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Despite the low prevalence of HIV-1 in Israel, continuous waves of immigration may have impacted the local epidemic. We characterized all people diagnosed with HIV-1 in Israel in 2010–2018. The demographics and clinical data of all individuals (n = 3639) newly diagnosed with HIV-1 were retrieved. Subtypes, transmitted drug-resistance mutations (TDRM), and phylogenetic relations, were determined in >50% of them. In 39.1%, HIV-1 transmission was through heterosexual contact; 34.3% were men who have sex with men (MSM); and 10.4% were people who inject drugs. Many (>65%) were immigrants. Israeli-born individuals were mostly (78.3%) MSM, whereas only 9% of those born in Sub-Saharan Africa (SSA), Eastern Europe and Central Asia (EEU/CA), were MSM. The proportion of individuals from SSA decreased through the years 2010–2018 (21.1% in 2010–2012; 16.8% in 2016–2018) whereas those from EEU/CA increased significantly (21% in 2010–2012; 27.8% in 2016–2018, p < 0.001). TDRM were identified in 12.1%; 3.7, 3.3 and 6.6% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively, with the overall proportion remaining stable in the studied years. None had integrase TDRM. Subtype B was present in 43.9%, subtype A in 25.2% (A6 in 22.8 and A1 in 2.4%) and subtype C in 17.1% of individuals. Most MSM had subtype B. Subtype C carriers formed small clusters (with one unexpected MSM cluster), A1 formed a cluster mainly of locally-born patients with NNRTI mutations, and A6 formed a looser cluster of individuals mainly from EEU. Israelis

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

We report an emergence and increase in poliovirus type 2 detection via routine wastewater surveillance in three non-overlapping regions in the Jerusalem region, Israel, between April and July 2022. Sequencing showed genetic linkage among isolates and accumulation of mutations over time, with two isolates defined as vaccine-derived polioviruses (VDPV). This demonstrates the emergence and potential circulation of type 2 VDPV in a high-income country with high vaccine coverage and underscores the importance of routine wastewater surveillance during the polio eradication.

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.

Using isolates of SARS-CoV-2 WT, Beta, Delta and most importantly Omicron we studied the capability of the BNT162b2 vaccine given in two or three doses to neutralize major SARS-CoV-2 variants of concern (VOC).We demonstrate low neutralization efficiency against delta and wild-type for vaccines with more than 5 months following the second BNT162b2 dose, with no neutralization efficiency against Omicron. We demonstrate the importance of a third dose, by showing a 100-fold increase in neutralization efficiency of Omicron following a third dose, with a 4-fold reduced neutralization compared to that against the Delta VOC. The durability of the effect of the third dose is yet to be determined.

In this report, we describe a national-scale monitoring of the SARS-COV-2 (SC-2) variant dynamics in Israel, using multiple-time sampling of twelve wastewater treatment plants. We used a combination of inclusive and selective quantitative PCR assays that specifically identify variants A19 or B.1.1.7 and tested each sample for the presence and relative viral RNA load of each variant. We show that between December-2020 and March-2021, a complete shift in the SC-2 variant circulation was observed, where the B.1.1.7 replaced the A19 in all examined test points. We further show that the normalized viral load (NVL) values and the average new cases per week reached a peak in January 2021, and then decreased gradually in almost all test points, in parallel with the progression of the national vaccination campaign, during February-March 2021. This study demonstrates the importance of monitoring SC-2 variant dynamics on a national scale through wastewater sampling. It also provides a proof-of-concept methodology for continuous surveillance by using a combination of inclusive and selective PCR tests, which is far more amendable for high throughput monitoring compared with sequencing. This approach may be useful for real-time dynamics surveillance of current and future variants, such as the Omicron (BA.1) variant.SynopsisThis study describes the continuous monitoring of the SARS CoV-2 variant B.1.1.7 circulation in wastewater in Israel using a positive/negative quantitative PCR assay.

