Risk Stratification Model for Severe COVID-19 Disease: A Retrospective Cohort Study.

BACKGROUND: Risk stratification models have been developed to identify patients that are at a higher risk of COVID-19 infection and severe illness. Objectives To develop and implement a scoring tool to identify COVID-19 patients that are at risk for severe illness during the Omicron wave. METHODS: This is a retrospective cohort study that was conducted in Israel's second-largest healthcare maintenance organization. All patients with a new episode of COVID-19 between 26 November 2021 and 18 January 2022 were included. A model was developed to predict severe illness (COVID-19-related hospitalization or death) based on one-third of the study population (the train group). The model was then applied to the remaining two-thirds of the study population (the test group). Risk score sensitivity, specificity, and positive predictive value rates, and receiver operating characteristics (ROC) were calculated to describe the performance of the model. RESULTS: A total of 409,693 patients were diagnosed with COVID-19 over the two-month study period, of which 0.4% had severe illness. Factors that were associated with severe disease were age (age > 75, OR-70.4, 95% confidence interval [CI] 42.8-115.9), immunosuppression (OR-4.8, 95% CI 3.4-6.7), and pregnancy (5 months or more, OR-82.9, 95% CI 53-129.6). Factors that were associated with a reduced risk for severe disease were vaccination status (patients vaccinated in the previous six months OR-0.6, 95% CI 0.4-0.8) and a prior episode of COVID-19 (OR-0.3, 95% CI 0.2-0.5). According to the model, patients who were in the 10th percentile of the risk severity score were considered at an increased risk for severe disease. The model accuracy was 88.7%. CONCLUSIONS: This model has allowed us to prioritize patients requiring closer follow-up by their physicians and outreach services, as well as identify those that are most likely to benefit from anti-viral treatment during the fifth wave of infection in Israel, dominated by the Omicron variant.

Long COVID symptoms in Israeli children with and without a history of SARS-CoV-2 infection: a cross-sectional study.

OBJECTIVES: To estimate the prevalence of long COVID symptoms in children with and without a history of SARS-CoV-2 infection and to evaluate factors associated with long COVID. DESIGN: A nationwide cross-sectional study. SETTING: Primary care. PARTICIPANTS: 3240 parents of children aged 5-18 with and without SARS-CoV-2 infection completed an online questionnaire (11.9% response rate); 1148 and 2092 with/without a history of infection, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the prevalence of long COVID symptoms in children with/without a history of infection. Secondary outcomes were the factors associated with the presence of long COVID symptoms and with failure to return to baseline health status in children with a history of infection including gender, age, time from illness, symptomatic illness and vaccine status. RESULTS: Most long COVID symptoms were more prevalent in children with a history of SARS-CoV-2 infection: headaches (211 (18.4%) vs 114 (5.4%), p<0.001), weakness (173 (15.1%) vs 70 (3.3%), p<0.001), fatigue (141 (12.3%) vs 133 (6.4%), p<0.001) and abdominal pain (109 (9.5%) vs 79 (3.8%), p<0.001). Most long COVID symptoms in children with a history of SARS-CoV-2 infection were more prevalent in the older age group (12-18) compared with the younger age group (5-11). Some symptoms were more prevalent in children without a history of SARS-CoV-2 infection, including attention problems with school malfunctioning (225 (10.8%) vs 98 (8.5%), p=0.05), stress (190 (9.1%) vs 65 (5.7%), p<0.001), social problems (164 (7.8%) vs 32 (2.8%)) and weight changes (143 (6.8%) vs 43 (3.7%), p<0.001). CONCLUSION: This study suggests that the prevalence of long COVID symptoms in children with a history of SARS-CoV-2 infection might be higher and more prevalent in adolescents than in young children. Some of the symptoms, mainly somatic symptoms, were more prevalent in children without a history of SARS-CoV-2 infection, highlighting the impact of the pandemic itself rather than the infection.

Data-Driven Assessment of Adolescents' Mental Health During the COVID-19 Pandemic.

OBJECTIVE: Adolescents' mental health was severely compromised during the COVID-19 pandemic. Longitudinal real-world studies on changes in the mental health of adolescents during the later phase of the pandemic are limited. We aimed to quantify the effect of COVID-19 pandemic on adolescents' mental health outcomes based on electronic health records. METHOD: This was a retrospective cohort study using the computerized database of a 2.5 million members, state-mandated health organization in Israel. Rates of mental health diagnoses and psychiatric drug dispensations were measured among adolescents 12 to 17 years of age with and without pre-existing mental history, for the years 2017 to 2021. Relative risks were computed between the years, and interrupted time series (ITS) analyses evaluated changes in monthly incidence rates of psychiatric outcomes. RESULTS: The average population size was 218,146 in 2021. During the COVID-19 period, a 36% increase was observed in the incidence of depression (95% CI = 25-47), 31% in anxiety (95% CI = 23-39), 20% in stress (95% CI = 13-27), 50% in eating disorders (95% CI = 35-67), 25% in antidepressant use (95% CI = 25-33), and 28% in antipsychotic use (95% CI = 18-40). A decreased rate of 26% (95% CI = 0.80-0.88) was observed in ADHD diagnoses. The increase of the examined outcomes was most prominent among youth without psychiatric history, female youth, general secular Jewish population, youth with medium-high socioeconomic status, and those 14 to 15 years of age. ITS analysis confirmed a significantly higher growth in the incidence of psychiatric outcomes during the COVID-19 period, compared to those in previous years. CONCLUSION: This real-world study highlights the deterioration of adolescents' mental health during the COVID-19 pandemic and suggests that youth mental health should be considered during health policy decision making. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Association Between AZD7442 (Tixagevimab-Cilgavimab) Administration and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection, Hospitalization, and Mortality.

