COVID-19 Scan for Sep 28, 2020

News brief

More data needed for convalescent plasma COVID treatment, experts say

A review by members of the National Institutes of Health COVID-19 Treatment Guidelines Panel finds insufficient data to recommend for or against convalescent plasma for treating COVID-19.

The Food and Drug Administration (FDA) approved convalescent plasma for treatment under an emergency use authorization (EUA) in August. An EUA does not confer FDA approval but allows the use of unapproved treatments during a public health emergency, provided that the therapy shows promise, benefits outweigh risks, and no alternatives are available.

Immunotherapeutic approaches have been shown to be effective for other viral illnesses such as hepatitis B and varicella. But few randomized controlled trials (RCTs) exist demonstrating the safety and efficacy of convalescent plasma in viral illness.

The Annals of Internal Medicine review evaluated observational data used to support the EUA, including a Broad Institute cohort of 4,330 patients and a Mayo Clinic analysis of 3,082 patients. The Broad Institute data compared patients younger than 80 and found a difference in 7-day mortality for patients receiving high- and low-titer convalescent plasma of 6.3% versus 11.3% (P = 0.0008). The Mayo Clinic data evaluated patient outcomes for three different antibody levels, finding a statistically insignificant 4.7-percentage-point difference in 30-day mortality rate between high- and low-titer groups (24.7% vs 29.1%).

While the authors acknowledged the inherent tension between expediting access to promising therapies and establishing scientific evidence for safety and efficacy, they stressed the necessity of RCTs during an outbreak as the fastest way to identify effective therapies. RCTs for convalescent plasma therapy—such as those that recently demonstrated the efficacy of remdesivir and dexamethasone in treating COVID-19—are under way in the United States.

"Taking everything into account, the Panel has determined that currently the data are insufficient to recommend for or against convalescent plasma for treating COVID-19," the authors conclude. "Prospective, well-controlled, and adequately powered RCTs are needed to determine whether convalescent plasma and other passive immunotherapies are effective and safe for COVID-19 treatment. Although providers have access to this therapy, the Panel cannot recommend it as a standard of care for treating COVID-19 at this time."
Sep 25 Ann Intern Med study

Last-resort life support—ECMO—improves COVID-19 survival, study finds

A large-scale, international study in The Lancet shows that extracorporeal membrane oxygenation (ECMO) improves survival for critical COVID-19 patients. A technique that removes blood from the body for oxygenation when a patient's lungs are compromised by severe lung damage, ECMO has been used successfully to treat patients suffering from acute respiratory distress (ARDS) and other types of viral pneumonia.

The study included 1,035 severely ill, ventilated COVID-19 patients in 213 hospitals at high risk of death due to lung failure. Patients started on ECMO from Jan 16 to May 1 were followed until death, discharge from the hospital, or until Aug 5—whichever occurred first. At the end of the study period, 380 study patients had died in the hospital; 588 had either been discharged to home, a rehabilitation center, or another long-term acute care center; and 67 patients remained in the hospital.

Nearly all of the patients in the study suffered from acute hypoxaemic respiratory failure, with 79% of patients meeting the criteria for ARDS. After ECMO treatment, their actual death rate was 37.4%, as determined by a competing risk statistical analysis of 90-day in-hospital mortality (95% confidence interval, 34.4% to 40.4%).

The study authors stated, "Our findings provide provisional support for the use of ECMO in COVID-19-related acute hypoxaemic respiratory failure." Lead author Ryan Barbaro, MD, MS, of the University of Michigan, said in a university press release, "These results support recommendations to consider ECMO in COVID-19 if the ventilator is failing. We hope these findings help hospitals make decisions about this resource-intensive option."

The study also identified a number of increased mortality risk factors for ECMO-supported patients with COVID-19—age, immunocompromised state, acute kidney injuries, chronic respiratory disease, and COVID-related cardiac arrests—that could inform decision-making for families and care providers. "All of this knowledge can help centers and families understand what patients might face if they are placed on ECMO," Barbaro said.

