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Background Methodologically 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 early real-world VE in a closely monitored population. Methods We 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. Results Of the 1567 HCP enrolled between December 27, 2020 and February 15, 2021, 1250 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. Conclusions Our 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 infection in recently vaccinated HCP during a period of predominant alpha variant circulation. Funding Clalit Health Services.

The SARS-CoV-2 pandemic led to unprecedented testing demands, causing significant testing delays globally. One strategy used for increasing testing capacity was pooled-testing, using a two-stage technique first introduced during WWII. Here we report the development, validation and clinical application of P-BEST - a single-stage pooled-testing strategy that was approved for clinical use in Israel. P-BEST was clinically evaluated using 3,636 side-by-side tests and was able to correctly detect all positive samples and accurately estimate their Ct value. P-BEST was then used to clinically test 837,138 samples using 270,095 PCR tests - a 3.1 fold reduction in the number of tests. Importantly, P-BEST was also used during the Alpha and Delta waves, when positivity rates exceeded 10%, rendering traditional pooling non-practical. We also describe a tablet-based solution that allows performing manual single-stage pooling in settings where liquid dispensing robots are not available. Our data provides a proof-of-concept for large-scale clinical implementation of single-stage pooled-testing for continuous surveillance of multiple pathogens with reduced test costs, and as an important tool for increasing testing efficiency during pandemic outbreaks.

Background The incidence of invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from nonpharmaceutical interventions. We used multiple ongoing cohort surveillance projects in children Methods The first SARS-CoV-2 cases were detected in February 2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory infections necessitating chest X-rays (NA-LRIs), nasopharyngeal pneumococcal carriage in nonrespiratory visits, nasopharyngeal respiratory virus detection (by polymerase chain reaction), and nationwide IPD. Monthly rates (January 2020 through February 2021 vs mean monthly rates 2016–2019 [expected rates]) adjusted for age and ethnicity were compared. Results CAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios [IRRs]: .07 and .19, respectively); NA-LRIs and nonpneumonia IPD were also reduced by a lesser magnitude (IRRs: .46 and .42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced, and density of colonization and pneumococcal serotype distributions were similar to previous years. The decline in pneumococcus-associated disease was temporally associated with a full suppression of respiratory syncytial virus, influenza viruses, and human metapneumovirus, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels. Conclusions Reductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic in Israel were not predominantly related to reduced pneumococcal carriage and density but were strongly associated with the disappearance of specific respiratory viruses.

Background During the early Covid-19 pandemic, we observed a close-to-full disappearance of the activity of 4 respiratory viruses (RSV, hMPV, influenza, and parainfluenza), followed by an off-season sequential re-emergence in 2021. Surprisingly, a striking similarity between the dynamics of pneumococcus-associated disease (PAD; namely community-acquired alveolar pneumonia [CAAP; often considered pneumococcal] and bacteremic-pneumococcal pneumonia [IPD-Pneumonia]), was also observed. In contrast, adenovirus and rhinovirus activities did not change during COVID-19. We examined the association between PAD and RSV, hMPV, influenza, and parainfluenza (PAD-viruses). Methods Surveillance of CAAP and IPD-Pneumonia incidences and viral activity in children < 5 years was described in detail previously [Danino D. et al. Clin Infect Dis. 2022, https://doi.org/10.1093/cid/ciab1014]. We extended the observations until December 2021, to capture the sequential re-emergence of the 4 PAD-viruses. A hierarchical linear regression model was used to quantify the association between PAD-viruses (each virus individually and combined), adenovirus and PAD. After fitting the models, the contribution of each virus was estimated. Results The Figure shows striking similarities in the dynamics of CAAP, IPD-Pneumonia, and PAD-viruses both before and during the COVID-19 pandemic. During the expected peak season (Oct 2020 – Apr 2021) PAD episodes were extremely low. However, off-season peaks were seen during May – Dec 2021. Overall, 78% and 25% of all CAAP and IPD-Pneumonia episodes, respectively, were attributable to these viruses in children < 5 (Table). In CAAP, cases were attributable to each of the 4 PAD-viruses individually throughout the first 5 years of life: RSV and hMPV combined contributed 80%, 63%, and 42% of all CAAP episodes in children aged < 1, 1, and 2-4 years, respectively. The respective figures for influenza and parainfluenza combined were 13%, 21%, and 22%. Only RSV significantly contributed to IPD-Pneumonia (19%). Adenovirus did not contribute to PAD episodes. Conclusion Our model suggests an important causative association between RSV, hMPV, influenza, and parainfluenza viruses and CAAP, and between RSV and IPD-Pneumonia. Disclosures All Authors: No reported disclosures.

