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0 0.5 1 1.5 2+ Mortality -16% Improvement Relative Risk Casirivimab/i..  Iustila-Maran et al.  ICU PATIENTS Is very late treatment with casirivimab/imdevimab beneficial for COVID-19? Retrospective 95 patients in Germany (August 2021 - February 2022) Study underpowered to detect differences c19early.org Iustila-Maran et al., Research Square, Apr 2024 Favors casirivimab/im.. Favors control

Course of inflammation and infection markers differ in ICU patients with severe COVID-19 under casirivimab- and/or tocilizumab application: an observational study

Iustila-Maran et al., Research Square, doi:10.21203/rs.3.rs-4090027/v1, NCT06233357
Apr 2024  
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16th treatment shown to reduce risk in March 2021
 
*, now known with p = 0.000018 from 28 studies, recognized in 42 countries. Efficacy is variant dependent.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19early.org
Retrospective 95 ICU patients showing no significant difference in mortality with casirivimab/imdevimab. There was significantly higher mortality with tocilizumab.
Efficacy is variant dependent. In Vitro research suggests a lack of efficacy for many omicron variants Haars, Liu, Pochtovyi, Sheward, Tatham, VanBlargan.
risk of death, 16.0% higher, RR 1.16, p = 0.80, treatment 14 of 50 (28.0%), control 7 of 29 (24.1%), C or C+T vs. N.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Iustila-Maran et al., 5 Apr 2024, retrospective, Germany, preprint, 4 authors, study period August 2021 - February 2022, trial NCT06233357 (history). Contact: manfred.weiss@uniklinik-ulm.de.
This PaperCasirivimab/i..All
Course of inflammation and infection markers differ in ICU patients with severe COVID-19 under casirivimab- and/or tocilizumab application: an observational study
Stana-Nicoleta Iustila-Maran, Amelie Orlet, Karl Traeger, Prof. Dr Manfred Weiss
doi:10.21203/rs.3.rs-4090027/v1
Background: The outcome and longitudinal course of inflammation and infection markers were unknown in COVID-19 patients on the ICU treated without (N) or with SARS-CoV-2 specific monoclonal antibodies (casirivimab / imdevimab, C) or antibodies against interleukin-6 (IL-6) receptors (tocilizumab, T), solely, or in combination of both (C + T). Methods: In a retrospective observational study, in critically ill N, C, T, C+ T COVID-19 patients admitted to the ICU with the CoV-2 delta-variant between August 2021 and February 2022, 28-day mortality and 30-day time course of infection and inflammation markers were evaluated. Results: Out of 95 patients with COVID-19, 29 patients were not treated (N), 17 with C, 16 with T, 33 with C + T. Mortality rates in N, C, T, and C + T, were 24%, 35%, 56%, and 24%, being higher in T compared to N and C + T (p = 0.05). Prolonged leukocyte, procalcitonin (PCT), C-reactive protein (CRP) and interleukin 6 (IL-6) elevations were detected in nonsurvivors compared to survivors in C + T within the first two weeks, IL-6 in the first days in T. In N, higher PCT, CRP, IL-6 and ferritin occured in nonsurvivors in the first days. Conclusion: Sporadically measured IL-6 and CRP in T is less useful. Longlasting IL-6 receptor blockade may be deleterious in COVID-19. High IL-6 may hint at poor prognosis within the first days in T, leukocytes, PCT, CRP and IL-6 in the first two weeks in C + T, and PCT, CRP, IL-6 and ferritin within the first days in N.
Abbreviations C: casirivimab / imdevimab; 95% CI: 95% confidence interval; CoV-2: corona virus 2; C + T: casirivimab / imdevimab plus tocilizumab; CRP: C reactive protein; ECMO: extracorporeal membrane oxygenation; IL-6: interleukin 6; IL-6R: interleukin 6 receptor; LOS: length of stay; N: no casirivimab / imdevimab and no tocilizumab; NonSu: nonsurvivors; n. s.: not significant; Su: survivors; PCT: procalcitonin; T: tocilizumab; WHO: World Health Organization. Authors' contributions MW, NM, AO and KT contributed to the conception and design of the study. AO, NM, KT and MW generated, collected and assembled the data. Data analysis and interpretation: MW and NM analyzed and interpreted the data and drafted the manuscript. All authors read and approved the final manuscript. Ethics approval and consent to participate Ethics approval has been given by the ethics commssion of the university Ulm, application nr. 129/22; NCT 06233357. Due to the fact, that clinical and laboratory data were gathered in routine care, no additional blood has been drawn, no diagnostic and no intervention in addition had been performed, the ethic's committe waived informed consent. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests.
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Late treatment
is less effective
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