COVID-19 Scan for Jun 02, 2021

News brief

Hydroxychloroquine doesn't prevent COVID-19, study finds

Prophylactic hydroxychloroquine treatment was not associated with any risk difference for COVID-19 infection, according to an International Journal of Infectious Diseases study yesterday.

The researchers followed a cohort of all 5,488 Danish people who used hydroxychloroquine in both 2019 (for non–COVID-19 reasons) and 2020 and matched them with 54,846 non-users by age and sex. The primary outcome was a COVID-19 diagnosis from Feb 27 to Nov 27, 2020.

Infection rates were comparable between the two groups, with 3.4% of the hydroxychloroquine group and 3.7% of the control group receiving positive diagnoses. Final modeling adjusted for comorbidities and pharmaceutical treatments and resulted in a hazard ratio of 0.90 (95% confidence interval, 0.76 to 1.07).

"Our study, which is the largest to investigate the primary prophylactic effect of hydroxychloroquine against SARS-CoV-2, does not support any prophylactic benefit of hydroxychloroquine in the prevention of infection with SARS-CoV-2," write the researchers.

Currently, the World Health Organization does not recommend using hydroxychloroquine to prevent or treat COVID-19 infections.
Jun 1 Int J Infect Dis study

COVID-19 hospitalization, ICU admission higher in HIV patients

Adult COVID-19 patients diagnosed as having HIV had higher rates of hospital and intensive care unit (ICU) admission than those without HIV, according to an Open Forum Infectious Diseases study yesterday. Thirty-day mortality, however, was similar between the two groups.

The researchers looked at 297,194 COVID-19 infections confirmed in US adults in 2020, of which 0.6% were in people who also had HIV. Those with HIV had higher COVID-19 hospitalization rates (16.5% vs 7.6%; odds ratio [OR], 1.26), ICU admission (4.2% vs 2.3%), and mechanical ventilation (2.4% vs 1.6%), but 30-day mortality was comparable, at 2.9% in the HIV group and 2.3% in the non-HIV group.

Severe COVID-19 disease in HIV patients was associated with older age (adjusted OR [aOR], 8.33) and CD4 levels of less than 200 cells per cubic millimeter (aOR, 8.33), although the researchers note that only 14.0% of people with HIV reported CD4 count. CD4, or cluster of differentiation 4, is a glycoprotein on the surface of immune cells.

Overall, HIV patients had more COVID-19 symptoms and elevated procalcitonin and interleukin-6, both markers of inflammation.

COVID-19 patients with HIV were more commonly younger than those without HIV (average, 43.3 vs 46.5 years), male (69.4% vs 44.3%), Black or Hispanic (49.1% vs 19.7%, 18.1% vs 15.2%), and less healthy, with comorbidities such as cardiovascular disease (46.8% vs 26.1%), obesity (24.7% vs 14.8%), and diabetes (21.9% vs 12.8%). They were also more likely to have a history of smoking, alcohol, and drug use.

"We hypothesize that the reasons for these findings may be related to the combined effects of the high prevalence of underlying comorbidities coupled with the possibility of a more vigorous manifestation of the cytokine release syndrome in [people with HIV]," the researchers write, adding that the higher hospitalization risk persisted after propensity score matching.
Jun 1 Open Forum Infect Dis study

Few randomized, controlled COVID drug trials echo observational results

Most non-randomized study results looking at potential COVID-19 drugs were not able to be replicated in randomized, controlled trials (RCTs), according to a Journal of Antimicrobial Chemotherapy article today.

The researchers looked at 133 trial arms in 117 studies published from Jan 1 to Oct 27, 2020. The most commonly examined drug was hydroxychloroquine on its own or with other drugs such as azithromycin (49 arms total), and other frequent interventions were interleukin-6 inhibitors (36) and corticosteroids (26).

Most intervention arms were in non-randomized cohorts (78.2%, 104). Of these, 30.8% (32) showed significant survival benefits. Comparatively, 6.9% of RCTs (2 of 29) reported significant survival benefit, both for corticosteroids. Overall, the researchers say that 87.5% of non-randomized trials that showed survival benefits did not have replicated results in corresponding RCTs.

"The results of most non-randomized studies reporting survival benefit of potential anti–COVID-19 drugs were not replicated by large RCTs," they conclude. "Regulators and healthcare professionals should exercise caution and resist the pressure to approve and prescribe drugs of unproven efficacy and potential toxicity to optimize patient care and maintain public trust in medical science."

Data showed that RCTs had a larger median patient sample (243 vs 191 participants) and were more likely to be multicentered (69.0% vs 39.4%) and published in journals with a higher impact factor, a measure of how many citations a journal has received in the past 2 years (median score, 45.5 vs 4.3). RCTs were also less likely to have survival as a primary outcome (10.3% vs 38.5%).
Jun 2 J Antimicrob Chemother study

News Scan for Jun 02, 2021

News brief

Study identifies metrics tied to respiratory infection antibiotic overuse

More than two thirds of antibiotics prescribed for respiratory tract infections at primary care practices within an academic health system were inappropriate, with unnecessary prescribing strongly linked to respiratory infections that almost never require antibiotics, researchers reported today in Infection Control & Hospital Epidemiology.

The retrospective study by researchers with the University of Pennsylvania and the Centers for Disease Control and Prevention looked at antibiotic prescribing for respiratory tract diagnoses (RTDs) at 32 primary care practices within the University of Pennsylvania Health in 2016. The researchers reviewed the medical records for 1,200 randomly selected office visits in which an antibiotic was prescribed for an RTD, then evaluated RTD metrics to determine their association with appropriateness. They also looked at provider characteristics associated with inappropriate prescribing.

