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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

OBJECTIVE: We compared neonatal immunity after vaccination against SARS-CoV-2 during pregnancy to that achieved after maternal infection. STUDY DESIGN: We tested cord blood from women infected with SARS-CoV-2 during pregnancy (group 1, n = 29), women who were vaccinated during pregnancy (group 2, n = 29) and from women not infected and not vaccinated (Group 3, n = 21) for titers of antibodies to both SARS-CoV-2 spike and 'N' proteins. RESULTS: Seventy-nine women were included: Antibodies against SARS-CoV-2 spike protein were detected in all samples from Group 1 and 2. Antibodies to the 'N' protein were detected in 25/29 samples in Group 1. None of the samples from Group 3 had antibodies to either protein. Mean titers of SARS-CoV-2 antibodies were significantly higher in Group 2 than in Group 1 (p < 0.05). CONCLUSIONS: Neonates born to mothers vaccinated during pregnancy have higher antibody titers and may therefore have more prolonged protection than those born to women infected during pregnancy.

Aims In breastfeeding women, anti-epileptic therapy can lead to infant toxicities, even with newer anti-epileptic drugs such as levetiracetam. This study assessed levetiracetam breastmilk excretion and its correlation with the maternal oral dose and serum concentrations. Methods Women with epilepsy treated with levetiracetam were recruited to this study and completed a questionnaire. Levetiracetam concentrations were determined in serial breastmilk samples (pre-dose to 12 h post-dose period) and in a single pre-dose maternal serum sample. Results Twenty breastfeeding women and 21 infants (one woman with twins; 16 fully and five partially breastfed infants) participated in this study. The trough breastmilk/serum ratio of levetiracetam was 0.98 ± 0.20. The infant levetiracetam daily dose was 5.39 ± 1.96 and 2.70 ± 0.98 mg. kg-1. d-1 , and the relative infant dose (RID) was 13.8 ± 3.1% and 6.9 ± 1.6% in the fully and partially breastfed infants, respectively. Substantial correlations between the levetiracetam dose, maternal serum and breastmilk trough concentrations, and breastmilk AUC values were found. Three women reported somnolence in their fully breastfed infants, which resolved shortly after switching to partial breastfeeding. All the infants gained weight according to their age. Conclusions Infant levetiracetam exposure via the breastmilk was close to the safety thresholds (trough breastmilk/serum ratio slightly below 1, RID > 10% in fully breastfed infants), and infant somnolescence reports could be related to exposure of the infants to levetiracetam via breastmilk. Further studies are warranted to reveal the short- and long-term safety of levetiracetam in breastfeeding.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients may lead to accelerated viral mutation rate, immune evasion and persistent viral shedding over many months. Here we report the case of a severely immunocompromised cancer patient infected with the Delta variant of SARS-CoV-2 for over 8 months. Genome sequencing of samples taken after repeated monoclonal antibody treatments reveal the emergence and accumulation of mutations enabling escape from neutralization by antibodies. Mutations emerging in accessory and non-structural viral proteins target specific residues of immunomodulatory domains, potentially leading to loss of some functions, while preserving others. The mutated virus managed to completely overcome neutralization by monoclonal antibodies while remaining viable and infective. Our results suggest that the loss of specific immunomodulatory viral functions might confer a selective advantage in immunocompromised hosts. We also compare between mutations emerging in the presence and absence of neutralizing antibodies.HighlightsSARS-CoV-2 undergoes rapid evolution in an immunocompromised, chronically infected cancer patient, overcoming neutralization by two monoclonal antibody cocktail treatmentsReceptor binding domain (RBD) mutations emerging after monoclonal antibody treatment enable effective escape from neutralization in the absence of adaptive immunitySome emerging mutations are predicted to disrupt immunomodulatory viral proteins, including prevention of ORF8 homodimerization, mis-localization of ORF3a in host cells and alteration of the host-suppressive function of NSP1

The concentration of SARS-CoV-2-specific serum antibodies, elicited by vaccination or infection, is a primary determinant of anti-viral immunity, which correlates with protection against infection and COVID-19. Serum samples were obtained from 25 897 participants and assayed for anti-SARS-CoV-2 spike protein RBD IgG antibodies. The cohort was composed of newly vaccinated BNT162b2 recipients, in the first month or 6 months after vaccination, COVID-19 patients and a general sample of the Israeli population. Antibody levels of BNT162b2 vaccine recipients were negatively correlated with age, with a prominent decrease in recipients over 55 years old, which was most significant in males. This trend was observable within the first month and 6 months after vaccination, while younger participants were more likely to maintain stable levels of serum antibodies. The antibody concentration of participants previously infected with SARS-CoV-2 was lower than the vaccinated and had a more complex, non-linear relation to age, sex and COVID-19 symptoms. Taken together, our data supports age and sex as primary determining factors for both the magnitude and durability of humoral response to SARS-CoV-2 infection and the COVID-19 vaccine. Our results could inform vaccination policies, prioritizing the most susceptible populations for repeated vaccination.

Serum antibody levels to SARS-CoV-2 in infants born to mothers who had received 2 doses of the BNT2b2 vaccine during pregnancy correlated positively with increasing gestational age at vaccination (P < .01) and negatively with increasing time from vaccination (P < .01), with a significant drop in infants aged >60 days (P = .045).

