Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation
et al., Critical Care Explorations, doi:10.1097/CCE.0000000000000284, Nov 2020
HCQ for COVID-19
1st treatment shown to reduce risk in
March 2020, now with p < 0.00000000001 from 424 studies, used in 59 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,200+ studies for
200+ treatments. c19early.org
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Retrospective 11 critically ill COVID-19 ICU patients with organ failure treated with camostat mesylate (6 patients) or HCQ (5 patients). Over an 8 day period, the severity of COVID-19 decreased in the camostat group as measured by a decline in the SOFA score, inflammatory markers, and improvement in oxygenation. A similar effect was not seen in the HCQ group.
Study covers camostat and HCQ.
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risk of death, 140.0% higher, RR 2.40, p = 0.55, treatment 2 of 5 (40.0%), control 1 of 6 (16.7%).
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ICU time, 157.1% higher, relative time 2.57, treatment 5, control 6.
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SOFA, 125.0% higher, RR 2.25, treatment 5, control 6, day 8.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Hofmann-Winkler et al., 16 Nov 2020, retrospective, Germany, peer-reviewed, 19 authors, study period March 2020 - May 2020, this trial compares with another treatment - results may be better when compared to placebo.
Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation
Critical Care Explorations, doi:10.1097/cce.0000000000000284
Objectives: Severe acute respiratory syndrome coronavirus 2 cell entry depends on angiotensin-converting enzyme 2 and transmembrane serine protease 2 and is blocked in cell culture by camostat mesylate, a clinically proven protease inhibitor. Whether camostat mesylate is able to lower disease burden in coronavirus disease 2019 sepsis is currently unknown. Design: Retrospective observational case series. Setting: Patient treated in ICU of University hospital Göttingen, Germany. Patients: Eleven critical ill coronavirus disease 2019 patients with organ failure were treated in ICU. Interventions: Compassionate use of camostat mesylate (six patients, camostat group) or hydroxychloroquine (five patients, hydroxychloroquine group). Measurements and Main Results: Clinical courses were assessed by Sepsis-related Organ Failure Assessment score at days 1, 3, and 8. Further, viral load, oxygenation, and inflammatory markers were determined. Sepsis-related Organ Failure Assessment score was comparable between camostat and hydroxychloroquine groups upon ICU admission. During observation, the Sepsis-related Organ Failure Assessment score decreased in the camostat group but remained elevated in the hydroxychloroquine group. The decline in disease severity in camostat mesylate treated patients was paralleled by a decline in inflammatory markers and improvement of oxygenation. Conclusions: The severity of coronavirus disease 2019 decreased upon camostat mesylate treatment within a period of 8 days and a similar effect was not observed in patients receiving hydroxychloroquine. Camostat mesylate thus warrants further evaluation within randomized clinical trials.
References
Bardou, Menou, François, Membrane-anchored serine protease matriptase is a trigger of pulmonary fibrogenesis, Am J Respir Crit Care Med
Cavalcanti, Zampieri, Rosa, Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19, New Engl J Med
Corman, Landt, Kaiser, Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR, Euro Surveill
Das, Bhowmick, Tiwari, An updated systematic review of the therapeutic role of hydroxychloroquine in coronavirus disease-19 (COVID-19), Clin Drug Investig
Gibo, Ito, Kawabe, Camostat mesilate attenuates pancreatic fibrosis via inhibition of monocytes and pancreatic stellate cells activity, Lab Invest
Hoffmann, Kleine-Weber, Schroeder, SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell
Hoffmann, Mösbauer, Hofmann-Winkler, Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2, Nature
Iwata-Yoshikawa, Okamura, Shimizu, TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection, J Virol
Maisonnasse, Guedj, Contreras, Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates, Nature
Puelles, Lütgehetmann, Lindenmeyer, Multiorgan and renal tropism of SARS-CoV-2, N Engl J Med
Wu, Wang, Kuo, An update on current therapeutic drugs treating COVID-19, Curr Pharmacol Rep, doi:10.1007/s40495-020-00216-7
Zhou, Vedantham, Lu, Protease inhibitors targeting coronavirus and filovirus entry, Antiviral Res
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DOI record:
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"abstract": "<jats:sec>\n <jats:title>Objectives:</jats:title>\n <jats:p>Severe acute respiratory syndrome coronavirus 2 cell entry depends on angiotensin-converting enzyme 2 and transmembrane serine protease 2 and is blocked in cell culture by camostat mesylate, a clinically proven protease inhibitor. Whether camostat mesylate is able to lower disease burden in coronavirus disease 2019 sepsis is currently unknown.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Design:</jats:title>\n <jats:p>Retrospective observational case series.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Setting:</jats:title>\n <jats:p>Patient treated in ICU of University hospital Göttingen, Germany.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Patients:</jats:title>\n <jats:p>Eleven critical ill coronavirus disease 2019 patients with organ failure were treated in ICU.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Interventions:</jats:title>\n <jats:p>Compassionate use of camostat mesylate (six patients, camostat group) or hydroxychloroquine (five patients, hydroxychloroquine group).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Measurements and Main Results:</jats:title>\n <jats:p>Clinical courses were assessed by Sepsis-related Organ Failure Assessment score at days 1, 3, and 8. Further, viral load, oxygenation, and inflammatory markers were determined. Sepsis-related Organ Failure Assessment score was comparable between camostat and hydroxychloroquine groups upon ICU admission. During observation, the Sepsis-related Organ Failure Assessment score decreased in the camostat group but remained elevated in the hydroxychloroquine group. The decline in disease severity in camostat mesylate treated patients was paralleled by a decline in inflammatory markers and improvement of oxygenation.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions:</jats:title>\n <jats:p>The severity of coronavirus disease 2019 decreased upon camostat mesylate treatment within a period of 8 days and a similar effect was not observed in patients receiving hydroxychloroquine. Camostat mesylate thus warrants further evaluation within randomized clinical trials.</jats:p>\n </jats:sec>",
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Late treatment
is less effective
is less effective
hofmannwinkler