In this report, we describe four RT-qPCR assays that enable rapid identification of the newly emerging SARS-COV-2 Omicron (B.1.1.529) variant of concern. The assays target Omicron characteristic mutations in the nsp6 (Orf1a), spike and nucleocapsid genes. We demonstrate that the assays are straightforward to assemble and perform, are amendable for multiplexing, and may be used as a reliable first-line tool to identify B.1.1.529 suspected samples. Importantly, this is a preliminary development report. Further validation and optimization of the assays described herein will be published hereafter.

In this report, we describe the development of an RT-qPCR assay, termed Alpha Delta assay, which can detect SARS-COV-2 (SC-2) and distinguish between the Alpha (B.1.1.7) and Delta (B.1.617.2) variants. The Alpha- and Delta-specific reactions in the assay target mutations that are strongly linked to the target variant. The Alpha reaction targets the D3L substitution in N gene, and the Delta reaction targets the spike gene 156-158 mutations. Additionally, we developed a second Delta-specific assay, used as a confirmatory test for the Alpha Delta assay that targets the 119-120 deletion in the Orf8 gene. Both reactions have similar sensitivities of 15-25 copies per reaction, similar to the sensitivity of commercial SC-2 detection tests. The Alpha Delta assay and the Orf8-119del assay were successfully used to classify clinical samples that were subsequently analyzed by whole genome sequencing. Lastly, we show that the Alpha Delta and Orf8-119del assays correctly identified the presence of Alpha and Delta lineages RNA in wastewater samples. This study provides a rapid, sensitive and cost-effective tool for detecting and classifying two worldwide dominant SC-2 variants. It also highlights the importance of a timely diagnostic response to the emergence of new SC-2 variants with significant consequences on global health.

A nosocomial outbreak of SARS-CoV-2 Delta variant infected 42 patients, staff and family members; 39 were fully vaccinated. The attack rate was 10.6% (16/151) among exposed staff and reached 23.7% (23/97) among exposed patients in a highly vaccinated population, 16–26 weeks after vaccination (median: 25 weeks). All cases were linked and traced to one patient. Several transmissions occurred between individuals wearing face masks. Fourteen of 23 patients became severely sick or died, raising a question about possible waning immunity.

BackgroundMethodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate real-world VE in a closely monitored population.MethodsWe conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples – at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher’s exact test.FindingsOf the 1,567 HCP enrolled between December 27, 2020 and February 15, 2021, 1,250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR- confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant.InterpretationOur prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 during a period of predominant alpha variant circulation.FundingClalit Health Services

Nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks among health care workers have been scarcely reported so far. This report presents the results of an epidemiologic and molecular investigation of a SARS-CoV-2 outbreak among laundromat facility workers in a large tertiary centre in Israel. Following the first three reported cases of SARS-CoV-2 among laundromat workers, all 49 laundromat personnel were screened by qRT-PCR tests using naso- and oropharingeal swabs. Epidemiologic investigations included questionnaires, interviews and observations of the laundromat facility. Eleven viral RNA samples were then sequenced, and a phylogenetic analysis was performed using MEGAX. The integrated investigation defined three genetic clusters and helped identify the index cases and the assumed routes of transmission. It was then deduced that shared commute and public showers played a role in SARS-CoV-2 transmission in this outbreak, in addition to improper PPE use and social gatherings (such as social eating and drinking). In this study, we present an integrated epidemiologic and molecular investigation may help detect the routes of SARS-CoV-2 transmission, emphasising such routes that are less frequently discussed. Our work reinforces the notion that person-to-person transmission is more likely to cause infections than environmental contamination (e.g. from handling dirty laundry).

