Revealing misattributed parentage through the integration of genetic information into the electronic health record.

The integration of genetic information (GI) into the electronic health record (EHR) seems inevitable as the mainstreaming of genomics continues. Such newly provided accessibility to GI could be beneficial for improving health care, as well as for supporting clinical decision-making and health management. Notwithstanding these promising benefits, the automatic integration of GI into the EHR, allowing unrestricted access to one's GI through patient portals, carries various knowledge-related risks for patients. This article is focused on the potential case of inadvertently revealing misattributed parentage through such practice. The article aims to identify key clinical and ethical implications of such revelation for adult patients. Clinical implications include, for example, altering the physician-patient interaction and the need to enhance physician's genetic literacy to improve genetic-information-specific communication skills. Ethical implications yield arguments supporting disclosure of MP, such as autonomy, individuals' right to know medical information pertaining to them, and the right to know one's genetic origins. Arguments opposing disclosure of MP centre on the right not to know GI and concerns for post-disclosure family relationships. Following the clinical and ethical analyses of these respective implications, we consider how such integration of GI into the EHR ought to be carried out, ethically. We therefore suggest a solution, featuring an autonomy-based approach, built around EHR users' right not to know. Our solution of nuanced consent options (including a 'genetic ignorance option') is designed to enable patients' informed exposure to GI through the EHR, allowing them some control over their self- and familial narrative.

Supplement of Vitamin D for early-stage Chronic Lymphocytic Leukemia Patients is Associated with a Longer Time to first Treatment.

Low levels of vitamin D are associated with a shorter time to first treatment (TTFT) and inferior overall survival in patients with Chronic Lymphocytic leukemia. But whether vitamin D supplement affects the clinical course of CLL patients, remains an open question. In the current study, we aimed to retrospectively explore the clinical benefit of Vitamin D supplement, or one of its analogues, on TTFT and treatment-free survival (TFS) in a large cohort of patients with asymptomatic CLL, who were under watch and wait approach. Among the 3,474 patients included in the study, 931 patients (26.8%) received either vitamin D supplement or its analogue, for a minimum of 6 months. We found that vitamin D supplement was statistically significant for longer TTFT in the young cohort (age<=65) and was associated with a longer TFS for all ages (p-value=0.004). Among non-vitamin D users, the median TFS was found to be 84 months, while among vitamin D supplement users the median TFS extended to 169 months. In conclusion, our long-term retrospective study demonstrates that the administration of vitamin D to patients with CLL in a watch and wait active surveillance is significantly associated with a longer treatment free survival (in any age) and a longer time to first treatment among young patients (age<=65). A prospective clinical trial is needed to validate results.

Real-world effectiveness of sodium-glucose cotransporter-2 inhibitors on the progression of chronic kidney disease in patients without diabetes, with and without albuminuria.

AIM: To examine the renal effects of sodium-glucose cotransporter-2 (SGLT2) inhibition among non-diabetic individuals with chronic kidney disease (CKD) in a real-world setting. METHODS: We collected de-identified data on adults without diabetes and with an estimated glomerular filtration rate (eGFR) of 25-60 mL/min/1.73 m2, who initiated the SGLT2 inhibitors dapagliflozin or empagliflozin between September 2020 and November 2022 at Maccabi Healthcare Services, an Israeli health maintenance organization. We assessed the effects of SGLT2 inhibitors on renal function (changes in eGFR slope/time). Index date was defined as the date of the first dispensing of SGLT2 inhibitors. Annual baseline slope was calculated using all eGFR measurements during the 2 years prior to index date (median = 7 measurements), while annual follow-up slope was calculated from all evaluations during 90-900 days post index date, along with baseline measurement at index date (median = 6 measurements). Paired t tests were used to compare differences between baseline and follow-up annual slopes. RESULTS: Of a total of 354 participants with CKD, without diabetes, who received SGLT2 inhibitors and were followed for a median of 527 days, the mean age was 72.8 ± 11.8 years, 26% were female, and 91% used renin-angiotensin system blockade. The mean eGFR was 45.4 ± 9.5 mL/min/1.73 m2. The mean body mass index was 29.1 ± 5.4 kg/m2. During the year before index date, 146 participants (41%) had a urinary albumin to creatinine ratio (UACR) <30 mg/g, 81 (23%) had a UACR of 30-300 mg/g, 74 (21%) had a UACR >300 mg/g, and 53 (15%) had no UACR evaluation. The mean eGFR slope over time was -5.6 ± 7.7 mL/min/1.73 m2 per year at baseline, which improved to -1.7 ± 6.8 mL/min/1.73 m2 per year after SGLT2 inhibitor administration (p <0.001). This effect was independent of UACR. CONCLUSION: In a real-world study of primarily older non-diabetic adults with CKD, SGLT2 inhibition was associated with a slower rate of kidney function decline, regardless of baseline UACR level.

