News Scan for May 27, 2021

News brief

Two inactivated Chinese COVID-19 vaccines found 73% to 78% effective

A randomized controlled trial of two inactivated (vero cell) COVID-19 vaccines made in China finds a vaccine efficacy of 73% in one and 78% in the other, according to a study yesterday in JAMA.

The whole-virus inactivated vaccines were developed with strains of the virus taken from patients in Wuhan, China.

The phase 3 trial included approximately 40,000 adults in the United Arab Emirates and Bahrain who were assigned to receive either a vaccine (WIV04 or HB02) or an alum-only injection. Both vaccines are two-dose inactivated injections, and the primary end point of the trial was symptomatic COVID-19 at least 14 days after the second injection.

During a median follow-up of 77 days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 cases per 1,000 person-years; 95% confidence interval [CI], 8.3 to 17.8]), 21 in the HB02 group (9.8 per 1,000 person-years; 95% CI, 6.4-15.0), and 95 in the alum-only group (44.7 per 1,000 person-years; 95% CI, 36.6-54.6), the authors wrote. This resulted in efficacy rates of 72.8% and 78.1%, respectively against symptomatic COVID-19 cases.

Mild adverse events were described in 44.2% of participants in the WIV04 group and 41.7% in the HB02 group and included pain at the injection site and headache.

Neither vaccine was tested against emerging variant strains of COVID-19, the authors warned. The authors also said that, compared with trails of mRNA and adenovirus-based vaccines, trial participants were younger (median age 36.1 years), and mostly male (84.4%).

"In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19. Data collection for the final analysis is pending," the authors concluded.
May 26 JAMA study

Review finds persistent symptoms in 73% of COVID-19 patients

Almost three quarters of patients reported at least one persisting COVID-19 symptom during follow-up, with the most common being shortness of breath and fatigue, according to a literature review published in JAMA Network Open yesterday.

The researchers looked at 45 studies published from Jan 1, 2020, to Mar 11, 2021, and defined long-haul COVID as either 60 days after diagnosis, symptom onset, or hospitalization, or at least 30 days after acute illness recovery or hospital discharge. The largest proportion of studies came from China (7), followed by the United Kingdom (6), Spain (6), Italy (5), France (4), and the United States (3).

The total cohort was 9,751 inpatients and outpatients, and 30 studies involved patients with mean or median ages younger than 60. Among all patients, 54.0% were male.

In 16 studies, mostly of previously hospitalized patients, a median 72.5% had at least one persisting COVID-19 symptom during follow-up, even through 6 months. Of the most prevalent symptoms, a median of 40.0% of participants reported fatigue in 25 studies, 36.0% reported shortness of breath in 26 studies, and 29.4% reported sleep disorders in 8 studies. A total of 84 signs or symptoms and 19 lab or imaging measurements were looked at across the study pool, but the researchers note that the studies had limited comparability.

The researchers conclude, "This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life; however, methodological improvements are needed to reliably quantify these risks."
May 26 JAMA Netw Open study

State COVID-19 vaccine websites found wanting in accessibility, usability

Many state-run COVID-19 vaccine websites could improve their accessibility and usability, according to a research letter yesterday in JAMA Network Open.

The researchers conducted a qualitative study on each state's website for COVID-19 vaccine information and looked at accessibility and usability from the standpoint of someone who was trying to understand vaccine eligibility, wanting to schedule an appointment online, or needing to be added to a wait list.

The average website accessibility was 82%. Seven websites weren't available to view completely via smartphone, and nine were only in the English language. Not all states included vaccine eligibility information on their sites. Of the 47 that had a median readability of 15.6 out of 100 (the lower score, the more readable), 39 (83.0%) were rated at a post–high school reading level.

Regarding usability, the researchers found that 40 of the 47 states with vaccine eligibility information had no indicator of when the information was last updated, and 27 (57.4% of 47) did not support methods to verify eligibility.

Half of all states provided web-based appointment scheduling, but 23 required people to search vaccine locations one by one. Only three states offered wait-list or follow-up options, and nine states did not offer web-based scheduling or follow-up at all.

"State health department COVID-19 vaccine website accessibility and usability challenges create frustration, may promote health disparities, and contribute to overall ineffective and inequitable distribution," the researchers write.
May 26 JAMA Netw Open study

Stewardship / Resistance Scan for May 27, 2021

News brief

CARB-X to fund development of CRISPR-based drug for E coli infections

CARB-X announced today that it is awarding up to $3.9 million to a Danish microbiome biotechnology company to develop a CRISPR-based drug to prevent Escherichia coli infections in cancer patients.

The award will help Copenhagen-based SNIPR BIOME ApS develop its lead drug candidate, SNIPR001, which uses CRISPR/Cas DNA editing technology to selectively eradicate E coli bacteria in the gut and prevent translocation of the bacteria to the bloodstream while sparing other beneficial bacteria in the patient's microbiome.