Background Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) and to a lesser extent, parainfluenza and influenza viruses have been associated with pneumonia in young children. In contrast, adenovirus (AdV) and rhinovirus (RhV) are usually not associated with pneumonia. We aimed to evaluate the involvement of the four pneumonia associated viruses (grouped as PAV) in pediatric CAAP, before and during the COVID-19 pandemic. Methods CAAP incidence and viral activity surveillance in southern Israel in children < 5y and virological detection methods were described previously (Danino. CID 2022, https://doi.org/10.1093/cid/ciab1014). We reviewed the period of Jan 2016 - Mar 2022. Most cases of COVID-19 in children < 5y occurred during Dec 2021 - Mar 2022 (Figure 1); Over 95% of children admitted for respiratory disease were tested for COVID-19 (PCR). Since AdV and RhV activity was previously not associated with CAAP and tended to be equally involved in mixed and single infections, the current analysis was done for the four PAV only. Results CAAP incidence dynamics closely resembled the four PAV (grouped) activity dynamics (Figure 2A, 2B) with very low activity during the expected peak in winter 2020-2021, but with an off-season resurgence from spring 2021. Even though most CAAP episodes during the pandemic coincided with peak COVID-19 rates, only 9 CAAP episodes were COVID-19 positive (7 in 2022, of which 5 were RSV positive). Out of 3,430 CAAP episodes 55% were tested for PAV, of which 61% were positive, with similar rates before and during the pandemic. RSV was the most common involved virus, followed by hMPV. The virus distribution in CAAP during the entire period reflected their activity in the community (Figure 2C). Unlike pre-pandemic years where all four PAV appeared almost simultaneously, in 2021 PAV resurged sequentially, resulting in successive involvement in CAAP episodes, suggesting a causative association. Conclusion 1. SARS-CoV-2 was only rarely involved in CAAP in young children. 2. PAV were involved in 61% of CAAP episodes in children < 5y with predominance of RSV and hMPV. 3. The atypical dynamics imposed by the COVID-19 pandemic suggests a causative association between PAV and CAAP. Disclosures All Authors: No reported disclosures.

