A study published yesterday in Clinical Infectious Diseases reveals that use of the antiviral drug remdesivir was tied to lower all-cause death rates among hospitalized COVID-19 patients with weakened immune systems throughout the SARS-CoV-2 pre-Delta, Delta, and Omicron variant periods.

A team led by researchers at remdesivir developer Gilead Sciences analyzed data from the US PINC AI Healthcare Database on hospitalized adult COVID-19 patients with impaired immune systems from December 2020 to April 2022. A total of 14,169 remdesivir patients who started intravenous remdesivir within 2 days of hospitalization were matched with 5,341 non-remdesivir patients. Another 5,015 remdesivir patients were not matched.

Remdesivir an important option

In the matched group, 59% of patients were 65 years or older, 40% did not require supplemental oxygen, 39% required low-flow oxygen, 19% required high-flow oxygen, and 2% required invasive mechanical ventilation/extracorporeal membrane oxygenation at baseline. The median length of remdesivir therapy was 5 days, and 68.2% and 1.8% of patients completed the full 5-day and 10-day course, respectively.

Overall, 11.1% and 17.7% of remdesivir patients died within 14 and 28 days, respectively, compared with 15.4% and 22.4% of those who didn't receive the drug. Remdesivir was linked to lower death rates at 14 days (hazard ratio [HR], 0.70) and 28 days (HR, 0.75). The survival benefit remained significant throughout periods dominated by the pre-Delta, Delta, and Omicron variants.

Remdesivir is an important option for this group of patients, who lack the COVID-19 treatment options available to non-immunocompromised patients, the study authors said. "There is a high risk of drug-drug interactions between the oral antiviral ritonavir-boosted nirmatrelvir, used for early treatment of COVID-19, and cornerstone immunosuppressant medications for solid organ transplant recipients," they wrote.

"There are also concerns and hesitation regarding intensifying background immunosuppression with drugs, such as dexamethasone, since this may further prolong SARSCoV-2 replication, increase the risk of secondary infections with other pathogens, and worse[n] outcomes, including selection and transmission of new SARS-CoV-2 variants," they added.

Patients who received maintenance dialysis in 2021 and 2022 had higher rates of COVID-19 infection and death than the rest of the US population during the SARS-CoV-2 Delta and early Omicron variant waves, although the difference was lessened by vaccination, according to a study led by researchers from the Centers for Disease Control and Prevention (CDC).

For the study, published today in Morbidity and Mortality Weekly Report, the investigators analyzed weekly COVID-19 case and death data on dialysis patients from the CDC's National Healthcare Safety Network (NHSN) from June 30, 2021, to September 27, 2022.

During the COVID-19 public health emergency, the Centers for Medicare & Medicaid Services implemented emergency requirements through the End-stage Renal Disease Network, mandating the reporting of infections, deaths, and vaccination status among dialysis facility patients and staff.

"Persons receiving maintenance dialysis are at increased risk for SARS-CoV-2 infection and its severe outcomes, including death," the study authors wrote.

Vaccination is key

During the study period, 7,848 dialysis facilities reported weekly COVID-19 cases and related deaths among 518,798 patients to NHSN. The infection rate among maintenance dialysis recipients was 30.5 per 10,000 patient-weeks (39.6 among unvaccinated patients and 27.2 among patients who had completed a primary COVID-19 vaccination series). The death rate was 1.7 per 10,000 patient-weeks.

COVID-19 and death rates varied by age-group, and the differences were most apparent in the first Omicron wave. The infection rate in the non-dialysis population was 20.7 per 10,000 population-weeks during Delta, 43.6 per 10,000 population-weeks during the first Omicron wave, and 17.1 per 10,000 population-weeks during the second Omicron wave.

In the non-dialysis population, COVID-19 death rates were 0.2 per 10,000 population-weeks amid Delta, 0.3 per 10,000 population-weeks during the first Omicron wave, and 0.1 per 10,000 population-weeks during the second Omicron wave. Case and death rates among dialysis patients followed similar patterns as those in the overall population over time.

"Implementing recommended infection control measures in dialysis facilities and ensuring patients and staff members are up to date with recommended COVID-19 vaccination is critical to limiting COVID-19–associated morbidity and mortality," the researchers wrote.

Analysis of a nationally representative sample of outpatient visits for respiratory conditions found that the odds of an antibiotic prescription were 30% higher when an advanced practice clinician (APC) was present, US researchers reported yesterday in Infection Control & Hospital Epidemiology.

Using data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 2010 to 2018, researchers with the Centers for Disease Control and Prevention, the University of Utah, and the Boston Children's Hospital compared antibiotic prescribing for acute respiratory tract infections (ARTIs) during visits when physicians provided care and when APCs provided care. APCs include nurse practitioners and physician assistants, and previous studies have indicated APCs prescribe antibiotics more frequently than physicians for patients with similar diagnoses.

Based on an unweighted sample of 43,935 visits, there were an estimated 95.3 million visits per year for ARTIs in ambulatory care settings. Overall, 11% of these visits included an APC, and 45% were for diagnoses in which antibiotics are rarely indicated (tier 3 diagnoses). The proportion of visits in which antibiotics were prescribed was higher for APCs (58%) than for physicians (52%), and the difference was most pronounced in the subgroups of visits among children (56% vs 49%), in offices (60% vs 52%), and for diagnoses for which antibiotics are sometimes indicated (tier 2 diagnoses, 72% vs 66%).

In a multivariate logistic regression analysis that controlled for patients and clinician characteristics, the adjusted odds ratio (aOR) of an antibiotic prescription from an APC compared with a physician was 1.3 (95% confidence interval [CI], 1.1 to 1.7). Higher odds of prescribing during APC visits extended to tier 2 diagnoses (aOR, 1.2; 95% CI, 1.0 to 1.6) and tier 3 diagnoses (aOR, 1.4; 95% CI, 1.0 20 2.0).

More emphasis on stewardship needed for APCs

The study authors say the reasons for this difference are likely multifactorial, though difference in educational emphasis on antibiotic stewardship may play a role.

"Due to increasing contributions of APCs to outpatient care and antibiotic prescribing, antibiotic stewardship interventions should better incorporate APCs alongside all clinician specialties," they wrote.

Though COVID-19 cases and deaths don't accurately reflect global trends due to decreased testing and reporting, the indicators declined over the past 28 days except for in the Western Pacific region, where South Korea is reporting a steady rise in cases, the World Health Organization (WHO) said today in its latest weekly COVID-19 update.

A number of countries are leaning more on hospitalization and intensive care unit (ICU) admission trends to gauge COVID activity, but the WHO notes that very few countries are reporting those numbers. Of 17 countries that consistently report hospitalization data, only two reported rises of 20% or more over the last month: Bangladesh and Kyrgyzstan. The United States and Greece reported smaller rises. Of 13 countries that consistently report ICU admissions, three showed an increase of 20% or more over the last 4 weeks: Latvia, Ireland, and Greece.

In its discussion of variant trends, the WHO said EG.5 has been reported from 48 countries and is currently the only variant showing increasing proportions. Yesterday, the WHO published a risk assessment of EG.5 and elevated it to a variant of interest alongside XBB.1.5 and XBB.1.16.

Though EG.5 is increasing in proportions as hospitalizations rise, albeit at lower levels than earlier waves, in countries such as South Korea and Japan, no associations have been made between the two trends. "However, due to its growth advantage and immune escape characteristics, EG.5 may cause a rise in case incidence and become dominant in some countries or even globally," it said.