Post-acute sequelae of COVID-19 infection.

To determine if people infected with SARS-CoV-2 were at higher risk of developing selected medical conditions post-recovery, data were extracted from the database of a large health maintenance organization (HMO) in Israel between March 2020 and May 2021. For each condition, a condition-naïve group prior to COVID-19 (PCR-positive) infection were compared to a condition-naïve, non-COVID-19 infected group, matched by gender, age, socioeconomic status, minority group status and number of months visited primary care physician (PCP) in previous year. Diagnosis and recuperation dates for each COVID-19 infected participant were applied to their matched comparison participant (1:1 ratio). Incidence of each condition was measured between date of recuperation and end of study period for each group and Cox regression models developed to determine hazard ratios by group status, controlling for demographic and health variables. Crude and adjusted incidence rates were higher for the COVID-19 infected group than those not infected with COVID-19 for treatment for depression/anxiety, sleep disturbance, diagnosis of deep venous thrombosis, lung disease and fibromyalgia. Differences in incidence were no longer observed between the two groups for treatment of sleep disturbance, and diagnosis of lung disease when those hospitalized during the acute-phase of illness (any reason) were excluded. No difference was found by COVID-19 infection status for post-acute incidence of diabetes, cerebrovascular accident, myocardial infarction, acute kidney disease, hypertension and ischemic heart disease. Patients post-COVID-19 infection should be evaluated for depression, anxiety, sleep disturbance, DVT, lung disease and fibromyalgia.

Dynamics in COVID-19 Symptoms During Different Waves of the Pandemic Among Children Infected with SARS-CoV-2 (preprint)

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 Organisation 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 - April 30, 2021, and June 1, 2021 - 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.

Mental health assessment of Israeli adolescents before and during the COVID-19 pandemic (preprint)

The measures used to contain the COVID-19 pandemic caused severe disruption to the lives of children and adolescents, compromising their mental health and wellbeing. In this study we assessed the incidence rates of psychiatric diagnoses and drugs in Israeli adolescents before and during the COVID-19 pandemic. Analysis of health records data of over 200,000 12-17 years old adolescents identified a significant increase in all mental health diagnoses and most psychiatric drugs dispensation during the COVID-19 period compared to a corresponding pre-COVID period. A gender sub-analysis revealed that most of this increase was associated with adolescent girls. Girls exhibited increases of 68% in depression, 67% in eating disorders, 42% in anxiety and 29% in stress-related diagnoses during the COVID-19 period, which are significantly higher rates than those seen in boys and in the pre-COVID period. Sector sub-analysis showed that the increase was mainly in the general Jewish sector with almost no significant increases in the Arab and ultra-orthodox sectors. Our study highlights the mental health burden of Israeli adolescents during the pandemic and suggests that careful consideration should be given to it while deciding on measures to mitigate the pandemic.

Effectiveness of the mRNA BNT162b2 vaccine six months after vaccination: findings from a large Israeli HMO (preprint)

Israel is currently experiencing a new wave of CoVid-19 infection, six months after implementing a national vaccination campaign. We carried out three discrete analyses using data from a large Israeli HMO to determine whether IgG levels of those fully vaccinated drop over time, the relationship between IgG titer and subsequent PCR-confirmed infection, and compare PCR-confirmed infection rates by period of vaccination. We found that mean IgG antibody levels steadily decreased over the six-month period in the total tested population, and in all age groups. An inverse relationship was found between IgG titer and subsequent CoVid-19 infection (PCR-positive). Those participants vaccinated in the first two months of the campaign were more likely to become infected than those subsequently vaccinated. The 60+ vaccinated had lower initial IgG levels, and were at greater risk of infection. The findings support the decision to add a booster vaccine for those aged 60 and over. Article Summary LineThe BNT162b2 vaccine was found to be less effective in protecting against Covid-19 infection after six months, and vaccination with a third dose is indicated.

