Athanassios Karageorgos

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. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04398004.

BACKGROUND: The accuracy of a new optical biosensor (OB) point-of-care device for the detection of severe infections is studied. METHODS: The OB emits different wavelengths and outputs information associated with heart rate, pulse oximetry, levels of nitric oxide and kidney function. At the first phase, recordings were done every two hours for three consecutive days after hospital admission in 142 patients at high-risk for sepsis by placing the OB on the forefinger. At the second phase, single recordings were done in 54 patients with symptoms of viral infection; 38 were diagnosed with COVID-19. RESULTS: At the first phase, the cutoff value of positive likelihood of 18 provided 100% specificity and 100% positive predictive value for the diagnosis of sepsis. These were 87.5 and 91.7% respectively at the second phase. OB diagnosed severe COVID-19 with 83.3% sensitivity and 87.5% negative predictive value. CONCLUSIONS: The studied OB seems valuable for the discrimination of infection severity.

ABSTRACT Background To study the efficacy 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 the 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 Th1 to Th2 mononuclear responses; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. Conclusions Early clarithromycin treatment provides most of clinical improvement in moderate COVID-19 ( Trial Registration: ClinicalTrials.gov, NCT04398004 )