May 11, 2023

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Clinical Reports

Impact of SARS-CoV-2 Variants on Inpatient Clinical Outcome
- Inpatients with COVID-19 at 5 hospitals in the eastern United States were included if they had hypoxia, tachypnea, tachycardia, or fever, and SARS-CoV-2 variant data, determined from whole-genome sequencing or local surveillance inference. Analyses were stratified by history of SARS-CoV-2 vaccination or infection. The average effect of SARS-CoV-2 variant on 28-day risk of severe disease, defined by advanced respiratory support needs, or death was evaluated using models weighted on propensity scores derived from baseline clinical features. Severe disease or death within 28 days occurred for 977 (29%) of 3369 unvaccinated patients and 269 (22%) of 1230 patients with history of vaccination or prior SARS-CoV-2 infection. Among unvaccinated patients, the relative risk of severe disease or death for Delta variant compared with ancestral lineages was 1.30 (95% confidence interval [CI]: 1.11–1.49). Compared with Delta, the risk for Omicron patients was .72 (95% CI: .59–.88) and compared with ancestral lineages was .94 (.78–1.1). Among Omicron and Delta infections, patients with history of vaccination or prior SARS-CoV-2 infection had half the risk of severe disease or death (adjusted hazard ratio: .40; 95% CI: .30–.54), but no significant outcome difference by variant. Although risk of severe disease or death for unvaccinated inpatients with Omicron was lower than with Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated inpatients, with no difference between Delta and Omicron infections.

Antiviral Therapeutics and Vaccines

Immunogenicity and tolerability of a bivalent virus-like particle norovirus vaccine candidate in children from 6 months up to 4 years of age: A phase 2 randomized, double-blind trial
- Researchers conducted a dose-finding phase 2 study of the HilleVax bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in two cohorts of children, 6-≤12 months and 1-≤4 years of age (N = 120 per cohort), in Panama and Colombia (ClinicalTrials.gov, identifier NCT02153112). On Day 1, children randomized to one of the four equal groups received intramuscular injections of four different HIL-214 formulations containing 15/15, 15/50, 50/50, or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3. On Day 29, half the children in each group received a second vaccination (N = 60), while the other half received saline placebo injections to maintain the blind. VLP-specific ELISA Pan-Ig and histo-blood group binding antigen-blocking antibodies (HBGA) were measured on Days 1, 29, 57 and 210. On Day 29, after one dose, there were large Pan-Ig and HBGA responses in both age cohorts with some indication of dose-dependence, and higher geometric mean titers (GMT) in the older children. A further increase in titers was observed 28 days after a second dose in the 6-≤12-month-old groups, but less so in the 1-≤4-year-old groups; GMTs at Day 57 were broadly similar across doses and in both age groups. GMTs of Pan-Ig and HBGA persisted above baseline up to Day 210. All formulations were well tolerated with mostly mild-to-moderate transient solicited adverse events reported by parents/guardians, and no vaccine-related serious adverse events occurred. Further development of HIL-214 is warranted to protect the most susceptible young children against norovirus.
An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults
- Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem. This first-in-human dose-escalation open-label phase 1 clinical trial (NCT03814720) tested an HA stabilized stem ferritin nanoparticle vaccine (H1ssF) based on the H1 HA stem of A/New Caledonia/20/1999. Fifty-two healthy adults aged 18 to 70 years old enrolled to receive either 20 μg of H1ssF once (n = 5) or 60 μg of H1ssF twice (n = 47) with a prime-boost interval of 16 weeks. Thirty-five (74%) 60-μg dose participants received the boost, whereas 11 (23%) boost vaccinations were missed because of public health restrictions in the early stages of the COVID-19 pandemic. The primary objective of this trial was to evaluate the safety and tolerability of H1ssF, and the secondary objective was to evaluate antibody responses after vaccination. H1ssF was safe and well tolerated, with mild solicited local and systemic reactogenicity. The most common symptoms included pain or tenderness at the injection site (n = 10, 19%), headache (n = 10, 19%), and malaise (n = 6, 12%). We found that H1ssF elicited cross-reactive neutralizing antibodies against the conserved HA stem of group 1 influenza viruses, despite previous H1 subtype head-specific immunity. These responses were durable, with neutralizing antibodies observed more than 1 year after vaccination. These results support this platform as a step forward in the development of a universal influenza vaccine.
Targeted Vaccine Messaging to Promote COVID-19 Vaccines for Children and Youth
- Researchers collected data through the Voices of Child Health in Chicago Parent Panel Survey from October to November 2021. Parents were randomly assigned to read 1 of 4 vaccine message types and then report their intentions to vaccinate each COVID-19–unvaccinated child (0–17 years) in their household (n= 1453). The sample included 898 parents. Compared with a control group (37.5%), the proportion of parents who were very likely to vaccinate their children was higher when messages highlighted that other trusted parents have vaccinated their children (53.3%) or that the vaccine is safe and thoroughly tested (48.9%) but not when messages highlighted that the vaccine is well-tolerated (41.5%). After adjusting for parent and child characteristics, the odds of being very likely to vaccinate remained higher in the trusted parents group but not in the safe/thoroughly tested group. Unlike the control and well-tolerated groups, there were no racial/ethnic disparities in the unadjusted proportion of parents who were very likely to vaccinate in the trusted parents and safe/thoroughly tested groups. Message types affected the unadjusted proportion of COVID-19-unvaccinated parents who were very likely to vaccinate their children. Messages that focus on trusted parents choosing to vaccinate their children were more effective at promoting parents’ COVID-19 vaccination intentions for their children than alternative messages. These findings have implications for public health messaging and pediatric providers’ communications with parents.
Vaccines and Related Biological Products Advisory Committee Meeting June 15, 2023 Announcement
- On June 15, 2023, the committee will meet in open session to discuss and make recommendations on the selection of strain(s) to be included in the periodic updated COVID-19 vaccines for the 2023-2024 vaccination campaign. This discussion will include consideration of the vaccine composition for fall to winter, 2023-2024.
Gut microbiota‐derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID‐19: An open‐label pilot study
- Gut dysbiosis is associated with immune dysfunction and severity of COVID‐19. Whether targeting dysbiosis will improve outcomes of COVID‐19 is unknown. This study aimed to assess the effects of a novel gut microbiota‐derived synbiotic formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID‐19 patients. This was an open‐label, proof‐of‐concept study. Consecutive COVID‐19 patients admitted to an infectious disease referral center in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID‐19 patients and healthy population. COVID‐19 patients who were admitted under another independent infectious disease team during the same period without receiving SIM01 acted as controls. All patients received standard treatments for COVID‐19 according to the hospital protocol. Researchers assessed antibody response, plasma proinflammatory markers, nasopharyngeal SARS‐CoV‐2 viral load, and fecal microbiota profile from admission up to week 5. Twenty‐five consecutive COVID‐19 patients received SIM01 for 28 days; 30 patients who did not receive the formula acted as controls. Significantly more patients receiving SIM01 than controls developed SARS‐CoV‐2 IgG antibody (88% vs 63.3%; P = 0.037) by Day 16. One (4%) and 8 patients (26.7%) in the SIM01 and control group, respectively, failed to develop positive IgG antibody upon discharge. At week 5, plasma levels of interleukin (IL)‐6, monocyte chemoattractant protein‐1 (MCP‐1), macrophage colony‐stimulating factor (M‐CSF), tumor necrosis factor (TNF‐α), and IL‐1RA reduced significantly in the SIM01 but not in the control group. There was a significant negative correlation of nasopharyngeal SARS‐CoV‐2 viral load and SIM01 intervention. Metagenomic analysis showed that bacterial species in SIM01 formula were found in greater abundance leading to enrichment of commensal bacteria and suppression of opportunistic pathogens in COVID‐19 patients by week 4 and week 5. This proof‐of‐concept study suggested that the use of a novel gut microbiota‐derived synbiotic formula, SIM01, hastened antibody formation against SARS‐CoV‐2, reduced nasopharyngeal viral load, reduced pro‐inflammatory immune markers, and restored gut dysbiosis in hospitalized COVID‐19 patients.