BNT162b2 mRNA Vaccine Effectiveness Given Confirmed Exposure; Analysis of Household Members of COVID-19 Patients (preprint)

Importance While the mRNA BNT162b2 vaccine effectiveness was demonstrated in general population, the question of effectiveness given confirmed exposure has yet been answered, though it has policy implications, as the need for self-quarantine when exposed and protective measures for vaccinated in high-risk areas. Objective Assessing the BNT162b2 vaccine effectiveness in preventing SARS-CoV-2 infection given high-risk exposure, through analysis of household members of confirmed cases. Design Retrospective cohort study. Data of household members of confirmed SARS-CoV-2 cases between 20/12/2020 and 17/03/2021 were collected. Setting Nationally centralized database of Maccabi Healthcare Services (MHS), the second largest Healthcare Maintenance Organization in Israel. Participants 2.5 million MHS members were considered, of which we included only households with two adult members, given possible lower transmission and susceptibility among children. Households with no prior confirmed infections and a confirmed index case during the study period were included. Exposure Participants were classified into three vaccination groups in time of the index case (the confirmed exposure)- Unvaccinated; Fully Vaccinated(7 or more days post second dose) and a reference control group of Recently Vaccinated Once(0-7 days from the first dose, presumably still unprotected). Main Outcomes and Measures Assessing the probability of an additional SARS-CoV-2 infection in the household occurring within 10 days of an index case, calculated separately for the three vaccination groups. Main outcome was vaccine effectiveness given confirmed exposure. High testing rates among household members enabled us to estimate with a high degree of confidence effectiveness against asymptomatic SARS-CoV-2 infection as well. Results A total of 173,569 households were included, out of which 6,351 households had an index infection (mean [SD] age, 58.9 [13.5] years; 50% were women). Vaccine effectiveness of Fully Vaccinated compared to Unvaccinated participants was 80.0% [95% CI, 73.0-85.1] and 82.0% [95% CI, 75.5-86.7] compared to those Recently Vaccinated Once. Conclusion and Relevance The BNT162b2 vaccine is effective in a high-risk, real life, exposure scenario, but the protection rates afforded in these settings are lower than those previously described. Household members of COVID-19 patients and any individual with a confirmed exposure to COVID-19 are still at a considerable risk of being infected even if fully vaccinated.

Survey of Behaviour Attitudes Towards Preventive Measures Following COVID-19 Vaccination (preprint)

Following the widespread vaccination program for COVID-19 carried out in Israel, a survey was conducted to preliminarily assess behavior changes in the vaccinated population, prior to the expected upcoming policy change as to mask wearing and social distancing regulation in Israel. 200 people answered at least one question pertaining to preventive behaviour. Among the respondents, 21.1% reported a decrease in mask wearing compared to 47.3% who reported a decrease in social distancing. There was no difference in these measures between the sexes. However, people under the age of 50 were more likely to decrease mask wearing (28.1%) and decrease social distancing (56.1%), as compared with people over the age of 50 (17.2% and 41.8%, respectively). Among health care workers, there was a minimal decrease in mask wearing (1/23 people) compared to a more widespread decrease in social distancing (10/23). These data suggest that preventive attitudes change following COVID-19 vaccination, with less adherence to social distancing as compared to mask wearing, and should be taken into account when planning public policy in the future.

A 1 to 1000 SARS-CoV-2 reinfection proportion in members of a large healthcare provider in Israel: a preliminary report (preprint)

With more than 100 million confirmed COVID-19 cases as of March 2021, reinfection is still considered to be rare. In light of increasing reports of reinfected COVID-19 patients, the need to better understand the real risk for reinfection is critical, with potential effects on public health policies aimed at containing the spread of SARS-CoV-2. In this descriptive preliminary report, we conducted a large-scale assessment on the country level of the possible occurrence of COVID-19 reinfection within the members of a large healthcare provider in Israel. Out of 149,735 individuals with a documented positive PCR test between March 2020 and January 2021, 154 had two positive PCR tests at least 100 days apart, reflecting a reinfection proportion of 1 per 1000. Given our strict inclusion criteria, we believe these numbers represent true reinfection incidence in MHS and should be clinically regarded as such.

Kinetics of SARS-CoV-2 anti-s IgG after BNT162b2 vaccination (preprint)

Deployment of the BNT162b2 mRNA Covid-19 Vaccine in Israel began in December 2020. This is a retrospective analysis of serological data, describing SARS-CoV-2 anti-S IgG kinetics in 116 Israeli healthcare workers administrated the BNT162b2 vaccine. Seroconversion occurred by day 14 in all individuals, with IgG levels peaking approximately 30 days post inoculation. This study demonstrated the kinetics of the antibody response post vaccination with BNT162b2. The robustness of seroconversion was observed, alongside a statistically significant difference in IgG levels between employees over and younger 50 years of afge. Further research is required in order to examine the antibody kinetics overtime, as well as whether the age-dependent difference persists.