SummaryBACKGROUNDIn young children, rates of lower respiratory infections (LRI) and invasive pneumococcal disease (IPD) have been associated with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (flu), and parainfluenza (PIV) (collectively termed here as pneumonia and pneumococcal disease-associated viruses [PDA-viruses]). However, their contribution to the pathogenesis of these disease endpoints has not yet been elucidated. The COVID-19 pandemic provided a unique opportunity to examine the question.METHODSThis prospective study comprised all children FINDINGSDuring 2016 through 2021, 3,204, 26,695, 257, and 619 episodes of CAAP, non-CAAP LRI, pneumococcal bacteremic pneumonia and non-pneumonia IPD, respectively, were reported. Compared to 2016-2019, broad declines in the disease endpoints were observed shortly after the pandemic surge, coincident with a complete disappearance of all PDA-viruses and continued circulation of rhinovirus (RhV) and adenovirus (AdV). From April 2021, off-season and abrupt surges of all disease endpoints occurred, associated with similar dynamics among the PDA-viruses, which re-emerged sequentially. Using our model fit to the entire 2016-2021 period, 82% (95% CI, 75-88%) of CAAP episodes in 2021 were attributable to the common respiratory viruses, as were 22%-31% of the other disease endpoints. Virus-specific contributions to CAAP were: RSV, 49% (95% CI, 43-55%); hMPV, 13% (10-17%); PIV, 11% (7-15%); flu, 7% (1-13%). RhV and AdV did not contribute. RSV was the main contributor in all endpoints, especially in infants. Pneumococcal carriage prevalence remained largely stable throughout the study.INTERPRETATIONRSV and hMPV play a critical role in the burden of CAAP and pneumococcal disease in children. Interventions targeting these viruses could have a secondary effect on the burden of disease typically attributed to bacteria.FUNDINGThere was no funding for this study.Research in ContextEvidence before this studyLower respiratory infections (LRI) and invasive pneumococcal disease (IPD) in young children, have often been associated with specific respiratory viruses, namely respiratory syncytial virus (RSV), human metapneumovirus (hMPV) influenza viruses (flu), and parainfluenza viruses (PIV) (termed in the current article pneumonia and pneumococcal disease-associated viruses [PDA-viruses]). However, their causative role as co-pathogens has not yet been fully elucidated. There is already ample evidence that bacteria and viruses interact to cause severe disease. This could be seen after the introduction of pneumococcal conjugate vaccines (PCVs), when there was a significant reduction in hospitalisation for viral lower respiratory infections (LRIs). This suggests that viral-pneumococcal coinfections are common and play a role in the pathogenesis of pneumococcal respiratory infections. To demonstrate the contribution of viruses to the burden of pneumococcal disease specifically, and pneumonia in general, it would be necessary to eliminate one or more of the respiratory viruses. Shortly after the start of the COVID-19 pandemic, multiple reports demonstrated reduced IPD and LRI rates among young children, coincident with dramatically reduced rates of the PDA-viruses globally. Initially, the reduced rates of pneumococcal disease were attributed to non-pharmaceutical interventions that might reduce pneumococcal transmission in the community. However, continuous, virtually unchanged pneumococcal carriage rates were reported in multiple studies, strongly suggesting the reduced circulation ofS. pneumoniaewas not significantly contributing to disease reduction. Surprisingly, pneumococcus-associated diseases and PDA-viruses simultaneously re-emerged in 2021 during the off-season. In contrast to PDA-viruses, other viruses, such as adenovirus and rhinovirus did not show any of the patterns discussed above. We searched PubMed on June 1st, 2022, for studies since 2020 using the following terms: (“COVID-19” or “SARS-Cov-2”) and (“S. pneumoniae” or “pneumococcus” or “IPD” or “respiratory virus” or respiratory syncytial virus” or “hMPV” or “influenza” or “parainfluenza” or “adenovirus” or “rhinovirus” or “lower respiratory infection”). The search was for English literature and unrestricted by date.Added value of this studyThree unique characteristics of the COVID-19 pandemic-induced abnormal dynamics, coupled with multiple ongoing cohort studies in young children, contributed to the historic opportunity to model and quantify the attributable role of the various common respiratory viruses to four pneumococcus-associated disease endpoints (in particular community-acquired alveolar pneumonia (CAAP), non-CAAP LRIs, pneumococcal bacteremic pneumonia and non-pneumonia IPD): First, the full seasonal disappearance of all PDA-viruses shortly after the start of the pandemic, in the presence of continuous, uninterrupted pneumococcal carriage and continuous unchanged rhinovirus and adenovirus activity. Second, the off-season resurgence of the PDA-viruses in 2021. Third, the sequential, rather than simultaneous, re-emergence of the PDA-viruses. The analysis in this study suggests that several of the respiratory viruses, particularly RSV and hMPV, play an important causative role in the pathogenesis of pneumococcal diseases and other respiratory infections. Furthermore, the proportion attributable to each of the PDA-viruses for each of the four studied disease endpoints, and each of the age groups (Implication of all the available findingsOur findings add evidence about the absolute and relative contribution of common respiratory viruses to the burden of pneumonia and pneumococcal diseases and related conditions in young children. The strong contribution of RSV to disease burden compared to other viruses in all studied disease endpoints suggests that interventions that target viruses could have secondary effects on the burden of diseases typically attributed to bacteria.

