Doxycycline Not Helpful in Community Treatment of COVID-19

By Scott Baltic

August 24, 2021

NEW YORK (Reuters Health) - Community treatment with doxycycline did not reduce time to recovery or rates of hospital admission or death in patients with suspected COVID-19 who were at high risk of adverse outcomes, according to randomized trial from the U.K.

"Our findings, from this study among older adults and those with comorbidities, do not support the routine use of doxycycline for suspected COVID-19 in the community in the absence of other indications such as bacterial pneumonia," researchers write in The Lancet Respiratory Medicine.

"Emerging evidence suggests that bacterial co-infection in COVID-19 is uncommon, therefore antibiotic treatment is unlikely to benefit most individuals with COVID-19 in the community in well resourced countries, and wider use without clear benefit could lead to public health harm through increased antibiotic resistance," they add.

Lead author Dr. Christopher Butler of the University of Oxford told Reuters Health by email, "Doxycycline was thought to have antiviral, anti-inflammatory and antibacterial properties, any of which may have helped people with COVID-19 recover quicker, especially if they went on to develop bacterial pneumonia, which we now know is a very rare complication of COVID-19."

To the researchers' knowledge, theirs was the first randomized controlled trial to evaluate the efficacy of doxycycline as a stand-alone treatment for patients with COVID-19 in the community.

Participants were either age 65 or older, or age 50 or older with comorbidities, including a weakened immune system, heart disease, hypertension, asthma or lung disease, diabetes, mild hepatic impairment, stroke or another neurological problem, and obesity.

All had symptoms ongoing for up to 14 days from PCR-confirmed SARS-CoV-2 infection or suspected COVID-19, as indicated by U.K. National Health Service criteria of high temperature, new continuous cough, or change in sense of smell or taste.

In all, 1,792 patients (mean age, 61; 93% white) were enrolled, 1,563 of whom had comorbidities.

Patients were randomized to usual care, which was largely supportive, or usual care plus oral doxycycline (200 mg on day 1, followed by 100 mg once daily for the following six days).

The median time to first self-reported recovery 9.6 days with usual care plus doxycycline versus 10.1 days with usual care only (hazard ratio, 1.04; 95% Bayesian Credible Interval, 0.93 to 1.17), and the probability of a clinically meaningful benefit (defined as at least 1.5 days) was 10%.

Hospitalization or COVID-19-related death occurred in 5.3% of the participants given usual care plus doxycycline group and in 4.5% of those given usual care only, a non-significant difference.

Six months after randomization began, the trial steering committee recommended stopping randomization to doxycycline (other arms of this study are evaluating other COVID-19 treatments), because the prespecified futility criterion had been met.

Dr. Butler said an interim analysis of another arm of this study found that people with COVID-19 in the community who took inhaled budesonide recovered around three days sooner, were less ill while recovering, remained recovered more often over 28 days, and were less likely to need hospital admission.

Dr. Alexandre Malek, an assistant professor of internal medicine at LSU Health Shreveport, Louisiana, who was not involved in research, told Reuters Health by email, "this is a sophisticated trial and reflects the real-world experience of patients with confirmed or suspected COVID-19."

Dr. Bradley Langford, a pharmacist with Public Health Ontario and the Hotel Dieu Shaver Health and Rehabilitation Centre, in St. Catharines, Canada, said a number of antibiotics have been used in COVID-19.

told Reuters Health in an e-mail that certain antibiotics, including doxycycline, have been used in COVID-19 for several reasons.

In a recent study, Dr. Langford, who specializes in antimicrobial stewardship, and colleagues found that bacterial co-infection in COVID-19 is quite uncommon, at 5% or lower.

"So the practice of prescribing antibiotics to these patients can lead to significant overuse, which can do more harm than good, including causing side effects, C. difficile diarrhea, and hastening antimicrobial resistance," Dr. Langford, who also was not involved in the new study, told Reuters Health by email.

SOURCE: The Lancet Respiratory Medicine, online July 27, 2021.