Wed, 04/15/2020 - 22:00
Dear colleagues,
I would like to propose three interesting papers, one more clinical and the other more basic:
- A nice overview of hematological and other lab findings, summarizing in text and Tables lots of evidence that various parameters have a geat potential as predictive parameters for severity. We know them already: lymphopenia, thrombocytopenia and neutrophilia (raised neutrophils) not only predict ARDS, but also cardiovascular complications. Raised procalcitonin, ferritin, LDH, IL-6 and CRP and of course the coagulation disorders (D-dimer, increased fibrin degradation, PTT and aPT). To prevent intravascular coagulation, there is a clear advice NOT to use direct oral anticoagulants, because they could have problems of drug-drug interactions with protease inhibitors and azithromycin, but low molecular or unfractionated heparin (LMWH).
The practical advice is summarized on p. 14:
- Early diagnosis and follow-up of DIC, by applying the ISTH score (platelet count, PT, fibrinogen, D-dimer, antithrombin and protein C activity monitoring)
- Do this not only in hospitalized, but also ambulatory patients (How feasible is this?)
- Use of LMWH, which has not only anti-trombothic, but also anti-inflammatory effects (?)
- Other antithrombotic treatments such as antithrombin, and recombinant thrombomodulin may be useful
However practical, unfortunately, this overview does not provide more insight on how precisely this dangerous “storm” is initiated…
- A very nice overview on potential epitopes for B and T cells for SARS-Cov-2, deduced mainly from experimental data on SARS-CoV-1 on one hand, the homology between SARS-CoV-1v and -2 (nicely illustrated in Fig 1 p. 3) and a bio-informatics approach, finally coming up with a limited number of B and T epitopes mainly in the S, M, N structural proteins and also some T cell epitopes in the Orf1a,b (the replicase complex) and in Orf3a.
Clearly, this looks as if your logical intuition with regard “the usual suspects” (i.e. the more abundant structural protein and the polymerase) has indeed been confirmed. Now we can line them up to identify the “good and the bad guys”. In other words, this is a good starting point and a kind, but urgent invitation for cellular immunologists to perform ELISPOT experiments to see whether these predicted “dominant” epitopes actually are recognized by the T and B cells of COVID patients. If so, the next question is whether they elicit polyfunctional responses and whether there is any correlation with clinical progression or recovery.
- So far, so good, but then I wondered: why is it that there are no predicted epitopes in the most conserved protein E? Could that small envelope protein not be a good target for T or B immunity or even vaccination? I searched for it, but no info on the E protein of SARS-Cov-2. However, in tempore non suspectu (May 2019), there was this exhaustive review on E of CoV in general and SARS in particular….
As you can read in the next attachment, E is really an amazing little devil. It has a lot of interactions with host proteins, such as the anti-apoptotic Bclxl, NA+/K+ ATPases and others (that I never heard of). What is also intriguing is that it induces inflammation (that can be blocked by amantadine) and that the virus becomes very cripple if this protein is knocked out. There is even preliminary evidence that a SARS-CoV-1 E knock-out can be used as an efficient vaccine!
Isn’t that interesting, dear colleagues?
I leave you with this consideration for today, but I do hope you feel inspired indeed.
Best wishes,
Guido