Hospital surveillance of respiratory viruses during the COVID-19 pandemic and beyond: contribution to the WHO mosaic framework, Israel, 2020 to 2023.

BackgroundA new respiratory virus surveillance platform, based on nationwide hospital laboratory data, was established in Israel during the COVID-19 pandemic.AimWe aimed to evaluate the performance of this platform with respect to the detection of influenza and respiratory syncytial virus (RSV) from week 36 in 2020 to week 15 in 2023, and how it fits with the World Health Organization (WHO) mosaic surveillance framework.MethodsData of respiratory samples from hospitalised patients sent for laboratory confirmation of influenza virus or RSV from 25 general hospital laboratories nationwide were collected. We analysed the weekly number and percentage of samples positive for influenza virus or RSV vis-à-vis SARS-CoV-2 activity and compared data from the new surveillance platform with existing surveillance platforms. Using data in the new surveillance platform, we analysed early stages of a 2021 out-of-season RSV outbreak and evaluated the capabilities of the new surveillance system with respect to objectives and domains of the WHO mosaic framework.ResultsThe new hospital-laboratory surveillance platform captured the activity of influenza virus and RSV, provided crucial data when outpatient sentinel surveillance was not operational and supported an out-of-season RSV outbreak investigation. The new surveillance platform fulfilled important objectives in all three domains of the mosaic framework and could serve for gathering additional information to fulfil more domain objectives.ConclusionThe new hospital laboratory surveillance platform provided essential data during the COVID-19 pandemic and beyond, fulfilled important domain objectives of the mosaic framework and could be adapted for the surveillance of other viruses.

Incidence of laboratory-confirmed influenza and RSV and associated presenteeism and absenteeism among healthcare personnel, Israel, influenza seasons 2016 to 2019.

BackgroundHealthcare personnel (HCP) are at high risk for respiratory infections through occupational exposure to respiratory viruses.AimWe used data from a prospective influenza vaccine effectiveness study in HCP to quantify the incidence of acute respiratory infections (ARI) and their associated presenteeism and absenteeism.MethodsAt the start and end of each season, HCP at two Israeli hospitals provided serum to screen for antibodies to influenza virus using the haemagglutination inhibition assay. During the season, active monitoring for the development of ARI symptoms was conducted twice a week by RT-PCR testing of nasal swabs for influenza and respiratory syncytial virus (RSV). Workplace presenteeism and absenteeism were documented. We calculated incidences of influenza- and RSV-associated ARI and applied sampling weights to make estimates representative of the source population.ResultsThe median age of 2,505 participating HCP was 41 years, and 70% were female. Incidence was 9.1 per 100 person-seasons (95% CI: 5.8-14.2) for RT-PCR-confirmed influenza and 2.5 per 100 person-seasons (95% CI: 0.9-7.1) for RSV illness. Each season, 18-23% of unvaccinated and influenza-negative HCP seroconverted. The incidence of seroconversion or RT-PCR-confirmed influenza was 27.5 per 100 person-seasons (95% CI: 17.8-42.5). Work during illness occurred in 92% (95% CI: 91-93) of ARI episodes, absence from work in 38% (95% CI: 36-40).ConclusionInfluenza virus and RSV infections and associated presenteeism and absenteeism were common among HCP. Improving vaccination uptake among HCP, infection control, and encouraging sick HCP to stay home are important strategies to reduce ARI incidence and decrease the risk of in-hospital transmission.

Vaccine Coverage Associated With Ending a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Wave: A Retrospective Longitudinal Analysis.