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.

BNT162b2 mRNA COVID-19 Vaccine Effectiveness in Patients with Coeliac Disease Autoimmunity: Real-World Data from Mass Vaccination Campaign.

BACKGROUND: Data on COVID-19 vaccine effectiveness among patients with coeliac disease are currently lacking because patients with immune conditions were excluded from clinical trials. We used our coeliac disease autoimmunity (CDA) cohort to explore the effectiveness of the BNT162b2 mRNA COVID-19 vaccine in preventing SARS-CoV-2 infection among patients with CDA. METHODS: This retrospective cohort study included patients with positive autoantibodies against tissue transglutaminase (tTG-IgA). In the primary analysis, the cohort included CDA patients who received two vaccine doses against COVID-19 and matched patients in a 1:3 ratio. Patients were divided into subgroups based on their positive tTG-IgA level at diagnosis and their current serology status. RESULTS: The cohort included 5381 vaccinated patients with CDA and 14,939 matched vaccinated patients. The risk for breakthrough SARS-CoV-2 infection evaluated with Kaplan-Meier survival analysis via log-rank tests was similar between groups (p = 0.71). In a Cox regression survival analysis, the hazard ratio for breakthrough infection among patients with CDA compared to matched patients was 0.91 (95% confidence interval = 0.77-1.09). CONCLUSIONS: COVID-19 vaccination is effective in patients with coeliac disease autoimmunity. Vaccine effectiveness was comparable to the reference population.

Clinical Outcomes of COVID-19 in Mycosis Fungoides and Sezary Syndrome.

INTRODUCTION: Haemato-oncologic patients are more susceptible to severe infections with SARS-CoV-2. We aimed to assess the clinical outcomes of SARS-CoV-2 infection among patients with Mycosis Fungoides and Sezary Syndrome (MF/SS). METHODS: The data were retrieved from anonymized electronic medical records of Maccabi Healthcare Services (MHS), the second-largest healthcare organization in Israel. Patients diagnosed with MF/SS were included in the study. COVID-19 PCR test results together with sociodemographic and clinical data were extracted and analyzed to evaluate the association of COVID-19 with clinical outcomes. RESULTS: In the period of 2020-2022, 1,472 MF/SS patients were included in the study. Among them, 768 (52%) had SARS-CoV-2 infection. The hospitalization rate was 2.9% and infection by the Delta variant was associated with the highest hospitalization rate (7.7%). The hospitalization rate was lower among fully vaccinated patients (p = 0.032) but higher for patients older than 65 (p < 0.001) and patients with SS (vs. MF) (p < 0.001) or COPD (p = 0.024) diagnosis. There was a tendency for decreased hospitalization among patients treated with nirmatrelvir + ritonavir within 5 days of infection, with a 79% risk reduction, although it was not statistically significant (p = 0.164). CONCLUSION: Patients with MF/SS do not necessarily have worse COVID-19 outcomes compared to the general population.

Pregnancy Course of 10 Women Diagnosed with Chronic Lymphocytic Leukemia.

Pregnancies following diagnosis of chronic lymphocytic leukemia (CLL) are rare events, mainly because the disease is typically diagnosed in the elderly. Literature on the topic is based only on case reports, and limited data are available on the influence of pregnancy on CLL course. In this retrospective study, we aimed to summarize the clinical and laboratory course of 10 women with CLL who became pregnant. None of the patients had significant changes in blood count during or after pregnancy or had complications such as infection, autoimmune phenomenon, or preeclampsia. Four out of 10 pregnancies were terminated with an early miscarriage. Following labor, 1 patient started anti-CLL treatment due to preexisting anemia, but none of the women required therapy during CLL progression during the first 2 years of follow-up. We conclude that based on our serial, pregnancy does not negatively impact on CLL course.

