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

BackgroundProtection 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. MethodsThis 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 (50{micro}g 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 (ID50) 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. ResultsFrom 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). ConclusionsHigher 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. Clinicaltrials.govNCT05289037

High Burden of COVID-19 among Unvaccinated Law Enforcement Officers and Firefighters

Law Enforcement Officers (LEOs), firefighters, and other first responders are at increased risk of SARS-CoV-2 infection compared to healthcare personnel but have relatively low COVID-19 vaccine uptake. Resistance to COVID-19 vaccine mandates among first responders has the potential to disrupt essential public services and threaten public health and safety. Using data from the HEROES-RECOVER prospective cohorts, we report on the increased illness burden of COVID-19 among unvaccinated first responders. From January to September 2021, first responders contributed to weekly active surveillance for COVID-19-like illness (CLI). Self-collected respiratory specimens collected weekly, irrespective of symptoms, and at the onset CLI were tested by Reverse Transcription Polymerase Chain Reaction (RT-PCR) assay for SARS-CoV-2. Among 1415 first responders, 17% were LEOs, 68% firefighters, and 15% had other first responder occupations. Unvaccinated (41%) compared to fully vaccinated (59%) first responders were less likely to believe COVID-19 vaccines are very or extremely effective (17% versus 54%) or very or extremely safe (15% versus 54%). From January through September 2021, among unvaccinated LEOs, the incidence of COVID-19 was 11.9 per 1,000 person-weeks (95%CI=7.0-20.1) compared to only 0.6 (95%CI=0.2-2.5) among vaccinated LEOs. Incidence of COVID-19 was also higher among unvaccinated firefighters (9.0 per 1,000 person-weeks; 95%CI=6.4-12.7) compared to those vaccinated (1.8 per 1,000; 95%CI=1.1-2.8). Once they had laboratory-confirmed COVID-19, unvaccinated first responders were sick for a mean{+/-}SD of 14.7{+/-}21.7 days and missed a mean of 38.0{+/-}46.0 hours of work. These findings suggest that state and local governments with large numbers of unvaccinated first responders may face major disruptions in their workforce due to COVID-19 illness.

Phylogenetic analyses reveal extensive cryptic speciation and host specialization in an economically important mite taxon.

The wheat curl mite (WCM) is a major pest in cereal crops around the world and the vector of at least four known pathogens capable of reducing yields in crops such as wheat, corn, barley, oats, millet and rye. Current taxonomy recognizes WCM as a single species, Aceriatosichella; however, recent genetic, physiological and ecological studies have shown that WCM is likely to be a species complex. In this study we assessed genetic variation and phylogenetic relationships among WCM from four continents and a wide range of host plants using DNA sequence data from one mitochondrial gene, one nuclear gene and a single nuclear intergenic spacer region. Phylogenetic analyses revealed 11 unique mite lineages associated with specific plant hosts including wheat and barley. Host associations were consistent across continents, often with a single haplotype dominating a host plant regardless of geographic origin. The genetic and ecological differences identified in this study support the notion that WCM is a species complex in need of major taxonomic revision. These findings have implications for control of WCM globally, particularly within the context of identifying plants that form 'green bridge' refuges, assessing disease transmission risk, and identifying resistance in cereal genotypes to WCM and associated pathogens.

Controlled cardiac reoxygenation does not improve myocardial function following global myocardial ischemia.

BACKGROUND: It has been shown that abrupt re-exposure of ischemic myocardium to oxygen can lead to increased peroxidative damage to myocytes (oxygen paradox). Controlled cardiac reoxygenation, as an adjunct to substrate-enhanced cardioplegia, has been shown to improve myocardial function and limit reperfusion injury when utilizing standardized hyperoxic cardiopulmonary bypass (CPB). The objective of our study was to evaluate the effect of controlled reoxygenation on myocardial function following global ischemia employing normoxic CPB. STUDY DESIGN: Nineteen female swine (30-40kg) were placed on vented, normoxic CPB. They were subjected to 45-50min of unprotected global ischemia (aortic cross clamping) followed by 30min of controlled cardiac reperfusion utilizing substrate-enhanced cardioplegia. Group 1 maintained normoxic pO(2) (O(2) tension of 90-110mmHg). In Group 2, reoxygenation was titrated gradually and increased from venous to arterial levels (O(2) tensions from 40 to 110mmHg over 15min). We measured coronary sinus blood samples for CK, CK-MB, nitric oxide, and conjugated dienes at baseline, 5min into the cardioplegic resuscitation, 5min after the cross clamp removal, and just prior to the termination of the study. Hearts were pathologically studied and scored for evidence of tissue peroxidation. RESULTS: Although not significantly different, Group 1 (normoxic reperfusion) animals were more likely to wean from CPB (p=0.141) and had a higher mean arterial pressure (p=0.556). In Group 1, conjugated dienes were significantly higher 5min into the resuscitative protocol (p=0.018) and at the termination of bypass (p=0.035). Five of six animals in Group 1 eventually attained normal sinus rhythm as opposed to three out of 13 in Group 2 (p=0.041). There was no significant difference in histology scoring between the two groups for tissue peroxidation. CONCLUSION: This study of controlled cardiac reoxygenation in a lethal ischemic swine model failed to demonstrate that the use of controlled reoxygenation on the myocardial function following global ischemia was better with maintained normoxic pO(2) (with O(2) tensions of 90-110mmHg) than when reoxygenation was titrated gradually and increased from venous to arterial levels (O(2) tensions from 40 to 110mmHg over 15min).

Coronary artery bypass graft surgery outcomes among African-Americans and Caucasian patients.

There have been few studies to date that investigate the effect of race on outcomes related to coronary artery bypass grafting. The objective of the present study was to investigate race as an independent predictor of outcomes among patients undergoing coronary artery bypass graft (CABG). A nested case-control study from a twelve-year hospitalization cohort (N=9671) in which data were collected prospectively was conducted. Cases were African-American patients undergoing CABG (N=644). Controls were randomly selected Caucasian patients undergoing CABG (N=1932). Controls were matched to cases 3:1 on year of surgery. Fifteen preoperative and intraoperative risk factors and 14 outcomes were examined. The 14 outcomes of interest were length of stay, readmission to ICU, total ICU stay, total hours on ventilator post-op, reoperation for bleeding/tamponade, deep sternal wound infection, neurological complications, pneumonia, other pulmonary complications, renal failure, gastrointestinal complications, atrial fibrillation requiring treatment, in-hospital mortality, and intraoperative complications. Regression analysis was used to control for risk factors. Multivariate analysis revealed African-Americans were at greater risk for renal complications (OR 1.88, 95% CI 1.27-2.77), neurological complications (OR 1.34, 95% CI 1.01-1.77), and pulmonary complications (OR 2.11, 95% CI 1.72-2.59). African Americans had a significantly longer hospitalization post-operatively (OR 0.79, 95% CI 0.66-0.96), but were less likely to experience post-operative atrial fibrillation requiring treatment than Caucasians (OR 0.64, 95% CI 0.49-0.84). Even after multiple adjustments, African-Americans undergoing CABG surgery had significantly greater morbidity compared to Caucasian patients.