News Scan for Jan 13, 2022

News brief

CRISPR-based E coli drug gets go-ahead for first human trial

Danish microbiome technology company SNIPR Biome ApS announced this week that the US Food and Drug Administration has approved the company's application to initiate the first human clinical trial of its CRISPR-based drug for preventing Escherichia coli infections in cancer patients.

The clinical trial for SNIPR001, which uses CRISPR/Cas DNA editing technology to selectively target and eradicate E coli bacteria in the gut and prevent translocation of the bacteria to the bloodstream while leaving other commensal bacteria unaffected, will investigate safety and tolerability of the drug in healthy volunteers. Investigators will also evaluate the effect of SNIPR001 on gut E coli.

Patients with cancer of the blood, bone marrow, and lymph nodes are at increased risk of life-threatening bloodstream infections because of immune-suppressing chemotherapy treatments and pathogen translocation from the gut, and E coli can pose a heightened risk for such infections.

Company officials say they believe the approach could transform the way E coli infections are prevented and treated, in cancer wards and beyond.

"Based on our pre-clinical data with SNIPR001, we believe that our technology holds a huge potential in designing tomorrow's CRISPR-based medicines against life-threatening infections and to modulate microbiome-associated diseases," Milan Zdravkovic, MD, PhD, chief medical officer at SNIPR Biome, said in a company press release.

SNIPR Biome received $3.9 million in funding from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) to develop SNIPR001 in May 2021.
Jan 11 SNIPR Biome press release

H5N6 avian flu sickens 5 more in China, 2 fatally

China reported five more human H5N6 avian flu cases in three provinces, all but one in people who had contact with poultry, Hong Kong's Centre for Health Protection (CHP) said today in a statement.

All are adults with illness onsets in December 2021, ranging in age from 28 to 75 years old. Two men from different cities in Sichuan province died from their infections. The cases also include two men from the same city in Guangxi province who are hospitalized in serious or critical condition. The fifth person is a woman from Zhejiang province who is listed in critical condition.

All had contact with domestic or dead poultry, except for one of the men from Guangxi province. His exposure is pending confirmation.

Since 2014, China has reported 63 human cases, but last year the country reported a sharp rise. The latest cases push the number of cases for 2021 to 36. Earlier this week, officials reported the first case of 2022.

H5N6 infections are often severe or fatal. The virus has been detected in birds in four Asian countries, but China and Laos are the only ones that have reported human cases.
Jan 13 CHP statement
Jan 10 CIDRAP News scan

COVID-19 Scan for Jan 13, 2022

News brief

Omicron likely less susceptible to antibodies from vaccinated people

Austrian scientists writing in a letter in the New England Journal of Medicine yesterday demonstrate poor neutralization of the Omicron variant when using serum from vaccinated or recovered COVID-19 patients, potentially signaling a need for variant-specific vaccines.

The highly transmissible Omicron (B.1.1.529) variant has caused COVID-19 cases and hospitalizations to skyrocket across the globe, even though it might cause less severe disease than previous variants.

The researchers used blood from a variety of patients: 10 had been infected with the Alpha variant, 8 with Beta, and 7 with Delta. Ten had received two doses of the Moderna vaccine, 10 the AstraZeneca-Oxford vaccine, and 20 the Pfizer-BioNTech vaccine; 20 participants had received both AstraZeneca and Pfizer vaccines. In addition, 5 donors had been infected and subsequently received one or two doses of Pfizer, and 5 had been vaccinated with two doses of one of the three vaccines and had breakthrough infections.

The team didn't analyze serum samples from people who had received a booster vaccine dose.

Serum samples from vaccinated persons neutralized the Omicron variant to a much lesser extent than Alpha, Beta, or Delta. The investigators found some cross-neutralization of Omicron in samples obtained from people who had received either the Pfizer vaccine or the AstraZeneca-Pfizer combo but not in samples from persons who had received AstraZeneca only. They didn't detect neutralizing antibodies against Omicron in blood samples obtained 4 to 6 months after receipt of the second Moderna dose.

