Interferon-β Therapy in a Patient with Incontinentia Pigmenti and Autoantibodies against Type I IFNs Infected with SARS-CoV-2

Bastard, Paul; Lévy, Romain; Henriquez, Soledad; Bodemer, Christine; Szwebel, Tali‐Anne; Casanova, Jean‐Laurent

doi:10.1007/s10875-021-01023-5

Cited by 43 publications

(60 citation statements)

References 6 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this figure, although not significant, a trend of a higher risk of death can be found with the presence of neutralizing autoantibodies subcutaneous IFN-beta in hospitalized patients with severe or critical respiratory condition did not improve the clinical response or outcomes, as described previously in clinical trials [25]. These results suggest that a rapid determination of anti-IFN autoantibodies at admission would be a very useful tool in the stratification of patients, to adopt early IFN-beta and/or early intensification of their treatment to minimize the risks of adverse outcomes, as described recently in a patient with incontinentia pigmenti and autoantibodies to type I IFNs [30]. This may be even more pertinent in patients with lower lymphocyte counts well below 0.5 10E3/μL and C-RP higher than 300 (mg/L), analytes which show a strong correlation with the presence of neutralizing autoantibodies.…”

Section: Discussionsupporting

confidence: 69%

Neutralizing Autoantibodies to Type I IFNs in >10% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background In a recent study, autoantibodies neutralizing type I interferons (IFNs) were present in at least 10% of cases of critical COVID-19 pneumonia. These autoantibodies neutralized most type I IFNs but rarely IFN-beta. Objectives We aimed to define the prevalence of autoantibodies neutralizing type I IFN in a cohort of patients with severe COVID-19 pneumonia treated with IFN-beta-1b during hospitalization and to analyze their impact on various clinical variables and outcomes. Methods We analyzed stored serum/plasma samples and clinical data of COVID-19 patients treated subcutaneously with IFNbeta-1b from March to May 2020, at the Infanta Leonor University Hospital in Madrid, Spain. Results The cohort comprised 47 COVID-19 patients with severe pneumonia, 16 of whom (34%) had a critical progression requiring ICU admission. The median age was 71 years, with 28 men (58.6%). Type I IFN-alpha-and omega-neutralizing autoantibodies were found in 5 of 47 patients with severe pneumonia or critical disease (10.6%), while they were not found in any of the 118 asymptomatic controls (p = 0.0016). The autoantibodies did not neutralize IFN-beta. No demographic, comorbidity, or clinical differences were seen between individuals with or without autoantibodies. We found a significant correlation between the presence of neutralizing autoantibodies and higher C-reactive protein levels (p = 5.10e −03 ) and lower lymphocyte counts (p = 1.80e −02 ). No significant association with response to IFN-beta-1b therapy (p = 0.34) was found. Survival analysis suggested that neutralizing autoantibodies may increase the risk of death (4/5, 80% vs 12/42, 28.5%). Conclusion Autoantibodies neutralizing type I IFN underlie severe/critical COVID-19 stages in at least 10% of cases, correlate with increased C-RP and lower lymphocyte counts, and confer a trend towards increased risk of death. Subcutaneous IFN-beta treatment of hospitalized patients did not seem to improve clinical outcome. Studies of earlier, ambulatory IFN-beta treatment are warranted.Keywords COVID-19 . subcutaneous interferon-beta 1b . type I IFN neutralizing autoantibodies . severity biomarkers Jesús Troya and Aurora Pujol contributed equally to this work.

show abstract

Section: Discussionsupporting

confidence: 69%

Neutralizing Autoantibodies to Type I IFNs in >10% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast, interferon treatment may be a suitable therapeutic option early when the patient becomes symptomatic [50,51]. Early type I interferon administration might also be beneficial in selected patients with IEI or auto antibodies impairing type I interferon response [52,53].…”

Section: Discussionmentioning

confidence: 99%

COVID-19 in the Context of Inborn Errors of Immunity: a Case Series of 31 Patients from Mexico