Variants of concern (VOC) of SARS-CoV2 and waning immunity pose a serious global problem. Overall, vaccination and prior infection provide significant protection, but some individuals remain susceptible to infection and severe disease. Rigorously identifying correlates of protection (COP) is necessary to identify these susceptible populations. We conducted a multicenter prospective study assessing the association between serological profiles and the risk for SARS-CoV-2 infection, comparing those vaccinated with three to four doses of Pfizer BNT162b2 vaccine. We identified several IgG and IgA binding markers that were COPs. The strongest COP was reduced IgG levels to RBD mutants and IgA levels to VOCs (three-dose-group HR=6.34, p=0.008; four-dose-group HR=8.14, p=0.018). Most importantly, we identified a subset of vaccinated individuals with low antibody levels that generated a significant boost in neutralizing antibody titers after a fourth dose, but were still at significantly increased susceptibility to infection.

Background Immunomodulators and anti tumor-necrosis-α antibodies (anti-TNFs) have been implicated in increased risk of Epstein–Barr virus (EBV)–driven B-cell lymphoproliferative disorders in inflammatory bowel disease (IBD) patients. However, the underlying mechanisms are poorly understood. Methods An in-vitro model of lymphoblastoid cell line (LCL) was established by co-incubation of EBV-infected human peripheral blood mononuclear cells (PBMC) with Cyclosporin-A (CSA). After 4 weeks, the resultant LCLs were analyzed by flow cytometry, telomerase activity assay, and next generation sequencing. Subsequently, LCLs were explored in the presence of therapeutic agents for IBD (anti-TNFs, vedolizumab, 6-Mercaptopurine [6MP], methotrexate). Epstein–Barr virus titers were quantitated by real-time polymerase chain reaction. Results In cultures of PBMC with EBV and CSA, LCLs were characterized as an expanded, long lived population of CD58+CD23hi B-cells with high telomerase activity and clonal expansion. Upon addition to the cell cultures, LCL percentages were higher with infliximab (median 19.21%, P = 0.011), adalimumab (median 19.85%, P = 0.003), and early washed-out 6MP (median 30.57%, P = 0.043) compared with PBMC with EBV alone (median 9.61%). However, vedolizumab had no such effect (median 8.97%; P = 0.435). Additionally, LCL expansion was accompanied by increase in intracellular, rather than extracellular, EBV viral copies. Compared with PBMC with EBV alone, high levels of LCL were subsequently observed after triple depletion of NK cells, CD4+ T cells, and CD8+ T cells (median 52.8% vs 16.4%; P = 0.046) but also in cultures depleted solely of CD4+ T cells (median 30.7%, P = 0.046). Conclusions These results suggest that both anti-TNFs and 6MP, but not vedolizumab, propagate EBV-driven lymphoblastoid transformation in an in vitro model of lymphoma. This model may prove useful for studying mechanisms underlying proneoplastic viral immune interactions of novel drugs in IBD therapy.

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

BackgroundInvasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from non-pharmacological interventions. We used multiple ongoing cohort surveillance projects in children MethodsThe first SARS-CoV-2 cases were detected in February-2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), non-alveolar lower respiratory infections necessitating chest X-rays (NA-LRI), nasopharyngeal pneumococcal carriage in non-respiratory visits, nasopharyngeal respiratory virus detection (by PCR), and nationwide invasive pneumococcal disease (IPD). Monthly rates (January-2020 through February-2021 vs. mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity, were compared.FindingsCAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios, [IRRs] 0η07 and 0η19, respectively); NA-LRI and non-pneumonia IPD were also reduced, with a lesser magnitude (IRRs, 0η46 and 0η42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced and density of colonization and pneumococcal serotype distributions were similar to previous years. The pneumococcus-associated disease decline was temporally associated with a full suppression of RSV, influenza viruses, and hMPV, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels.InterpretationReductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic were not predominantly related to reduced pneumococcal transmission and carriage but were strongly associated with the complete disappearance of specific respiratory viruses.FundingPartially funded by Pfizer, Inc.

