20 July Episode 276 : Usefulness of booster and treatment of mild COVID

Episode 276: Usefulness of booster and treatment of mild COVID

Dear colleagues,

This is the last episode, before a break, I promise… With contributions from Patrick Smits and Suzy Huijghebaert.

First I will come back on the importance of boosting with Wuhan strain-based vaccines (1st  and 2nd boost) and then a short update on how to treat mild COVID, which remains rather difficult.

BOOST

Ep 276-1: Bowen in Science 19 July provides data that are not really new, but more comprehensive and very didactically represented than earlier papers.

• Omicron variants show increased receptor binding (i.e. lower Kd or dissociation constant), but lower fusogenicity than D614G (the “European” 2020 strain) or delta.  The authors interpret the former finding to explain higher infectivity (but they do not interpret the effect of lower fusogenicity, which logically implies lower cell-to-cell spread).    

• As we know, omicron variants are less neutralized by sera from individuals who were previously infected or vaccinated with whatever vaccine

• But boosting by any Wuhan-based vaccine (including the Adeno-viral or inactivated ones) strongly upregulates the neutralizing activity.

Some remarks:

• • Reading the legend indicates that this is a “composite” figure, not really standardized with regard to timing after boost (ranging from 5 tot 89 days after boost!).  So difficult to compare the various conditions.
  • Nevertheless, once again, the mRNA and protein (Novavax) vaccines are superior to various Adeno and inactivated
  • The Ad26 (Janssen booster) provides the weakest effect, but this is only a second dose.

Ep 276-2: Clear consensus of EDCDC on second boost:

Also, at this stage of the pandemic, the objective of COVID-19 vaccination campaigns should be to reduce COVID-19 hospitalisation, severe disease and death, and to protect healthcare systems. People over the age of 60 years and with underlying comorbidities remain at the greatest risk of severe disease. Mathematical modelling suggests clear benefits of an early second booster roll-outfor protecting people over the age of 60 years. Therefore, an early second booster roll-out should be considered not only for the population aged 80 years and above but also for adults between the ages of 60 and 79 years and individuals with underlying conditions regardless of age to prevent severe disease and safeguard health system capacity

MEDICATION FOR MILD COVID

Ep 276-3: Sidik in Nature Briefing 18 July 2022 discusses the need for such drugs.  Many “repurposed” drugs such as the anti-depressant Fluvoxamine, the asthma drug Fluticasone or new antivirals such as Paxlovid were tested to reduce hospitalization in at risk patients, but not really to relieve symptoms in mild/moderate COVID.    

Ep 276-4: Elizabeth Clarke Glycobiology May 2021 on inhibitory activity of imino-sugars

Structure

Celgosivir                                                                                 UV-4

Mechanism of action

In vitro activity

In fact less than 1 log inhibition at high micromolar concentration in vitro → unlikely that it will be useful in vivo.

Nevertheless, clinical trials are in progress

Ep 274-5: Tandon Lancet Reg. Health South-Asia: Nitric oxide nasal spray (NONS) accelerated SARS-CoV-2 clearance

Randomized controlled study with 150 comparable recently infected subjects (18-70 years): 6 X per day NONS nasal spray

1. Slightly more pronounced reduction of viral load by NONS

Clear difference in log over time, BUT mean/median VL at start also slightly lower in NONS group

2. Faster negativation  of nasal PCR

p-value just below 0.05 (0.044)

3. Also slightly faster improvement of symptoms

All in all not very convincing….

Ep 276-5: Dr Suzy Huijghebaert (s.huijghebaert@gmail.com) sent me a summary of the effects of saline (0.9 % NaCl), used as nebulization; nasal irrigation/hydration or gargling.  Nebulization was shown to be safe and irrigation/gargling could reduce the viral load.  Feedback to her are welcome.

Conclusions  

1. Second vaccine boost with Wuhan-based mRNA is indicated for the older population.
2. The treatment of mild COVID remains challenging.  Well-controlled clinical trials should be set up.

That’s it for this month!  See you in August

Best wishes,

Guido