The SARS-Coronavirus-2 (SARS-CoV-2) driven pandemic was first recognized in late 2019, and the first few months of its evolution were relatively clock-like, dominated mostly by neutral substitutions. In contrast, the second year of the pandemic was punctuated by the emergence of several variants that bore evidence of dramatic evolution. Here, we compare and contrast evolutionary patterns of various variants, with a focus on the recent Delta variant. Most variants are characterized by long branches leading to their emergence, with an excess of non-synonymous substitutions occurring particularly in the Spike and Nucleocapsid proteins. In contrast, the Delta variant that is now becoming globally dominant, lacks the signature long branch, and is characterized by a step-wise evolutionary process that is ongoing. Contrary to the “star-like” topologies of other variants, we note the formation of several distinct clades within Delta that we denote as clades A-E. We find that sequences from the Delta D clade are dramatically increasing in frequency across different regions of the globe. Delta D is characterized by an excess of non-synonymous mutations, mostly occurring in ORF1a/b, some of which occurred in parallel in other notable variants. We conclude that the Delta surge these days is composed almost exclusively of Delta D, and discuss whether selection or random genetic drift has driven the emergence of Delta D.

BackgroundIsraeli has vaccinated over 80% of its adult population, with two doses of the Pfizer BNT162b2 vaccine. This intervention has been highly successful in curtailing the coronavirus 2 outbreak. One major concern is the ability of the virus to mutate which potentially can cause SARS-CoV-2 to partially escape from the immune system. Here we evaluate the efficacy of the Pfizer vaccine against the B.1.351 variant.MethodsThe Ministry of Health, initiated sequencing of selected positive swab samples identified as being of interest. We used logistic regression, with variant type as the dependent variable, vaccination status as the main explanatory variable, controlling for age, sex, subpopulation, place of residence and time of sample, to estimate the odds ratio for a vaccinated case to have the B. 1.351 versus the B.1.1.7 variant, within vaccinated and unvaccinated persons who tested positive.FindingsThere were 19 cases of B.1.351 variant (3.2%) among those vaccinated more than 14 days before the positive sample and 88 (3.5%) among the unvaccinated. The estimated odds ratio was 1.29 [95% CI: 0.66-2.50]. From this result, assuming the efficacy against the B.1.1.7 variant to be 95%, the estimated efficacy against the B.1.351 variant was 94% [95% CI: 87-97%].InterpretationDespite the concerns caused by the B.1.351 variant, the BNT162b2 vaccine seems to provide substantial immunity against both that variant and the B.1.1.7. Our results suggest that from 14 days following the second vaccine dose the efficacy of BNT162b2 vaccine is at most marginally affected by the B.1.351 variant.FundingNo funding

Emerging SARS-CoV-2 variants may threaten global vaccination efforts and the awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.

Emerging SARS-CoV-2 variants may threaten global vaccination efforts and awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.

West Nile virus is a notable cause of neuroinvasive disease, damage to the central nervous system, or even death. In this study, using metagenomics analysis and quantitative real-time PCR validation, we identified a JC virus infection in urine and cerebrospinal fluid samples of a West Nile virus patient with severe neurological symptoms and extended disease. JC virus is known to be involved in neurological complications, especially in immunocompromised individuals thus suggesting that the coinfection with JC virus is involved with the West Nile virus infection persistence and severe symptoms. JC virus was identified in urine samples from additional West Nile virus patients via quantitative real-time PCR, however, JC virus was not found in any cerebrospinal fluid samples of West Nile virus patients, suggesting that JC virus does not regularly infect the central nervous system of WNV patients. Overall, this study highlights the importance of identifying infection by opportunistic viruses in already-diagnosed patients and highlights the advantages of next-generation sequencing and metagenomics for viral diagnosis.

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501YV2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected., Wellcome Open Research, 6

Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may influence the effectiveness of existing laboratory diagnostics. In the current study we determined whether the British (20I/501Y.V1) and South African (20H/501Y.V2) SARS-CoV-2 variants of concern are detected with an in-house S1-based antigen detection assay, analyzing spiked pools of quantitative reverse-transcription polymerase chain reaction–negative nasopharyngeal swab specimens. The assay, combining 4 monoclonal antibodies, allowed sensitive detection of both the wild type and the variants of concern, despite accumulation of several mutations in the variants’ S1 region—results suggesting that this combination, targeting distinct epitopes, enables both specificity and the universality.

