A post hoc analysis of a phase 3 randomized, controlled trial estimates that two doses of the Novavax (NVX-CoV2373) COVID-19 vaccine were 100% effective against hospitalization by 95 days during a period dominated by the SARS-CoV-2 Alpha variant.

For the analysis, published late last week in Vaccine, Novavax researchers parsed data from the PREVENT-19 trial of two doses of the Novavax vaccine or a placebo given 21 days apart to 25,482 patients in the United States and Mexico. PREVENT-19 evaluated vaccine effectiveness (VE) against moderate to severe infection but not hospitalization.

The US Food and Drug Administration (FDA) issued an emergency use authorization of Novavax on July 13, 2022. "Due to the relatively short time span since the authorization of NVX-CoV2373, real-world effectiveness data that may inform its impact on hospitalization are not yet available," the researchers wrote.

No vaccine recipients were hospitalized

From January 25 to April 30, 2021, four hospitalizations occurred among 77 events in the per-protocol efficacy population (17,312 Novavax recipients with confirmed polymerase chain reaction [PCR] infections, 8,140 controls). The hospitalizations were all among placebo recipients, for a post hoc VE of 100% (95% confidence interval [CI], 28.8% to 100%). One case was moderate, and three were severe.

In a post hoc analysis of an expanded efficacy population, which included COVID-19 hospitalizations without a requirement for PCR testing, 12 hospitalizations occurred, all among placebo recipients, for a VE against hospitalization of 100% (95% CI, 83.1% to 100%). Three infections were moderate, and eight were severe, including one death.

These results suggest that the vaccine is effective in reducing the risk of hospitalization due to COVID-19, especially in populations with pre-existing comorbid conditions and higher BMIs.

The authors noted that hospitalized patients had a high prevalence of chronic conditions, such as obesity (body mass index [BMI] of 30 or more), high blood pressure, and diabetes.

"These results suggest that the vaccine is effective in reducing the risk of hospitalization due to COVID-19, especially in populations with pre-existing comorbid conditions and higher BMIs," they wrote. "Moving forward, real-world evidence studies on the effectiveness of NVX-CoV2373 in reducing hospitalization, particularly in high-risk populations, are needed to inform global public health policies and ensure the continued success of vaccination campaigns."

The Centers for Disease Control and Prevention (CDC) continues to investigate increased reports of brain abscesses in children, which includes a 2022 cluster from Nevada's Clark County that was detailed last week at the CDC Epidemic Intelligence Service (EIS) annual meeting in Atlanta.

Doctors in other locations are seeing similar cases, according to CNN.

In the Nevada cluster, health officials in October received reports of a higher-than-expected number of kids who had intracranial abscesses. The investigation by EIS officials found that, from 2015 to 2021, Clark County averaged about four such cases a year. However, 18 cases were reported in 2022, none of them fatal. Fifteen patients required surgery. The median age was 12, and 14 of the patients were boys. Streptococcus intermedius was the most common bacterial pathogen.

Nine patients had experienced cold symptoms, and none had been diagnosed as having COVID-19. Three had ear infections, and one patient had a sinus infection.

Seeking risk factors, causes

Investigators said more research is needed to identify risk factors and causes of the rare conditions.

Experts told CNN that possible explanations could be less exposure to pathogens during the earlier phases of the pandemic or a higher disease burden in the past year, now that COVID-19 cases have fallen.

A September 2022 report in Morbidity and Mortality Weekly Report examined a possible increase in pediatric streptococcal brain abscesses and epidural empyemas, finding a decline at the start of the pandemic, with an increase in the summer of 2021 and a peak in March 2022. The authors said cases were consistent with seasonal fluctuations and redistribution of cases during the pandemic, but that epidemiologic monitoring continues.

A Seattle hospital reported last week that an outbreak of Klebsiella pneumoniae has infected 31 patients, with seven deaths.

According to a press release, the outbreak at Virginia Mason Medical Center's downtown campus was first detected in October 2022, and the most recent case was confirmed on April 3. The hospital says it's unclear whether the K pneumoniae infections caused or contributed to the seven patient deaths, which have all occurred since the investigation began.