Co-author Robert Bartlett, MD, helped pioneer the first use of ECMO in adults in the 1980s and led the development of initial guidance for the use of ECMO in COVID-19. Bartlett said in the release, "ECMO is the final step in the algorithm for managing life-threatening lung failure in advanced [intensive care units]. Now we know it is effective in COVID-19."
Sep 25 Lancet study
Sep 25 University of Michigan news release

Non-COVID-19 hospital admissions rebounding, study finds

Dramatic declines in US hospital admissions for non–COVID-19 reasons at the onset of the pandemic have reversed since the lowest point in April, but such hospitalizations remain lower than pre-pandemic baseline levels, particularly for patients from Hispanic-majority neighborhoods, according to a Health Affairs study.

The study included data from about 1 million hospital admissions at 201 US hospitals, tracking admissions for the top 20 acute medical conditions from early February through early July. From February to April, declines in non–COVID-19 hospital admissions exceeded 20% for all medical conditions, and did not show significant differences across patient demographic subgroups of age, race, and ethnicity.

"The most plausible explanation for the broad-based declines in medical admissions is that patients avoided seeking hospital care, perhaps in response to fear of contagion arising from media reports, or as a result of state stay-at-home orders," the study authors wrote.

Fewer hospitalizations for critical medical conditions could explain higher out-of-hospital deaths. The authors noted, "One study of five states affected by COVID-19's initial surge found higher mortality for heart disease, Alzheimer's Disease, and diabetes among those not diagnosed with COVID-19," leading to concerns that failure to seek hospital treatment could lead to higher overall death rates.

April was the nadir of the non-COVID-19 admission decline (43% from pre-pandemic levels) followed by a rebound during late June and early July to within 16% of baseline. But the admissions recovery was not consistent across demographic subgroups; Hispanic-majority ZIP codes remained 31.8% below baseline hospitalization levels.

Senior author Jonathan Skinner, MD, PhD, of Dartmouth College, said in a university news release, "Our study shows that patients from Hispanic neighborhoods did not have the same rebound in non-COVID-19 admissions as other groups, which points to a much broader issue of healthcare access and equity for lower-income and minority patients. As a result, these barriers may have contributed to higher in-hospital mortality rates in April for this group than for others."
Sep 24 Health Aff study
Sep 25 Dartmouth College news release

News Scan for Sep 28, 2020

News brief

WHO experts recommend strains for Southern Hemisphere 2021 flu vaccine

World Health Organization (WHO) flu vaccine advisors recently met to recommend the strains to include in vaccines for the Southern Hemisphere's 2021 season, which—when compared with the Northern Hemisphere upcoming-season version—swaps out the 2009 H1N1 strain.

For the egg-based H1N1 vaccine component, the experts recommend replacing the A/Guangdong-Maonan/SWL1536/2019-like virus with an A/Victoria/2570/2019-like virus. And for the cell-based H1N1 vaccine component, they recommend replacing the A/Hawaii/70/2019-like virus with an A/Wisconsin/588/2019-like virus.

When compared with the Southern Hemisphere's current-season vaccine, the group's recommendation swaps out both the 2009 H1N1 strains and the H3N2 strain for egg-based vaccines, switching from the A/South Australia/34/2019-like virus to an A/Hong Kong/2671/2019-like virus.

Recommendations for the other strains for both trivalent and quadrivalent formulations are the same as for the Northern Hemisphere.

The WHO noted that the COVID-19 pandemic has disrupted flu surveillance, and the Southern Hemisphere hasn't yet started its 2020 flu season. With that in mind, the amount of genetic and antigenic data were significantly lower than the advisory group typically has when making its flu vaccine virus recommendations.
Sep 25 WHO recommendations
Sep 25 WHO Q and A

FDA approves cefiderocol for hospital-acquired, ventilator-associated pneumonia

Japanese drug maker Shionogi, with US headquarters in Florham Park, New Jersey, announced today that the Food and Drug Administration (FDA) has approved the company's supplemental New Drug Application for cefiderocol.