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.

Immunosuppression as a Hub for SARS-CoV-2 Mutational Drift.

The clinical course of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is largely determined by host factors, with a wide range of outcomes. Despite an extensive vaccination campaign and high rates of infection worldwide, the pandemic persists, adapting to overcome antiviral immunity acquired through prior exposure. The source of many such major adaptations is variants of concern (VOCs), novel SARS-CoV-2 variants produced by extraordinary evolutionary leaps whose origins remain mostly unknown. In this study, we tested the influence of factors on the evolutionary course of SARS-CoV-2. Electronic health records of individuals infected with SARS-CoV-2 were paired to viral whole-genome sequences to assess the effects of host clinical parameters and immunity on the intra-host evolution of SARS-CoV-2. We found slight, albeit significant, differences in SARS-CoV-2 intra-host diversity, which depended on host parameters such as vaccination status and smoking. Only one viral genome had significant alterations as a result of host parameters; it was found in an immunocompromised, chronically infected woman in her 70s. We highlight the unusual viral genome obtained from this woman, which had an accelerated mutational rate and an excess of rare mutations, including near-complete truncating of the accessory protein ORF3a. Our findings suggest that the evolutionary capacity of SARS-CoV-2 during acute infection is limited and mostly unaffected by host characteristics. Significant viral evolution is seemingly exclusive to a small subset of COVID-19 cases, which typically prolong infections in immunocompromised patients. In these rare cases, SARS-CoV-2 genomes accumulate many impactful and potentially adaptive mutations; however, the transmissibility of such viruses remains unclear.

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 BNT162b2 Vaccine Against Infection in Adolescents in Israel.

BACKGROUND: The short-term effectiveness of a 2-dose regimen of the BioNTech/Pfizer BNT162b2 vaccine for adolescents has been demonstrated. However, little is known about the long-term effectiveness in this age group. It is known, however, that waning of vaccine-induced immunity against infection in adult populations is evident within a few months. METHODS: Leveraging the database of Maccabi Healthcare Services (MHS), we conducted a matched case-control design for evaluating the association between time since vaccination and the incidence of infections, where 2 outcomes were evaluated: documented SARS-CoV-2 infection (regardless of symptoms) and symptomatic infection (COVID-19). Cases were defined as individuals aged 12-16 with a positive polymerase chain reaction (PCR) test occurring between 15 June and 8 December 2021, when the Delta variant was dominant in Israel. Controls were adolescents who had not tested positive previously. RESULTS: We estimated a peak vaccine effectiveness between 2 weeks and 3 months following receipt of the second dose, with 85% (95% confidence interval [CI]: 84-86%) and 90% (95% CI: 89-91%) effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19), respectively. However, in line with findings for adults, waning effectiveness was evident. Long-term protection was reduced to 73% (95% CI: 68-77%) against infection and 79% (95% CI: 73-83%) against COVID-19 3-5 months after the second dose and waned to 53% (95% CI: 46-60%) against infection and 66% (95% CI: 59-72%) against COVID-19 after 5 months. CONCLUSIONS: Although vaccine-induced protection against both infection and COVID-19 continues over time in adolescents, the protection wanes with time since vaccination, starting 3 months after inoculation and continuing for more than 5 months.

Late diagnosis of autism spectrum disorder-Journey, parents' concerns, and sex influences.

Despite increasing awareness for diagnosing autism spectrum disorder (ASD) and initiating treatments early in life, many children and adolescents continue to be diagnosed at a relatively older age. Focusing on children who first received an ASD diagnosis at age six or older, this study aimed to describe the symptoms that parents reported when ASD was diagnosed, follow the patients' clinical trajectory prior to receiving the diagnosis, and describe differences in symptoms and prior diagnoses between males and females cases. We included 258 children (205 males and 53 females) who were first diagnosed with autism at age 6-18 in 2017-2018. We retrieved demographic information, neurologic and developmental symptoms, diagnoses, and medications dispensing history from the children's electronic medical charts. The data indicated that prior diagnoses of language delays and attention deficit hyperactivity disorder were common among children with a late ASD diagnosis. Two thirds of the children were prescribed one or more medications to treat psychosocial and behavioral conditions before receiving a late ASD diagnosis. Difficulties in social relationships with peers were the leading reported symptoms by parents at the time of ASD diagnosis. Across these different domains, some differences were found between males and females, including a somewhat higher cognitive level in males, who were also more likely to present aggressive behavior.