Nine of the 10 serum sample from convalescent-vaccinated or vaccinated-convalescent participants, however, were able to neutralize Omicron, although not as well as Delta.

The authors conclude, "Although receipt of a third dose (booster) of the [Pfizer] vaccine may increase the level of cross-neutralizing antibodies to the omicron variant, on the basis of the data from the present study, the rapid development of new, variant-adapted vaccines is warranted."
Jan 12 N Engl J Med letter

Less mobility in COVID-19 patients over 50 noted, even with milder disease

New data from a longitudinal study on aging Canadians shows that COVID-19 in those 50 and older led to decreased mobility, even when cases were mild to moderate and patients avoided hospitalization. The study was published yesterday in JAMA Network Open.

The ongoing study includes 51,338 community-living middle-aged and older adults, of whom 21,491 were 65 or older. The study relied on self-reporting of COVID-19 infections, and 2,748 individuals with confirmed, probable, or suspected COVID-19, were included and 94.2% of the 121 who had confirmed COVID-19 were not hospitalized.

Those with confirmed, probable, or suspected COVID-19 had almost twice the odds of worsening mobility and physical function compared with healthy peers.

After adjusting for covariates, adults with probable or confirmed COVID-19 had an 89% higher risk of problems doing household activity (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.11 to 3.22), a 91% higher risk of decreased physical activity (OR, 1.91; 95% CI, 1.32-2.76), and a 133% higher risk of experiencing problems when standing from a seated position (OR, 2.33; 95% CI, 1.06-5.11). The researchers found similar results for those with suspected COVID-19 (eg, OR for decreased household activity, 2.09; 95% CI, 1.82-2.41).

The study authors said this is the first study that addresses limited mobility in patients with non-severe COVID-19.

"Anecdotal reports, patient accounts on social media, and some preliminary research with convenience samples, have suggested that many patients who experience even mild COVID-19 have persistent and troublesome symptoms, including impaired physical function after their initial illness," the authors wrote. "Our results suggest a need for approaches to effectively restore functional mobility to predisease levels after COVID-19."
Jan 12 JAMA Netw Open study

Delta COVID-19 infection linked to fetal death, distress in pregnant women

A pair of case reports published today in The Journal of Infectious Diseases detail fetal deaths and fetal distress in mothers who were unvaccinated and had mild COVID-19 infections involving the Delta (B1617.2) variant. In both reports, investigators describe inflammation that caused problems with placental circulation.

In the first report, researchers from Missouri describe a 25-year-old woman in her third trimester who sought emergency department care for mild COVID-19 symptoms. At the time, no fetal problems were noted, but 3 days later, the woman was seen again for vaginal bleeding and decreased fetal movement.

She went into active labor and delivered a boy, who was deceased. The mother experienced disseminated intravascular coagulation during postpartum recovery. Pathology examination of the placenta suggested Delta-induced cytokine storm caused severe placental inflammation and damage, which likely triggered placental abruption (separation from the wall of the uterus) and fetal death.

In the second report, researchers based at Massachusetts General Hospital described three similar cases, two involving fetal death and the other linked to severe fetal distress. The mothers were in their 30s and had been sick with Delta infections during the third trimester. The woman whose baby was born with severe fetal distress gave birth by emergency cesarean section due to problems seen on fetal heart rate monitoring.

Examination of all three placentas revealed signs of SARS-CoV-2 placentitis (placental inflammation).

The impact of COVID-19 variants on pregnant women and their babies requires greater scrutiny, given evidence of stillbirths and higher mortality in pregnant women infected with SARS-CoV-2, the team wrote. "Vaccination against COVID-19 will continue to play a critical role in protecting pregnant people from risks associated with Delta-variant COVID-19."
Jan 13 J Infect Dis report on Missouri case
Jan 13 J Infect Dis report on Massachusetts cases