Commentary: Why Haven’t We Found an Effective Treatment for COVID-19?

Brzoska, Josef; Eick, Harald von; Hündgen, Manfred

doi:10.3389/fimmu.2021.714175

Cited by 2 publications

(7 citation statements)

References 19 publications

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“…Only a high-dose therapy with a daily systemic administration of ≥25 MIU interferon given for ca. 5 consecutive days was successful ( 24 ).…”

Section: Some Important Aspects To Be Considered Using Interferons In...mentioning

confidence: 99%

“…The dosages used in these studies or local treatment, respectively, are probably not adequate in patients with an advanced stage of COVID-19. Moreover, with non-PEGylated formulations, a daily administration is necessary to achieve a persistent interferon serum level, which is probably important for a therapeutic effect in acute systemic viral diseases ( 5 , 24 ).…”

Section: Possible Reasons For the Failure Of Interferons In Phase Iii...mentioning

confidence: 99%

“…The dosage used in these studies corresponds to that employed for the long-term treatment of chronic viral hepatitis. This dosage is barely adequate for the therapy of an acute systemic viral disease as discussed elsewhere ( 5 , 24 ). The positive results obtained in the aforementioned Hong Kong trial ( 25 ) also suggest that the dosage of PEGylated interferon lambda-1a should be increased to achieve a higher efficacy in COVID-19 although at the cost of more side effects.…”

Section: Positive Effects In Covid-19 By Early Administration Of Inte...mentioning

confidence: 99%

“…However, a limitation of interferon beta is the fact that it has to be administered by the intravenous route if relatively high serum levels are required. This condition must probably be fulfilled to achieve a therapeutic effect in an acute systemic viral infection such as COVID-19 ( 5 , 24 ).…”

Section: How To Use Interferons For a Successful Treatment Of Covid-1...mentioning

confidence: 99%

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Interferons in COVID-19: missed opportunities to prove efficacy in clinical phase III trials?

Brzoska¹,

Eick²,

Hündgen³

2023

Front. Med.

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Interferons were repeatedly used in the therapy of COVID-19 due to their antiviral effects. Three recently published randomized controlled clinical phase III trials (WHO SOLIDARITY, ACTT-3, and SPRINTER) missed their primary objectives, i.e., a significant therapeutic effect of interferons was not demonstrated in these studies. In only one randomized controlled phase III trial (TOGETHER), a significant reduction in the hospitalization rate was revealed. Our study analyzes these findings, gives possible explanations for the failure of interferons, provides a proposal on how these agents could be successfully used, and also highlights the limitations of their employment in COVID-19. Interferons are apparently beneficial only if the patients are in the early stage of this disease and when they are usually not hospitalized, i.e., if the patients do not require oxygen support and/or if corticosteroids are not yet indicated. Furthermore, a higher dosage than the one used in the long-term treatment of multiple sclerosis with interferon beta or of chronic viral hepatitis with interferon alpha or lambda should be employed to achieve a better therapeutic effect in COVID-19.

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“…Only a high-dose therapy with a daily systemic administration of ≥25 MIU interferon given for ca. 5 consecutive days was successful ( 24 ).…”

Section: Some Important Aspects To Be Considered Using Interferons In...mentioning

confidence: 99%

Section: Possible Reasons For the Failure Of Interferons In Phase Iii...mentioning

confidence: 99%

Section: Positive Effects In Covid-19 By Early Administration Of Inte...mentioning

confidence: 99%

Section: How To Use Interferons For a Successful Treatment Of Covid-1...mentioning

confidence: 99%

See 2 more Smart Citations

Interferons in COVID-19: missed opportunities to prove efficacy in clinical phase III trials?

Brzoska¹,

Eick²,

Hündgen³

2023

Front. Med.

Self Cite

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“… 33 Noteworthy, due to the complexity of SARS-CoV-2 immunopathology, the use of a single drug to treat COVID-19 maybe not a feasible approach. 34 Among the candidate treatments, spike-specific monoclonal antibodies are promising immunotherapeutic agents. 35 , 36 Clinically relevant animal models for SARS-CoV-2 infection are thus required for rapid testing of potential vaccines and immunotherapeutics that target the human immune system.…”

Section: Introductionmentioning

confidence: 99%

Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2.HLA-DR4.Rag1KO.IL-2RγcKO.NOD) for COVID-19

Brumeanu

Vir

Karim

et al. 2022

Human Vaccines & Immunotherapeutics

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We report a Human Immune System (HIS)-humanized mouse model (“DRAGA”: HLA-A2.HLA-DR4.Rag1KO.IL-2 RγcKO.NOD) for COVID-19 research. DRAGA mice express transgenically HLA-class I and class-II molecules in the mouse thymus to promote human T cell development and human B cell Ig-class switching. When infused with human hematopoietic stem cells from cord blood reconstitute a functional human immune system, as well as human epi/endothelial cells in lung and upper respiratory airways expressing the human ACE2 receptor for SARS-CoV-2. The DRAGA mice were able to sustain SARS-CoV-2 infection for at least 25 days. Infected mice showed replicating virus in the lungs, deteriorating clinical condition, and human-like lung immunopathology including human lymphocyte infiltrates, microthrombi and pulmonary sequelae. Among the intra-alveolar and peri-bronchiolar lymphocyte infiltrates, human lung-resident (CD103 + ) CD8 + and CD4 + T cells were sequestered in epithelial (CD326 + ) lung niches and secreted granzyme B and perforin, suggesting anti-viral cytotoxic activity. Infected mice also mounted human IgG antibody responses to SARS-CoV-2 viral proteins. Hence, HIS-DRAGA mice showed unique advantages as a surrogate in vivo human model for studying SARS-CoV-2 immunopathological mechanisms and testing the safety and efficacy of candidate vaccines and therapeutics.

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Commentary: Why Haven’t We Found an Effective Treatment for COVID-19?

Cited by 2 publications

References 19 publications

Interferons in COVID-19: missed opportunities to prove efficacy in clinical phase III trials?

Interferons in COVID-19: missed opportunities to prove efficacy in clinical phase III trials?

Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2.HLA-DR4.Rag1KO.IL-2RγcKO.NOD) for COVID-19

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