Harnessing Type I IFN Immunity Against SARS-CoV-2 with Early Administration of IFN-β

Vinh, Donald C.; Abel, Laurent; Bastard, Paul; Cheng, Matthew P.; Condino‐Neto, Antônio; Gregersen, Peter K.; Haerynck, Filomeen; Cicalese, Maria-Pia; Hagin, David; Soler‐Palacín, Pere; Planas, Anna M.; Pujol, Aurora; Notarangelo, Luigi D.; Zhang, Qian; Su, Helen C.; Casanova, Jean‐Laurent; Meyts, Isabelle; Aiuti, Alessandro; Arkin, Lisa M.; Bolze, Alexandre; Charkravorty, Samya; Christodoulou, John; Colobran, Roger; Drolet, Beth A.; Fellay, Jacques; Froidure, Pr Antoine; Pape, Jean William; Halwani, Rabih; Mogensen, Trine H.; Novelli, Giuseppe; Resnick, Igor B.; Šedivá, Anna; Tancevski, Ivan; Turvey, Stuart E.

doi:10.1007/s10875-021-01068-6

Cited by 40 publications

(36 citation statements)

References 153 publications

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Section: Discussionmentioning

confidence: 99%

“…Insight into immune mechanisms responsible for SARS-CoV-2 immunity and inflammation is driving therapeuticl trials with IL-6 inhibition with tocilizumab, BTK inhibition with ibrutinib and acalabrutinib, or JAK-STAT inhibition with ruxolitinib in patients with severe hyperinflammation in the context of COVID-19 [ 98 , 99 , 100 ▪ ]. Early therapy with type I interferon has also been attempted in several patients, although the timing of this treatment is challenging [ 100 ▪ , 101 , 102 ]. Caution should be used with regard to convalescent plasma, which has been successfully administered to several patients with IEIs and prolonged COVID-19, but has also been found to harbor antitype I interferon autoantibodies [ 27 , 33 , 39 , 42 , 45 , 48 , 49 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

“…Caution should be used with regard to convalescent plasma, which has been successfully administered to several patients with IEIs and prolonged COVID-19, but has also been found to harbor antitype I interferon autoantibodies [ 27 , 33 , 39 , 42 , 45 , 48 , 49 , 76 ]. Therapeutic plasma exchange could be beneficial to remove deleterious autoantibodies and proinflammatory cytokines in critical patients, and it has been attempted with anecdotal positive results [ 100 ▪ , 103 – 105 ]. Monoclonal antibodies that neutralize SARS-CoV-2, such as the combination of casirivimab and imdevimab (Regen-Cov) or sotrovimab, have also proven effective as primary or secondary prevention of COVID-19 [ 106 , 107 ].…”

Section: Discussionmentioning

confidence: 99%

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Coronavirus disease 2019 in patients with inborn errors of immunity: lessons learned

Bucciol

Tangye

Meyts

2021

Current Opinion in Pediatrics

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Purpose of review The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused extreme concern for patients with inborn errors of immunity (IEIs). In the first 6 months of the pandemic, the case fatality rate among patients with IEIs resembled that of the general population (9%). This review aims at summarizing what we have learned about the course and outcome of coronavirus disease 2019 (COVID-19) in patients with different IEIs and what this can potentially teach us about the immune mechanisms that could confer protection or predisposition to severe disease. Recent findings A total of 649 patients with IEI and COVID-19 have been reported in the last year and a half, spanning all groups of the International Union of Immunological Societies classification of IEIs. For most patients, the underlying IEI does not represent an independent risk factor for severe COVID-19. In fact, some IEI may even be protective against the severe disease due to impaired inflammation resulting in less immune-mediated collateral tissue damage. Summary We review the characteristics of SARS-CoV-2 infection in a large number of patients with IEI. Overall, we found that combined immunodeficiencies, immune dysregulation disorders, and innate immune defects impairing type I interferon responses are associated with severe disease course.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Coronavirus disease 2019 in patients with inborn errors of immunity: lessons learned