The changing nature of the corona virus of the SARS-CoV-2 pandemic poses unprecedented challenges to the world’s health systems. New and virulent emerging spike gene variants, such as the UK 20I/501Y.V1 and South African 20H/501Y.V2, could jeopardize global efforts to produce immunity and reduce mortality. These challenges require effective real-time genomic surveillance solutions that the medical community can quickly adopt. The SARS-CoV-2 spike protein mediates host receptor recognition and entry into the cell and therefore, it is most susceptible to generation of variants with increased transmissibility and pathogenicity. The spike protein is also the primary target of neutralizing antibodies in COVID-19 patients and the most common antigen for induction of effective vaccine immunity. Therefore, tight monitoring of the spike protein gene variants is key to mitigating COVID-19 spread and vaccine escape mutants. Currently, the ARTIC method for SARS-CoV-2 whole genome sequencing is applied worldwide. However, this method commonly requires more than 96 hours (4–5 days) from start to finish and at present high sample sequence demands, sequencing resources are quickly exhausted. In this work, we present HiSpike, a method for high-throughput targeted next generation sequencing (NGS) of the spike gene. This simple three-step method can be completed in less than 30 hours and can sequence 10-fold more samples compared to the conventional ARTIC method and at a fraction of the cost. HiSpike was proven valid, and has identified, at high quality, multiple spike variants from real-time field samples, such as the UK and the South African variants. This method will certainly be effective in discovering future spike mutations. Therefore, running HiSpike for full sequencing of the spike gene of all positive SARS-CoV-2 samples could be considered for near real-time detection of known and emerging spike mutations as they evolve. HiSpike provides affordable sequencing options to help laboratories conserve resources, hence it provides a tool for widespread monitoring, that can support critical knowledge-based decisions.

Routine detection, surveillance and reporting of SARS-CoV-2 novel variants is important, as these threaten to hinder vaccination efforts. Herein we report a local novel strain that includes a non-synonymous mutation in the spike (S) protein - P681H and additional synonymous mutations. The P681H Israeli strain has not been associated with higher infection rates and was neutralized by sera from vaccinated individuals in comparable levels to the B.1.1.7 strain and a non-P681H strain from Israel.

One of the key questions regarding COVID19 vaccines is whether they can reduce viral shedding. To date, Israel vaccinated substantial parts of the adult population, which enables extracting real world signals. The vaccination rollout started on Dec 20th 2020, utilized mainly the BNT162b2 vaccine, and focused on individuals who are 60 years or older. By now, more than 75% of the individuals of this age group have been at least 14 days after the first dose, compared to 25% of the individuals between ages 40-60 years old. Here, we traced the Ct value distribution of 16,297 positive qPCR tests in our lab between Dec 1st to Jan 31st that came from these two age groups. As we do not have access to the vaccine status of each test, our hypothesis was that if vaccines reduce viral load, we should see a difference in the Ct values between these two age groups in late January but not before. Consistent with this hypothesis, until Jan 15th, we did not find any statistically significant differences in the average Ct value between the groups. In stark contrast, our results in the last two weeks of January show a significant weakening in the average Ct value of 60+ individuals to the 40-60 group. To further corroborate these results, we also used a series nested linear models to explain the Ct values of the positive tests. This analysis favored a model that included an interaction between age and the late January time period, consistent with the effect of vaccination. We then used demographic data and the daily vaccination rates to estimate the effect of vaccination on viral load reduction. Our estimate suggests that vaccination reduces the viral load by 1.6x to 20x in individuals who are positive for SARS-CoV-2. This estimate might improve after more individuals receive the second dose. Taken together, our findings indicate vaccination is not only important for individual’s protection but can reduce transmission.

The SARS-CoV-2 Lambda (Pango lineage designation C.37) variant of interest, initially identified in Peru, has spread to additional countries. First detected in Israel in April 2021 following importations from Argentina and several European countries, the Lambda variant infected 18 individuals belonging to two main transmission chains without further spread. Micro-neutralisation assays following Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer) vaccination demonstrated a significant 1.6-fold reduction in neutralising titres compared with the wild type virus, suggesting increased susceptibility of vaccinated individuals to infection.