Objective:To assess the impact of incorporating early rapid influenza diagnosis on antimicrobial usage, nosocomial influenza transmission, length of stay, and occupancy rates among hospitalized patients.Setting:A 1,100 bed tertiary-care hospital in southern Israel.Methods:We implemented early rapid detection of influenza with immediate communication of results. Using Orion methods, we compared the 2017–2018 influenza season to the prior season in our hospital and to the 2017–2018 occupancy rates at other Israeli hospitals.Results:During the intervention season, 5,006 patients were admitted; 1,824 were tested for influenza, of whom 437 (23.9%) were positive. In the previous season, 4,825 patients were admitted; 1,225 were tested and 288 (23.5%) were positive. Time from admission to test report decreased from 35.5 to 18.4 hours (P < .001). Early discharge rates significantly increased, from 21.5% to 41.6% at 36 hours, from 37.2% to 54.5% at 48 hours, and from 66% to 73.2% at 72 hours. No increase in repeat ER visits, readmission, or mortality rates was observed. Hospital occupancy decreased by 10% compared to the previous year and was 26% lower than the national rate. Hospital-acquired influenza cases were reduced from 37 (11.4%) to 12 (2.7%) (P < .001). Antibiotic usage was reduced both before and after notification of test results by 16% and 12%, respectively.Conclusions:Implementing this intervention led to earlier discharge of patients, lower occupancy in medical wards, reduced antibiotic administration, and fewer hospital-acquired influenza events. This strategy is useful for optimizing hospital resources, and its implementation should be considered for upcoming influenza seasons.

Background & objectives: Clinical diagnosis of cutaneous leishmaniasis (CL) may bear a high rate of false diagnosis. This study assessed CL-suspected episodes, in an attempt to differentiate confirmed CL and non-CL diagnoses. Methods: In this retrospective, case-control study, medical files of CL-suspected episodes, tested by a biopsy for Leishmania-PCR, from 2013 to 2016, were collected and analysed statistically. Results: Of 324 suspected CL episodes, 48.8% were PCR-confirmed CL (96.2% Leishmania major) and 51.2% were non-CL (57.1% bacterial infections). Overall, 59.3% episodes were in males. Mean (± SD) duration until diagnosis was 3.7 ± 7.2 months. Lesions (mean 2.9 ± 3.8 per episode) were mostly (60.8%) sampled from September through February. Ulcer, pain, itching, purulent discharge and fever were recorded in 55.2, 47, 42.9, 18.2 and 4.7% of episodes, respectively. Univariate analysis showed that male gender, multiple lesions, ulcer, >1-month duration until diagnosis, and seasonality were associated with CL. Empiric CL treatment was recorded in 63.4 and 16% of CL-confirmed and non-CL episodes, respectively (p 1-month until diagnosis. In multivariate analysis, seasonality (odds ratio, OR = 2.144), empiric CL treatment (OR = 5.144) and ulcer (OR = 2.459) were associated with CL. Empiric CL treatment was associated with Jewish ethnicity (OR = 2.446) and duration of >1-month until diagnosis (OR = 3.304). Interpretation & conclusion: CL diagnosis should be laboratory confirmed, as clinical appearance is often misleading. Seasonality, ulcer appearance and gender may aid in correct identification and treatment of CL cases.

The immune response to chlamydial infections and the role it plays in resistance to reinfection, resolution of ongoing infection, and development of persistent chlamydial infection is poorly understood. Inhibition of chlamydial growth as a result of deprivation of necessary metabolites, such as certain amino acids, has been described previously and shown to be serovar specific. Chlamydiae are obligate intracellular bacteria which parasitize the host cell for nutrients and energy. In the course of infection, the endocytosed parasites convert from their infectious form, elementary bodies, to their replicating form, reticulate bodies (RB). The RB multiply by means of binary fission within the inclusion present in the host cytoplasm until about 20 hours postinfection. The protection of the host cell by IFN is a function of the interferon concentration and the multiplicity of infection. The effect of IFN concentration on C. trachomatis infectious particle production was measured by one-step growth experiments.

SummaryThe SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. We performed a case-control study that examined the distribution of SARS-CoV-2 variants observed in infections of vaccinated individuals (“breakthrough cases”) and matched infections of unvaccinated individuals. We hypothesized that if there is lower vaccine effectiveness against one of the VOCs, its proportion among the breakthrough cases should be higher than among unvaccinated cases. Our results show that vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1). Those who tested positive between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs at particular time windows following vaccination. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high among those fully vaccinated. These results overall suggest that vaccine breakthrough infection may be more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.