BACKGROUND: Two SARS-CoV-2 waves in Israel ended while a substantial number of individuals remained unvaccinated or partially vaccinated. The indirect protective effect of the first BNT162b2 vaccination campaign in Israel was evaluated between 22 December 2020 and 18 May 2021. METHODS: The daily percentage of new polymerase chain reaction (PCR)-confirmed SARS-CoV-2 cases among unvaccinated individuals was analyzed for trends. Major shifts were identified using piecewise linear regression analysis. At these shifts, the percentage of naturally vaccinated (past SARS-CoV-2 cases) and the percentage of actively vaccinated (by inoculation) individuals were weighted and summed to determine the percentage of natural and active vaccination (NAV). RESULTS: A first decline among unvaccinated individuals occurred during a lockdown period, when the percentage of NAV was 8.16%. The major decline occurred after the end of the lockdown when the percentage of NAV reached 52.05%. SARS-CoV-2 cases ultimately declined among unvaccinated individuals when the percentage of NAV reached 63.55%. During the study period, the Alpha variant was prevalent and the use of nonpharmaceutical interventions, including social distancing, existed to varying degrees. CONCLUSIONS: The vaccination campaign played a major role in the decline of SARS-CoV-2 infection among unvaccinated individuals, leading to the end of the first 2021 SARS-CoV-2 wave (Alpha variant) in Israel. Infection in unvaccinated individuals stopped when two-thirds of the population were naturally or actively vaccinated. Any change in characteristics of the virus or the population can lead to a new outbreak.

Effectiveness of BNT162b2 Vaccine against Omicron Variant Infection among Children 5-11 Years of Age, Israel.

We assessed effectiveness of the BNT162b2 vaccine against infection with the B.1.1.529 (Omicron) variant (mostly BA.1 subvariant), among children 5-11 years of age in Israel. Using a matched case-control design, we matched SARS-CoV-2-positive children (cases) and SARS-CoV-2-negative children (controls) by age, sex, population group, socioeconomic status, and epidemiologic week. Vaccine effectiveness estimates after the second vaccine dose were 58.1% for days 8-14, 53.9% for days 15-21, 46.7% for days 22-28, 44.8% for days 29-35, and 39.5% for days 36-42. Sensitivity analyses by age group and period demonstrated similar results. Vaccine effectiveness against Omicron infection among children 5-11 years of age was lower than vaccine efficacy and vaccine effectiveness against non-Omicron variants, and effectiveness declined early and rapidly.

Effectiveness of BNT162b2 Vaccine Booster against SARS-CoV-2 Infection and Breakthrough Complications, Israel.

We estimated vaccine effectiveness (VE) of the BNT162b2 (Pfizer-BioNTech, https://www.pfizer.com) booster dose against SARS-CoV-2 infection and reduction of complications (hospitalization, severe disease, and death) among breakthrough cases in persons in Israel >16 years of age for <20 weeks. VE estimates reached 96.8% (95% CI 96.0%-97.5%) for persons 16-59 years of age and 93.1% (95% CI 91.8%-94.2%) for persons >60 years of age on week 3. VE estimates remained at these levels for 8 weeks in the 16-59 age group and 11 weeks in those >60. A slow decline followed, becoming more pronounced in the last 2-3 weeks of evaluation. Estimates in the last week of evaluation were 77.6% (95% CI 68.4%-84.2%) and 61.3% (52.5%-68.4%) for persons 16-59 years and >60 years, respectively. The more pronounced VE decline coincided with rapid increase in Omicron variant activity. Rate reduction of breakthrough complications remained moderate to high throughout the evaluation.

The impact of SARS-CoV-2 on respiratory syndromic and sentinel surveillance in Israel, 2020: a new perspective on established systems.

BackgroundThe COVID-19 pandemic presented new challenges for the existing respiratory surveillance systems, and adaptations were implemented. Systematic assessment of the syndromic and sentinel surveillance platforms during the pandemic is essential for understanding the value of each platform in the context of an emerging pathogen with rapid global spread.AimWe aimed to evaluate systematically the performance of various respiratory syndromic surveillance platforms and the sentinel surveillance system in Israel from 1 January to 31 December 2020.MethodsWe compared the 2020 syndromic surveillance trends to those of the previous 3 years, using Poisson regression adjusted for overdispersion. To assess the performance of the sentinel clinic system as compared with the national SARS-CoV-2 repository, a cubic spline with 7 knots and 95% confidence intervals were applied to the sentinel network's weekly percentage of positive SARS-CoV-2 cases.ResultsSyndromic surveillance trends changed substantially during 2020, with a statistically significant reduction in the rates of visits to physicians and emergency departments to below previous years' levels. Morbidity patterns of the syndromic surveillance platforms were inconsistent with the progress of the pandemic, while the sentinel surveillance platform was found to reflect the national circulation of SARS-CoV-2 in the population.ConclusionOur findings reveal the robustness of the sentinel clinics platform for the surveillance of the main respiratory viruses during the pandemic and possibly beyond. The robustness of the sentinel clinics platform during 2020 supports its use in locations with insufficient resources for widespread testing of respiratory viruses.

