News Scan for Jul 07, 2020

News brief

Obese COVID-19 patients at risk for respiratory failure but not hospital death

A retrospective cohort study of 1,687 COVID-19 patients at two New York City hospitals published yesterday in the Annals of Internal Medicine revealed that 31% were obese, and obese patients were at higher risk of respiratory failure.

Researchers at Weill Cornell Medicine studied the electronic medical record data of adults hospitalized with the novel coronavirus from Mar 3 to May 15 for outpatient body mass index (BMI) measurements recorded within 3 months after hospitalization. They defined obesity as a BMI of 30 or higher, and 31.1% of patients fit that category, with 5.4% of all patients being morbidly obese.

Most obese patients were younger than those with healthy BMIs. The fully adjusted risk of dying was highest for underweight patients, lowest for overweight patients, and progressively rose with greater obesity, but overall obesity did not raise the risk of in-hospital death. The fully adjusted hazard ratio for respiratory failure was lowest among normal-weight patients, advancing with increasing BMIs. The risk associated with obesity did not differ significantly across age, sex, or race.

The authors concluded that "obesity was an independent risk factor for respiratory failure but not for in-hospital mortality. Our findings, at least in part, explain the extensive use of invasive mechanical ventilation reported in the United States, where the prevalence of obesity exceeds 40%."

The researchers said that obesity could increase risk of COVID-19 complications through several mechanisms:

  • Fat-storage cells cause inflammation and increase the risk of blood clots and an overreaction of the immune system.
  • Obesity impairs lung function, leading to severe respiratory distress and failure.
  • Obesity increases the risk of lung injury by altering energy production in cells in the outer layer of the lungs.

Communities should consider their prevalence of obesity when planning their COVID-19 response, the authors said.
Jul 6 Ann Intern Med research letter

Study: Only 1 of 335 plane passengers likely infected with COVID-19 on board

An epidemiologic study published yesterday in Travel Medicine and Infectious Disease suggests that only 1 of 335 passengers on a flight from Singapore to Hangzhou, China, in late January was likely infected with COVID-19 while on board.

Chinese researchers collected the travelers' demographic information and illness descriptions before, during, and after the flight. Sixteen of 335 passengers (4.8%) were infected with COVID-19, and all but one of them had a history of exposure to the novel coronavirus before departure. That passenger had been seated near four infected passengers from Wuhan for about 1 hour and did not wear his face mask appropriately during the flight.

The attack rate was significantly higher among passengers who had departed from Wuhan, China, than among those who departed from other places.

"COVID-19 transmission may have occurred during the flight," the authors wrote. "However, the majority of the cases in the flight-associated outbreak could not be attributed to transmission on the flight but were associated with exposure to the virus in Wuhan or to infected members in a single tour group."
Jul 6 Travel Med Infect Dis abstract


Zika-exposed infants have wide variety of neurologic abnormalities

A study today in JAMA Network Open shows that children exposed to Zika virus prenatally suffer a wide array of neurologic issues, even when they did not display microcephaly, the most severe birth outcome linked to Zika.

The study was conducted on 219 children with prenatal exposure to Zika seen at a pediatric hospital in Rio de Janeiro, Brazil. The children ranged in age from 6 to 42 months and were exposed during the 2015-16 Zika epidemic. Children were evaluated monthly for the first 6 months of life, then every 3 months until the age of 4.

Fifty-three of the children had congenital microcephaly (MC), or a smaller-than-normal head, and the rest had normocephaly (NC). Although children with NC had fewer neurologic issues than those with MC, 68% displayed some sort of neurologic abnormality, including 29.3% with abnormal brain imaging results and 38.7% with abnormal tone.

The authors also found that NC children with smaller head circumferences (HCs) had increased neurocognitive delays.

"Although many children with NC were not born with an obvious congenital birth defect, neurodevelopmental abnormalities were found in 36% of the children who later underwent Bayley-III assessments. These results illustrate that antenatal ZIKV exposure may be associated with a wide clinical spectrum, with children exhibiting a variety of manifestations and outcomes," the authors concluded.