Overall, 69% of all antibiotic prescriptions for RTDs were determined to be inappropriate, with a range of 15% to 100% for individual providers. In univariate analysis, the individual RTD metric that was most strongly associated with inappropriate prescribing was the proportion of prescribing for visits in which a tier 3 RTD was coded. Tier 3 RTDs represents conditions for which antibiotics are almost never indicated, like bronchitis. There was also a strong association between inappropriate prescribing and the proportion of prescribing for all RTDs.

Provider characteristics associated with inappropriate prescribing included advanced practice provider versus physician (72% vs 58%), family medicine providers compared with internal medicine providers (76% vs 63%), board certification in 1997 or later compared with board certification before 1997 (75% vs 63%), nonteaching versus teaching practice (73% vs 51%), and nonurban compared with urban practice (77% vs 57%).

The study authors say identifying RTD metrics associated with inappropriate prescribing can help healthcare systems track and monitor antibiotic use and highlight provider prescribing patterns.

"These findings could inform design of interventions to improve prescribing and could represent an efficient way to track inappropriate prescribing," they wrote.
Jun 2 Infect Control Hosp Epidemiol abstract

FDA approves antifungal for vaginal yeast infections

Biotechnology company Scynexis announced today that the Food and Drug Administration (FDA) has approved the novel antifungal ibrexafungerp for treatment of vulvovaginal candidiasis (vaginal yeast infection).

Ibrexafungerp, sold under the brand name Brexafemme, represents the first approved drug in a novel antifungal class in more than 20 years. The first representative of a class of structurally distinct glucan synthase inhibitors known as triterpenoids, it has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the FDA for treatment of a variety of fungal infections caused by the Candida and Aspergillus species, including drug-resistant strains, but this is the first approved indication. The New Drug Application was approved yesterday by the FDA.

The approval was based on the results from two phase 3 studies in which oral ibrexafungerp demonstrated efficacy and a favorable tolerability profile in women with vulvovaginal candidiasis.

“The FDA approval of Brexafemme is the culmination of years of work and a significant milestone for Scynexis, marking our evolution to a commercial-stage antifungal company. We are pleased with the approved label, highlighting the unique attributes of Brexafemme, and thrilled to be able to offer a new treatment option to women with vaginal yeast infections,” Scynexis President and CEO Marco Taglietti, MD, said in a company press release.

Scynexis says it's completing a study of ibrexafungerp for the prevention of recurrent vaginal yeast infections, and will be submitting a supplemental NDA in 2022. Studies evaluating the efficacy in patients with invasive Candida auris infections are ongoing.
Jun 2 Scynexis press release

BARDA launches venture-capital pandemic preparedness accelerator

The US Department of Health and Human Services (HHS) yesterday announced the launch of a public-private partnership—modeled after venture capital practices—to develop new technologies to battle future pandemics and other health threats.

The program is run by HHS's Biomedical Advanced Research and Development Authority (BARDA) through a partnership with the nonprofit Global Health Investment Corporation (GHIC). In a statement, HHS said BARDA will provide GHIC with at least $50 million over 5 years, with the potential for $500 million over 10 years. GHIC will also launch a global health security fund to attract matching capital from other investors.

The goal is to link the investment community with sustained long-term efforts to identify, develop, and commercialize new technologies to help the nation respond to future health security events. BARDA said the new effort came from its past experiences with public-private partnerships, including CARB-X, an accelerator designed to combat antimicrobial resistance.

HHS Secretary Xavier Becerra said in the statement: "The pandemic has demonstrated that the U.S. needs transformative technology that is not only available but also widely accessible. Today we are announcing an innovative, cost-effective approach that puts us on a better path to take on the next public health crisis and improve U.S. health care."
Jun 1 HHS press release

FDA launches challenge to develop traceability tool for food outbreaks

In an effort to improve traceability tools used to identify sources in foodborne illness outbreaks, the FDA announced a new challenge to create low- or no-cost ways to alert people to outbreaks.

"Too many Americans suffer from foodborne illnesses every year. Making the food supply more digitally enabled and food more traceable will speed the response to outbreaks and deepen our understanding of what causes them and how to prevent them from happening again," said Acting FDA Commissioner Janet Woodcock, MD, in an FDA press release.

The challenge asks food technology solution providers, public health advocates, entrepreneurs, and innovators to create digital information tools that will quickly alert users to the source of food contamination.

The challenge is a goal outlined in the FDA's New Era of Smarter Food Safety Blueprint, first issued last summer.

The FDA will accept submissions from Jun 1 through Jul 30, and will announce as many as 12 winners as selected by judges from the federal government. The winners will present their ideas during a webinar in September.
Jun 1 FDA press release
FDA Food Safety blueprint

Lesotho reports its first H5 avian flu outbreak in poultry

In highly pathogenic avian flu developments reported to the World Organization for Animal Health (OIE), Lesotho reported its first H5 outbreak in poultry, and two European countries reported more H5N8 detections in poultry.

Lesotho's outbreak began on May 27 at a farm housing layers and cattle in the western Maseru district. The virus killed 816 of 3,000 susceptible birds, and the source of the virus is thought to be the introduction of new birds.

In Europe, Lithuania reported an event at a trading farm housing different poultry species in Taurage County in the west that began on May 27, killing 79 of 1,238 birds. Also, Germany reported an outbreak that began on May 22 at a backyard facility in Bremen housing layers and ducks. The virus killed 7 of 21 susceptible birds.
May 31 OIE report on H5 in Lesotho
May 31 OIE report on H5N8 in Lithuania
May 28 OIE report on H5N8 in Germany