Monitoring SARS-CoV-2 Activity with Sentinel Surveillance: Lessons Learned from the First Wave in Israel.

BACKGROUND: Guidelines for pandemic preparedness emphasize the role of sentinel and syndromic surveillance in monitoring pandemic spread. OBJECTIVES: To examine advantages and obstacles of utilizing a sentinel influenza surveillance system to monitor community severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity based on Israel's experience from mid-March to mid-May 2020. METHODS: Several modifications were applied to the influenza surveillance system. The clinical component relied mainly on pneumonia and upper respiratory infection (URI) consultations with primary care physicians as well as visits to emergency departments (ED) due to pneumonia. The virological data were based on nasopharyngeal swabs obtained from symptomatic patients who visited outpatient clinics. RESULTS: By week 12 of the pandemic, the crude and age-specific primary physician consultation rates due to URI and pneumonia declined below the expected level, reaching nadir that lasted from week 15 until week 20. Similarly, ED visits due to pneumonia were significantly lower than expected from weeks 14 and 15 to week 20. The virological surveillance started on week 13 with 6/253 of the swabs (2.3%) positive for SARS-CoV-2. There was a peak of 13/225 positive swabs on week 145.8%. During weeks 17-20, none of the swabs (47-97 per week) were positive for SARS-CoV-2. This trend was similar to national data. CONCLUSIONS: The virological component of the surveillance system showed the SARS-CoV-2 community spread, but had low sensitivity when virus activity was low. The clinical component, however, had no yield. Sentinel surveillance can assist in monitoring future novel pandemics and should be augmented in revised preparedness plans.

Effectiveness of BNT162b2 Vaccine in Adolescents during Outbreak of SARS-CoV-2 Delta Variant Infection, Israel, 2021.

In Israel, the BNT162b2 vaccine against severe acute respiratory syndrome coronavirus 2 was approved for use in adolescents in June 2021, shortly before an outbreak of B.1.617.2 (Delta) variant-dominant infection. We evaluated short-term vaccine effectiveness and found the vaccine to be highly effective among this population in this setting.

Delayed respiratory syncytial virus epidemic in children after relaxation of COVID-19 physical distancing measures, Ashdod, Israel, 2021.

Following low incidence of respiratory syncytial virus (RSV) infections in 2020 during the COVID-19 pandemic, we noted a resurgence in hospitalised children in spring/summer 2021 following relaxation of public health measures. We compared this outbreak to previous autumn/winter seasons. We found higher weekly case numbers and incidence rates, more cases from urban neighbourhoods with lower socioeconomic status, and similar clinical presentation and severity. Public health implications include the re-evaluation of palivizumab administration and the need for surge capacity planning.

Under-diagnosis of SARS-CoV-2 infections among children aged 0-15 years, a nationwide seroprevalence study, Israel, January 2020 to March 2021.

Until recently, children and adolescents were not eligible for COVID-19 vaccination. They may have been a considerable source of SARS-CoV-2 spread. We evaluated SARS-CoV-2 IgG antibody seroprevalence in Israeli children aged 0-15 years from January 2020 to March 2021. Seropositivity was 1.8-5.5 times higher than COVID-19 incidence rates based on PCR testing. We found that SARS-CoV-2 infection among children is more prevalent than previously thought and emphasise the importance of seroprevalence studies to accurately estimate exposure.

Enhanced control of Mycobacterium tuberculosis extrapulmonary dissemination in mice by an arabinomannan-protein conjugate vaccine.