Background: SARS-CoV-2 variant Beta (B.1.351) was designated as a Variant of Concern (VoC) after becoming the dominant strain in South Africa and spreading internationally. BNT162b2 showed lower levels of neutralizing antibodies against Beta than against other strains raising concerns about effectiveness of vaccines against infections caused by Beta. We estimated BNT162b2 effectiveness against Beta infections in Israel, a country with high vaccine uptake. Methods: The Ministry of Health (MoH) identified Beta cases through mandatory reporting of SARS-CoV-2 cases and whole genome sequencing (WGS) of specimens from vaccination-breakthrough infections, reinfections, arriving international travelers, and a selection of other infected persons. A cohort analysis was conducted of exposure events of contacts of primary Beta cases. WGS was conducted on available PCR-positive specimens collected from contacts. VE estimates with 95% confidence intervals (CIs) against confirmed and probable Beta infections were determined by comparing infection risk between unvaccinated and fully-vaccinated ( > 7 days after the second dose) contacts, and between unvaccinated and partially-vaccinated ( 16 years, were identified. 343/552 (62%) contacts were interviewed and tested. 71/343 (21%) contacts were PCR-positive. WGS was performed on 7/71 (10%) PCR-positive specimens; all were Beta. Among SARS-CoV-2-infected contacts, 48/71 (68%) were symptomatic, 10/71 (14%) hospitalized, and 2/71 (3%) died. Fully-vaccinated VE against confirmed or probable Beta infections was 72% (95% CI -5 - 97%; p =0.04) and against symptomatic confirmed or probable Beta infections was 100% (95% CI 19 - 100%; p =0.01). There was no evidence of protection in partially-vaccinated contacts. Interpretation: Two doses of BNT162b2 conferred protection against Beta infections and disease. Introductions of Beta did not interrupt control of the pandemic in Israel. Funding: None to declare. Declaration of Interest: Frederick Angulo, David Swerdlow, John McLaughlin, Farid Khan, Gabriel Mircus, Kaijie Pan, Jo Southern, and Luis Jodar hold stock and stock options in Pfizer Inc. Marc Lipsitch has provided advice on COVID-19 free of charge to Janssen, Astra-Zeneca, Pfizer, and COVAXX (United Biomedical), as well as to the nonprofit One Day Sooner and has received consulting income or honoraria from Merck, Pfizer, Bristol Meyers Squibb, Janssen, and Sanofi, and institutional research support from Pfizer. He is on the Scientific Advisory Committee of the Coalition for Epidemic Preparedness and Innovations (CEPI). All other authors report no conflicts. Ethical Approval: This study was approved by MoH’s Institutional Review Board (CoR-MoH-080-2021).

Severe acute respiratory disease coronavirus 2 (SARS-CoV-2) which causes corona virus disease (COVID-19) was first identified in Wuhan, China in December 2019 and has since led to a global pandemic. Importations of SARS-CoV-2 to Israel in late February from multiple countries initiated a rapid outbreak across the country. In this study, SARS-CoV-2 whole genomes were sequenced from 59 imported samples with a recorded country of importation and 101 early circulating samples in February to mid-March 2020 and analyzed to infer clades and mutational patterns with additional sequences identified Israel available in public databases. Recorded importations in February to mid-March, mostly from Europe, led to multiple transmissions in all districts in Israel. Although all SARS-CoV-2 defined clades were imported, clade 20C became the dominating clade in the circulating samples. Identification of novel, frequently altered mutated positions correlating with clade-defining positions provide data for surveillance of this evolving pandemic and spread of specific clades of this virus. SARS-CoV-2 continues to spread and mutate in Israel and across the globe. With economy and travel resuming, surveillance of clades and accumulating mutations is crucial for understanding its evolution and spread patterns and may aid in decision making concerning public health issues.

