Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose.

As the effectiveness of a two-dose messenger RNA (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen decreases with time, a third dose has been recommended. Here, we assessed immunogenicity, vaccine effectiveness and safety of the third BNT162b2 vaccine dose in a prospective cohort study of 12,413 healthcare workers (HCWs). Anti-RBD immunoglobulin G (IgG) levels were increased 1.7-fold after a third dose compared with following the second dose. Increased avidity from 61.1% (95% confidence interval (CI), 56.1-66.7) to 96.3% (95% CI, 94.2-98.5) resulted in a 6.1-fold increase in neutralization titer. Peri-infection humoral markers of 13 third-dose Delta variant of concern (VOC) breakthrough cases were lower compared with 52 matched controls. Vaccine effectiveness of the third dose relative to two doses was 85.6% (95% CI, 79.2-90.1). No serious adverse effects were reported. These results suggest that the third dose is superior to the second dose in both quantity and quality of IgG antibodies and safely boosts protection from infection.

Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months.

BACKGROUND: Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. METHODS: We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. RESULTS: The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman's rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). CONCLUSIONS: Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

Covid-19 Breakthrough Infections in Vaccinated Health Care Workers.

BACKGROUND: Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. METHODS: At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case-control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. RESULTS: Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. CONCLUSIONS: Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

The Association Between Prebooster Vaccination Antibody Levels and the Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

The correlation between anti-severe acute respiratory syndrome coronavirus 2 antibody levels and infection was reported. Here, we estimated the role of pre-fourth dose levels using data from 1098 healthcare workers. The risk of infection was reduced by 46% (95% confidence interval, 29%-59%) for each 10-fold increase in prebooster levels. Prebooster antibody levels could be used to optimally time boosters.

Early Immunogenicity and Safety of the Third Dose of BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccine Among Adults Older Than 60 Years: Real-World Experience.

BACKGROUND: Despite high vaccine coverage, an increase in breakthrough coronavirus disease 2019 (COVID-19) infections, prompted administration of a third BNT162b2 dose to people aged >60 years in Israel since July 2021. Here, we report real-world immunogenicity following third dose. METHODS: Overall, 208 healthcare workers aged >60 years were included. Paired pre- and post-second and/or third dose immunoglobulin G (IgG) and neutralizing antibody titers were compared. A subpopulation of low responders to the second dose was also tested for T-cell activation. For 25 paired serum samples, we tested neutralization of wild-type vs neutralization of Delta and Lambda variants, pre- and post-third dose. Active surveillance of vaccine adverse events was conducted through surveys. RESULTS: A pronounced immune response was observed following the third dose, including a 33-fold and 51-fold increase in IgG and neutralizing antibody, respectively. The neutralizing antibody levels post-third dose were 9.34 times higher than post-second dose (geometric mean titer, 2598 [95% confidence interval {CI}, 2085-3237] vs 207 [95% CI, 126-339]). Nine previously low responders had a significant antibody increase post-third dose, and 7 of 9 showed increase in T-cell activation. Additionally, sera obtained post-third dose highly and comparably neutralized the wild-type and Delta and Lambda variants. Of 1056 responders to the adverse-event survey, none had serious events. CONCLUSIONS: We demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals >60 years of age.

Omicron BA.2.75 variant is efficiently neutralised following BA.1 and BA.5 breakthrough infection in vaccinated individuals, Israel, June to September 2022.

We evaluated neutralising antibody titres against wild type (WT) SARS-CoV-2 and four Omicron variants (BA.1, BA.2, BA.5 and BA.2.75) in fully vaccinated (three doses of Comirnaty vaccine) healthcare workers (HCW) in Israel who had breakthrough BA.1/BA5 infections. Omicron breakthrough infections in vaccinated individuals resulted in increased neutralising antibodies against the WT and Omicron variants compared with vaccinated uninfected HCW. HCW who recovered from BA.1 or BA.5 infections showed similar neutralising antibodies levels against BA.2.75.

Comparing immunogenicity and efficacy of two different mRNA-based COVID-19 vaccines as a fourth dose; six-month follow-up, Israel, 27 December 2021 to 24 July 2022.

We assess the immunogenicity and efficacy of Spikevax and Comirnaty as fourth dose COVID-19 vaccines. Six months post-fourth-dose, IgG levels were higher than pre-fourth dose at 1.58-fold (95% CI: 1.27-1.97) in Spikevax and 1.16-fold (95% CI: 0.98-1.37) in Comirnaty vaccinees. Nearly 60% (159/274) of vaccinees contracted SARS-CoV-2. Infection hazard ratios (HRs) for Spikevax (0.82; 95% CI: 0.62-1.09) and Comirnaty (0.86; 95% CI: 0.65-1.13) vaccinees were similar, as were substantial-disease HRs, i.e. 0.28 (95% CI: 0.13-0.62) and 0.51 (95% CI: 0.27-0.96), respectively.