Castaño-Jaramillo¹,

Yamazaki‐Nakashimada²,

O’Farrill-Romanillos

et al. 2021

J Clin Immunol

126

View full text Add to dashboard Cite

Highlights1. What is already known about this topic? SARS-CoV-2 causes asymptomatic or mild infection in about 80% of humans, while an excessive immune response has killed millions. Differential susceptibility and risk factors became a concern early in the pandemic. Several monogenic defects that involve innate viral sensors or affect interferon response pathways, as well as autoantibodies against type 1 interferons, have been identified in 14% of patients with life-threatening COVID-19. The impact of the novel betacoronavirus infection in patients with known inborn errors of immunity is less clear. Case series and reports from different countries have suggested a minor impact or even a potential protective effect of the IEI for some patients.2. What does this article add to our knowledge? We describe findings and outcomes of COVID-19 in 31 pediatric and adult patients with known IEI from Mexico, 84% of whom survived. Pediatric patients had a higher hospitalization rate. Inpatient mortality was 40%, and ICU mortality was 63%. Six patients died of secondary bacterial infection or uncontrolled systemic inflammation, but not from overwhelming viral infection. One patient with an autoinflammatory disorder under treatment with anakinra had a catastrophic clinical course. Eighty percent of patients received IVIG as part of their treatment for acute SARS-CoV-2 infection.3. How does this study impact current management guidelines? We recommend continued and/or high-dose IVIG in patients with known IEI seeking care for COVID-19. Patients with autoinflammatory disorders, especially those with inflammasome dysregulation, should probably take extreme measures to prevent exposure, while doctors taking care of SARS-CoV-2 infected patients with immune deficiencies must do everything they can to prevent secondary bacterial infections. The high survival of patients with COVID-19 in the context of inborn errors of immunity worldwide (over 80%) might be the result of patientphysician awareness and special care.

show abstract

“…Indeed, the IFN‐α2b treatment showed a clinical benefit for two COVID‐19 patients with TLR3 or IRF3 mutation [143]. Importantly, even in COVID‐19 patient with autoantibodies against IFN‐α and IFN‐ω treatment with IFN‐β is shown to resolve syndromes [144], supporting the therapeutic application of IFN‐β in patients bearing anti‐IFN‐α/IFN‐ω autoantibodies. However, the timing of early type I IFN administration is critical in treating COVID‐19.…”

Section: Type I Ifn Immunity In Covid‐19mentioning

confidence: 99%

Infection‐induced inflammation from specific inborn errors of immunity to COVID‐19

Chen

Lai

2021

The FEBS Journal

View full text Add to dashboard Cite

Inborn errors of immunity (IEIs) are a group of genetically defined disorders leading to defective immunity. Some IEIs have been linked to mutations of immune receptors or signaling molecules, resulting in defective signaling of respective cascades essential for combating specific pathogens. However, it remains incompletely understood why in selected IEIs, such as X‐linked lymphoproliferative syndrome type 2 (XLP‐2), hypo‐immune response to specific pathogens results in persistent inflammation. Moreover, mechanisms underlying the generation of anticytokine autoantibodies are mostly unknown. Recently, IEIs have been associated with coronavirus disease 2019 (COVID‐19), with a small proportion of patients that contract severe COVID‐19 displaying loss‐of‐function mutations in genes associated with type I interferons (IFNs). Moreover, approximately 10% of patients with severe COVID‐19 possess anti‐type I IFN‐neutralizing autoantibodies. Apart from IEIs that impair immune responses to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), SARS‐CoV‐2 encodes several proteins that suppress early type I IFN production. One primary consequence of the lack of type I IFNs during early SARS‐CoV‐2 infection is the increased inflammation associated with COVID‐19. In XLP‐2, resolution of inflammation rescued experimental subjects from infection‐induced mortality. Recent studies also indicate that targeting inflammation could alleviate COVID‐19. In this review, we discuss infection‐induced inflammation in IEIs, using XLP‐2 and COVID‐19 as examples. We suggest that resolving inflammation may represent an effective therapeutic approach to these diseases.

show abstract

Interferon-β Therapy in a Patient with Incontinentia Pigmenti and Autoantibodies against Type I IFNs Infected with SARS-CoV-2

Abstract: Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Cited by 43 publications

References 6 publications

Neutralizing Autoantibodies to Type I IFNs in >10% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain

Neutralizing Autoantibodies to Type I IFNs in >10% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain

COVID-19 in the Context of Inborn Errors of Immunity: a Case Series of 31 Patients from Mexico

Infection‐induced inflammation from specific inborn errors of immunity to COVID‐19

Contact Info

Product

Resources

About