BACKGROUND: Intramuscular AZD7442 (Tixagevimab-Cilgavimab, (Evusheld)) has been found effective among immunocompromised individuals (ICI) in reducing Sars-Cov-2 infection and severe disease in ICIs. We evaluated the association between AZD7442 administration and SARS-CoV-2 infection and severe disease (COVID-19 hospitalization and all-cause mortality) among selected ICIs, during a fifth Omicron-dominated wave of COVID-19 (Dec 2021-April 2022) in Israel. METHODS: ICIs aged 12 and over identified in the Maccabi HealthCare Services database were invited by SMS/email to receive AZD7442. Demographic information, comorbidities, coronavirus vaccination and prior SARS-CoV-2 infection and COVID-19 outcome data (infection, severe disease), were extracted from the database. Rates of infection and severe disease were compared between those administered AZD7442 and those who did not respond to the invitation, over a three-month period. RESULTS: Of all 825 ICIs administered AZD7442, 29 (3.5%) became infected with SARS-CoV-2 compared to 308 (7.2%) of 4299 ICIs not administered AZD7442 (p < 0.001). After adjustment, the AZD7442 group were half as less likely to become infected with Sars-Cov-2 than the non-administered group (OR: 0.51, 95% CI: 0.30-0.84). One person in the AZD7442 group (0.1%) was hospitalized for COVID-19 compared to 27 (0.6%) in the non-administered group (p = 0.07). No mortality was recorded among the AZD7442 group, compared to 40 deaths (0.9%) in the non-administered group (p = 0.005). After adjustment, ICIs administered AZD7442 were 92% less likely to be hospitalized/die than those not administered AZD7442 (OR: 0.08, 95% CI: 0.01-0.54). CONCLUSIONS: AZD7442 among ICI may protect against Omicron variant infection and severe disease, and should be considered for pre-exposure prophylactic AZD7442.

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.

BNT162b2 mRNA Vaccine Effectiveness Given Confirmed Exposure: Analysis of Household Members of Coronavirus Disease 2019 Patients.

BACKGROUND: Although BNT162b2 vaccine-efficacy analyses have been published, the effectiveness of the vaccine in preventing coronavirus disease 2019 given confirmed exposure has not been previously demonstrated, even though it has policy implications, such as the need for self-quarantine when exposure has occurred. METHODS: In a retrospective cohort study, we used data collected between 20 December 2020 and 17 March 2021 from the second largest healthcare provider in Israel to analyze the probability of an additional household infection occurring within 10 days after an index infection. In model 1, vaccine effectiveness was described for Fully Vaccinated individuals (7 or more days from second dose) vs either Unvaccinated individuals or those Recently Vaccinated Once (0-7 days from the first dose, presumably still unprotected). Secondary analyses included correction for differing testing rates. In model 2, we conducted a separate analysis of households comprised of only adults with the same vaccination status. RESULTS: A total of 173 569 households were included, of which 6351 had an index infection (mean [standard deviation] age, 58.9 [13.5] years); 50% were women. Adjusted vaccine effectiveness of Fully Vaccinated compared with Unvaccinated participants was 80.3% (95% confidence interval [CI], 73.5-85.4) and 82.0% (95% CI, 75.6-86.8) compared with those Recently Vaccinated Once. CONCLUSIONS: The BNT162b2 vaccine is effective in high-risk real-life exposure scenarios, but the protection afforded in these settings is lower than that previously described. Individuals with a confirmed significant exposure to severe acute respiratory syndrome are still at risk of being infected even if fully vaccinated.

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.

Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals, a prospective longitudinal cohort study.

PURPOSE: As protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion. METHODS: A prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster. RESULTS: Among 110 participants,56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25-11.67) folds and 2.40 (95 %CI 1.90-3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5-79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1-34.7) fold in and immunocompetent group, was observed. CONCLUSION: A third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.

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

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

Kinetics of SARS-CoV-2 anti-S IgG after BNT162b2 vaccination.

Deployment of the BNT162b2 mRNA Covid-19 Vaccine in Israel began in December 2020. This is a retrospective analysis of serological data, showing SARS-CoV-2 anti-S IgG kinetics in 116 Israeli health care workers receiving BNT162b2. Sero-conversion occurred in 14 days in all study participants, with IgG levels peaking approximately 30 days after initiation of the vaccination series. A statistically significant difference was observed in IgG levels between subjects younger than 50 years and older participants, although in all cases, IgG levels were well above the level considered reactive by the test's manufacturer. The importance of this difference needs to be studied further, but a potential difference in vaccine efficacy and vaccine effect length could possibly be present between these two groups.