Safety of the fourth COVID-19 BNT162b2 mRNA (second booster) vaccine: a prospective and retrospective cohort study.

BACKGROUND: The effectiveness of the second BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 booster vaccine dose (ie, fourth inoculation) is well established, but its safety has yet to be fully understood. The absence of sufficient vaccine safety information is one of the key contributors to vaccine hesitancy. In this study, we aimed to evaluate the safety profile of the second BNT162b2 mRNA COVID-19 booster vaccine using data from a retrospective cohort and a prospective cohort. METHODS: To evaluate the safety profile of the second booster vaccine, we analysed its short-term effects and compared them to those of the first booster by using data from, first, a retrospective cohort of 250 000 random members of the second-largest health-care organisation in Israel (Maccabi Healthcare Services) and, second, a prospective cohort (the PerMed study) of 4698 participants from all across Israel. Individuals who were aged 18 years or older who received the second BNT162b2 mRNA COVID-19 vaccine booster during the vaccination campaign, from Dec 30, 2021, to July 22, 2022, were eligible for inclusion in the retrospective cohort analysis. To be included in the PerMed study, participants needed to be 18 years or older, members of Maccabi Healthcare Services at the time of enrolment, using their own smartphone, and be able to give informed consent by themselves. Participants from the prospective cohort received smartwatches, downloaded a dedicated mobile application, and granted access to their medical records. The smartwatches continuously monitored several physiological measures, including heart rate. For analysis of the prospective cohort data, we used the Kruskal-Wallis test to compare heart rate levels observed before and after vaccination. The mobile application collected daily self-reported questionnaires on local and systemic reactions. Medical records of the retrospective cohort were accessed to examine the occurrence of 25 potential adverse events, and we evaluated the risk differences between 42 days in the periods before and after vaccination in a pairwise method using non-parametric percentile bootstrap. FINDINGS: The retrospective cohort included 94 169 participants who received the first booster and 17 814 who received the second booster. Comparing the 42 days before and after vaccination, the second booster was not associated with any of the 25 adverse events investigated, including myocardial infarction (risk difference, 2·25 events per 10 000 individuals [95% CI -3·93 to 8·98]) and Bell's Palsy (-1·68 events [-5·61 to 2·25]). None of the individuals was diagnosed with myocarditis or pericarditis following vaccination with the second booster. The prospective cohort included 1785 participants who received the first booster and 699 who received the second booster. We found no significant differences after inoculation with the first booster compared with the second booster (heart rate: day 2 [p=0·3], day 6 [p=0·89]; extent of self-reported reactions [p=0·06]). We found a significant increase in mean heart rate relative to that observed during the week before vaccination (baseline) levels during the first 3 days following the second booster (p<0·0001), peaking on day 2 (mean difference of 1·61 bpm [1·07 to 2·16] compared with baseline). Mean heart rate values returned to baseline levels by day 6 (-0·055 bpm [-0·56 to 0·45] compared with baseline). INTERPRETATION: Both our retrospective and prospective analyses support the safety of the second booster, with our findings reflecting physicians' diagnoses, patients' objective physiological measures, and patients' subjective reactions. We believe this study provides safety assurances to the global population who are eligible to receive an additional COVID-19 booster inoculation. These assurances can help increase the number of high-risk individuals who opt to receive this booster vaccine and thereby prevent severe outcomes associated with COVID-19. FUNDING: European Research Council (ERC).

A Data-Driven Strategy for Identifying Individuals Resistant to SARS-CoV-2 Virus under In-Household Exposure.

