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.

Bivalent and Monovalent SARS-CoV-2 Variant Vaccine Boosters Improve coverage of the known Antigenic Landscape: Results of the COVID-19 Variant Immunologic Landscape (COVAIL) Trial.

Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.

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.

Facilitators and Barriers to the Implementation of Interventions in Washington, DC, to Improve Sexually Transmitted Infection Screening, Testing, and Treatment Among People with or at Risk of HIV.

Bacterial sexually transmitted infection (STI) incidences of gonorrhea, chlamydia, and syphilis are increasing in Washington, DC. Moreover, the availability of HIV pre-exposure prophylaxis for people at risk of HIV and condomless sex has increased, and bacterial STI rates have risen. This indicates the necessity of evidence-based strategies to ensure access to STI care and improve health outcomes for people with HIV in Washington, DC. Three clinics in Washington, DC, implemented three evidence-based interventions, including the use of a standardized audio computer-assisted self-interview to obtain an interval sexual history at each clinic visit, patient self-collection of chlamydia/gonorrhea nucleic acid amplification test specimens, and sexual minority welcoming clinical space indicators to normalize STI screening and testing. Three sites in Washington, DC, used a multi-level socioecological model to identify successes, challenges, and lessons learned from program implementation at the following three levels: (1) individual, (2) interpersonal, and (3) public policy. We conclude with a series of instructional strategies that may be useful for the implementation of similar interventions that may assist district-wide responses to decrease health disparities and increase STI prevention.

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.

Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries.

The chr12q24.13 locus encoding OAS1-OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.

Septic and Crystal-Induced Arthritis (Pseudogout) Post-COVID-19 Vaccination.

Severe acute respiratory syndrome coronavirus 2 infection has been a global public health crisis for the past two years. Vaccination has been a mainstay preventive approach among other strategies such as hand washing, social distancing, and wearing facemasks. Here, we present a case of concomitant calcium pyrophosphate deposition disease flare and septic arthritis of the right knee following coronavirus disease 2019 (COVID-19) booster vaccination in a 69-year-old African American male who presented with a painful swollen right knee with associated fever, chills, and rigors three days post-vaccination. Right knee synovial fluid aspirate appeared turbid with elevated white cell count, positive for both intra and extracellular calcium pyrophosphate crystals, and positive for beta-hemolytic Streptococcus group C. The swollen joint improved with right knee arthroscopic irrigation and intravenous antibiotics on admission. The patient subsequently completed a total of six weeks of antibiotics with clinical improvement and normalization of inflammatory markers. No reported incidence of gout or pseudogout post-COVID-19 vaccination has been reported despite reported cases of gout flares with other vaccines. Improper aseptic vaccination technique has been implicated as a possible cause of septic arthritis post-vaccination. Healthcare providers must discuss such adverse events with their patients prior to vaccine administration.

An Interesting Case of Klebsiella Pneumoniae Pylephlebitis.

Pylephlebitis is defined as suppurative thrombophlebitis of the portal venous system. It is a rare condition that can be fatal if left untreated. It is usually caused by polymicrobial bacteria, most commonly Escherichia coli and Streptococcus genus. Klebsiella pneumoniae have been identified but the literature does not suggest a percentage of cases caused by this organism. The presentation includes abdominal pain, signs of sepsis and even septic shock. We present a case of a middle-aged female with K. pneumoniae bacteremia and pylephlebitis, with portal vein thrombosis visualized on an abdominal ultrasound. Although the patient was treated with broad-spectrum antibiotics and anticoagulation, she succumbed to multiorgan failure and septic shock on day two of intensive care.

Absence of Antibody Reponses and Severe COVID-19 in Patients on Hemodialysis Following mRNA Vaccination.

Inpatient dialysis patients cannot isolate, resulting in a higher rate of coronavirus disease 2019 (COVID-19) infections, with increased severity and higher mortality rate [1]. We present 2 African American dialysis patients who developed severe COVID-19 infections after vaccination. Both patients had not mounted antibody response to the COVID-19 vaccine or to hepatitis B vaccination.

Underlying characteristics of patients harboring highly resistant Acinetobacter baumannii.

BACKGROUND: Highly resistant (HR) Acinetobacter baumannii (AB) are frequently hospital-acquired and may be important causes of severe nosocomial infections. OBJECTIVE: Determine risk factors associated with such colonization/infection. METHOD: Retrospective review in 2000 of all AB isolates from sterile (blood, cerebrospinal fluid [CSF]) and nonsterile (respiratory, urine, and miscellaneous) sites. HR was defined as resistance to amikacin and/or imipenem and/or ampicillin-sulbactam. Isolates were analyzed as representing infection or colonization. A database including prior hospitalization, prior antibiotic use, nursing home residency, and procedures undergone was compiled. RESULTS: One hundred twenty-two cases of AB were identified. Eighty-four met the definition of HR; 6 (4.9%) were completely resistant to all antibiotics. Four (4.7%) isolates were from sterile body sites (3 blood, 1 CSF); 43 (51.2%) were from respiratory sites; 20 (23.8%) were from urinary sites; and 17 (20.2%) were from "other" sites. Only 4 (20%) of the urinary, 6 (35.2%) of the miscellaneous, and 23 (53.4%) of the respiratory isolates were deemed true pathogens; all blood/CSF isolates were considered pathogens. Associated risk factors included prior antibiotic usage (71%); prior hospitalization (24%); prior nursing home residency (34%); ventilator use (77%); tracheostomy placement (56%); and Foley catheterization (85%). Twenty-seven (63%) of 43 respiratory, 8 (40%) of 20 urinary, and 6 (35%) of 17 "other" body isolates were treated. Outcome was not statistically significant in treated versus untreated patients. All patients with CSF/blood isolates underwent successful microbiologic eradication with 50% survival. The overall mortality rate was 10%. CONCLUSION: Antibiotics, Foley catheters, and tracheostomy/ventilator usage were strongly associated with AB isolation. Prior hospitalization and nursing home residency were less common risk factors. Outcome was not different in treated versus untreated patients, indicating colonization is a marker of severe illness but is not necessarily causal.

Completely resistant Acinetobacter baumannii strains.

Nosocomially acquired completely resistant Acinetobacter baumannii strains are a major clinical concern. We identified completely resistant A. baumannii in 6 (4.9%) of 122 A. baumannii isolates in a retrospective chart review at two teaching hospitals. All of these patients had received broad-spectrum antibiotics and had severe underlying comorbid illnesses, long hospitalizations, or recent surgical procedures; 3 had been in the intensive care unit. Five (83%) of the 6 patients were older than 70 years. Only one death occurred. Strict infection control measures may limit further spread.