A macrolide widely used in severe SARS-CoV and MERS-CoV is being trialled by UK respiratory experts as a potential treatment for patients with moderately severe COVID-19.

The multicentre phase II/III ATOMIC2 trial will compare azithromycin to standard care in adults presenting to hospital with COVID-19 symptoms who are not admitted at initial presentation.

Led by Professor Tim Hinks from the Respiratory Medicine Unit and National Institute for Health Research Oxford, the research team specifically targeted this patient population because they were generally at high-risk of readmission within the next two weeks yet, “not too late in the disease process for suppression of pulmonary macrophage-derived inflammatory cytokines to have a potentially clinically meaningful beneficial effect”.

The research team say azithromycin’s anti-inflammatory properties, rather than any antiviral effect, will be more important in the treatment of severe COVID-19 disease in secondary care.

“Antivirals are likely to have limited efficacy in severe disease as they are administered late in the disease, after viraemia has peaked,” they wrote in the study protocol published in Trials.

In the trial participants will be randomised in a 1:1 ratio to usual care or to azithromycin 500 mg orally daily for 14 days with telephone follow-up at days 14 and 28.

Its primary objective is to compare the proportion with either death or respiratory failure requiring invasive or non-invasive mechanical ventilation over 28 days from randomisation. 

Secondary objectives include mortality/respiratory failure in those with a PCR-confirmed diagnosis; all-cause mortality; progression to pneumonia; progression to severe pneumonia; peak severity of illness and mechanistic analysis of blood and nasal biomarkers.

The research team noted that as azithromycin was particularly prone to inducing antimicrobial resistance the restriction of unnecessary use was a clear priority.