Introduction The anti-inflammatory effect of macrolides prompted the
study of oral clarithromycin in moderate COVID-19. Methods An open-label
non-randomized trial in 90 patients with COVID-19 of moderate severity
was conducted between May and October 2020. The primary endpoint was
defined at the end of treatment (EOT) as no need for hospital
re-admission and no progression into lower respiratory tract infection
(LRTI) for patients with upper respiratory tract infection and as at
least 50% decrease of the respiratory symptoms score without
progression into severe respiratory failure (SRF) for patients with
LRTI. Viral load, biomarkers, the function of mononuclear cells and
safety were assessed. Results The primary endpoint was attained in
86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%);
this was 91.7% and 81.4% among patients starting clarithromycin the
first 5 days from symptoms onset or later (odds ratio after multivariate
analysis 6.62; p 0.030). The responses were better for patients infected
by non-B1.1 variants. Clarithromycin use was associated with decreases
in circulating C-reactive protein, tumour necrosis factor-alpha and
interleukin (IL)-6; by increase of production of interferon-gamma and
decrease of production of interleukin-6 by mononuclear cells; and by
suppression of SARS-CoV-2 viral load. No safety concerns were reported.
Conclusions Early clarithromycin treatment provides most of the clinical
improvement in moderate COVID-19