Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .

Immunogenicity of a 2-Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.

We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost.

Immunogenicity of a Two Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.

In this brief report, we compare the magnitude and durability of the serologic response of one versus two doses (separated by 56 days) of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults.

Immunogenicity of the BA.1 and BA.4/BA.5 SARS-CoV-2 Bivalent Boosts: Preliminary Results from the COVAIL Randomized Clinical Trial.

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent SARS-CoV-2 mRNA vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wildtype spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.

Immunogenicity of the BA.1 and BA.4/BA.5 Severe Acute Respiratory Syndrome Coronavirus 2 Bivalent Boosts: Preliminary Results From the COVAIL Randomized Clinical Trial.

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wild-type spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.

SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses.

Background: Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines. Methods: This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID 50 ) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination. Results: From March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907). Conclusions: Higher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines. Clinicaltrialsgov: NCT05289037.

Shift work influences the outcomes of Chlamydia infection and pathogenesis.

Shift work, performed by approximately 21 million Americans, is irregular or unusual work schedule hours occurring after 6:00 pm. Shift work has been shown to disrupt circadian rhythms and is associated with several adverse health outcomes and chronic diseases such as cancer, gastrointestinal and psychiatric diseases and disorders. It is unclear if shift work influences the complications associated with certain infectious agents, such as pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility resulting from genital chlamydial infection. We used an Environmental circadian disruption (ECD) model mimicking circadian disruption occurring during shift work, where mice had a 6-h advance in the normal light/dark cycle (LD) every week for a month. Control group mice were housed under normal 12/12 LD cycle. Our hypothesis was that compared to controls, mice that had their circadian rhythms disrupted in this ECD model will have a higher Chlamydia load, more pathology and decreased fertility rate following Chlamydia infection. Results showed that, compared to controls, mice that had their circadian rhythms disrupted (ECD) had higher Chlamydia loads, more tissue alterations or lesions, and lower fertility rate associated with chlamydial infection. Also, infected ECD mice elicited higher proinflammatory cytokines compared to mice under normal 12/12 LD cycle. These results imply that there might be an association between shift work and the increased likelihood of developing more severe disease from Chlamydia infection.

Primary Care Comprehensiveness and Care Coordination in Robust Specialist Networks Results in Lower Emergency Department Utilization: A Network Analysis of Medicaid Physician Networks.

Background: Care coordination is an essential and difficult to measure function of primary care. Objective: Our objective was to assess the impact of network characteristics in primary/specialty physician networks on emergency department (ED) visits for patients with chronic ambulatory care sensitive conditions (ACSCs). Subjects and Measures: This cross-sectional social network analysis of primary care and specialty physicians caring for adult Medicaid beneficiaries with ACSCs was conducted using 2009 Texas Medicaid Analytic eXtract (MAX) files. Network characteristic measures were the main exposure variables. A negative binomial regression model analyzed the impact of network characteristics on the ED visits per patient in the panel. Results: There were 42 493 ACSC patients assigned to 5687 primary care physicians (PCPs) connected to 11 660 specialist physicians. PCPs whose continuity patients did not visit a specialist had 86% fewer ED visits per patient in their panel, compared with PCPs whose patients saw specialists. Among PCPs connected to specialists in the network, those with a higher number of specialist collaborators and those with a high degree of centrality had lower patient panel ED rates. Conclusions: PCPs providing comprehensive care (ie, without specialist consultation) for their patients with chronic ACSCs had lower ED utilization rates than those coordinating care with specialists. PCPs with robust specialty networks and a high degree of centrality in the network also had lower ED utilization. The right fit between comprehensiveness of primary care, care coordination, and adequate capacity of specialty availability in physician networks is needed to drive outcomes.

A Spatial Analysis of Health Disparities Associated with Antibiotic Resistant Infections in Children Living in Atlanta (2002-2010).

BACKGROUND: Antibiotic resistant bacteria like community-onset methicillin resistant Staphylococcus aureus (CO-MRSA) have continued to cause infections in children at alarming rates and are associated with health disparities. Geospatial analyses of individual and area level data can enhance disease surveillance and identify socio-demographic and geographic indicators to explain CO-MRSA disease transmission patterns and risks. METHODS: A case control epidemiology approach was undertaken to compare children with CO-MRSA to a noninfectious condition (unintentional traumatic brain injury (uTBI)). In order to better understand the impact of place based risks in developing these types of infections, data from electronic health records (EHR) were obtained from CO-MRSA cases and compared to EHR data from controls (uTBI). US Census data was used to determine area level data. Multi-level statistical models were performed using risk factors determined a priori and geospatial analyses were conducted and mapped. RESULTS: From 2002-2010, 4,613 with CO-MRSA and 34,758 with uTBI were seen from two pediatric hospitals in Atlanta, Georgia. Hispanic children had reduced odds of infection; females and public health insurance were more likely to have CO-MRSA. Spatial analyses indicate significant 'hot spots' for CO-MRSA and the overall spatial cluster locations, differed between CO-MRSA cases and uTBI controls. CONCLUSIONS: Differences exist in race, age, and type of health insurance between CO-MRSA cases compared to noninfectious control group. Geographic clustering of cases is distinct from controls, suggesting placed based factors impact risk for CO-MRSA infection.

Rotavirus vaccination rate disparities seen among infants with acute gastroenteritis in Georgia.

OBJECTIVE: Rotavirus (RV) is one of the most common diarrheal diseases affecting children less than 5 years of age. RV vaccines have greatly reduced this burden in the United States. The purpose of this study was to determine possible disparities and socio-economic differences in RV vaccination rates. DESIGN: Children with acute gastroenteritis were enrolled. Stool was tested for presence of rotavirus using an enzyme immunoassay kit. Vaccination records were abstracted from the state immunization registry and healthcare providers to examine complete and incomplete vaccination status. Cases were identified as children receiving a complete RV dose series and controls were identified as children with incomplete RV doses. A logistic regression model was used to determine disparities seen amongst children with incomplete vaccination status. RESULTS: Racial differences between Black and white infants for RV vaccination rates were not significant when controlling for covariates (OR 1.15, 95% CI 0.74-1.78); however ethnicity (p-value .0230), age at onset of illness (p-value .0004), birth year (p-value < .0001), and DTaP vaccination status (p-value < .0001) were all significant in determining vaccination status for children. CONCLUSIONS: Racial disparities and socio-economic differences are not determinants in rotavirus vaccination rates; however, age and ethnicity have an effect on RV vaccine status.