The FDA's approval means that cefiderocol, sold under the brand name Fetroja, can be used to treat patients who have hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by gram-negative pathogens. The antibiotic was initially approved for treatment of complicated urinary tract infections.

The expanded indication is based on the results of a phase 3 APEKS-NP trial, which showed that cefiderocol was non-inferior to meropenem for treating HABP/VABP patients.

"Nosocomial pneumonia is one of the most common hospital-acquired infections and a rising number are caused by difficult-to-treat, multidrug-resistant pathogens, which can be a deadly threat for patients," lead trial investigator Richard Wunderink, MD, of Northwestern University's Feinberg School of Medicine, said in a company press release. "The results from the APEKS-NP study show that cefiderocol is a much-needed additional option for the treatment of patients with HABP and VABP due to multidrug-resistant gram-negative bacteria."

Cefiderocol is a cephalosporin antibiotic with a novel mechanism of penetrating the tough outer membrane of gram-negative bacteria with and the ability to overcome resistance mechanisms used by gram-negative pathogens to evade antibiotics.
Sep 28 Shionogi press release

Fecal transplant provides long-term C diff protection despite exposures

Mayo Clinic researchers report that a fecal microbiota transplant (FMT) was 78% effective at preventing Clostridioides difficile infection (CDI) recurrence at 1 year despite subsequent exposure to the toxoid in 460 FMT patients.

The retrospective study, published late last week in Clinical Infectious Diseases, found that 76.8% of adult patients were exposed to the healthcare system after FMT, and 78.1% of 374 patients with risk factor exposure had a durable response at 1 year.

The most common underlying diseases in the patients were inflammatory bowel disease (21.9%), chronic liver disease (12.8%), cancer (11.7%), and chronic kidney disease (3.9%). In total, 31.3% of patients received antibiotics for their infections, while 21.7% received acid suppressants. In multivariable analysis, use of antibiotics was independently tied to a less durable response (hazard ratio, 0.27).

The authors concluded, "Majority of patients had a durable response to FMT despite exposure to CDI risk factors." They called for larger studies to identify predictors of durable response in patients who have and have not taken antibiotics.

CDI, the leading cause of diarrhea in hospital patients is one of the most common infections associated with exposure to the healthcare system. FMT, which involves the transfer of stool from a healthy donor into the colon of an infected patient, is reserved for patients who have had several CDI bouts that didn't respond to antibiotic treatment.
Sep 25 Clin Infect Dis abstract

CDC closes investigation into Cyclospora outbreak that sickened 701

The US Centers for Disease Control and Prevention (CDC) announced late last week that it has ended its investigation into the 701-case, 14-state outbreak of Cyclospora tied to bagged salad mixes from the Fresh Express production facility in Streamwood, Illinois.

Outbreak cases were reported from May 11 to Jul 24. Thirty-eight people (5%) were hospitalized, but no deaths were reported. The numbers reflect 11 new cases since the CDC's previous update on Aug 14.

On Jun 27, Fresh Express issued a recall on the salads containing iceberg lettuce, red cabbage, or carrots produced at its Streamwood facility. The plant had also produced private-label bagged salads for sale at Aldi, Giant Eagle, Hy-Vee, Jewel-Osco, ShopRite, and Walmart.

According to an PDA update, the Cyclospora is believed—but not proven—to have originated in an irrigation canal that had supplied water to a farm in Port St. Lucie, Florida.

Cyclospora cayetanensis is a microscopic parasite that can cause diarrhea, loss of appetite, and other gastrointestinal symptoms.
Sep 24 CDC update
Sep 25 FDA update
Aug 17 CIDRAP News scan on previous update