News Scan for Dec 01, 2020

News brief

CARB-X to fund treatments for S aureus pneumonia, Pseudomonas

CARB-X today announced two new funding awards for German scientists working on therapies for difficult-to-treat bacterial infections.

The first award, worth up to $1.33 million, will go to researchers from the Helmholtz Centre for Infection Research (HZI) and the Lead Discovery Center GmbH for development of a small molecule that inhibits the Staphylococcus aureus toxin a-hemolysin, which damages lung tissue and immune cells. The drug would be used in combination with antibiotics to treat pneumonia caused by S aureus.

"We urgently need better treatment options for patients with pneumonia caused by S. aureus," Mark Bronstrup, lead researcher and head of chemical biology at the HZI, said in a CARB-X press release. "In the long term, however, we will not achieve this by killing the pathogens with antibiotics alone. Instead, we need preventive or accompanying therapies that prevent damage to the lungs by bacterial toxins."

Bronstrup and colleagues could be eligible for an additional $7.44 million from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) if the project meets certain milestones.

Another team of HZI researchers will receive $6.31 million from CARB-X to develop an innovative treatment for Pseudomonas aeruginosa infections in cystic fibrosis patients.

Since its launch in 2016, CARB-X has awarded more than $260 million for pre-clinical development of new antibiotics, vaccines, diagnostics, and other treatments for bacterial infections. There are currently 49 active projects focused exclusively on drug-resistant bacteria in the CARB-X portfolio.
Dec 1 CARB-X press release


GARDP announces joint effort on antibiotics, diagnostics for STIs

The Global Antibiotic Research and Development Partnership (GARDP) yesterday announced the signing of a memorandum of understanding with the Foundation for Innovative New Diagnostics (FIND) and the World Health Organization (WHO) to explore joint efforts that could improve sustainable access to antibiotics and protect them against the emergence of resistance.

The initial focus of the groups will be on sexually transmitted infections (STIs), including drug-resistant gonorrhea, which the WHO has identified as a priority infection urgently requiring new antibiotics. Their efforts will focus on strengthening STI case management by fostering access to new tests and treatments, evaluating public health needs for new diagnostic tests and treatments for gonorrhea, assessing appropriate use and stewardship of antibiotics, and defining strategies to monitor and delay the emergence of resistance to gonorrhea treatments.

GARDP is currently working with partners to develop a new treatment for gonorrhea, while FIND is working on rapid point-of-care diagnostics for gonorrhea, including tests that detect resistance. Both efforts have been aided by the WHO.
Nov 30 GARDP press release


Vaccine protects monkeys from Crimean-Congo hemorrhagic fever

A DNA-based vaccine for the tickborne Crimean-Congo hemorrhagic fever virus (CCHFV) given to cynomolgus macaques was shown to provide protection from the disease, according to a study published yesterday in Nature Microbiology.

The vaccine candidate uses two plasmids encoding the glycoprotein precursor (GP) and the nucleoprotein (NP) of CCHFV, and it was given to six female macaques at 3-week intervals in three dosages containing 1 milligram of each plasmid and followed by electroporation. Six female macaques were in the placebo group. After the vaccination period, all were infected with CCHFV; tested for symptoms and viral shedding at days 0, 3, 5, and 6 post-infection; and examined after euthanasia on day 6.

According to results of the study, which was sponsored by the National Institutes of Health (NIH), none of the macaques in the intervention or control group experienced significant adverse reactions during the vaccination period. Post-infection, the placebo group displayed significant virus RNA levels in their blood, significantly elevated aspartate aminotransferase values, and reduced platelets, total protein, and albumin levels.

The only change the intervention group displayed was a significantly elevated platelet count that was still within the normal range. A post-mortuary examination of the spleen and lymph nodes showed that treated macaques had significantly reduced CCHFV burdens, with a 100-fold reduction in viral burden in all tissues compared with the control group, as well as an absence of any CCHFV antigens in the liver.

CCHFV is a tickborne virus spread through Hyalomma ticks, infected fluids and tissues of people, and certain livestock species. It affects 15,000 people and causes 500 deaths per year, most commonly across the tick's habitat in the Middle East, Asia, Africa, and Europe, according to the WHO. Currently, there is no specific treatment or vaccine for CCHFV. While ribavirin can be used at early symptom onset, supportive care is all that can be done for severe disease.
Nov 30 Nat Microbiol study
Nov 30 NIH press release

COVID-19 Scan for Dec 01, 2020

News brief

Blood donations suggest COVID-19 was in US last December

A study in Clinical Infectious Diseases yesterday found that 1% of US blood donations late last year and in early 2020 contained SARS-CoV-2 antibodies, suggesting that the virus was present in the United States earlier than previously thought.

SARS-CoV-2, the virus that causes COVID-19, was first recognized in Wuhan, China, in December 2019, and the initial US case was identified on Jan 19.

Researchers conducted serologic testing of 7,389 blood samples collected via routine American Red Cross blood donations from Dec 13, 2019 to Jan 17, 2020 in nine states—California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington, and Wisconsin.  