In a commentary on the study in the same journal, Sarah B. Mulkey, MD, PhD, of the Prenatal Pediatrics Institute at Children's National Hospital in Washington, DC, wrote that the HC finding "provides a practical tool to help determine risk for adverse clinical outcomes in a ZIKV-exposed infant at birth that can be widely used in a variety of follow-up settings."
Jul 7 JAMA Netw Open study
Jul 7 JAMA Netw Open commentary


WHO committee extends polio public health emergency

The World Health Organization (WHO) polio emergency committee met for the 25th time on Jun 23 to discuss the latest polio developments and recommended that the international risk of poliovirus spread still remains a public health emergency of international concern (PHEIC) under the International Health Regulations. Director-General Tedros Adhanom Ghebreyesus, PhD, accepted the group's recommendations on Jul 3.

Among the group's concerns are that the increased number of wild poliovirus type 1 (WPV1) cases in Afghanistan and Pakistan in 2019 have continued into 2020. However, Nigeria was recently declared free of WPV1. The committee also raised concerns about multiple circulating vaccine-derived polio outbreaks in four WHO regions: African, Eastern Mediterranean, South East Asian, and Western Pacific.

In his remarks to the group, Tedros said the COVID-19 pandemic has significantly affected public health programs, including polio, and that the risk of international spread has probably increased. He also noted that a novel oral polio vaccine type 2, which will be made available for emergency use, is expected to help stop the cycles of using monovalent oral poliovirus type 2 (OPV2) vaccine to combat outbreaks, only to have OPV2 seed new outbreaks.

Along with the PHEIC recommendation, the group also tweaked its list of temporary measures for affected countries. WHO emergency committees typically meet every 3 months or more often as needed.
Jun 23 WHO statement

Stewardship / Resistance Scan for Jul 07, 2020

News brief

CARB-X to fund development of vaccine for resistant infections

CARB-X announced today that it is awarding $892,000 to Spanish biotechnology company Vaxdyn to develop a vaccine to prevent infections caused by multidrug-resistant bacterial pathogens.

The money will help Vaxdyn, of Seville, Spain, develop KapaVax, a multiple-antigen vaccine based on detoxified bacterial cells that could be used to prevent infections, including pneumonia, in multiple at-risk populations. KapaVax specifically targets infections caused by Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

Vaxdyn will receive an additional $6.36 million from CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) if certain project milestones are met.

"The threat of drug-resistance underscores the importance of vaccines as powerful weapons to prevent disease as well as the spread of deadly bacteria," CARB-X chief of research and development Erin Duffy, PhD, said in a press release. "The Vaxdyn project is in the early phases of development, but if successful and approved for use in patients, it could prevent drug-resistant pneumonia in patients with elevated risk, for example those with chronic lung disease or diabetes, or patients undergoing cancer treatment."

Since its launch in 2016, CARB-X has awarded more than $240 million to accelerate the development of 66 antibacterial products. This is the fourth vaccine in the CARB-X portfolio.
Jul 7 CARB-X press release


WHO, Pew Charitable Trusts call for efforts to boost antibiotic development

The World Health Organization (WHO) and the Pew Charitable Trusts today issued a call to action on antibiotic development.

Citing the dearth of new and novel antibiotic candidates, increased global drug resistance, and the financial challenges of developing new antibiotics, the groups urged policymakers, pharmaceutical companies, research funders, and other antibiotic innovation stakeholders to take action to "stabilize and revitalize" the broken antibiotic development pipeline and market. With many of the antibiotics we are currently using losing their efficacy, they said, novel antibiotics are urgently needed.

The letter follows separate reports released earlier this year by both groups that came to similar conclusions about the state of the antibiotic development pipeline. Both found that it is insufficient, with too many candidates that offer little benefit over current antibiotics and not enough innovative drugs that target the most critical drug-resistant pathogens. Both reports cited low sales volume and poor market conditions as significant hurdles that have led many major pharmaceutical companies to abandon antibiotic development and left many small companies struggling financially.

Their three specific requests include increased funding for early-stage research, more push and pull incentives to help successfully move antibiotics through clinical development, and different reimbursement models to help provide sufficient return on investment for new antibiotics. These efforts must be robust and sustained, they said.

"COVID-19 has so poignantly reminded us that we need to build more resilient health systems that include access to effective antibiotics to better tackle future outbreaks," the groups wrote. "Antibiotic resistance is a looming public health crisis also requiring improved preparedness, including a robust clinical antibacterial development pipeline."
Jul 7 WHO/Pew Charitable Trusts letter

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