Epidemiology

COVID-19 Surveillance After Expiration of the Public Health Emergency Declaration
- Authorizations to collect certain public health data expire at the end of the U.S. public health emergency declaration on May 11, 2023. Changes to the national COVID-19 monitoring strategy and COVID Data Tracker capitalize on marked improvements in multiple surveillance systems. Weekly COVID-19 hospital admission levels and the percentage of all COVID-19–associated deaths will be primary surveillance indicators. Emergency department visits and percentage of positive SARS-CoV-2 laboratory test results will help detect early changes in trends. Genomic surveillance will continue to help identify and monitor SARS-CoV-2 variants. COVID-19 is an ongoing public health problem that will be monitored with sustainable data sources to guide prevention efforts.
Provisional Mortality Data
- More than 3.2 million persons died in the United States during January–December 2022. The overall age-adjusted U.S. death rate decreased by 5.3% from 2021 to 2022. Overall death rates and COVID-19–associated death rates were highest among non-Hispanic Black or African American persons and non-Hispanic American Indian or Alaska Native persons. Provisional death estimates provide an early signal about shifts in mortality trends. Timely and actionable data can guide public health policies and interventions for populations experiencing higher mortality.

Prevalence of Post-Coronavirus Disease Condition 12 Weeks After Omicron Infection Compared With Negative Controls and Association With Vaccination Status
- Post-coronovirus disease (COVID) symptoms can persist several months after severe acute respiratory syndrome coronavirus 2 infection. Little is known, however, about the prevalence of post-COVID condition following infections from Omicron variants and how this varies according to vaccination status. This study evaluates the prevalence of symptoms and functional impairment 12 weeks after an infection by Omicron variants (BA.1 and BA.2) compared with negative controls tested during the same period. Outpatient individuals who tested positive or negative for COVID-19 infection between December 2021 and February 2022 at the Geneva University Hospitals were followed 12 weeks after their test date. Overall, 11.7% of Omicron cases had symptoms 12 weeks after the infection compared with 10.4% of individuals who tested negative during the same period (P < .001), and symptoms were much less common in vaccinated versus nonvaccinated individuals with Omicron infection (9.7% vs 18.1%; P < .001). There were no significant differences in functional impairment at 12 weeks between Omicron cases and negative controls, even after adjusting for multiple potential confounders. The differential prevalence of post-COVID symptoms and functional impairment attributed to Omicron BA.1 and BA.2 infection is low when compared with negative controls. Vaccination is associated with lower prevalence of post-COVID symptoms.