Blood samples were tested for anti–SARS-CoV-2 antibodies against the full viral spike protein using enzyme linked immunosorbent assay (ELISA), microneutralization tests, and receptor binding domain (RBD) blocking activity assays.

Of the 7,389 samples, 1.1%—84 samples from residents in all nine states—showed virus-neutralizing activity, binding activity, or RBD-blocking activity, suggesting the presence of anti–SARS-CoV-2–reactive antibodies. The mean age of reactive donors was 52 years, with a higher percentage of reactive donations in men (2.6% vs 1.4% from Dec 13 to Dec 16, 2019; 1.1% vs 0.7% from Dec 30, 2019 to Jan 17, 2020).

The earliest reactive samples came from donations collected from Dec 13 to Dec 16, 2019, from residents of California, Oregon, and Washington.

"The presence of these serum antibodies indicate that isolated SARS-CoV-2 infections may have occurred in the western portion of the United States earlier than previously recognized or that a small portion of the population may have pre-existing antibodies that bind SARS-CoV-2," the authors concluded.
Nov 30 Clin Infect Dis study


Study finds irreversible damage in COVID-19 lung transplant patients

A report in Science Translational Medicine yesterday detailed irreversible lung damage in three patients with severe COVID-19 infection who received lung transplants, with lung injury similar to that of end-stage pulmonary fibrosis. The study suggests that some COVID-19 patients develop fibrotic lung disease and that lung transplants may be a viable option for survival.

Researchers examined the lungs removed from three bilateral lung transplant patients with non-resolving COVID-19–associated respiratory failure and two patients who had died from COVID-19–associated pneumonia.

All patients had SARS-CoV-2–associated pneumonia and required prolonged mechanical ventilation and extracorporeal membrane oxygenation (ECMO) support.

The researchers found no evidence of SARS-CoV-2 RNA in the transplant patient lung samples using single-molecule fluorescent in situ hybridization but did find extensive injury and fibrosis—thickening or scarring of the air exchange tissues of the lung—that resembled end-stage pulmonary fibrosis.

Lung samples from transplant patients showed cavities with dead tissue that contained bacterial pathogens, suggesting acute secondary infections. All lung samples showed regions of diffuse hemorrhage, or bleeding, in the air sacs where gas exchange occurs.

The researchers compared RNA sequences of COVID-19 patients' lung tissue with samples from pulmonary fibrosis patients, finding similarities that suggest common pathways of tissue damage and fibrosis.

Transplant patients were treated with anti-rejection medications and antibiotics for secondary bacterial infections and showed improvement 3 months after transplant, with oxygen saturations over 95% on room air and improved cognitive status and muscular strength. No transplant patients showed evidence of COVID-19 reinfection.

While not supporting the routine use of lung transplant, the authors recommend bilateral transplant for patients with severe COVID-19 with extended mechanical ventilation and unlikely lung recovery. "Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is their only option for survival," the authors noted.
Nov 30 Sci Transl Med study


Two Korean studies suggest that children are unlikely to spread COVID-19

Two South Korean studies in Emerging Infectious Diseases yesterday add to growing evidence that children are less likely than adults to spread COVID-19.

The first study examined SARS-CoV-2 transmission from Feb 18 to Jun 7 among 12 children (younger than 19 years) and their uninfected guardians isolated together in seven Korean hospitals.

Infected children were encouraged to wear face masks, but compliance was low—only four children were reported to have worn personal protective equipment (PPE) most of the time. Guardians—10 mothers, one father, and one uncle—all complied with PPE recommendations, wearing a variety of protective masks and gloves, but with most reporting frequent close contact with the isolated child. Isolation was lifted after two consecutive negative respiratory samples at least 24 hours apart were obtained from the infected child.

None of the guardians were SARS-CoV-2–positive during the study, and no transmission from children to guardians was observed during the isolation period or within the 2 weeks after the end of isolation.

"Appropriate use of PPE, especially face masks, might have protected uninfected guardians in our study," the authors suggested. "The study adds to growing evidence that young children are less likely to contribute to the spread of COVID-19 among their adult guardians."

The second study evaluated SARS-CoV-2 exposure and transmission at a childcare center attended by a 4-year-old presymptomatic child. The facility had complied with local health protocols, including mask wearing for all adult staff, frequent hand hygiene, and surface disinfection, but children wore masks inconsistently.

The infected child attended the 17-classroom center from Feb 19 to 21, developed a fever on Feb 22, and was diagnosed with SARS-CoV-2 infection on Feb 27. The childcare center was closed after the identification of a positive case, and an investigation identified 190 contacts—154 children and 36 adults—at the center, including 13 4- or 5-year-old classmates and two teachers in the child's classroom.

All 190 people were negative for SARS-CoV-2 when tested 8 or 9 days after exposure and, although two close contacts showed symptoms on the last day of quarantine, subsequent test results were negative.

"This investigation adds indirect evidence of low potential infectivity in a child care setting with exposure to a presymptomatic child," the study authors wrote.
Nov 30 Emerg Infect Dis hospital isolation study and child care study

This week's top reads

Our underwriters