Currently there are a dozen or so of new vaccine candidates in clinical trials for prevention of tuberculosis (TB) and each formulation attempts to elicit protection by enhancement of cell-mediated immunity (CMI). In contrast, most approved vaccines against other bacterial pathogens are believed to mediate protection by eliciting antibody responses. However, it has been difficult to apply this formula to TB because of the difficulty in reliably eliciting protective antibodies. Here, we developed capsular polysaccharide conjugates by linking mycobacterial capsular arabinomannan (AM) to either Mtb Ag85b or B. anthracis protective antigen (PA). Further, we studied their immunogenicity by ELISA and AM glycan microarrays and protection efficacy in mice. Immunization with either Abg85b-AM or PA-AM conjugates elicited an AM-specific antibody response in mice. AM binding antibodies stimulated transcriptional changes in Mtb. Sera from AM conjugate immunized mice reacted against a broad spectrum of AM structural variants and specifically recognized arabinan fragments. Conjugate vaccine immunized mice infected with Mtb had lower bacterial numbers in lungs and spleen, and lived longer than control mice. These findings provide additional evidence that humoral immunity can contribute to protection against Mtb.

Nationwide epidemiology of early-onset sepsis in Israel 2010-2015, time to re-evaluate empiric treatment.

AIM: Early-onset neonatal sepsis (EOS) may lead to significant morbidity and mortality, yet the recommended antimicrobials have not changed for many years. We aimed to optimise EOS treatment by examining EOS pathogens, resistance rates and resistance risk factors. METHODS: A retrospective, nationwide cohort study analysing 2010-2015 EOS data in Israel. RESULTS: The 21 participating centres constitute 92% of the total birth cohort (around 180 000 live births/year). Of 549 EOS neonates (0.57/1000 live births), 306 (56%) and 243 (44%) were full-term and preterm, respectively (0.35 vs. 2.94 per/1000 live births). Gram-negative pathogens predominated, especially in preterms. Escherichia coli and Streptococcus agalactiae were most common pathogens (0.2 and 0.19 per 1000 live births, respectively). In 277 Gram-negatives, 16%, 14%, 8% and 3% were gentamicin-resistant, extended-spectrum beta-lactamase (ESBL)-positive, gentamicin-resistant and ESBL-positive, and amikacin-resistant, respectively; preterms had higher resistance rates. No risk factors for antimicrobial resistance were identified. Mortality was reported in 21% of Gram-negative EOS versus 7% of Gram-positive EOS [OR 3.4 (95% CI 1.8-6.2), p < 0.01]. CONCLUSION: In this nationwide study, EOS was caused predominantly by Gram-negatives, with high gentamicin resistance and ESBL phenotype rates, without identifiable resistance risk factors. As EOS is life-threatening, modification of empiric therapy for amikacin-based regimens should be considered, mainly in preterms.

Hospitalization for Respiratory Syncytial Virus Bronchiolitis in the Palivizumab Prophylaxis Era: Need for Reconsideration of Preventive Timing and Eligibility.

BACKGROUND: Respiratory syncytial virus (RSV)-related bronchiolitis is a common cause of morbidity in young infants. The recommendations for its passive prevention by palivizumab are currently under intensive debate. OBJECTIVES: To elucidate the optimal prevention strategy by studying the morbidity of RSV disease under the current recommendations for palivizumab prophylaxis in Israel. METHODS: We collected demographic and clinical data of all children hospitalized with microbiologically confirmed RSV bronchiolitis during 2015-2016 at Schneider Children's Medical Center. The seasonality of RSV disease was also studied for the period 2010-2017 in sentinel clinics scattered throughout Israel. RESULTS: Of the 426 hospitalized children, 106 (25%) had underlying diseases but were not eligible for palivizumab prophylaxis according to the current criteria in Israel. Their course was severe, with a mean hospital stay of 6.7 days and a 12% admission rate to the pediatric intensive care unit (PICU). Palivizumab-eligible children who did not receive the prophylaxis before hospitalization had the most severe course, with 22% admitted to the PICU. More children were diagnosed with RSV disease in October than in March among both hospitalized and ambulatory children; 44% of the palivizumab-eligible hospitalized children were admitted in the last 2 weeks of October, before 1 November which is the recommended date for starting palivizumab administration in Israel. CONCLUSIONS: According to the results of the present study we suggest advancing RSV prophylaxis in Israel from 1 November to mid-October. The precise palivizumab-eligible categories should be reconsidered.