Objectives Zika virus (ZIKV) infection during pregnancy may cause neurological abnormalities in the foetus, and therefore fast and accurate laboratory assays are critical for rapid diagnosis. ELISA based on ZIKV NS1 protein has been developed and shown to be sensitive and highly specific; however, its negative and positive predictive values have not been tested. In this study we evaluated the ability of the NS1-based ELISA to exclude ZIKV infection and serve as a first-line screening tool for travellers. Methods We tested samples obtained during the peak of ZIKV infection from 1188 symptomatic and asymptomatic Israeli travellers using NS1-based IgG and IgM ELISA, real-time RT-PCR analysis and ZIKV neutralization. The Kaplan–Maier method was used to evaluate the duration of ZIKV RNA in whole blood and urine samples. Results NS1-based ELISA identified 20 true-positive, five false-positive and four false-negative cases, resulting in sensitivity and specificity of 83.3% (95%CI: 62–94%) and 97.5% (95%CI: 94–99%) respectively, and positive and negative predictive values of 80% (95%CI: 59–92%) and 98% (95%CI: 95–99%) respectively. Based on 14 RT-PCR-positive cases, median time to detect ZIKV RNA in whole blood was 17.5 days (range 5–58 days) and in urine 10 days (range 5–26 days). Conclusions The NS1-based ELISA and RT-PCR in whole blood are highly reliable for identification of ZIKV-negative and -positive cases, respectively. Combination of both assays minimizes the risk of false-negative results, and thus allows the exclusion of ZIKV infection in travellers returning from ZIKV-endemic countries, including those who are pregnant or wish for preconception screening.

Background: SARS-CoV-2 variant Beta (B.1.351) was designated as a Variant of Concern (VoC) after becoming the dominant strain in South Africa and spreading internationally. BNT162b2 showed lower levels of neutralizing antibodies against Beta than against other strains raising concerns about effectiveness of vaccines against infections caused by Beta. We estimated BNT162b2 vaccine effectiveness (VE) against Beta infections in Israel, a country with high vaccine uptake. Methods: The Ministry of Health (MoH) identified Beta cases through mandatory reporting of SARS-CoV-2 cases and whole genome sequencing (WGS) of specimens from vaccination-breakthrough infections, reinfections, arriving international travelers, and a selection of other infected persons. A cohort analysis was conducted of exposure events of contacts of primary Beta cases. WGS was conducted on available PCR-positive specimens collected from contacts. VE estimates with 95% confidence intervals (CIs) against confirmed and probable Beta infections were determined by comparing infection risk between unvaccinated and fully-vaccinated (≥7 days after the second dose) contacts, and between unvaccinated and partially-vaccinated (

Accurate and timely diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is clinically essential, and is required also to monitor confirmed cases aiming to prevent further spread. Positive real-time PCR results at late time points following initial diagnosis may be clinically misleading as this methodology cannot account for the infection capabilities and the existence of whole genome sequences. In this study, 47 serial respiratory samples were tested by Allplex-nCoV test (Seegene), a triplex of three assays targeting the SARS-CoV-2 RdRP, E and N genes and subsequently assessed by next generation sequencing (NGS). COVID19 patients were tested at an early stage of the disease, when all these viral gene targets were positive, and at an advanced stage, when only the N gene target was positive in the Allplex-nCoV test. The corresponding NGS results showed the presence of complete viral genome copies at both early and advanced stages of the disease, although the total number of mapped sequences was lower in samples from advanced disease stages. We conclude that reduced viral transmission at this late disease stage may result from the low quantities of complete viral sequences and not solely from transcription favoring the N gene.

Respiratory virus infections are very common. Such infections impose an enormous economic burden and occasionally lead to death. Furthermore, every few decades, respiratory virus pandemics emerge, putting the entire world population at risk. Thus, there is an urgent need to quickly and precisely identify the infecting agent in a clinical setting. However, in many patients with influenza-like symptoms (ILS) the identity of the underlying pathogen remains unknown. In addition, it takes time and effort to individually identify the virus responsible for the ILS. Here, we present a new next-generation sequencing (NGS)-based method that enables rapid and robust identification of pathogens in a pool of clinical samples without the need for specific primers. The method is aimed at rapidly uncovering a potentially common pathogen affecting many samples with an unidentified source of disease.