The relationship between the number of COVID-19 vaccines and infection with Omicron ACE2 inhibition at 18-months post initial vaccination in an adult cohort of Canadian paramedics.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has rapidly evolved since late 2019, due to highly transmissible Omicron variants. While most Canadian paramedics have received COVID-19 vaccination, the optimal ongoing vaccination strategy is unclear. We investigated neutralizing antibody (NtAb) response against wild-type (WT) Wuhan Hu-1 and Omicron BA.4/5 lineages based on the number of doses and past SARS-CoV-2 infection, at 18 months post-initial vaccination (with a Wuhan Hu-1 platform mRNA vaccine [BNT162b2 or mRNA-1273]). Demographic information, previous COVID-19 vaccination, infection history, and blood samples were collected from paramedics 18 months post-initial mRNA COVID-19 vaccine dose. Outcome measures were ACE2 percent inhibition against Omicron BA.4/5 and WT antigens. We compared outcomes based on number of vaccine doses (two vs. three) and previous SARS-CoV-2 infection status, using the Mann-Whitney U test. Of 657 participants, the median age was 40 years (IQR 33-50) and 251 (42 %) were females. Overall, median percent inhibition to BA.4/5 and WT was 71.61 % (IQR 39.44-92.82) and 98.60 % (IQR 83.07-99.73), respectively. Those with a past SARS-CoV-2 infection had a higher median percent inhibition to BA.4/5 and WT, when compared to uninfected individuals overall and when stratified by two or three vaccine doses. When comparing two vs. three WT vaccine doses among SARS-CoV-2 negative participants, we did not detect a difference in BA.4/5 percent inhibition, but there was a difference in WT percent inhibition. Among those with previous SARS-CoV-2 infection(s), when comparing two vs. three WT vaccine doses, there was no observed difference between groups. These findings demonstrate that additional Whttps://www.covid19immunitytaskforce.ca/citf-databank/#accessing https://www.covid19immunitytaskforce.ca/citf-databank/#accessinguhan Hu-1 platform mRNA vaccines did not improve NtAb response to BA.4/5, but prior SARS-CoV-2 infection enhances NtAb response.

Eleven-month SARS-CoV-2 binding antibody decay, and associated factors, among mRNA vaccinees: implications for booster vaccination.

Background: We examined the 11 month longitudinal antibody decay among two-dose mRNA vaccinees, and identified factors associated with faster decay. Methods: The study included samples from the COVID-19 Occupational Risk, Seroprevalence and Immunity among Paramedics (CORSIP) longitudinal observational study of paramedics in Canada. Participants were included if they had received two mRNA vaccines without prior SARS-CoV-2 infection and provided two blood samples post-vaccination. The outcomes of interest were quantitative SARS-CoV-2 antibody concentrations. We employed spaghetti and scatter plots (with kernel-weighted local polynomial smoothing curve) to describe the trend of the antibody decay over 11 months post-vaccine and fit a mixed effect exponential decay model to examine the loss of immunogenicity and factors associated with antibody waning over time. Results: This analysis included 652 blood samples from 326 adult paramedics. Total anti-spike antibody levels peaked on the twenty-first day (antibody level 9042 U ml-1) after the second mRNA vaccine dose. Total anti-spike antibody levels declined thereafter, with a half-life of 94 [95 % CI: 70, 143] days, with levels plateauing at 295 days (antibody level 1021 U ml-1). Older age, vaccine dosing interval <35 days, and the BNT162b2 vaccine (compared to mRNA-1273 vaccine) were associated with faster antibody decay. Conclusion: Antibody levels declined after the initial mRNA series with a half-life of 94 days, plateauing at 295 days. These findings may inform the timing of booster vaccine doses and identifying individuals with faster antibody decay.

Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals.

SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman correlation coefficients between wild-type viral neutralizing antibody titers and: anti-spike (total and IgG), anti-receptor-binding-domain (RBD), and anti-N-terminal-domain (NTD) antibodies; and ACE-2 binding by RBD. We performed three secondary analyses, dichotomizing samples by the first vaccination-to-blood collection interval, second vaccination-to-blood collection interval, and by the vaccine dosing interval (all groups divided by the median), and compared correlation coefficients (Fisher's Z test). Of 120 participants, 63 (53%) were women, 91 (76%) and 29 (24%) received BNT162b2 and mRNA-1273 vaccines, respectively. Overall, live viral neutralization was correlated with anti-spike total antibody (correlation coefficient = 0.80), anti-spike IgG (0.63), anti-RBD IgG (0.62), anti-NTD IgG (0.64), and RBD ACE2 binding (0.65). Samples with long (>158 days) first vaccination-to-blood collection and long (>71 days) second vaccination-to-blood collection intervals demonstrated higher correlation coefficients, compared with short groups. When comparing cases divided by short (≤39 days) versus long vaccine dosing intervals, only correlation with RBD-ACE-2 binding inhibition was higher in the long group. Among COVID-negative mRNA vaccinees, anti-spike antibody and ACE-2 inhibition concentrations are correlated with live viral neutralizing antibody titers. Correlation was stronger among samples collected at later durations from vaccination. IMPORTANCE Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. Using samples from 120 two-dose mRNA vaccinees without previous COVID-19, we found that live viral neutralization was correlated with COVID-19 antibody and ACE2 binding levels. When grouping samples by the time interval between vaccination and sample blood collection, samples collected over 158 days after the first vaccine and over 71 days from the second vaccine demonstrated stronger correlation between live viral neutralization titers and both antibody and ACE2 levels, in comparison to those collected earlier.

Comparative 6-Month Wild-Type and Delta-Variant Antibody Levels and Surrogate Neutralization for Adults Vaccinated with BNT162b2 versus mRNA-1273.

While mRNA vaccines are highly efficacious against short-term COVID-19, long-term immunogenicity is less clear. We compared humoral immunogenicity between BNT162b2 and mRNA-1273 vaccines 6 months after the first vaccine dose, examining the wild-type strain and multiple Delta-variant lineages. Using samples from a prospective observational cohort study of adult paramedics, we included COVID-19-negative participants who received two BNT162b2 or mRNA-1273 vaccines, and provided a blood sample 170 to 190 days post first vaccine dose. We compared wild-type spike IgG concentrations using the Mann-Whitney U test. We also compared secondary outcomes of: receptor binding domain (RBD) wild-type antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to spike proteins from the wild-type strain and five Delta-variant lineages. We included 571 adults: 475 BNT162b2 (83%) and 96 mRNA-1273 (17%) vaccinees, with a mean age of 39 (SD = 10) and 43 (SD = 10) years, respectively. Spike IgG antibody concentrations were significantly higher (P < 0.0001) for those who received mRNA-1273 (GM 601 BAU/mL [GSD 2.05]) versus BNT162b2 (GM 375 BAU/mL [GSD 2.33) vaccines. Results of RBD antibody comparisons (P < 0.0001), and inhibition of ACE-2 binding to the wild-type strain and all tested Delta lineages (all P < 0.0001), were consistent. Adults who received two doses of mRNA-1273 vaccines demonstrated improved wild-type and Delta variant-specific humoral immunity outcomes at 6 months compared with those who received two doses of the BNT162b2 vaccine. IMPORTANCE The BNT162b2 and mRNA-1273 mRNA SARS-CoV-2 vaccines have demonstrated high efficacy for preventing short-term COVID-19. However, comparative long-term effectiveness is unclear, especially pertaining to the Delta variant. We tested virus-specific antibody responses 6 months after the first vaccine dose and compared individuals who received the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines. We found that individuals who received the mRNA-1273 vaccine demonstrated superior serological markers at 6 months in comparison with those who received the BNT162b2 vaccine.

A Higher Antibody Response Is Generated With a 6- to 7-Week (vs Standard) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Dosing Interval.

The optimal dosing interval for severe acute respiratory syndrome coronavirus 2 vaccines remains controversial. In this prospective study, we compared serology results of paramedics vaccinated with mRNA vaccines at the recommended short (17-28 days) vs long (42-49 days) interval. We found that a long dosing interval resulted in higher spike, receptor binding domain, and spike N terminal domain antibody concentrations.

A pragmatic parallel group implementation study of a prehospital-activated ECPR protocol for refractory out-of-hospital cardiac arrest.

