Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation
PhD Heike Hofmann-Winkler, MD Onnen Moerer, MD Sabine Alt-Epping, MD Anselm Bräuer, MD Benedikt Büttner, MD Martin Müller, Torben Fricke, Julian Grundmann, MD Lars-Olav Harnisch, MD Daniel Heise, Andrea Kernchen, MD Meike Pressler, MD Caspar Stephani, MD Björn Tampe, PhD Artur Kaul, Sabine Gärtner, Stefanie Kramer, PhD Stefan Pöhlmann, Martin Sebastian Winkler
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.
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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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