COVID-19 mortality (1-20%). However, admission rates to ICU were higher and the average age was lower in PID-affected patients than in the general population.

Sadly, nine of the 94 patients passed away from COVID-19 (9.6%), which is within the range of global data of COVID-19 mortality (1-20%). However, admission rates to ICU were higher and the average age was lower in PID-affected patients than in the general population.

"Our findings warrant a recommendation for further stringent personal protective measures for patients affected by PIDs," says Professor Meyts.

Similar to the general population, adult patients in the study cohort who succumbed to SARS-CoV-2 infection had existing comorbidities, such as heart failure, chronic kidney or lung disease, and diabetes. 

Searching for genes essential for COVID-19 defence

The study further revealed insights for the components of the immune system that may be involved in SARS-CoV-2 immune defence.

"More than half the patients we surveyed (56%) had a deficiency in their ability to produce antibodies. Surprisingly, these patients had similar outcomes to the rest of the cohort. And patients who were completely unable to produce antibodies all recovered following infection," says Professor Meyts.

The findings also revealed that patients with gene defects that resulted in the body being unable to respond to the pro-inflammatory effects of interleukin 6 (IL-6) developed little or no disease when infected with the SARS-CoV-2 virus. IL-6 is a signalling molecule released by the body in response to infections and helps regulate the human immune response.  

"Our findings suggest that certain forms of immune suppression, which reduce the function of IL-6, are protective against the pathological effects of the cytokine storm frequently observed in patients," says Professor Tangye.

The researchers say further studies are needed to gain a comprehensive understanding of which components of the immune system are crucial to a successful coronavirus defence. "We hope such studies will contribute to a greater understanding of COVID-19 disease progression and new therapeutic approaches," says Professor Tangye.

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