6 June More on genetics RCT with plasma and HCQ and neurological complications

Sat, 06/06/2020 - 21:04

Dear colleagues,

  1. News on potential genetic determinants of severe disease : comparing COVD patients with respiratory failure with  the general population in a genome-wide association study in Italy and Spain, pointed to polymorphism in gene clusters in particular regions of chromosome 3 and 9:
  • The cluster on chr3 includes Sodium/Imino-acid (proline) Transporter 1 (SIT1) that functionally interacts with ACE-2, the SARS-CoV-2 receptor, but also chemokine receptors CCR9 and CXCR6 (regulating T cell pulmonary movement .
  • The cluster on chr9 relates to ABO blood groups, with a clear exacerbating effect of group A (OR = 1.45) and protective effect of group O (OR = 0.65), confirming earlier observations.  There are also possible links with interleukin-6 and the coagulation system (referring to the “cytokine storm” and the coagulopathy).

(Paper published in medRxiv = non-peer reviewed)


  1. First RCT with convalescent plasma in 103 patients in Wuhan: some improvement in severely ill, but not in critically ill subjects. May seem disappointing, but as the comment point out: plasma therapy should preferentially be given at early stage: when there is not too much virus and the secondary immune pathology is not yet present, because later on, it is too late for effect.  Clearly, we need more data.

(In JAMA: full paper not available to me, but Comment is complete)


  1. The never ending chloroquine story:

3.1.  The Mehra paper in Lancet (showing very serious arrythmias and increased mortality of CQ and HCQ) has been retracted, because the data were not correct. See comments https://gellerreport.com/2020/06/lancet-debunked.html/ .  In addition Mehra et al had to retract an earlier paper in NEJM on cardiovascular disease, drug therapy and mortality.  Really very bad for a “top researcher”: publish 2 major studies during the same month in NEJM and Lancet and then be forced to retract them because of “major misconduct”!

3.2. RCT of post-exposure  prophylaxis with HCQ in over 700 subjects with high risk for infection showed no protection against confirmed SARS-CoV-2 or suspected symptoms (NEJM paper see Table 2 p. 6).   

3.3. Also bad news from therapeutic front: HCQ was … tested in the Recovery trial, run across 176 NHS hospitals and led by scientists at Oxford University.  Some 25.7 per cent of patients on the drug died within 28 days, compared to 23.5 per cent of those receiving the usual care. The trial was stopped by DSMB.  

Peter Horby from Oxford: "Although it is disappointing that this treatment has been shown to be ineffective it does allow us to focus care and research on more promising drugs.”

These quotes are NOT from a scientific paper, but from ‘”The Telegraph” 5 June.  See https://news.yahoo.com/researchers-halt-trial-hydroxychloroquine-found-153441151.html


  1. Neurological complication: I gathered 3 recent reviews. Clearly, neurological complications are probably quite common: , dizziness, fatigue can be signs of neurological pathology, including meningo-encephalopathy, myalgia.  Cerebro-vascular accidents also occur (ischemic, hemorrhagic..) also seizures and Guillain-Barré have been described.  All of these complication occur in rather serious cases, sometimes in rather young patients. Anosmia/ageusia  occurs often in mild cases and can be the only symptom of COVID.

At the other end of the spectrum is invasion of cardio-respiratory center that may result in fatal respiratory failure


A nice overview is Table 1 p. 293 in Munhoz paper.


Obviously, cerebro-vascular history, metabolic and heart diseases are also risk factors and that type of  patients could present those complications during any serious disease ( thus not necessarily typical for COVID).  Nevertheless, it is possible that SARS-CoV-2 enters the CNS via the lamina cribriforma (upper nose) to produce the anosmia/aguesie, but the virus could also infect endothelial cells and thus breach the blood-brain barrier or via synaptic transfer.       


There  is still a lot to learn about COVID….