Seasonal Influenza Vaccine Effectiveness in Preventing Laboratory-Confirmed Influenza in Primary Care in Israel, 2016-2017 Season: Insights Into Novel Age-Specific Analysis.

Background: The 2016-2017 influenza season in Israel was dominated by the circulation of influenza A(H3N2). Influenza vaccine is recommended for the entire population in Israel aged >6 months. The inactivated influenza vaccine was chosen for use this season. Methods: We estimated the 2016-2017 end-of-season influenza vaccine effectiveness (VE) in preventing influenza-like illness due to influenza A(H3N2), using the test-negative design. Age-specific VE was estimated using a moving age window and weekly analysis. Results: During the 2016-2017 season, 1267 samples were collected; 467 (36.9%) were positive for influenza, with 97.9% A(H3N2), 0.2% A(H1N1)pdm09, and 1.9% B. A total of 1088 individuals were found eligible to be included in VE assessment. All vaccinated individuals included in the VE assessment received the inactivated influenza vaccine. Adjusted VE against influenza A(H3N2) was 29.0% (95% confidence interval [CI], 0.3%-49.5%). Age group-specific adjusted VE was 69.2% (95% CI, 19.4%-88.3%) for children aged 5-17 years and 58.8% (95% CI, .8%-82.9%) for adults aged 45-64 years. Other age groups demonstrated lower VE estimates that were not statistically significant. Adjusted VE estimates using a moving window of 15 years and weekly VE analyses provided a more defined understanding of age-specific VE during the 2016-2017 season. Conclusions: Estimating VE using a moving age window as well as weekly VE analysis may provide more detailed information regarding the relationship between VE and age.

Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI): study protocol.

BACKGROUND: The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. METHODS: Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. DISCUSSION: SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. TRIAL REGISTRATION: NCT03331991 . Registered on November 6, 2017.

Effectiveness of influenza vaccine in preventing medically-attended influenza virus infection in primary care, Israel, influenza seasons 2014/15 and 2015/16.

IntroductionInfluenza vaccine is recommended for the entire population in Israel. We assessed influenza vaccine effectiveness (VE) for the 2014/15 and 2015/16 seasons in Israel, for the first time. Methods: Combined nose and throat swab specimens were collected from patients with influenza-like illness (ILI) presenting to sentinel primary care clinics and tested for influenza virus by RT-PCR. VE of the trivalent inactivated vaccine (TIV) was assessed using test-negative case-control design. Results: During the 2014/15 season 1,142 samples were collected; 327 (28.6%) were positive for influenza, 83.8% A(H3N2), 5.8% A(H1N1)pdm09, 9.2% B and 1.2% A un-subtyped. Adjusted VE against all influenza viruses for this influenza season was -4.8% (95% confidence interval (CI): -54.8 to 29.0) and against influenza A(H3N2), it was -15.8% (95% CI: -72.8 to 22.4). For the 2015/16 season, 1,919 samples were collected; 853 (44.4%) were positive for influenza, 43.5% A(H1N1)pdm09, 57% B, 0.7% A(H3N2) and 11 samples positive for both A(H1N1)pdm09 and B. Adjusted VE against all influenza viruses for this influenza season was 8.8% (95% CI: -25.1 to 33.5), against influenza A(H1N1)pdm09, it was 32.3% (95% CI: (-4.3 to 56.1) and against influenza B, it was -2.2% (95% CI: (-47.0 to 29.0). Conclusions: Using samples from patients with ILI visiting sentinel clinics in Israel, we demonstrated the feasibility of influenza VE estimation in Israel.

Mosquito Surveillance for 15 Years Reveals High Genetic Diversity Among West Nile Viruses in Israel.

West Nile Virus (WNV) is endemic in Israel and has been the cause of several outbreaks in recent years. In 2000, a countrywide mosquito survey was established to monitor WNV activity and characterize viral genotypes in Israel. We analyzed data from 7135 pools containing 277 186 mosquitoes collected over the past 15 years and, here, report partial sequences of WNV genomes obtained from 102 of the 336 positive mosquito pools. Phylogenetic analysis demonstrated that cluster 4 and the Mediterranean and Eastern European subtypes of cluster 2 within WNV lineage 1 circulated in Israel, as did WNV lineage 2, highlighting a high genetic diversity of WNV genotypes in our region. As a major crossroads for bird migration between Africa and Eurasia and with a long history of human infection, Israel serves as a resource hub for WNV in Africa and Eurasia and provides valuable information on WNV circulation in these regions.

