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

Hofmann-Winkler et al., Critical Care Explorations, doi:10.1097/CCE.0000000000000284

Nov 2020

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HCQ for COVID-19

1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 419 studies, recognized in 46 countries.

Lower risk for mortality, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine treatments.

5,100+ studies for 109 treatments. c19hcq.org

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.

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Study covers camostat and HCQ.

risk of death, 140.0% higher, RR 2.40, p = 0.55, treatment 2 of 5 (40.0%), control 1 of 6 (16.7%).

ICU time, 157.1% higher, relative time 2.57, treatment 5, control 6.

SOFA, 125.0% higher, RR 2.25, treatment 5, control 6, day 8.

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.

This Paper HCQ All

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.

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

Zhu, Zhang, Wang, China Novel Coronavirus Investigating and Research Team: A novel coronavirus from patients with pneumonia in China, N Engl J Med

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Whether camostat ' 'mesylate is able to lower disease burden in coronavirus disease 2019 sepsis is currently ' 'unknown.\n' ' \n' ' \n' ' Design:\n' ' Retrospective observational case series.\n' ' \n' ' \n' ' Setting:\n' ' Patient treated in ICU of University hospital Göttingen, ' 'Germany.\n' ' \n' ' \n' ' Patients:\n' ' Eleven critical ill coronavirus disease 2019 patients with organ failure ' 'were treated in ICU.\n' ' \n' ' \n' ' Interventions:\n' ' Compassionate use of camostat mesylate (six patients, camostat group) or ' 'hydroxychloroquine (five patients, hydroxychloroquine group).\n' ' \n' ' \n' ' Measurements and Main Results:\n' ' 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. 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