This report describes the development of a data-driven approach for identifying individuals who tested negative to a SARS-CoV-2 infection, despite their residence with individuals who had confirmed infections. Household studies have demonstrated efficiency in evaluating exposure to SARS-CoV-2. Leveraging earlier studies based on the household unit, our analysis utilized close contacts in order to trace chains of infection and to subsequently categorize TEFLONs, an acronym for Timely Exposed to Family members Leaving One Not infected. We used over one million anonymized electronic medical records, retrieved from Maccabi Healthcare Services' centralized computerized database from March 2020 to March 2022. The analysis yielded 252 TEFLONs, who were probably at very high risk of infection and yet, demonstrated clinical resistance. The exposure extent in each household positively correlated with household size, reflecting the in-house rolling transmission event. Our approach can be easily implemented in other clinical fields and should spur further research of clinical resistance to various infections.

SARS-CoV-2 spike IgG titres up to 137 days following Comirnaty mRNA COVID-19 vaccination, Israel, February to May 2021.

BackgroundData regarding the long-term protection afforded by vaccination for the SARS-CoV-2 infection are essential for allocation of scarce vaccination resources worldwide.MethodsWe conducted a retrospective cohort study aimed at studying the kinetics of IgG antibodies against SARS-CoV-2 in COVID-19-naïve patients fully vaccinated with two doses of Comirnaty mRNA COVID-19 vaccine. Geometric mean concentrations (GMCs) of antibody levels were reported. Linear models were used to assess antibody levels after full vaccination and their decline over time.ResultsThe study included 4,740 patients and 5,719 serological tests. Unadjusted GMCs peaked 28-41 days after the first dose at 10,174 AU/mL (95% CI: 9,211-11,237) and gradually decreased but remained well above the positivity cut-off. After adjusting for baseline characteristics and repeated measurements, the antibodies half-life time was 34.1 days (95% CI: 33.1-35.2), and females aged 16-39 years with no comorbidities had antibody levels of 20,613 AU/mL (95% CI: 18,526-22,934) on day 28 post-first-dose. Antibody levels were lower among males (0.736 of the level measured in females; 95% CI: 0.672-0.806), people aged 40-59 (0.729; 95% CI: 0.649-0.818) and ≥ 60 years (0.452; 95% CI: 0.398-0.513), and patients having haematological (0.241; 95% CI: 0.190-0.306) or solid malignancies (0.757; 95% CI: 0.650-0.881), chronic kidney disease with glomerular filtration rate (GFR) ≥ 30 (0.434; 95% CI: 0.354-0.532) or with GFR < 30 mL/min (0.176; 95% CI: 0.109-0.287), and immunosuppression (0.273; 95% CI: 0.235-0.317). Body mass index, cardiovascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes and inflammatory bowel diseases were not associated with antibody levels.ConclusionsVaccination with two doses resulted in persistently high levels of antibodies (≥ cut-off of 50 AU/mL) up to 137 days post-first-dose. Risk factors for lower antibody levels were identified.

Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study.

OBJECTIVE: Evaluating the prevalence of long-COVID symptoms in patients with a history of mild or asymptomatic infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the factors associated with developing long-COVID. DESIGN: A nationwide cohort study. Using a centralized database, we have identified patients with and without a history of SARS-CoV-2 infection 1-6 months before data collection. Patients were asked to fill out an online questionnaire through text messages. SETTING: Israeli general practice. SUBJECTS: 2755 persons participated in the study in September 2021 (a response rate of 7.5%): 819 with and, 936 without a history of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: We asked patients to provide details about their demographic status, medical history, COVID-related variables and the presence of long-COVID symptoms. RESULTS: Most prevalent long-COVID symptoms were decreased smell sensation (35.1% vs. 4.3%, p < 0.001), decreased taste sensation (25.2% vs. 3.2%, p < 0.001), memory disturbances (36.9% vs. 14.4%, p < 0.001), dyspnea (24.2% vs. 10.7%, p < 0.001) and arthralgia (33% vs. 16.3%, p < 0.001). Risk factors associated with long-COVID included female gender, symptomatic COVID-19, overweight or obesity and the presence of dyslipidemia. About 34.6% of participants reported not returning to their baseline health condition after the acute illness. CONCLUSION: Long-COVID is frequently seen following a mild symptomatic COVID-19 infection and, to a lesser extent, following an asymptomatic SARS-CoV-2 infection. Primary care physicians should be aware of these symptoms and consider this option in their differential diagnosis. Health policymakers should expect a significant impact of this syndrome on public health.Key PointsLong-COVID has emerged as a significant health problem with a serious impact on normal daily function• Long-COVID symptoms were evident in patients with mild symptomatic disease and in asymptomatic patients to a lesser extent.• Risk factors for having Long-COVID symptoms include female gender, symptomatic disease, increased BMI, and the presence of dyslipidemia.• Fatigue, dyspnea, weakness, decreased libido, weight changes, memory, and sleep disturbances were associated with not returning to the baseline health state.

