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Coronavirus disease 2019 in patients with inborn errors of immunity

Published:September 24, 2020

There is much uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients affected by inborn errors of immunity, a group of > 430 rare inherited disorders (IEI) in which one or more components of the human immune system fail. Epidemiological studies indicate that COVID-19 mortality increases with each decade of life beyond age 50y and suggest that co-morbidities such as chronic heart or lung disease, obesity, diabetes, hypertension, are associated with a more severe disease course. Intuitively, patients affected by IEI are predicted to be at higher risk of severe SARS-CoV2 disease (COVID19). However, the consequences of SARS-CoV2 in IEI have only been reported in a handful of case reports.

In a multicenter international study recently published in The Journal of Allergy and Clinical Immunology (JACI), Meyts et al. report on the impact of SARS-CoV2 infection in patients with IEI. The outcomes of the study are meaningful not only for the patients affected by IEI and for their treating physicians, but they also provide a glimpse into the redundancy of several components of the immune system in the context of SARS-CoV2 infection.

The study gathered information on 94 IEI patients with SARS-CoV-2 infection. Median age category was 25-34 years. 53 patients suffered from primary antibody deficiency, 9 had immune dysregulation syndrome, 6 a phagocyte defect, 7 auto-inflammatory disorder, 14 a combined immunodeficiency, 3 an innate immune defect, and 2 bone marrow failure. Interestingly, ten infected patients were asymptomatic, including 4 who had pre-existing lung disease. 25 patients had mild disease and were treated as out-patients, including several patients with multiple pre-existing co-morbidities. 15 patients needed invasive ventilation. Unfortunately, nine patients (seven adults, two children) died. All deceased adults and children had significant co-morbidities. There was no significant association between type of IEI and outcome.

While this study suggests mortality and risk in patients with IEI are by and large comparable to the general population, there are several caveats. First, there is tremendous inclusion bias. Second, the cohort is rather limited and only a fraction of all 430 different IEI are included, rendering it difficult to generate any firm or definitive conclusions. For instance, no patients with a proven defect in type I interferon production or response, recently described as risk factor for severe COVID19, are included. Nevertheless, some signatures emerge from this study. First it seems that younger IEI patients are more severely affected and more often admitted to intensive care as compared to the general population. Second, patients with agammaglobulinemia, auto-inflammatory disease, phagocyte disorders and disorders of IL-6 signaling have relatively mild disease, highlighting potentially non-essential (or detrimental) roles of several immune components in human host defense against SARS-Cov2.

In summary, the study provides initial insight into the severity of SARS-CoV2 infection in IEI patients. Although the final outcome is not much different than the general population, younger patients are more severely affected. Further large-scale studies of IEI patients, in addition to further research on the interindividual variability in susceptibility to SARS-CoV2, is needed to better define the populations at particular risk. In the meantime, continuation of protective measures is strongly recommended.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI,  and is the most-cited journal in the field of allergy and clinical immunology.

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