COVID-19 vaccination and BA.1 breakthrough infection induce neutralising antibodies which are less efficient against BA.4 and BA.5 Omicron variants, Israel, March to June 2022.

This work evaluated neutralising antibody titres against wild type (WT) SARS-CoV-2 and four Omicron variants (BA.1, BA.2, BA.4 and BA.5) in healthcare workers who had breakthrough BA.1 infection. Omicron breakthrough infection in individuals vaccinated three or four times before infection resulted in increased neutralising antibodies against the WT virus. The fourth vaccine dose did not further improve the neutralising efficiency over the third dose against all Omicron variants, especially BA.4 and BA.5. An Omicron-specific vaccine may be indicated.

The association between witnessing patient death and mental health outcomes in frontline COVID-19 healthcare workers.

BACKGROUND: Healthcare workers (HCW) treating coronavirus disease 2019 (COVID-19) patients face high levels of psychological stress. We aimed to compare mental health outcomes, risk and protective factors for posttraumatic stress symptoms (PTSS), probable depression, and anxiety between HCW working in COVID-19 and non-COVID-19 wards. METHODS: A self-report survey, administered in a large tertiary hospital in Israel during the peak of the COVID-19 outbreak was completed by 828 HCW (42.2% physicians, 57.8% nurses. Patient-Reported Outcomes Measurement Information System; the Patient Health Questionnaire-9; the Primary Care-Post Traumatic Stress Disorder Screen for DSM-5 (PC-PTSD-5) were used for assessing anxiety, depression, and PTSS, respectively. Pandemic-related stress factors, negative experiences, and potential protective factors were also assessed. RESULTS: Median PC-PTSD scores differed significantly between study teams (χ2 [5] = 17.24; p = .004). Prevalence of probable depression and anxiety were similar in both groups. Risk factors for mental health outcomes included mental exhaustion, anxiety about being infected and infecting family. Overall, higher proportion of the COVID-19 team witnessed patient deaths as compared to the non-COVID-19 team (50.2% vs. 24.7%). Witnessing patient death at the COVID-19 wards was associated with a four-fold increased likelihood of PTSS (odds ratio [OR] = 3.97; 95% confidence interval [CI], 1.58-9.99; p = .0007), compared with the non-COVID-19 wards (OR 0.91; 95% CI, 0.51-1.61; p = .43). CONCLUSIONS: Witnessing patient death appears to be a risk factor for PTSS unique to HCW directly engaged in treating patients with COVID-19. Our findings suggest that helping HCW cope with COVID-19 related deaths might reduce their risk of posttraumatic stress.

Establishing a COVID-19 treatment centre in Israel at the initial stage of the outbreak: challenges, responses and lessons learned.

Anticipating the need for a COVID-19 treatment centre in Israel, a designated facility was established at Sheba Medical Center-a quaternary referral centre. The goals were diagnosis and treatment of patients with COVID-19 while protecting patients and staff from infection and ensuring operational continuity and treatment of patients with non-COVID. Options considered included adaptation of existing wards, building a tented facility and converting a non-medical structure. The option chosen was a non-medical structure converted to a hospitalisation facility suited for COVID-19 with appropriate logistic and organisational adaptations. Operational principles included patient isolation, unidirectional workflow from clean to contaminated zones and minimising direct contact between patients and caregivers using personal protection equipment (PPE) and a multimodal telemedicine system. The ED was modified to enable triage and treatment of patients with COVID-19 while maintaining a COVID-19-free environment in the main campus. This system enabled treatment of patients with COVID-19 while maintaining staff safety and conserving the operational continuity and the ability to continue delivery of treatment to patients with non-COVID-19.

Buying Time with COVID-19 Outbreak Response, Israel.

Israel's response during the containment phase of the COVID-19 outbreak in early 2020 led to a delay in sustained community transmission and effective mitigation. During February-April 2020, a total of 15,981 confirmed cases resulted in 223 deaths. A total of 179,003 persons reported electronically to self-quarantine and were entitled to paid sick leave.

Anxiety, pandemic-related stress and resilience among physicians during the COVID-19 pandemic.

BACKGROUND: Physicians play a crucial frontline role in the COVID-19 pandemic, which may involve high levels of anxiety. We aimed to investigate the association between pandemic-related stress factors (PRSF) and anxiety and to evaluate the potential effect of resilience on anxiety among physicians. METHODS: A self-report digital survey was completed by 1106 Israeli physicians (564 males and 542 females) during the COVID-19 outbreak. Anxiety was measured by the 8-item version of the Patient-Reported Outcomes Measurement Information System. Resilience was evaluated by the 10-item Connor-Davidson Resilience Scale. Stress was assessed using a PRSF inventory. RESULTS: Physicians reported high levels of anxiety with a mean score of 59.20 ± 7.95. We found an inverse association between resilience and anxiety. Four salient PRSF (mental exhaustion, anxiety about being infected, anxiety infecting family members, and sleep difficulties) positively associated with anxiety scores. CONCLUSIONS: Our study identified specific PRSF including workload burden and fear of infection that are associated with increased anxiety and resilience that is associated with reduced anxiety among physicians.

