Preventie van ernstige Covid-19 vanuit een kwetsbaarheidsmodel

12 augustus 2020

Door: Fokje Russchen


Waarom is Covid-19 geëxplodeerd tot een pandemie? Om dat te kunnen begrijpen moeten we twee vragen beantwoorden. Wat is er specifiek aan dat wat SARS-CoV-2 teweegbrengt? En welke gastheerfactoren beïnvloeden het beloop van de ziekte? We kijken daarvoor naar zes factoren: virusbinding aan ACE2, RAS-balans, gewicht, geslacht, leeftijd en comorbiditeit. We brengen ze samen in een ‘kwetsbaarheidsmodel’, waar we conclusies aan verbinden. En bij elk van de factoren noemen we natuurlijke middelen met een mogelijke therapeutische rol.

Factor 1: virusbinding aan ACE2. SARS-CoV-2 dringt cellen binnen door te binden aan ACE2. De ernst van het verloop van de infecties is evenredig aan deze bindingsaffiniteit. Binding van virus wordt gevolgd door opname van ACE2 in de cel en vermindering van ACE2-activiteit op het celoppervlak. ACE2 is onderdeel van RAS (renine-angiotensine-systeem).
Ons begrip van RAS is verre van compleet. Het is een ingenieus systeem van controle en balans. Het zorgt voor vaatvernauwende, pro-proliferatieve en pro-inflammatoire effecten en, met moleculen die qua structuur slechts weinig van elkaar verschillen, voor tegengestelde effecten. Bovendien kan binding van hetzelfde molecuul aan verschillende receptoren tegengestelde effecten hebben. Waar ACE belangrijk is voor de pro-inflammatoire effecten van RAS staat ACE2 voor anti-inflammatoire effecten. Een verlaging van ACE2 door SARS-CoV-2-binding kan dus nadelig zijn in het ziekteproces.

Het ligt enerzijds voor de hand te streven naar een compensatie van het ACE2-verlies, maar anderzijds zou dit kunnen betekenen dat het virus meer bindingsplaatsen gepresenteerd krijgt. Vanwege deze gedachte is er ook twijfel geweest of de bloeddrukverlagende ACE-remmers (ACEI’s) en angiotensine-II-type 1-receptorblokker (ARB’s), het risico op een ernstig beloop van Covid-19 zouden kunnen vergroten. Dit is in een aantal studies onderzocht. Vooralsnog lijkt het gebruik van ARB’s of ACEi’s geen, of zelfs een licht verlagend, effect te hebben op sterfte door Covid-19.1,2-6
Er zijn alternatieven voor ACEi’s en ARB’s. In de natuur komen stoffen voor, met name flavonoïden,7 met ACE-remmende effecten. Luteoline, maar ook quercetine, rutine, kaempferol, rhoifoline, apigenine K,8,9 catechines10 en pycnogenol11 kunnen ACE remmen. Hun effect op ACE2 is minder onderzocht. Resveratrol blijkt te werken als een ARB en bovendien een angiotensine-II-type 2-receptor(AT2R)agonist te zijn.12,13

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