ABSTRACT
OBJECTIVES: The dosing interval of a primary vaccination series can significantly impact on vaccine immunogenicity and efficacy. The current study compared 3 dosing intervals for the primary vaccination series of the BNT162b2 mRNA COVID-19 vaccine, on humoral immune response and durability against SARS-CoV-2 ancestral and Beta variants up to 9 months post immunization. METHODS: Three groups of age- and sex-matched healthcare workers (HCW) who received 2 primary doses of BNT162b2 separated by 35-days, 35-42 days or >42-days were enrolled. Vaccine induced antibody titers at 3 weeks, 3 and 6-9 months post-second dose were assessed. RESULTS: There were 309 age- and sex-matched HCW (mean age 43 [sd 13], 58% females) enrolled. Anti-SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibody titers showed significant waning in levels beyond 35 days post first dose. The second dose induced a significant rise in antibody titers, which peaked at 3 weeks and then declined at variable rates across groups. The magnitude, consistency and durability of response was greater for anti-Spike than anti-RBD antibodies; and for IgG than IgA or IgM. Compared to the shorter schedules, a longer interval of >42 days offered the highest binding and neutralizing antibody titers against SARS-CoV-2 ancestral and Beta (B1.351) variants beyond 3 months post-vaccination. CONCLUSIONS: This is the first comprehensive study to compare 3 dosing intervals for the primary vaccination of BNT162b2 mRNA COVID-19 vaccine implemented in the real world. These findings suggest that delaying the second dose beyond 42 days can potentiate and prolong the humoral response against ancestral and Beta variants of SARS-CoV-2 up to 9 months post-vaccination.
Subject(s)
COVID-19 Vaccines , COVID-19 , Female , Humans , Adult , Male , BNT162 Vaccine , Immunity, Humoral , Prospective Studies , COVID-19/prevention & control , SARS-CoV-2/genetics , Health Personnel , RNA, Messenger , Antibodies, Neutralizing , Immunoglobulin A , Immunoglobulin G , Immunoglobulin M , Antibodies, Viral , VaccinationABSTRACT
SARS-CoV-2 mRNA vaccines have been critical to curbing pandemic COVID-19; however, a major shortcoming has been the inability to assess levels of protection after vaccination. This study assessed serologic status of breakthrough infections in vaccinated patients at a Veterans Administration medical center from June through December 2021 during a SARS-CoV-2 delta variant wave. Breakthrough occurred mostly beyond 150 days after two-dose vaccination with a mean of 239 days. Anti-SARS-CoV-2 spike (S) IgG levels were low at 0 to 2 days postsymptoms but increased in subjects presenting thereafter. Population measurements of anti-S IgG and angiotensin converting enzyme-2 receptor (ACE2-R) binding inhibition among uninfected, vaccinated patients suggested immune decay occurred after 150 days with 62% having anti-S IgG levels at or below 1,000 AU comparable with breakthrough patients at 0 to 2 days postsymptom onset. In contrast, vaccination after resolved infection conferred robust enduring anti-S IgG levels (5,000 to >50,000 AU) with >90% ACE2-R binding inhibition. However, monoclonal antibody (MAb)-treated patients did not benefit from their prior infection suggesting impaired establishment of B cell memory. Analysis of boosted patients confirmed the benefit of a third vaccine dose with most having anti-S IgG levels above 5,000 AU with >90% ACE2-R binding inhibition, but a subset had levels <5,000 AU. Anti-S IgG levels >5,000 AU were associated with >90% ACE2-R binding inhibition and no documented breakthrough infections, whereas levels falling below 5,000 AU and approaching 1,000 AU were associated with breakthrough infections. Thus, quantitative antibody measurements may provide a means to guide vaccination intervals for the individual. IMPORTANCE Currently, clinicians have no guidance for the serologic assessment of SARS-Cov-2 postvaccination status regarding protection and risk of infection. Vaccination and boosters are administered blindly without evaluation of need or outcome at the individual level. The recent development of automated quantitative assays for anti-SARS-CoV-2 spike protein IgG antibodies permits accurate measurement of humoral immunity in standardized units. Clinical studies, such as reported here, will help establish protective antibody levels allowing identification and targeted management of poor vaccine responders and vaccinated subjects undergoing immune decay.
