Influence of anti-Spike protein antibody levels on tocilizumab efficacy in hospitalized patients with severe COVID-19 pneumonia: a post-hoc analysis of the COVACTA trial
Abstract Background Our aim in this work is to find biomarkers to optimize therapy with IL-6 inhibitors, as not all clinical trials have shown clear benefits on mortality or mechanical ventilation progression. Given the link between delayed seroconversion and higher complication risks, we aim to tes...
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BMC
2025-05-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-025-11001-6 |
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| author | José Aguareles Carles Forné Ana García-Casas Guillermo Santamaría-Corral Daniel Carnevali-Ruiz Gabriel Sotres-Fernández Javier T Solera Pablo Guisado-Vasco |
| author_facet | José Aguareles Carles Forné Ana García-Casas Guillermo Santamaría-Corral Daniel Carnevali-Ruiz Gabriel Sotres-Fernández Javier T Solera Pablo Guisado-Vasco |
| author_sort | José Aguareles |
| collection | DOAJ |
| description | Abstract Background Our aim in this work is to find biomarkers to optimize therapy with IL-6 inhibitors, as not all clinical trials have shown clear benefits on mortality or mechanical ventilation progression. Given the link between delayed seroconversion and higher complication risks, we aim to test if evaluating SARS-CoV-2 spike protein antibody status before treatment could enhance IL-6 inhibitor therapy effectiveness in COVID-19 patients. Methods We conducted a post hoc analysis of the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial of the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19. Cox and logistic regression analysis were used to assess the tocilizumab’s efficacy in severe COVID-19 patients on survival and ICU stay at day 28, based on SARS-CoV-2 S-spike and neutralizing antibody levels. Results Tocilizumab reduced 28-day mortality over placebo in patients with low S-spike antibody titers (20% vs. 29%). No benefit was observed for higher antibody levels. Patients with low S-spike antibody levels treated with tocilizumab exhibited a lower probability of ICU stay at day 28 compared to those treated with placebo (63% vs. 82%). No significant differences were noted in mortality and ICU stay based on whole neutralizing antibody titers. Conclusions Our findings suggest that using IL-6 inhibitors in severe COVID-19 patients with low S-spike antibody titers may improve clinical outcomes. Clinical trial Not applicable. |
| format | Article |
| id | doaj-art-b0468b913e324a149c0c0ef0b5b84366 |
| institution | OA Journals |
| issn | 1471-2334 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Infectious Diseases |
| spelling | doaj-art-b0468b913e324a149c0c0ef0b5b843662025-08-20T02:15:16ZengBMCBMC Infectious Diseases1471-23342025-05-012511910.1186/s12879-025-11001-6Influence of anti-Spike protein antibody levels on tocilizumab efficacy in hospitalized patients with severe COVID-19 pneumonia: a post-hoc analysis of the COVACTA trialJosé Aguareles0Carles Forné1Ana García-Casas2Guillermo Santamaría-Corral3Daniel Carnevali-Ruiz4Gabriel Sotres-Fernández5Javier T Solera6Pablo Guisado-Vasco7Internal Medicine Department, Hospital Universitario Quirónsalud MadridHeorfy ConsultingInternal Medicine Department, Hospital Universitario Quirónsalud MadridInternal Medicine Department, Hospital Universitario Quirónsalud MadridInternal Medicine Department, Hospital Universitario Quirónsalud MadridInternal Medicine Department, Hospital Universitario Quirónsalud MadridInternal Medicine Department, Hospital Universitario Quirónsalud MadridInternal Medicine Department, Hospital Universitario Quirónsalud MadridAbstract Background Our aim in this work is to find biomarkers to optimize therapy with IL-6 inhibitors, as not all clinical trials have shown clear benefits on mortality or mechanical ventilation progression. Given the link between delayed seroconversion and higher complication risks, we aim to test if evaluating SARS-CoV-2 spike protein antibody status before treatment could enhance IL-6 inhibitor therapy effectiveness in COVID-19 patients. Methods We conducted a post hoc analysis of the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial of the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19. Cox and logistic regression analysis were used to assess the tocilizumab’s efficacy in severe COVID-19 patients on survival and ICU stay at day 28, based on SARS-CoV-2 S-spike and neutralizing antibody levels. Results Tocilizumab reduced 28-day mortality over placebo in patients with low S-spike antibody titers (20% vs. 29%). No benefit was observed for higher antibody levels. Patients with low S-spike antibody levels treated with tocilizumab exhibited a lower probability of ICU stay at day 28 compared to those treated with placebo (63% vs. 82%). No significant differences were noted in mortality and ICU stay based on whole neutralizing antibody titers. Conclusions Our findings suggest that using IL-6 inhibitors in severe COVID-19 patients with low S-spike antibody titers may improve clinical outcomes. Clinical trial Not applicable.https://doi.org/10.1186/s12879-025-11001-6TocilizumabSARS-CoV-2COVID-19AntibodiesSerostatusIL-6 inhibitors |
| spellingShingle | José Aguareles Carles Forné Ana García-Casas Guillermo Santamaría-Corral Daniel Carnevali-Ruiz Gabriel Sotres-Fernández Javier T Solera Pablo Guisado-Vasco Influence of anti-Spike protein antibody levels on tocilizumab efficacy in hospitalized patients with severe COVID-19 pneumonia: a post-hoc analysis of the COVACTA trial BMC Infectious Diseases Tocilizumab SARS-CoV-2 COVID-19 Antibodies Serostatus IL-6 inhibitors |
| title | Influence of anti-Spike protein antibody levels on tocilizumab efficacy in hospitalized patients with severe COVID-19 pneumonia: a post-hoc analysis of the COVACTA trial |
| title_full | Influence of anti-Spike protein antibody levels on tocilizumab efficacy in hospitalized patients with severe COVID-19 pneumonia: a post-hoc analysis of the COVACTA trial |
| title_fullStr | Influence of anti-Spike protein antibody levels on tocilizumab efficacy in hospitalized patients with severe COVID-19 pneumonia: a post-hoc analysis of the COVACTA trial |
| title_full_unstemmed | Influence of anti-Spike protein antibody levels on tocilizumab efficacy in hospitalized patients with severe COVID-19 pneumonia: a post-hoc analysis of the COVACTA trial |
| title_short | Influence of anti-Spike protein antibody levels on tocilizumab efficacy in hospitalized patients with severe COVID-19 pneumonia: a post-hoc analysis of the COVACTA trial |
| title_sort | influence of anti spike protein antibody levels on tocilizumab efficacy in hospitalized patients with severe covid 19 pneumonia a post hoc analysis of the covacta trial |
| topic | Tocilizumab SARS-CoV-2 COVID-19 Antibodies Serostatus IL-6 inhibitors |
| url | https://doi.org/10.1186/s12879-025-11001-6 |
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