An Outbreak of Parvovirus B19 in Israel.

Human parvovirus B19 (B19V) has a wide clinical spectrum, ranging from an asymptomatic infection to a life threatening one. During pregnancy, it can lead to fetal loss and hydrops fetalis. This retrospective study examined the incidence rates of B19V in Israel, analyzing anonymized electronic medical records of 2.7 million individuals between January 2015 and September 2023. A generalized linear model with a Poisson distribution was fit to the data, adjusting for potential confounders. A marked increase in B19V was observed in 2023, with an adjusted incidence rate ratio (IRR) of 6.6 (95% CI 6.33-6.89) when comparing 2023 to previous years. When specifically comparing 2023 to COVID-19 years (2020-2022), adjusted IRR climbs to 9.21 (8.66-9.80). Moreover, in 2023, previously existing seasonality has largely disappeared. High SES characterized most infected individuals with a marked discrepancy in social sectors; the Arab population was significantly less likely to be found B19V positive, even when adjusting for SES. Most infections occurred in school-aged children (6-11 years old). Pregnant women experienced the most significant rise in B19V, with an adjusted IRR of 11.47 (9.44-13.97) in 2023 compared to previous years; most cases were diagnosed in the first trimester. This study demonstrates that Israel is currently experiencing the largest and longest reported outbreak of B19V to date. Policymakers should consider setting screening policies in place, at least for populations at risk, while specifically studying and potentially targeting low socioeconomic populations and specific social sectors to avoid health inequalities.

Mpox Patient Journey in Israel.

Reports on Mpox have, thus far, characterized the disease, but mostly through a single timepoint view. The aim of this study was to characterize Mpox in the Israeli setting, in general, alongside compiling a detailed patient journey from multiple in-depth interviews with infected individuals. This descriptive study followed two complimentary paths: retrospective and prospective. The first consisted of interviews with Mpox patients, while the retrospective part included the retrieval of anonymized electronic medical records of patients diagnosed with Mpox between May and November 2022. Patient characteristics in Israel were, overall, comparable to global reports. We found that the median time from symptoms to first suspicion of Mpox was 3.5 days, while the median time from the first symptom to a confirmatory test was 6.5 days, which could explain the surge in Israel. The duration of lesions did not alter in terms of their anatomical location, while lower Ct values correlated both with a longer symptom duration and more symptoms. Most patients reported anxiety to a high degree. Clinical trials that consist of a long-term relationship with the medical researchers contribute greatly to a deeper understanding of the patient journey, especially for unfamiliar or stigmatized diseases. Emerging infections, such as Mpox, should be further investigated to assess asymptomatic carriers, especially when rapidly spreading.

Hybrid immunity against reinfection with SARS-CoV-2 following a previous SARS-CoV-2 infection and single dose of the BNT162b2 vaccine in children and adolescents: a target trial emulation.

BACKGROUND: Although most children and adolescents have had a previous SARS-CoV-2 infection and many continue to receive COVID-19 vaccinations, studies of the effectiveness of hybrid immunity against reinfection with the omicron (B.1.1.529) variant are scarce. We aimed to examine the effectiveness of vaccination in convalescent children and adolescents against reinfection with the delta (B.1.617.2) variant and the BA.1 and BA.2 and BA.4 and BA.5 omicron subvariants. METHODS: This retrospective cohort study was devised to emulate a target randomised control trial using a retrospective dataset of anonymised health records of children (5-11 years old) and adolescents (12-16 years old) who were members of the Maccabi Healthcare Services, Israel. The design emulated 91 randomised trials by devising a series of multiple nested trials, compiling the results into a single dataset, and fitting Cox proportional hazards models to estimate adjusted hazard ratios (HRs) with 95% CIs of each measured outcome. The primary aim was to assess the protection from reinfection with the delta variant and the BA.1 and BA.2 and BA.4 and BA.5 omicron subvariants associated with hybrid immunity as a result of a previous SARS-CoV-2 infection followed by vaccination with the BNT162b2 (Pfizer-BioNTech) vaccine. FINDINGS: Data from between from March 1, 2020, to July 31, 2022, for 163 812 individuals (120 721 children [59 404 girls and 61 317 boys], median age 8·0 years [IQR 6·7 to 10·2]; and 43 091 adolescents [21 239 girls and 21 852 boys], median age 13·5 years [12·6 to 14·8]) were included in at least one trial. A single dose of the BNT162b2 vaccine in convalescent children and adolescents confers statistically significant protection against the delta variant (78% [95% CI 72 to 83] in adolescents and 64% [3 to 87] in children) and the omicron BA.1 and BA.2 subvariants (54% [50 to 57] in adolescents and 71% [67 to 73] in children) compared with children who had a previous infection but were unvaccinated. However, the vaccine was not found to confer statistically significant protection against the BA.4 and BA.5 omicron subvariants in adolescents (8% [-18 to 29]) and children (12% [-6 to 27]). INTERPRETATION: Decision makers in BA.4 and BA.5 dominant regions should re-examine whether convalescent individuals aged 5-16 years should receive the BNT162b2 vaccine to prevent future reinfection, especially in light of reports that show that most children and adolescents have already been infected with SARS-CoV-2. FUNDING: None.

