PMID- 32548551
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230328
IS  - 2475-0379 (Electronic)
IS  - 2475-0379 (Linking)
VI  - 4
IP  - 4
DP  - 2020 May
TI  - COVID-19 hypothesis: Activated protein C for therapy of virus-induced pathologic 
      thromboinflammation.
PG  - 506-509
LID - 10.1002/rth2.12362 [doi]
AB  - Seriously ill patients with coronavirus disease 2019 (COVID-19) at risk for death 
      exhibit elevated cytokine and chemokine levels and D-dimer, and they often have 
      comorbidities related to vascular dysfunctions. In preclinical studies, activated 
      protein C (APC) provides negative feedback downregulation of excessive 
      inflammation and thrombin generation, attenuates damage caused by 
      ischemia-reperfusion in many organs including lungs, and reduces death caused by 
      bacterial pneumonia. APC exerts both anticoagulant activities and direct 
      cell-signaling activities. Preclinical studies show that its direct 
      cell-signaling actions mediate anti-inflammatory and anti-apoptotic actions, 
      mortality reduction for pneumonia, and beneficial actions for 
      ischemia-reperfusion injury. The APC mutant 3K3A-APC, which was engineered to 
      have diminished anticoagulant activity while retaining cell-signaling actions, 
      was safe in phase 1 and phase 2 human trials. Because of its broad spectrum of 
      homeostatic effects in preclinical studies, we speculate that 3K3A-APC merits 
      consideration for clinical trial studies in appropriately chosen, seriously ill 
      patients with COVID-19.
CI  - (c) 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published 
      by Wiley Periodicals LLC on behalf of International Society on Thrombosis and 
      Haemostasis (ISTH).
FAU - Griffin, John H
AU  - Griffin JH
AUID- ORCID: 0000-0002-4302-2547
AD  - Department of Molecular Medicine The Scripps Research Institute La Jolla 
      California USA.
AD  - Department of Medicine University of California San Diego California USA.
FAU - Lyden, Patrick
AU  - Lyden P
AD  - Department of Neurology Cedars-Sinai Medical Center Los Angeles California USA.
LA  - eng
GR  - R01 HL133728/HL/NHLBI NIH HHS/United States
GR  - R01 HL142975/HL/NHLBI NIH HHS/United States
GR  - U01 NS088312/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20200612
PL  - United States
TA  - Res Pract Thromb Haemost
JT  - Research and practice in thrombosis and haemostasis
JID - 101703775
PMC - PMC7292662
OTO - NOTNLM
OT  - COVID-19
OT  - D-dimer
OT  - SARS-CoV-2
OT  - activated protein C
OT  - coronavirus
OT  - cytokine
EDAT- 2020/06/18 06:00
MHDA- 2020/06/18 06:01
PMCR- 2020/06/12
CRDT- 2020/06/18 06:00
PHST- 2020/04/10 00:00 [received]
PHST- 2020/04/22 00:00 [revised]
PHST- 2020/04/29 00:00 [accepted]
PHST- 2020/06/18 06:00 [entrez]
PHST- 2020/06/18 06:00 [pubmed]
PHST- 2020/06/18 06:01 [medline]
PHST- 2020/06/12 00:00 [pmc-release]
AID - S2475-0379(22)02024-6 [pii]
AID - RTH212362 [pii]
AID - 10.1002/rth2.12362 [doi]
PST - epublish
SO  - Res Pract Thromb Haemost. 2020 Jun 12;4(4):506-509. doi: 10.1002/rth2.12362. 
      eCollection 2020 May.