Pregnancy outcomes after SARS-CoV-2 infection by trimester: A large, population-based cohort study.

OBJECTIVES: Data regarding women infected with SARS-CoV-2 during early trimesters are scarce. We aimed to assess preterm birth (PTB) and small-for-gestational-age (SGA) rates in a large and unselected cohort by trimester at infection and overall. DESIGN: A retrospective cohort study including all women with a positive SARS-CoV-2 RT-PCR test during a non-ectopic singleton pregnancy between February 21st 2020 and July 2nd 2021 (N = 2753). Each infected woman was matched to a non-infected pregnant woman by age, last menstruation date, sector, and socioeconomic status. METHODS: Logistic regression was conducted to assess the risks of PTB and SGA including an interaction between group and trimester of infection. Multivariable models included underlying diseases, previous abortions and null parity. Subgroup analyses were conducted on symptomatic infected women and matched non-infected women. RESULTS: A total of 2753 /2789 (98.7%) eligible women that were infected during pregnancy could be matched, among them, 17.4% and 48.4% were infected during the first and third trimesters, respectively. While first and second trimester infections were not associated with PTB (p>0.8), third trimester infections and in particular after 34 weeks of gestation had a greater risk of PTB with adjusted ORs of 2.76 (95% CI 1.63-4.67) and 7.10 (95% CI 2.44-20.61), respectively. PTB risk was further heightened in symptomatic third trimester infections (OR = 4.28, 95% CI 1.94-9.25). SGA risk was comparable between study groups across all trimesters of infection. Pregnancy loss incidence was similar in both groups (adjusted OR = 1.16; 95% CI 0.90-1.50). CONCLUSION: SARS-CoV-2 infection was associated with increased risk of PTB only among women infected during late pregnancy, particularly among symptomatic women.

Dynamics in COVID-19 symptoms during different waves of the pandemic among children infected with SARS-CoV-2 in the ambulatory setting.

The aim of this real-life, big data population-based study was to evaluate differences in symptomatic presentation of children infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) between the third and fourth waves of the pandemic in Israel, dominated by the Alpha and Delta variants, respectively. Our cohort included all children and adolescents, members of the second-largest Health Maintenance Organization in Israel that had positive real-time polymerase chain reaction (RT-PCR) test during the third and fourth waves of the pandemic (December 1, 2020, to April 30, 2021, and June 1, 2021, to October 10, 2021, respectively). A total of 32,485 and 44,130 children and adolescents in the third and fourth waves were included in the final analysis. The rate of children with symptomatic disease among patients with documented SARS-CoV-2 infection was higher in the fourth wave compared to the third wave (49.9% vs. 37.5%). The most commonly reported symptom and the only symptom that substantially differed between waves was fever, with 33% of SARS-CoV-2 infected children in the fourth wave vs. 13.6% in the third wave. Preschool children had the lowest prevalence of febrile illness compared to other age groups. CONCLUSION: Children and adolescents infected during the fourth wave of the pandemic in Israel, a Delta-dominant period, had a significantly higher rate of symptomatic febrile illness than the Alpha-dominant period. This phenomenon occurred across all age groups. WHAT IS KNOWN: • There are differences in COVID-19 severity among adults and children during different waves of the pandemic. • There is a paucity of data regarding symptomatic characteristics in children in large-scale cohorts aside from hospital settings. WHAT IS NEW: • In a time period dominated by the Delta variant, there were substantially more children with symptomatic disease and febrile illness compared to a period dominated by the alpha variant. • Preschool children had the lowest rate of febrile illness among all age groups.

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.