Orthopedic Activity in Field Hospitals Following Earthquakes in Nepal and Haiti : Variability in Injuries Encountered and Collaboration with Local Available Resources Drive Optimal Response.

BACKGROUND: Field hospitals have been deployed by the Israel Defense Forces (IDF) Medical Corps in numerous disaster events. Two recent deployments were following earthquakes in Haiti in 2010 and in Nepal in 2015. Despite arrival in similar timetables, the mode of operation was different-independently in Haiti and in collaboration with a local hospital in Nepal. The pathology encountered in the two hospitals and the resultant treatment requirements were significantly different between the two events. The purpose of this study was to analyze these differences and their implications for preparation and planning of future deployments. METHODS: Data were obtained from IDF records and analyzed using SPSS™ software. RESULTS: 1686 patients were treated in Nepal versus 1111 in Haiti. The caseload in Nepal included significantly less earthquake-related injuries (26 vs. 66 %) with 28 % of them sustaining fractures versus 47 % in Haiti. Femoral fractures accounted for 7.9 % of fractures in Nepal versus 26.4 % in Haiti with foot fractures accounting for 23.8 and 6.4 %, respectively. The rate of open fracture was similar at 29.4 % in Nepal and 27.5 % in Haiti. 18.1 % of injured patients in Nepal underwent surgery, and 32.9 % of which was skeletal compared to 32 % surgical cases (58.8 % skeletal) in Haiti. 74.2 % of patients in Nepal and 34.3 % in Haiti were treated for pathology unrelated to the earthquake. CONCLUSIONS: The reasons for the variability in activities between the two hospitals include the magnitude of the disaster, the functionality of the local medical system which was relatively preserved in Nepal and destroyed in Haiti and the mode of operation which was independent in Haiti and collaborative with a functioning local hospital in Nepal. Emergency medical teams (EMTs) may encounter variable caseloads despite similar disaster scenarios. Advance knowledge of the magnitude of the disaster, the functionality of the local medical system, and the collaborative possibilities will help in planning and preparing EMTs to function optimally and appropriately. However, as this information will often be unavailable, EMTs should be capable to adapt to unexpected conditions.

Cognitive-Behavioural Therapy and Psychodynamic Psychotherapy in the Treatment of Combat-Related Post-Traumatic Stress Disorder: A Comparative Effectiveness Study.

UNLABELLED: This study compared the effectiveness of two psychotherapy approaches for treating combat veterans with chronic post-traumatic stress disorder (PTSD): cognitive-behavioural therapy (CBT) and psychodynamic psychotherapy (PDT). These treatments are routinely used by the Unit for Treatment of Combat-Related PTSD of the Israel Defense Forces (IDF). IDF veterans with chronic PTSD were assigned to either CBT (n = 148) or PDT (n = 95) based on the nature of their complaint and symptoms. Psychiatric status was assessed at baseline, post-treatment and 8-12 months follow-up using the Clinician-Administered PTSD Scale, the PTSD Questionnaire, the Montgomery and Asberg Depression Rating Scale and the Psychotherapy Outcome Assessment and Monitoring System-Trauma Version assessment questionnaire. Both treatment types resulted in significant reduction in symptoms and with improved functioning from pre-treatment to post-treatment, which were maintained at follow-up. No differences between the two treatments were found in any the effectiveness measures. At post-treatment, 35% of the CBT patients and 45% of the PDT patients remitted, with no difference between the groups. At follow-up, remission rates were 33% and 36% for the CBT and PDT groups, respectively. The study recommends further randomized controlled trials to determine treatment efficacy. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Both cognitive-behavioural therapy and psychodynamic psychotherapy have to be treatments offered in clinics for treating PTSD. Therapists who treat PTSD should be familiar with cognitive-behavioural and dynamic methods. The type of treatment chosen should be based on thorough psychosocial assessment.

Lessons learned from the Syrian sarin attack: evaluation of a clinical syndrome through social media.

On the night of 21 August 2013, sarin was dispersed in the eastern outskirts of Damascus, killing 1400 civilians and severely affecting thousands more. This article aims to delineate the clinical presentation and management of a mass casualty event caused by a nerve agent as shown in the social media. Authors searched YouTube for videos uploaded of this attack and identified 210 videos. Of these, 67 met inclusion criteria and were evaluated in the final analysis.These videos displayed 130 casualties; 119 (91.5%) of which were defined as moderately injured or worse. The most common clinical signs were dyspnea (53.0%), diaphoresis (48.5%), and loss of consciousness (40.7%). Important findings included a severe shortage of supporting measures and lack of antidotal autoinjectors. Decontamination, documented in 25% of the videos, was done in an inefficient manner. Protective gear was not noticed, except for sporadic use of latex gloves and surgical masks.This is believed to be the first time that social media was used to evaluate clinical data and management protocols to better prepare against future possible events.