Case series of COVID-19 outcomes in adult patients with inborn errors of immunity

In March 2020, Coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 was declared a global pandemic (Cucinotta and Vanelli 2020; Kahn and Mcintosh 2005). Among previously healthy individuals, the clinical spectrum of COVID-19 is broad, ranging from asymptomatic infection to severe respiratory complications, myocarditis, and multi-system failure. Given the high burden of disease seen in many immunocompetent hosts, concern has risen in regards to the possible impact of COVID-19 on immunocompromised patients. Indeed, reports published during the early stages of the pandemic showed evidence of hyperinflammation, acute respiratory distress syndrome, cytopenias, and increased mortality among patients with inborn errors of immunity (IEI) (van Damme et al. 2020; Jin et al. 2020; Castano-Jaramillo et al. 2021; Shields et al. 2021; Meyts et al. 2021). Additionally, a prolonged recovery period of up to 60 days was reported in patients with X-linked agammaglobulinemia (Giardino et al. 2022; Esenboga et al. 2021).

Since the publication of the above reports, additional variables have entered the clinical equation of COVID-19 in IEI patients. These have included the availability of vaccines against SARS-CoV-2, specific therapies such as monoclonal neutralizing antibodies, and the rise of new variants and subvariants. Thus, it is pertinent to continuously re-evaluate the severity of COVID-19 in IEI patients and determine the need for targeted interventions in this population. We hereby review our center’s recent experience in following 10 adult patients with a wide variety of IEI affected by COVID-19. All patients had been fully vaccinated against SARS-CoV-2, and most had also been receiving immunoglobulin replacement. Our patients, including those with underlying lung disease, overall showed mild disease symptoms with no complications or need for hospital admission.

In this retrospective study, we reviewed the charts of patients with IEI followed in our center who were diagnosed with COVID-19 infection between December 2021–July 2022. Patients were included if they consented to participate in the Canadian Centre for Primary Immunodeficiency Registry and Tissue Bank, approved by the Hospital for Sick Children Research Ethics Board (REB protocol # 1000005598). Information regarding patient demographics, underlying immune diagnoses, presence of an underlying lung disease, clinical course of COVID-19 infection, laboratory evaluation and therapeutic measures used, was collected.

We report the clinical manifestations and outcomes of 10 adult patients with IEI. This heterogeneous cohort includes patients with humoral immunodeficiency such as hypogammaglobulinemia, combined immunodeficiency such as DOCK8 deficiency, syndromic immunodeficiency (Roifman syndrome), immune dysregulation disorders, and CGD. All patients had an uncomplicated clinical course without the need for hospital admission, even in those with underlying lung disease.

Compared with previous reports of higher disease severity in IEI patients, a number of protective factors may have contributed to milder disease in our cohort. First, all patients in our cohort were diagnosed with COVID-19 between December 2021–July 2022, a period of predominance of the omicron variant, as opposed to the alpha and delta strains likely impacting patients in earlier reports (Araf et al. 2022). Additionally, 7 of 10 patients had been receiving immunoglobulin replacement, likely providing patients with some degree of passive immunity. It is noteworthy that our center has diligently recommended vaccination against SARS-CoV-2 for all patients with IEI, including those with humoral deficiency. Indeed, while specific antibody responses may be variable in such patients, cellular immunity may still be highly beneficial. Finally, specific treatment with sotrovimab or paxlovid were initiated by community practitioners in 50% of our patients, although it remains unclear whether mild symptoms and disease resolution occurred in these patients due to this treatment. It remains unclear under what circumstances and in which IEI patients this treatment should be administered.

We conclude that patients affected by IEI may show clinical resilience in the face of COVID-19 infection, with vaccination against SARS-CoV-2 and immunoglobulin replacement therapy representing possible protective factors in this patient population. Diligent long-term follow-up studies are warranted and are ongoing to ensure no severe or unique complications develop in this patient population.