ABSTRACT
To date, the COVID-19 pandemic has resulted in over 570 million cases and over 6 million deaths worldwide. Predominant clinical testing methods, though invaluable, may create an inaccurate depiction of COVID-19 prevalence due to inadequate access, testing, or most recently under-reporting because of at-home testing. These concerns have created a need for unbiased, community-level surveillance. Wastewater-based epidemiology has been used for previous public health threats, and more recently has been established as a complementary method of SARS-CoV-2 surveillance. Here we describe the application of wastewater surveillance for SARS-CoV-2 in two university campus communities located in rural Lincoln Parish, Louisiana. This cost-effective approach is especially well suited to rural areas where limited access to testing may worsen the spread of COVID-19 and quickly exhaust the capacity of local healthcare systems. Our work demonstrates that local universities can leverage scientific resources to advance public health equity in rural areas and enhance their community involvement.
Subject(s)
COVID-19 , Public Health , COVID-19/epidemiology , Humans , Pandemics , SARS-CoV-2 , Universities , Wastewater , Wastewater-Based Epidemiological MonitoringABSTRACT
INTRODUCTION: The U.S. Army developed a new tool called the Behavioral Health Readiness and Suicide Risk Reduction Review (R4) for suicide prevention. A 12-month evaluation study with the primary objective of testing the hypothesis (H1) that Army units receiving R4 would demonstrate improved outcomes in suicidal-behavior measures following the intervention, relative to control, was then conducted. The results of analyses to answer H1 are herein presented. MATERIALS AND METHODS: The R4 intervention (R4-tools/instructions/orientation) evaluation study, Institutional Review Board approved and conducted in May 2019-June 2020, drew samples from two U.S. Army divisions and employed a repeated measurement in pre-/post-quasi-experimental design, including a nonequivalent, but comparable, business-as-usual control. Intervention effectiveness was evaluated using self-report responses to suicide-related measures (Suicide Behaviors Questionnaire-Revised/total-suicide behaviors/ideations/plans/attempts/non-suicidal self-injuries) at 6-/12-month intervals. Analyses examined baseline to follow-up linked and cross-sectional cohorts, incidence/prevalence, and intervention higher-/lower-use R4 subanalyses. RESULTS: Both divisions demonstrated favorable in-study reductions in total-suicide burden, with relatively equivalent trends for total-suicide behaviors, total-suicide risk (Suicide Behaviors Questionnaire-Revised), suicidal ideations, and non-suicidal self-injuries. Although both demonstrated reductions in suicide plans, the control showed a more robust trend. Neither division demonstrated a significant reduction in suicide attempts, but subgroup analyses showed a significant reduction in pre-coronavirus disease 2019-attempt incidence among those with higher-use R4 relative to control. CONCLUSIONS: There is no evidence of harm associated with the R4 intervention. R4 effectiveness as a function of R4 itself requires confirmatory study. R4 is judged an improvement (no evidence of harm + weak evidence of effectiveness) over the status quo (no safety data or effectiveness studies) with regard to tool-based decision-making support for suicide prevention in the U.S. Army.
Subject(s)
Coronavirus Infections/complications , Hypoxia/physiopathology , Pneumonia, Viral/complications , Respiratory Insufficiency/virology , Thrombophilia/virology , Anticoagulants/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/physiopathology , Critical Illness , Humans , Pandemics , Pneumonia, Viral/physiopathology , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , Risk Assessment , SARS-CoV-2 , Salvage Therapy , Thrombophilia/drug therapyABSTRACT
Technologic advances have resulted in the expansion of web-based conferencing and education. While historically video-conferencing has been used for didactic educational sessions, we present its novel use in virtual radiology read-outs in the face of the COVID-19 pandemic. Knowledge of key aspects of set-up, implementation, and possible pitfalls of video-conferencing technology in the application of virtual read-outs can help to improve the educational experience of radiology trainees and promote potential future distance learning and collaboration.