High colchicine doses are more effective in COVID-19 outpatients than nirmatrelvir/ritonavir, remdesivir, and molnupiravir

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Abstract
Colchicine has an excellent basis for being effective against COVID-19 due to its anti-inflammatory, immunomodulatory, and cardioprotective effects, as well as its role in preventing microvascular thrombosis. In addition, colchicine also has antiviral effects, an extremely favorable safety profile, and–since it does not exert any overt immunosuppressive activity–does not interfere with effective viral clearance, nor is it associated with the occurrence of secondary infections. However, all studies to date on the effects of low-dose colchicine for COVID-19 treatment are conflicting and rather disappointing. As colchicine has the remarkable ability to accumulate intensively in leukocytes–where the cytokine storm is generated–we initiated high but safe doses of colchicine for COVID-19 patient treatment. Our assumption was that a safe increase in colchicine dosage to reach micromolar concentrations in leukocytes would result in NLRP3 inflammasome/cytokine storm inhibition and would enhance its antiviral effect by inducing microtubule dissociation. Outpatients’ high-dose colchicine treatment practically prevents hospitalizations. Total colchicine uptake analysis demonstrates an inverse relationship with hospitalization. The duration of colchicine uptake also shows an inverse relationship with hospitalization and post-COVID-19 symptoms. Unlike the WHO-recommended antiviral preparations molnupiravir, remdesivir, and paxlovid, colchicine–in addition to its antiviral effect–prevents the cytokine storm and therefore has a strong effect not only in outpatients but also in inpatients. Unlike antivirals, colchicine significantly reduces post-COVID-19 symptoms. The side effects of colchicine are similar to those of paxlovid. The price of colchicine is incomparably lower, and it is also easily available.
Funding Information
  • Bulgarian National Science Fund

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