Coronavirus disease-2019 (COVID-19) wordt veroorzaakt door het severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Belangrijke risicofactoren voor ernstige COVID-19 zijn leeftijd, obesitas, mannelijk geslacht en obesitasgeassocieerde morbiditeit zoals hypertensie, diabetes mellitus type 2, hart-vaatziekte en chronische nierziekte. De gemeenschappelijke noemer is metaflammatie, een samentrekking van metabolisme en inflammatie. Indien een persoon met metaflammatie besmet raakt met SARS-CoV-2, wordt in eerste instantie geen toestemming verleend om een energieconsumerende en schadeveroorzakende immuunreactie te starten. Een vroege productie van interferonen type I blijft uit. Type I-interferonen hebben antivirale eigenschappen en voorkómen een snelle virusvermenigvuldiging en -verspreiding. Door de interferonsignalering te verstoren doet SARS-CoV-2 daar een forse schep bovenop. De bij metaflammatie heersende chronisch licht verhoogde spiegels van pro-inflammatoire cytokinen, leptine en insuline veroorzaken leptine- en insulineresistentie in (onder andere) het immuunsysteem. Verhoogde pro-inflammatoire cytokinen en leptine zijn bij obesitas afkomstig uit het ontstoken vetweefselcompartiment, drijven de leptine- en insulineresistentie, en de bijbehorende hyperleptinemie, hyperinsulinemie, hypertensie, hyperglycemie, hyperlipidemie en andere symptomen van het metabool syndroom. Mechanistisch wordt de leptineresistentie veroorzaakt door de inductie van suppressor of cytokine signaling 1 en 3 (SOCS1/3). Een consequentie is dat glucose niet kan worden opgenomen voor de activering van het immuunsysteem. SOCS1/3 wordt ook door het virus geïnduceerd. Door de late immuunreactie ontstaat grote schade door virus en immuunsysteem, dat vervolgens over-reageert. Er ontstaat een cytokinestorm, ernstige endotheelschade, hypercoagulatie en ernstige COVID-19. Het superponeren van een acute verstoring, zoals een SARS-CoV-2-infectie, op metaflammatie stelt de veerkracht sterk op de proef. Op lange termijn veroorzaakt metaflammatie de pathologie die we intussen goed kennen als de ‘typisch westerse’ ziekten die geassocieerd zijn met het metabool syndroom. Ernstige COVID-19 en andere ernstig verlopende infectieziekten kunnen daaraan als korte-termijnrisicofactoren worden toegevoegd. Voorkómen van besmetting, vaccinatie en verbetering van leefstijl zijn de beste preventieve maatregelen.
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