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\begin{document}

\title{Effect of increasing doses of colchicine on the treatment of 333
COVID-19 inpatients}



\author[1]{Rumen Tiholov}%
\author[2]{Aleksander Lilov}%
\author[1]{Gergana Georgieva}%
\author[3]{Kiril Palaveev}%
\author[4]{Konstantin Tashkov}%
\author[5]{Vanyo Mitev}%
\affil[1]{MHAT “Sv Ivan Rilsky”}%
\affil[2]{SHATPPD Sofia district}%
\affil[3]{SHATPPD  Sofia district  }%
\affil[4]{Medical University-Sofia Faculty of Pharmacy}%
\affil[5]{Medical University-Sofia}%


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  \date{May 18, 2024}


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\begin{abstract}
Recently we demonstrated that in 452 COVID-19 inpatients higher
colchicine doses reduced the mortality about 5 times. Here we report
another 333 cases of COVID-19 inpatients, treated with different doses
of colchicine. There was a clear trend of reduction in the mortality of
inpatients with increasing doses of colchicine between 2- and 7-fold.
Colchicine loading doses of 4 mg are more effective than those with 2
mg. Despite higher than the so-called ``standard doses'' of colchicine,
our doses are completely safe. The World Health Organization
(WHO)-recommended strategy to inhibit viral replication had partial
success because there is no direct link between viral load and the
hyperactivation of the NLRP3 inflammasome. The neutralization of the
IL-6 effects with anti-receptor antibodies and the inhibition of the
tyrosine kinase JAK can be compromised if NLRP3 continues to be
hyperactive and generates a cytokine storm. Our treatment strategy to
inhibit the SARS-CoV-2 entry into the cell with inhaled bromhexine and
the hyperactivated NLRP3 inflammasome with higher doses of colchicine,
as the source of the cytokine storm practically solves the problem of
treating COVID-19. The timing of initiation of treatment is critical.%
\end{abstract}%



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