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Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation.

ABSTRACT: 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.

SUBMITTER: Hofmann-Winkler H

PROVIDER: S-EPMC7671878 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation.

Hofmann-Winkler Heike H Moerer Onnen O Alt-Epping Sabine S Bräuer Anselm A Büttner Benedikt B Müller Martin M Fricke Torben T Grundmann Julian J Harnisch Lars-Olav LO Heise Daniel D Kernchen Andrea A Pressler Meike M Stephani Caspar C Tampe Björn B Kaul Artur A Gärtner Sabine S Kramer Stefanie S Pöhlmann Stefan S Winkler Martin Sebastian MS

Critical care explorations 20201116 11

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.<h4>Design</h4>Retrospective observational case series.<h4>Setting</h4>Patient treated in ICU of University hospital Göttingen, Germany.<h4>Patients</h4>El ...[more]

PMID: 33225308

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Project description:SubjectsEarly detection of coronavirus disease 2019 in patients likely to develop severe manifestations enables appropriate interventions, including rapid ICU admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of coronavirus disease 2019.InterventionsNot applicable.Measurements and main resultsThis is single-center study, national center hospital designated for infectious disease. Fifty-eight patients who tested positive for severe acute respiratory syndrome coronavirus 2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction were retrospectively studied. Urinary β2-microglobulin, liver-type fatty acid-binding protein were serially measured. Serum interferon-γ and monocyte chemotactic protein-1 were also evaluated. The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group (n = 12). Patients treated with oxygen were assigned to the moderate group (n = 13). Other patients were assigned to the mild group (n = 33). Urine tests revealed that low β2-microglobulin and liver-type fatty acid-binding protein levels were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, liver-type fatty acid-binding protein tended to be persistently high. The resulting cutoff values were β2-microglobulin; severe versus moderate + mild: 2,457 μg/dL (specificity 76.9% and sensitivity 90.0%, area under the receiver operating characteristic curve 85.9%), liver-type fatty acid-binding protein; severe versus moderate + mild: 22.0 μg/gCre (specificity 84.6% and sensitivity 90%, area under the receiver operating characteristic curve 91.8%). Urinary β2-microglobulin and serum interferon-γ/monocyte chemotactic protein-1 showed a similar trend.ConclusionsEvaluating urinary biomarkers such as β2-microglobulin and liver-type fatty acid-binding protein may allow determination of coronavirus disease 2019 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.

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Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation.

Publications

Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation.

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