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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' <jats:p>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). \n'
'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. \n'
'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. \n'
'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. \n'
'Trial registration: ClinicalTrials.gov Identifier: NCT06233357, retrospectively registered, '
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