Association of Human Antibodies to Arabinomannan With Enhanced Mycobacterial Opsonophagocytosis and Intracellular Growth Reduction.

BACKGROUND: The relevance of antibodies (Abs) in the defense against Mycobacterium tuberculosis infection remains uncertain. We investigated the role of Abs to the mycobacterial capsular polysaccharide arabinomannan (AM) and its oligosaccharide (OS) fragments in humans. METHODS: Sera obtained from 29 healthy adults before and after primary or secondary bacillus Calmette-Guerin (BCG) vaccination were assessed for Ab responses to AM via enzyme-linked immunosorbent assays, and to AM OS epitopes via novel glycan microarrays. Effects of prevaccination and postvaccination sera on BCG phagocytosis and intracellular survival were assessed in human macrophages. RESULTS: Immunoglobulin G (IgG) responses to AM increased significantly 4-8 weeks after vaccination (P < .01), and sera were able to opsonize BCG and M. tuberculosis grown in both the absence and the presence of detergent. Phagocytosis and intracellular growth inhibition were significantly enhanced when BCG was opsonized with postvaccination sera (P < .01), and these enhancements correlated significantly with IgG titers to AM (P < .05), particularly with reactivity to 3 AM OS epitopes (P < .05). Furthermore, increased phagolysosomal fusion was observed with postvaccination sera. CONCLUSIONS: Our results provide further evidence for a role of Ab-mediated immunity to tuberculosis and suggest that IgG to AM, especially to some of its OS epitopes, could contribute to the defense against mycobacterial infection in humans.

Review of Israel's action and response during the COVID-19 pandemic and tabletop exercise for the evaluation of readiness and resilience-lessons learned 2020-2021.

Background: Reevaluating response plans is essential to ensuring consistent readiness and resilience to the COVID-19 pandemic. The "During Action Review" and Tabletop (DART) methodology provides a retrospective and prospective assessment to inform the adaptive response. Israel introduced COVID-19 vaccinations in December 2020 and was the first country to implement booster vaccination to address waning immunity and surges caused by new variants. We assessed Israel's readiness and resilience related to COVID-19 response while capturing the pre-vaccination and vaccination periods. Methods: A DART analysis was conducted between December 2020 and August 2021 among experts involved in the management of the COVID-19 pandemic in Israel. During the retrospective stage, a role-based questionnaire and discussions were undertaken in a participant-led review of the response, focusing on epidemiology and surveillance, risk communication, and vaccines. The prospective stage included tabletop exercises to evaluate short to long-term simulated scenarios. Results: Participants emphasized the pivotal role of Israel globally by sharing experiences with the pandemic, and vaccination. Perceived strengths included multi-sectoral collaboration between the Ministry of Health, healthcare providers, academia, military, and others, stretching capacities, expanding laboratory workload, and establishing/maintaining surveillance. The vaccine prioritization plan and strong infrastructure, including computerized databases, enabled real-life assessment of vaccine uptake and impact. Challenges included the need to change case definitions early on and insufficient staffing. Quarantine of patients and contacts was particularly challenging among underprivileged communities. Risk communication approaches need to focus more on creating norms in behavior. Trust issues and limited cooperation were noted, especially among ethnic and religious minorities. To ensure readiness and resiliency, participants recommended establishing a nationally deployed system for bringing in and acting upon feedback from the field, especially concerning risk communication and vaccines. Conclusion: Our study appraised strengths and weaknesses of the COVID-19 pandemic response in Israel and led to concrete recommendations for adjusting responses and future similar events. An efficient response comprised multi-sectoral collaboration, policy design, infrastructure, care delivery, and mitigation measures, including vaccines, while risk communication, trust issues, and limited cooperation with minority groups were perceived as areas for action and intervention.