Hospitals officials say they notified all patients who tested positive for the bacterium and immediately implemented increased safety measures to reduce transmission, including conducting environmental sampling, updating facility infrastructure, and reviewing cleaning and infection prevention practices.

"While the risk of transmission is extremely low for patients, we continue to take proactive steps to avoid additional transmission," said Sydney Bersante, Virginia Mason's interim president. "We are continuing to investigate the source of this outbreak jointly with local and state public health partners."

While the risk of transmission is extremely low for patients, we continue to take proactive steps to avoid additional transmission.

The Public Health Department of Seattle & King County said on its website that whole-genome sequencing was used to identify cases associated with the outbreak strain, which carries an enzyme that makes it resistant to certain antibiotics. The rate of cases associated with the strain has decreased since the investigation began.

The Antimicrobial Resistance (AMR) Action Fund announced last week that it has added two more companies to its investment portfolio.

The recipients of the latest round of funding are Vedanta Biosciences, whose lead candidate is a microbiome-directed therapy for recurrent Clostridioides difficile infection (rCDI), and diagnostics company Pattern Bioscience, which is developing a diagnostics platform to rapidly identify bacterial pathogens and determine their antibiotic susceptibility.

Established in 2020 and backed by some of the world's largest pharmaceutical companies and other stakeholders, the AMR Action Fund plans to invest $1 billion in small- and mid-size biotech companies over the decade, with the aim of bring two to four new antibiotics to market by 2030.

The money from the AMR Action Fund is part of the $106.5 million raised by Vedanta to support pivotal-stage development of VE303, a defined bacterial consortium consisting of eight non-pathogenic, non-toxic commensal strains of Clostridia. Recently published results of a phase 2 trial found that high doses of VE303 prevented rCDI compared with placebo. The investment will help fund a phase 3 trial.

"Our Phase 2 clinical data and this new funding enable us to continue advancing the microbiome field beyond products made from fecal donations, and towards pharmaceutical-grade, defined medicines," Vedanta co-founder and CEO Bernatt Olle, PhD, said in a company press release. 

Our Phase 2 clinical data and this new funding enable us to continue advancing the microbiome field.

Pattern Biosciences says it will use the $28.7 million raised from the AMR Action Fund and others to complete development of a rapid phenotypic test platform based on single-cell analysis of microorganisms combined with machine learning. The company's first test, which was granted Breakthrough Device Designation by the US Food and Drug Administration, will be for patients hospitalized with pneumonia.

"We believe our technology will significantly impact patient outcomes and help tackle the growing challenge of antibiotic resistance," Pattern Biosciences co-founder and CEO Nick Arab said in a company press release.

Our technology will significantly impact patient outcomes and help tackle the growing challenge of antibiotic resistance.

• The World Health Organization (WHO) said today that its COVID-19 emergency committee will meet on May 4 to assess if the situation still warrants a public health emergency of international concern (PHEIC), which it declared on Jan 30, 2020. The committee typically meets every 3 months, or more often as needed. At a media briefing last week, WHO Director-General Tedros Adhanom Ghebreyesus, PhD, said the virus is still changing and is still capable of causing more waves of infections and deaths, but he said the WHO hopes that the group can declare and end of the PHEIC sometime this year.
• Nigeria is experiencing a large Lassa fever outbreak, with case levels higher than previous epidemic seasons, the WHO said in an outbreak announcement today. So far this year, nearly 5,600 cases have been reported, 877 of them confirmed, in 26 of 36 states. There are 152 deaths among the confirmed cases. Though Nigeria is skilled at managing Lassa fever outbreaks, the risk to the country is high, owing to the multiple outbreaks and humanitarian situations health officials are juggling. Lassa fever is mainly spread via contact with food our household items that are contaminated by rat droppings and urine, though human-to-human transmission can occur.
• Indonesia since 2022 has reported an increase in suspected and confirmed measles cases compared to previous years, the WHO said in an Apr 28 statement. Since January, 2,161 cases, 848 of them lab-confirmed, have been reported in 18 of the country's 38 provinces. Though the disease is endemic in Indonesia, there were significant increases in 2022 and 2023. Suboptimal immunity is a factor: Among cases this year, 75% occurred in people who had not received any doses of measles-containing vaccine.