Neutralizing antibodies targeting the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) block viral entry to host cells, preventing disease and further spread of the pathogen. The presence of SARS-CoV-2 antibodies in serum is a reliable indicator of infection, used epidemiologically to estimate the prevalence of infection and clinically as a measurement of an antigen-specific immune response. In this study, we analyzed serum Spike protein-specific IgG antibodies from 26,170 samples, including convalescent individuals who had coronavirus disease 2019 (COVID-19) and recipients of the BNT162b2 vaccine. We find distinct serological patterns in COVID-19 convalescent and vaccinated individuals, correlated with age and gender and the presence symptoms.

Patients with hematologic malignancies have an increased risk of severe COVID‐19 infection. Vaccination against COVID‐19 is especially important in these patients, but whether they develop an immune response following vaccination is unknown. We studied serologic responses to the BNT162b2 vaccine in this population. A lower proportion of patients were seropositive following vaccination (75%) than in a comparison group (99%; p

Since COVID-19 risk of reinfection is of great concern, the safety and efficacy of the mRNA-based vaccines in previously infected populations should be assessed. We studied 78 individuals previously infected with SARS-CoV-19, who received a single dose of BNT162b2 mRNA COVID-19 vaccine, and 1:2 ratio matched infection-naïve cohort who received two injections. The evaluation procedure included symptom monitoring, and serological tests. Among the post-infected population, the median IgG-S response after the first vaccine dose was 2260 AU/ml, compared to 238 AU/ml after the second vaccine injection in the infection naive group. A strong correlation was demonstrated between IgG-S level before vaccination, and the corresponding responses after a single vaccine dose (r = 0.8, p

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: The possible differences in characteristics and prognosis, among patients with coronavirus disease 2019 (COVID-19), with vs. without changes in red cell distribution width (RDW) during hospitalization, have not been investigated. Methods: For 477 adults hospitalized with COVID-19, demographic, laboratory and clinical characteristics, in-hospital outcomes and all-cause mortality were compared according: to high (>14.7%, n=146) vs. normal (≤14.7%, n=331) RDW values at admission, and according to RDW changes (n=150) vs. stable RDW (n=262) during hospitalization. Results: Both high RDW at admission and change in RDW during hospitalization were significantly associated with older age, more severe clinical and laboratory characteristics, and poor in-hospital outcomes. On median follow-up lasting 83 days, the mortality rates were higher among patients with high vs. normal RDW on admission (26.7% vs. 10.0%, P < .001) and RDW changes vs. stable RDW (34.7% vs. 5.7%, P < .001). On multivariate analysis, change in RDW was strongly associated with decreased survival (relative risk 1.50 and 95% confidence interval 1.29–1.75), while high RDW on admission was not found to be most significantly associated with mortality. Conclusions: Among patients with COVID-19, RDW changes during hospitalization were associated with a severe clinical profile, poor in-hospital outcomes and increased short-term mortality. Repeated assessment of RDW may provide useful information for improving the care of hospitalized patients with COVID-19.

Background An Israeli national taskforce performed a multi-center clinical and analytical validation of seven serology assays to determine their utility and limitations for SARS-CoV-2 diagnosis. Methods Serology assays from Roche, Abbott, Diasorin, BioMerieux, Beckman-Coulter, Siemens, and Mt.-Sinai ELISA were included. Negative samples from 2391 individuals representative of the Israeli population, and 698 SARS-CoV-2 PCR positive patients, collected between March and May 2020, were analyzed Findings Immunoassays sensitivities between 81.5%-89.4% and specificities between 97.7%-100% resulted in a profound impact on the expected Positive Predictive Value (PPV) in low (

Background: Pediatric eating disorders (PED) patients are prone to nutritional deficiencies. Thiamine deficiency is well described in other malnutrition states but is not routinely screened for in PED. In the current study we evaluated the prevalence of thiamine deficiency among PED patients on their first admission to an outpatient day hospital for eating disorders (DH). Methods: In this prospective cohort study, we measured whole blood thiamine pyrophosphate concentrations (TPP) in addition to a routine laboratory workup in 69 girls on their first admission to DH. Two subgroup analyses were performed: (I) Patients with a previous dietary intervention ("diet" group, n = 30) or na&iuml, ve-to-treatment patients ("na&iuml, ve" group, n = 39) and (II) Type of PED: Restrictive (group R, n = 44) or binge-eating/purging (group BP, n = 25). Results: Thiamine deficiency was identified in four girls (6%), all in the "na&iuml, ve" group. Three of them had BP, and one had R. Patients in the "diet" group had a significantly higher TPP compared to the "na&iuml, ve" group (55.5 &micro, g/L vs. 46.7 &micro, g/L, p = 0.004). TPP levels returned to normal after two weeks of the treatment program in all deficient patients. Conclusion: Thiamine deficiency was uncommon among PED patients and was easily replenished. Screening for deficiency should be performed among treatment-na&iuml, ve patients. Keynotes: Whole blood thiamine pyrophosphate concentrations (TPP) are seldom screened for among PED patients. In the current study, we detected thiamine deficiency in only 6% of patients on their first admission to an outpatient day hospital for eating disorders. All deficient patients did not have a recent dietary intervention. We recommend considering screening for thiamine deficiency in treatment-na&iuml, ve PED patients.