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Widely available antibiotic found to prevent COVID-19 patients needing intensive care

An international study co-led by Southampton’s Professor Ratko Djukanovic has shown that a common antibiotic could reduce intensive care unit (ICU) admissions caused by COVID-19.

The results, published in PLOS ONE, show that hospitalised patients at risk of severe COVID-19 who took doxycycline were less likely to be admitted to ICU.

Doxycycline is a safe, inexpensive, and widely available antibiotic with anti-inflammatory and anti-oxidative properties. It could, therefore, be rapidly rolled out in hospitals to save patients’ lives.

The drug had very few side effects, with no patients stopping treatment because of them.

The randomised, clinical, multicentre trial was carried out in India on a mini-budget of less than £10,000. It was the work of a small but agile global team during the height of the pandemic.

Less likely to need intensive care

Overall, 387 patients aged 40–90 years and admitted to hospital with COVID-19 took part in the trial. They were randomly allocated to receive either standard care with doxycycline or standard care alone.

The researchers then recorded how many patients deteriorated to the point where they needed transfer to an intensive care unit (ICU). In total 77 of the patients developed critical disease needing ICU admission.

Doxycycline reduced the need to be transferred to an ICU by 43%.

Prof Djukanovic, Professor of Medicine at the University of Southampton and Respiratory Consultant at University Hospital Southampton NHS Foundation Trust, said:

“The addition of doxycycline substantially reduced the progression of patients to intensive care in this trial. This suggests that this globally available, safe and inexpensive antibiotic has potential to become an effective option in the continuing global battle against COVID-19.”

Anti-oxidative and anti-inflammatory properties

Former Southampton colleagues Prof Stephan Gadola and Prof Djukanovic conceived the study during the first COVID-19 wave in 2020.

The core study team was joined by John Kirkpatrick, a statistical scientist and former industrial colleague of Prof Gadola, and Dr Raja Dhar, a pulmonologist at Calcutta Medical Research Institute (India) and long-term colleague of Prof Djukanovic.

Clinicians at six medical centres in India as well as a microbiologist and data scientists from Germany and the UK complemented the study team.

Prof Gadola, Visiting Professor of Immunology at the University of Southampton and chief physician at Bethesda Hospital Basel (Switzerland), said:

“The data show that the benefits for patients in this trial are not explained by doxycycline’s antimicrobial properties, indicating they are related to its anti-oxidative and anti-inflammatory properties.

“This makes doxycycline a potential candidate drug for other infectious diseases that are accompanied by severe inflammatory complications.”

Innovative data acquisition and processing

John Kirkpatrick, joined by his colleague and data analyst, Laura Gilbert, conceived and developed a tailormade novel software application (App) for data collection.

Prof Djukanovic explained: “This study was unique amongst the many COVID-19 trials conducted worldwide. Although it was conducted in particularly difficult times, unlike many COVID-19 trials, it was inexpensive and did not depend on complex and expensive research systems.

“Instead of relying on expensive and complicated data collection platforms, investigators could use John’s app that was easy to use, requiring no more than a couple of minutes for each of the four pages to collect all the relevant data.”

Enrolment into the trial started on in November 2020 and continued for 27 weeks.

Dr Dhar said: “The trial was carried out in the midst of the deadly second COVID-19 wave in India and circumstances could not have been more challenging. This has been an excellent, pragmatic and very friendly collaboration by experts across multiple continents, and we are greatly encouraged by the findings for this well-known and widely available antibiotic.”

Prof Gadola said: “The impressive results of this trial could have significant implications for both patients and health services, in particular in countries where, because of limited financial resources, ICU admission is dependent on accessibility and affordability rather than clinical indication. A similar study is now needed to seek evidence of treatment on mortality.”


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