Recombinant ACE2-IgG Fusion Treatment
SARS-CoV-2 binds to the ACE2 transmembrane protein to gain entry to cells, which is the first step in infection. Researchers are using this knowledge to develop a novel treatment against the virus. Normally, the virus binds to ACE2 on the cell surface, which allows the virus to be pulled into the cell in a process called endocytosis. But, what if the virus encountered ACE2 proteins floating in the blood stream which were connected to immune-globulins. Instead of binding to cell surfaces and invading cells, viral particles would be bound in the blood stream by these ACE2-IgG proteins and would then be destroyed by other immune cells and/or other parts of the immune system. You can think of this therapy as presenting the virus with a decoy receptor. This therapy is being tested in mice and has been demonstrated to be effective at binding to SARS-CoV-2. Here is an excerpt from the paper
"After we identified that ACE2 fusion proteins binds with high affinity to the RBD, we next sought to test the inhibitory activity of ACE2 fusion proteins against 2019-nCoV and compare it with that against SARS-CoV, we used viruses pseudotyped with the S glycoprotein of SARS-CoV and 2019-nCoV. Our data shows that Both SARS-CoV and 2019-nCoV viruses were potently neutralized by ACE2-Ig and mACE2-Ig. The IC50 of SARS-CoV and 2019-nCoV viruses neutralized by ACE2-Ig were 0.8 and 0.1 μg/ml, respectively."
Using D-dimer to Guide Anticoagulation in Covid-19 Patients
"[1]N. Tang, H. Bai, X. Chen, J. Gong, D. Li, and Z. Sun, "Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy," Journal of Thrombosis and Haemostasis, vol. n/a, no. n/a, doi: 10.1111/jth.14817."
This study is pre-print and not yet peer-reviewed, and it’s out of China. But, it is suggestive that in severely ill Covid-19 patients with elevated D-dimer, there is a correlation with improved mortality outcomes and therapeutic anticoagulation as D-dimer increases. D-dimer >3 seems to look like a reasonable cutoff which was also the conclusion of the authors.
Excerpts and data from this study
"severe COVID-19 was defined as meeting any one of following items, according to the Diagnosis and Treatment Plan of COVID-19 suggested by National Health Commission of China [9]: Respiratory rate ≥30 breaths /min; Arterial oxygen saturation≤93% at rest; PaO2/FiO2 ≤300 mmHg"
"The association between heparin treatment and outcome in stratified patients according to SIC score or D-dimer result were evaluated (Table 4 and Figure 2). The heparin treat was associated with lower mortality in patients with SIC score ≥4 (40.0% vs 64.2%, P=0.029), but not in those with SIC score <4 (29.0% vs 22.6%, P=0.419). As patients were stratified by D-dimer result, the mortality in heparin users basically maintained at same level, but in nonusers, the mortality rised with the rising D-dimer. When D-dimer exceeding 3.0 ug/mL (6 fold of upper limit of normal, 6 ULN), approximate 20% reduction in mortality with heparin treat was found (32.8% vs 52.4%, P=0.017)."
" In addition, the hypoxia found in severe COVID-19 can stimulate thrombosis through not only increasing blood viscosity, but also a hypoxia-inducible transcription factor-dependent signaling pathway [14]. As evidence, occlusion and microthrombosis formation in pulmonary small vessels of critical patient with COVID-19 has been reported from a recent lung organ dissection [15]."
EmCrit’s Resource on This Topic
For more discussion of this general topic, see EmCrit’s resource on management of DIC/thrombosis in the setting of Covid-19 here