OBJECTIVES: Extracorporeal membrane oxygenation within CPR (ECPR) may improve survival among patients with refractory out-of-hospital cardiac arrest (OHCA). We evaluated outcomes after incorporating ECPR into a conventional resuscitation system. METHODS: We introduced a prehospital-activated ECPR protocol for select refractory OHCAs into one of four metropolitan regions in British Columbia. We prospectively identified ECPR-eligible patients in both the ECPR region and the three other regions to serve as the control group. We compared the proportion with favorable neurological outcomes at hospital discharge (cerebral performance category ≤2) and used logistic regression to estimate the association with treatment region. RESULTS: The study was terminated prematurely due to changes in hospital protocols and COVID-19. In the ECPR region, 15/58 (25.9%) patients had favourable neurological outcomes owing to conventional resuscitation and 2/58 (3.4%) owing to ECPR, for a total of 17/58 (29.3%). In the control regions, 67/250 (26.8%) patients had a favourable outcome owing to conventional resuscitation, for a between-group difference of 2.5% (95% CI -10 to 15%). We did not detect a statistically significant association between treatment region and outcomes. CONCLUSION: In this prematurely-terminated study of ECPR for refractory OHCA, we did not detect an association between a regional ECPR protocol and neurologically favorable outcomes. However, our data suggests that outcomes owing to conventional resuscitation were similar, with the potential for additional survivors due to ECPR therapies.

North American validation of the Bokutoh criteria for withholding professional resuscitation in non-traumatic out-of-hospital cardiac arrest.

BACKGROUND: Certain subgroups of patients with out-of-hospital cardiac arrest (OHCA) may not benefit from treatment. Early identification of this cohort in the prehospital (EMS) setting prior to any resuscitative efforts would prevent futile medical therapy and more appropriately allocate EMS and hospital resources. We sought to validate a clinical criteria from Bokutoh, Japan that identified a subgroup of OHCAs for whom withholding resuscitation may be appropriate. METHODS: We performed a secondary analysis of the "Trial of Continuous or Interrupted Chest Compressions during CPR", which enrolled EMS-treated adult non-traumatic OHCA. We classified patients as per the Bokutoh criteria ("Bokutoh Positive": age ≥ 73, unwitnessed arrest, non-shockable initial rhythm) and calculated test performance for the primary outcome of favourable neurologic outcome (mRS ≤ 3) at hospital discharge. We calculated the number of EMS-hours and hospital days per patient with a favourable neurologic outcome. RESULTS: Of 26,148 patients in the parent trial, 5442 (21%) were "Bokutoh Positive", among whom 0.51% (95% CI 0.35- 0.75%) had favourable neurologic outcomes, and 1.2% (95% CI 0.92-1.5%) survived. The positive predictive value was 0.995 (95% CI 0.992-0.997). EMS and hospital-based resource utilization per favourable neurological outcome was 91 h and 199 days for in the "Bokutok Positive" group, respectively, and 5.7 h and 33 hospital days in the "Bokutok Negative" group. CONCLUSION: In this validation of the Bokutoh criteria in a large North American cohort of OHCA patients, 0.51% meeting criteria had favourable neurological outcomes. This may rapidly and reliably identify the one-fifth of OHCA who are very unlikely to benefit from resuscitation.

Ethical choice in the medical applications of information theory.

BACKGROUND: Alongside advances in medical information technology (IT), there is mounting physician and patient dissatisfaction with present-day clinical practice. The effect of introducing increasingly complex medical IT on the ethical dimension of the clinical physician's primary task (identified as direct patient care) can be scrutinized through analysis of the EMR software platform. QUESTIONS/PURPOSES: We therefore (1) identify IT changes burdensome to the clinician in performing patient care and which therefore lower quality of care; and (2) suggest methods for clinicians to maintain high quality patient care as IT demands increase. METHODS: Elemental relationships from information theory and physical chemistry are applied to the profit-generating creation and flow of medical information between patients, physicians, administrators, suppliers, and insurers. Ethical implications for patient care and the doctor-patient relationship are drawn in the light of these relationships. WHERE ARE WE NOW?: Little has been accomplished, or even discussed, regarding limiting healthcare IT growth. Quality of patient care is expected to suffer unless physicians carefully scrutinize, refine and occasionally reject portions of the increasing healthcare IT burden being placed upon them. WHERE DO WE NEED TO GO?: Better medicine, simply understood as more effective prevention and treatment of musculoskeletal disease, is our professional goal. We need to establish mechanisms whereby we can limit, control or even reverse IT changes that hinder this goal. Clinicians must confront the negative impact many healthcare IT changes have on patient care. HOW DO WE GET THERE?: Suggestions for maintaining high standards of practice in the face of the new IT burden include: (1) Increasing IT time-awareness. Clinicians should examine actual time spent in clinical versus computer-based activity and implement changes if that ratio is too high. (2) Increasing IT goal awareness. (3) Examine the software creating a medical record to see how much of what it records is there for financial, as opposed to medical reasons. Is the software helping my patient or someone else's bottom line? Is it for talking to colleagues about sick people or to insurance companies?