International study reports on the impact of COVID-19 in patients with primary immunodeficiencies

'Coronavirus disease 2019 in patients with inborn errors of immunity: An international study' 1

Patients with primary immunodeficiencies (defined as 'inborn errors of immunity' in this study) are at an increased risk of severe COVID-19 disease. 

Conclusions and summary

  • A large proportion of patients with PIDs and COVID-19 infection had mild disease or were asymptomatic.
  • Some of the risk factors for severe disease and mortality were in line with the general population. 
  • However, the study revealed that the disease was more severe in younger patients with PIDs and led to increased ICU admissions than in the general population.
  • Therefore, it is important to recommend strict measures to protect the more susceptible PID population.
  • There is a need to conduct further studies to continue learning about the types of PID patients at increased risk of severe COVID-19 disease. Future studies should also look at the long-term impact of the disease, including in recovering patients.

The objectives of the study were to evaluate how infection with the COVID-19 virus presents itself in patients with primary immunodeficiencies (PIDs) and its impact. The study also aimed at increasing understanding of the body's defence mechanisms against this virus.

This study is significant as it is the first global and large-scale one looking at the impact of the COVID-19 virus on this high-risk patient population.

Methods:

The study was led by Prof. Isabelle Meyts, MD, PhD from the University Hospitals Leuven and Prof. Stuart G. Tangye PhD, from the Garvan Institute of Medical Research, Australia.

A web-based survey was sent to many scientific, medical, and patient organisations involved in the management of patients with primary immunodeficiencies. It ran between 16 March 2020 and 30 June 2020.

The countries involved were: USA, UK, France, Spain, Italy, Germany, Netherlands, Chile, Belgium, Mexico, Brazil, Argentina.

Results:

Reports were received for 94 patients with primary immunodeficiency (PID) and who had been infected by COVID-19. The breakdown of PIDs was as follows:

  • Primary antibody deficiency was the main type in 53 (56%) patients
  • Other types of PIDs were: immune dysregulation syndrome in 9 (9.6%) patients, 6 (6.4%) had a phagocyte defect, 7 (7.4%) had an autoinflammatory disorder, 14 (15%) had a combined immunodeficiency, 3 (3%) had an innate immune defect and 2 (2%) suffered from bone marrow failure.

With regards to age, approximately one third of patients were less than 18 years old. The average (median) patient age group was 25-34 years old.

The most frequent reported symptoms associated with COVID-19 infection were: fever (69%), cough (47%), runny nose, sneezing ('upper respiratory tract symptoms'; 19%) and shortness of breath (13%). Some patients also reported diarrhoea and vomiting ('gastrointestinal symptoms'; 14%) and muscle pain ('myalgia' 16%).

Key findings were as follows:

  • 10 (11%) patients did not have any symptoms of COVID-19 (they were asymptomatic)
  • 24 (25%) patients suffered from mild COVID-19 disease and did not have to be admitted to hospital (outpatient treatment)
  • 59 (63%) patients were hospitalised. Of those hospitalised:
    • 28 patients did not require treatment in intensive care unit (ICU) or breathing assistance (ventilation)
    • 18 patients were admitted to ICU
  • 9 patients died (7 adults and 2 children); all had other medical conditions (comorbidities)
  • The patients received a variety of treatments, quite different across the many countries involved in the study.

Interestingly, many of the findings were similar to those in people not affected by PIDs (general population):

  • The way the COVID-19 infection manifested itself and the risk factors for the severe form of the disease
  • The proportion of people who died from the COVID-19 infection (case-fatality) was about 10%. This is within the range (1-20%) of the global data from the general population, seen in other studies
  • Male patients were more at risk of COVID-19 infection and admission to ICU, in line with other studies

However, there were some key differences compared with other studies in the general population:

  • The average age of patients with PIDs and COVID-19 infection (25-34 years old) was lower
  • The rate of ICU admission was higher
  • Young male patients with PIDs were more at risk of severe COVID-19 and need for ICU admission

This study enabled the researchers to understand better the way the body responds to COVID-19 infection:

  • The different components of the immune system play a different role in controlling the disease - some are more important than others
  • This may explain why specific types of PIDs led to either milder or more severe forms of disease

1. Reference: Meyts I, Bucciol G, Quinti I, Neven B, Fischer A, Seoane E, Lopez-Granados E, Gianelli C, Robles-Marhuenda A, Jeandel PY, Paillard C, Sankaran VG, Demirdag YY, Lougaris V, Aiuti A, Plebani A, Milito C, Dalm VA, Guevara-Hoyer K, Sánchez-Ramón S, Bezrodnik L, Barzaghi F, Gonzalez-Granado LI, Hayman GR, Uzel G, Mendonça LO, Agostini C, Spadaro G, Badolato R, Soresina A, Vermeulen F, Bosteels C, Lambrecht BN, Keller M, Mustillo PJ, Abraham RS, Gupta S, Ozen A, Karakoc-Aydiner E, Baris S, Freeman A, Yamazaki-Nakashimada M, Scheffler-Mendoza S, Espinosa-Padilla S, Gennery AR, Jolles S, Espinoza Y, Poli MC, Fieschi C, Hauck F, Cunningham-Rundles C, Mahlaoui N; IUIS Committee of Inborn Errors of Immunity, Warnatz K, Sullivan KE, Tangye SG. (2020), "Coronavirus Disease 2019 in patients with inborn errors of immunity: an international study". J Allergy Clin Immunol, DOI: https://doi.org/10.1016/j.jaci.2020.09.010

This article was written by Valerie Brisse-Uhlig, a volunteer for PID UK, and was approved by the Chair of the PID UK Medical Panel.

Posted December 2020