Dynamics of Naturally Acquired Immunity Against Severe Acute Respiratory Syndrome Coronavirus 2 in Children and Adolescents.

OBJECTIVE: To evaluate the duration of protection against reinfection conferred by a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. STUDY DESIGN: We applied 2 complementary approaches: a matched test-negative, case-control design and a retrospective cohort design. A total of 458 959 unvaccinated individuals aged 5-18 years were included. The analyses focused on the period July 1, 2021, to December 13, 2021, a period of Delta variant dominance in Israel. We evaluated 3 SARS-CoV-2-related outcomes: documented polymerase chain reaction-confirmed infection or reinfection, symptomatic infection or reinfection, and SARS-CoV-2-related hospitalization or death. RESULTS: Overall, children and adolescents who were previously infected acquired durable protection against reinfection with SARS-CoV-2 for at least 18 months. Importantly, no SARS-CoV-2-related deaths were recorded in either the SARS-CoV-2-naïve group or the previously infected group. The effectiveness of naturally acquired immunity against a recurrent infection reached 89.2% (95% CI, 84.7%-92.4%) at 3-6 months after the first infection and declined slightly to 82.5% (95% CI, 79.1%-85.3%) by 9-12 months after infection, with a slight nonsignificant waning trend seen up to 18 months after infection. Additionally, children aged 5-11 years exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in those aged 12-18 years was more prominent but still mild. CONCLUSIONS: Children and adolescents who were previously infected with SARS-CoV-2 remain protected to a high degree for 18 months. Further research is needed to examine naturally acquired immunity against Omicron and newer emerging variants.

Waning effectiveness of the third dose of the BNT162b2 mRNA COVID-19 vaccine.

The duration of protection of the third (booster) dose of the BioNTech/Pfizer BNT162b2 mRNA Coronavirus Disease 2019 vaccine has been the subject of recent investigations, as global discussions around the necessity and effectiveness of a fourth dose are already underway. By conducting a retrospective study implementing a test-negative case-control design, analyzing 546,924 PCR tests performed throughout January 2022 by 389,265 persons who received at least two doses, we find that the effectiveness in each month-since-vaccination decreases significantly. Compared to those vaccinated five months prior to the outcome period, on August 2021, relative protection against infection waned from 53.4% a month after vaccination to 16.5% three months after vaccination. These results suggest that there is a significant waning of vaccine effectiveness against the Omicron variant of the third dose of the BNT162b2 vaccine within a few months after administration. Additional information could assist to comprehensively estimate the effectiveness of the three-dose-strategy.

Short term, relative effectiveness of four doses versus three doses of BNT162b2 vaccine in people aged 60 years and older in Israel: retrospective, test negative, case-control study.