Bucciol

Tangye

Meyts

2021

Current Opinion in Pediatrics

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“…These findings revealed that patients with inborn errors of type I IFN immunity, particularly those with recessive deficiencies of IRF7 or IFNAR1, whose biochemical defects are complete, are at high risk of life-threatening COVID-19 pneumonia ( 21 ). They further suggested that the early administration of IFN-α or -β in the course of SARS-CoV-2 infection might benefit patients with inborn errors impairing the production of type I IFNs ( 22 ), whereas IFN-β administration may be beneficial in patients with neutralizing auto-Abs against IFN-α but not IFN-β ( 23 , 24 ). Moreover, these findings suggested that patients with inborn errors of the type I IFN response pathway or with auto-Abs neutralizing both IFN-α and IFN-β should be treated differently, perhaps with monoclonal antibodies (mAbs) against SARS-CoV-2 ( 25 – 27 ).…”

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confidence: 99%

Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child

Lévy

Zhang

Bastard

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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We describe an unvaccinated child at risk for life-threatening COVID-19 due to an inherited deficiency of IRF9, which governs ISGF-3–dependent responses to type I and III interferons (IFN). She was admitted, with a high nasal SARS-CoV-2 load on day 1 of upper respiratory tract infection. She was viremic on day 2 and received casirivimab and imdevimab. Her clinical manifestations and viremia disappeared on days 3 and 4, respectively. Circulating SARS-CoV-2 virus induced the expression of IFN-stimulated genes in leukocytes on day 1, whereas the secretion of blood type I IFNs, which peaked on day 4, did not. Antibody-mediated SARS-CoV-2 neutralization is, therefore, sufficient to overcome a deficiency of antiviral IFNs.

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“…The results of an early time-dependent induction of IFNb in our study are in line with studies on genetic and autoimmune defects in the type-I IFN pathway that were correlated to severe COVID-19 24,35,36 . These findings have prompted to propose early and transient intervention with recombinant type-I IFN such as IFNb as a treatment option in severe COVID-19 patients 38 . Parallel to IFNb, we observed substantially enhanced early IP10/CXCL10 levels without other signs of systemic inflammation in mild patients.…”

Section: Discussionmentioning

confidence: 99%

Deep immune profiling reveals early-stage and highly coordinated immune responses in mild COVID-19 patients

Capelle

Ciré

Domingues

et al. 2021

Preprint

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While immunopathology has been widely studied in severe COVID-19 patients, immunoprotective factors in non-hospitalized patients have remained largely elusive. We systematically analyzed 484 peripheral immune cell signatures, various serological parameters and TCR repertoire in a longitudinal cohort of 63 mild and 15 hospitalized patients versus 14 asymptomatic and 26 control individuals. Within three days following PCR diagnosis, we observed coordinated responses of CD4 and CD8 T cells, various antigen presenting cells and antibody-secreting cells in mild, but not hospitalized COVID-19 patients. This early-stage SARS-CoV-2-specific response was predominantly characterized by substantially expanded clonotypes of CD4 and less of CD8 T cells. The early-stage responses of T cells and dendritic cells were highly predictive for later seroconversion and protective antibody levels after three weeks in mild non-hospitalized, but not in hospitalized patients. Our systemic analysis provides the first full picture and early-stage trajectory of highly coordinated immune responses in mild COVID-19 patients.

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Harnessing Type I IFN Immunity Against SARS-CoV-2 with Early Administration of IFN-β

Cited by 40 publications

References 153 publications

Coronavirus disease 2019 in patients with inborn errors of immunity: lessons learned

Coronavirus disease 2019 in patients with inborn errors of immunity: lessons learned

Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child

Deep immune profiling reveals early-stage and highly coordinated immune responses in mild COVID-19 patients

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