Toward eradicating the COVID-19 pandemic, vaccines that induce high humoral and cellular immune responses are essential. However, SARS-CoV-2 variants have begun to emerge and raise concerns, as they may potentially compromise vaccine efficiency. Here, we monitored neutralization potency of convalescent or Pfizer-BTN162b2 post-vaccination sera against pseudoviruses displaying spike proteins derived from wild-type SARS-CoV-2, or its UK-B.1.1.7 and SA-B.1.351 variants. Compared to convalescent sera, vaccination induces high titers of neutralizing antibodies, which exhibit efficient neutralization potential against pseudovirus carrying wild-type SARS-CoV-2. However, while wild-type and UK-N501Y pseudoviruses were similarly neutralized, those displaying SA-N501Y/K417N/E484K spike mutations moderately resist neutralization. Contribution of single or combined spike mutations to neutralization and infectivity were monitored, highlighting mechanisms by which viral infectivity and neutralization resistance are enhanced by N501Y or E484K/K417N mutations. Our study validates the importance of the Pfizer vaccine but raises concerns regarding its efficacy against specific SARS-CoV-2 circulating variants., Graphical abstract, Kuzmina and colleagues monitored the neutralization potential of convalescent sera or sera from Pfizer-vaccinated individuals against pseudoviruses displaying wild-type, B.1.1.7, or B.1.351 SARS-CoV-2 spike proteins. While vaccine sera comparably neutralizes wild-type and B.1.1.7 pseudoviruses, the B.1.351 variant moderately resists vaccine-mediated neutralization, highlighting the importance of monitoring the emergence of variants.

SUMMARYTowards eradicating COVID19, developing vaccines that induce high levels of neutralizing antibodies is a main goal. As counter measurements, viral escape mutants rapidly emerge and potentially compromise vaccine efficiency. Herein we monitored ability of convalescent or Pfizer-BTN162b2 post-vaccination sera to neutralize wide-type SARS-CoV2 or its UK-B.1.1.7 and SA-B.1.351 variants. Relative to convalescent sera, post-vaccination sera exhibited higher levels of neutralizing antibodies against wild-type or mutated viruses. However, while SARS-CoV2 wild-type and UK-N501Y were similarly neutralized by tested sera, the SA-N501Y/K417N/E484K variant moderately escaped neutralization. Significant contribution to infectivity and sensitivity to neutralization was attributed to each of the variants and their single or combined mutations, highlighting alternative mechanisms by which prevalent variants with either N501Y or E484K/K417N mutations spread. Our study validates the clinical significance of currently administered vaccines, but emphasizes that their efficacy may be compromised by circulated variants, urging the development of new ones with broader neutralization functions.

Background There are limited data on influenza vaccine effectiveness (IVE) in preventing laboratory-confirmed influenza illness among healthcare personnel (HCP). Methods HCP with direct patient contact working full-time in hospitals were followed during three influenza seasons in Israel (2016–2017 to 2018–2019) and Peru (2016 to 2018). Trivalent influenza vaccines were available at all sites, except during 2018–2019 when Israel used quadrivalent vaccines; vaccination was documented by electronic medical records, vaccine registries, and/or self-report (for vaccinations outside the hospital). Twice-weekly active surveillance identified acute respiratory symptoms or febrile illness (ARFI); self-collected respiratory specimens were tested by real-time reverse transcription polymerase chain reaction (PCR) assay. IVE was 100 × 1-hazard ratio (adjusted for sex, age, occupation, and hospital). Results Among 5,489 HCP who contributed 10,041 person-seasons, influenza vaccination coverage was 47% in Israel and 32% in Peru. Of 3,056 ARFIs in Israel and 3,538 in Peru, A or B influenza virus infections were identified in 205 (7%) in Israel and 87 (2.5%) in Peru. IVE against all viruses across seasons was 1% (95% confidence interval [CI] = −30%, 25%) in Israel and 12% (95% CI = −61%, 52%) in Peru. Conclusion Estimates of IVE were null using person-time models during six study seasons in Israel and Peru.