OBJECTIVE: To examine the relative effectiveness of a fourth dose of the Pfizer-BioNTech mRNA (BNT162b2) vaccine compared with three vaccine doses over the span of 10 weeks. DESIGN: Retrospective, test negative, case-control study, with a matched analysis and an unmatched multiple tests analysis. SETTING: Nationally centralised database of Maccabi Healthcare Services, an Israeli national health fund for 2.5 million people; from 10 January 2022 (seven days after the fourth dose was first given to eligible individuals) to 13 March 2022, an omicron dominant period in Israel. PARTICIPANTS: 97 499 Maccabi Healthcare Services members aged 60 years and older, who were eligible to receive a fourth vaccine dose and obtained at least one polymerase chain reaction (PCR) test during the study. MAIN OUTCOME MEASURES: Breakthrough SARS-CoV-2 infection, defined as a positive PCR test performed seven or more days after inoculation with the BNT162b2 vaccine; and breakthrough SARS-CoV-2 infection resulting in severe covid-19 disease, defined as hospital admission or death related to covid-19. RESULTS: 27 876 participants received the fourth BNT162b2 vaccine dose and 69 623 received three doses only. Of 106 participants who died during the follow-up period, 77 had had their third doses only and 23 had had their fourth doses during the first three weeks after inoculation. In the first three weeks, a fourth dose provided additional protection against both SARS-CoV-2 infection and severe disease relative to three doses of the vaccine. However, relative vaccine effectiveness against infection quickly decreased over time, peaking during the third week at 65.1% (95% confidence interval 63.0% to 67.1%) and falling to 22.0% (4.9% to 36.1%) by the end of the 10 week follow-up period. Unlike relative effectiveness against SARS-CoV-2 infection, the relative effectiveness of a fourth dose against severe covid-19 was maintained at a high level (>72%) throughout follow-up. However, severe disease was a relatively rare event, occurring in <1% of study participants who received four doses or three doses only. CONCLUSIONS: A fourth dose of the BNT162b2 vaccine appears to have provided additional protection against both SARS-CoV-2 infection and severe covid-19 disease relative to three vaccine doses. However, relative effectiveness of the fourth dose against infection appears to wane sooner than that of the third dose.

Pfizer-BioNTech vaccine effectiveness against Sars-Cov-2 infection: Findings from a large observational study in Israel.

Development of an effective vaccine against Covid-19 is crucial to reducing infection. mRNA BNT162b2, developed and manufactured by Pfizer-BioNTech, was one of the first FDA-approved vaccinations reporting high efficacy (95%) and minimal side effects. Evaluating effectiveness of BNT162b2 in a general population has been made possible after the implementation of a nation-wide vaccination program in Israel. This retrospective cohort study was carried out in Maccabi HealthCare services, Israel among 1.6 million members aged 16 and over. The population was divided into those who were at least seven days post- second vaccination and those who had not been vaccinated. Number of days till the end of the study or Covid-19 infection, Covid-19-related hospitalization and mortality was calculated for each participant between 18.1.2021 to 25.4.2021. Participants who had reached day eight after second vaccination during the study period could contribute days to both groups. Vaccine efficacy (VE) was calculated using a conditional Poisson model, controlling for age group, gender, hypertension, diabetes and obesity, fitted within clusters defined by geographical statistical area and calendar week. BNT162b2 was found effective for the total population group for infection, hospitalization and mortality, with adjusted VE of 93·0% (CI:92·6-93·4%), 93·4% (CI:91·9-94·7%) and 91·1% (CI:86·5-94·1%) respectively. VE for infection was lower for participants aged 75 and over, and for those with hypertension, diabetes and obesity. This study strengthens the evidence that the Pfizer-BioNTech vaccination is effective in preventing infection, hospitalization and mortality.

Effectiveness of mRNA BNT162b2 Vaccine 6 Months after Vaccination among Patients in Large Health Maintenance Organization, Israel.

Israel experienced a new wave of coronavirus disease during June 2021, six months after implementing a national vaccination campaign. We conducted 3 discrete analyses using data from a large health maintenance organization in Israel to determine whether IgG levels of fully vaccinated persons decrease over time, describe the relationship between IgG titer and subsequent PCR-confirmed infection, and compare PCR-confirmed infection rates by period of vaccination. Mean IgG levels steadily decreased over the 6-month period in the total tested population and in all age groups. An inverse relationship was found between IgG titer and subsequent PCR-positive infection. Persons vaccinated during the first 2 months of the campaign were more likely to become infected than those subsequently vaccinated. The vaccinated group >60 years of age had lower initial IgG levels and were at greater risk for infection. The findings support the decision to add a booster vaccine for persons >60 years of age.

Effectiveness of a Third Dose of BNT162b2 mRNA Vaccine.

A retrospective cohort study was carried out in a large Israeli health maintenance organization to determine vaccine effectiveness (VE) of a third dose of BNT162b2 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Of nearly 1 million members receiving 2 doses of BNT162b2 in January-February 2021, infection rates (based on polymerase chain reaction results) were compared between those who received a third dose with those who did not during August-October 2021 (maximum, 70 days). Crude VE was 92.9% (95% confidence interval [CI], 92.6%-93.2%) and adjusted VE was 89.1% (95% CI, 87.5%-90.5%). We conclude that the third dose provides added protection against SARS-CoV-2 infection for those vaccinated 6 months ago.