Cancer patients with hematologic malignancies are often at increased risk of bloodstream infections because of the disease and chemotherapy treatment, with E coli posing a heightened risk. They are typically treated with broad-spectrum antibiotics.

"There is an increasing awareness of the importance for human health of microbial diseases and anti-microbial resistance," SNIPR BIOME Chief Medical Officer Milan Zdravkovic, MD, PhD, said in a CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) press release. "We see that SNIPR001 has the potential to contribute to addressing unmet medical needs in a novel way in people at high risk of severe E. coli infections, and we look forward to working with CARB-X in bringing SNIPR001 into clinical trials."

SNIPR BIOME may be eligible for an additional $6.3 million if the project achieves certain milestones. The company hopes to begin a first in-human study in the first half of 2022.

Since its launch in 2016, CARB-X has announced 90 awards to product developers in 12 countries. The awards are worth more than $337 million.
May 27 CARB-X press release

New WHO guidance aims to help nations implement stewardship steps

The World Health Organization (WHO) has published new guidance for countries on how to implement antimicrobial stewardship (AMS) activities in healthcare facilities in an integrated, comprehensive manner.

The guidance, which was requested by member states and is intended for policy makers at national ministries of health and national antimicrobial resistance (AMR) coordinating bodies, was developed by WHO staff with input from an international group of experts, including those from the University of Minnesota's Centers for Infectious Disease Research and Policy, publisher of CIDRAP News.

The guidance is organized into five key pillars and 12 interventions that countries need to consider to implement comprehensive and integrated AMS activities in healthcare facilities. The WHO defines AMS as a coherent set of integrated actions that promote responsible and appropriate use of antimicrobials and help improve patient outcomes across the continuum of care.

The five key pillars of the guidance are: (1) Establish and develop national coordinating mechanisms for antimicrobial stewardship and develop guidelines; (2) ensure access to and regulation of antimicrobials; (3) improve awareness, education, and training; (4) strengthen water, sanitation, and hygiene and infection prevention and control (IPC); and (5) conduct surveillance, monitoring, and evaluation.

Interventions include establishing a national coordination mechanism for AMS activities that can function at national, subnational, and district levels, developing national treatment and stewardship guidelines, regulating responsible and appropriate use of antimicrobials, implementing IPC core components in health facilities, and establishing surveillance systems for antibiotic use and AMR.

"AMS activities are best implemented in an integrated manner to optimize antimicrobial prescribing and ensure patient and public safety," the guidance states. "It is important that the central coordination unit takes the lead, involving all relevant stakeholders in national policy development and strategic planning processes to identify the priority objectives, inputs and resources required and, finally, to implement the policy."

The guidance also advises that the central coordination unit should consider national and local context and the structure of the health system in carrying out AMS activities, prioritize activities that are likely to provide the greatest benefit, and ensure strong links between relevant areas and disciplines related to AMR.
May 20 WHO policy guidance

Study examines inadequate antibiotics in patients tested for COVID-19

Inadequate antibiotic therapy (IET) in hospital patients with positive bacterial cultures who were tested for SARS-CoV-2 was associated with a significant increase in mortality and longer hospital stays compared with those who received adequate therapy, US researchers reported yesterday in Open Forum Infectious Diseases.

The multicenter retrospective study, conducted by scientists with Merck & Co. and Becton, Dickinson and Company, looked at in-hospital mortality and hospital and intensive care unit (ICU) length of stay (LOS) in patients who were tested for SARS-CoV-2 and had a positive bacterial culture at 201 US hospitals from March to November 2020. While high rates of empiric antibiotic use have been reported in COVID-19 patients throughout the pandemic, little research has been conducted on the impact of IET—defined as therapy not active against the identified bacteria or no antibiotic therapy in the 48 hours following culture—on patient outcomes.

Of the 438,888 patients who were tested for COVID-19, 39,203 (8.9%) had positive bacterial cultures. Among the patients with positive cultures, 3,764 (9.4%) were SARS-CoV-2–positive, 74.4% had a gram-negative pathogen, and 25.6% had a gram-positive pathogen. Overall, 17,295 (44.1%) of these patients received IET, with the absence of empiric treatment within 48 hours more common than antibiotic therapy that was not active against the identified bacteria.

In multivariable analysis, IET was associated with a 21% increase in mortality (odds ratio, 1.21; 95% confidence interval, 1.10 to 1.33) compared with adequate antibiotic therapy, and a significant increase in hospital LOS (16.1 days vs 14.5 days). The difference in ICU LOS was not statistically significant (8.2 days vs 8.0 days). Both mortality and hospital LOS findings remained consistent for patients who tested positive for SARS-CoV-2 and those who tested negative.

"Our data indicate that underlying gram-positive and gram-negative bacteria continue to play an important role in hospital outcomes during the COVID19 pandemic, and one with the potential to be adequately managed to help ensure more favorable outcomes," the authors wrote, adding that they hope the study enables stewardship programs to educate and contain IET in hospitals for all patients with bacterial infections.
May 26 Open Forum Infect Dis abstract