BACKGROUND: COVID-19 continues to spread throughout the world. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) is used to diagnose COVID-19, with its cycle threshold (Ct) value inversely related to the viral load. The association between Ct values and COVID-19 related outcomes has been studied in the hospital setting but less so in the community. We aimed to estimate the association between Ct values and the severity of community-diagnosed COVID-19 to provide evidence on the utility of Ct testing in this setting.

METHODS: This was a retrospective cohort study based on data from Israel's largest health organization. The study population included 34,658 individuals who tested positive for COVID-19 by RT-PCR and had available Ct values between June 1st and December 21st, 2020. Outcomes included COVID-19 related symptoms, hospitalization, severe disease, and death. Ct values were modelled both as discrete and continuous exposures.

RESULTS: After adjusting for known risk factors for severe COVID-19, low Ct values were associated with symptomatic disease (odds ratio [OR]: 1.51; 95% confidence interval [CI]:1.21-1.84), hospitalization (OR: 1.27; 95%CI: 1.12-1.49), severe disease (OR: 1.80; 95%CI: 1.43-2.27), and death (OR: 1.64; 95%CI: 1.06-2.59). By modelling the exposure as continuous, we noticed a dose-response relationship, with the risk gradually rising with lower Ct values.

CONCLUSIONS: This study found a significant association between low Ct values and severe COVID-19 related outcomes, with a dose-response relationship. This suggests that Ct values could be helpful in identifying high-risk patients diagnosed in the community.

Heart failure (HF) prevalence is increasing worldwide and is associated with significant morbidity and mortality. Guidelines emphasize prevention in those at-risk, but HF-specific risk prediction equations developed in United States population-based cohorts lack external validation in large, real-world datasets outside of the United States. The purpose of this study was to assess the model performance of the pooled cohort equations to prevent HF (PCP-HF) within a contemporary electronic health record for 5- and 10-year risk. Using a retrospective cohort study design of Israeli residents between 2008 and 2018 with continuous membership until end of follow-up, HF, or death, we quantified 5- and 10-year estimated risks of HF using the PCP-HF equations, which integrate demographics (age, gender, and race) and risk factors (body mass index, systolic blood pressure, glucose, medication use for hypertension or diabetes, and smoking status). Of 1,394,411 patients included, 56% were women with mean age of 49.6 (SD 13.2) years. Incident HF occurred in 1.2% and 4.5% of participants over 5 and 10 years of follow-up. The PCP-HF model had excellent discrimination for 5- and 10-year predictions of incident HF (C Statistic 0.82 [0.82 to 0.82] and 0.84 [0.84 to 0.84]), respectively. In conclusion, HF-specific risk equations (PCP-HF) accurately predict the risk of incident HF in ambulatory and hospitalized patients using routinely available clinical data.

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.

Children unvaccinated against SARS-CoV-2 may still benefit through protection from vaccinated contacts. We estimated the protection provided to children through parental vaccination with the BNT162b2 vaccine. We studied households without prior infection, consisting of two parents and unvaccinated children, estimating the effect of parental vaccination on the risk of infection for unvaccinated children. We studied two periods separately- an early period (January 17, 2021 - March 28, 2021, Alpha variant, two doses vs. no vaccination) and a late period (July 11, 2021 - September 30, 2021, Delta variant, booster dose vs. two-vaccine doses). We found that having a single vaccinated parent was associated with a 26.0% and 20.8% decreased risk, and having two vaccinated parents was associated with a 71.7% and 58.1% decreased risk, in the early and late periods, respectively. To conclude, parental vaccination confers substantial protection for unvaccinated children in the household.

BACKGROUND: COVID-19 continues to spread throughout the world. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) is used to diagnose COVID-19, with its cycle threshold (Ct) value inversely related to the viral load. The association between Ct values and COVID-19 related outcomes has been studied in the hospital setting but less so in the community. We aimed to estimate the association between Ct values and the severity of community-diagnosed COVID-19 to provide evidence on the utility of Ct testing in this setting.

METHODS: This was a retrospective cohort study based on data from Israel's largest health organization. The study population included 34,658 individuals who tested positive for COVID-19 by RT-PCR and had available Ct values between June 1st and December 21st, 2020. Outcomes included COVID-19 related symptoms, hospitalization, severe disease, and death. Ct values were modelled both as discrete and continuous exposures.

RESULTS: After adjusting for known risk factors for severe COVID-19, low Ct values were associated with symptomatic disease (odds ratio [OR]: 1.51; 95% confidence interval [CI]:1.21-1.84), hospitalization (OR: 1.27; 95%CI: 1.12-1.49), severe disease (OR: 1.80; 95%CI: 1.43-2.27), and death (OR: 1.64; 95%CI: 1.06-2.59). By modelling the exposure as continuous, we noticed a dose-response relationship, with the risk gradually rising with lower Ct values.

CONCLUSIONS: This study found a significant association between low Ct values and severe COVID-19 related outcomes, with a dose-response relationship. This suggests that Ct values could be helpful in identifying high-risk patients diagnosed in the community.

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.

Heart failure (HF) prevalence is increasing worldwide and is associated with significant morbidity and mortality. Guidelines emphasize prevention in those at-risk, but HF-specific risk prediction equations developed in United States population-based cohorts lack external validation in large, real-world datasets outside of the United States. The purpose of this study was to assess the model performance of the pooled cohort equations to prevent HF (PCP-HF) within a contemporary electronic health record for 5- and 10-year risk. Using a retrospective cohort study design of Israeli residents between 2008 and 2018 with continuous membership until end of follow-up, HF, or death, we quantified 5- and 10-year estimated risks of HF using the PCP-HF equations, which integrate demographics (age, gender, and race) and risk factors (body mass index, systolic blood pressure, glucose, medication use for hypertension or diabetes, and smoking status). Of 1,394,411 patients included, 56% were women with mean age of 49.6 (SD 13.2) years. Incident HF occurred in 1.2% and 4.5% of participants over 5 and 10 years of follow-up. The PCP-HF model had excellent discrimination for 5- and 10-year predictions of incident HF (C Statistic 0.82 [0.82 to 0.82] and 0.84 [0.84 to 0.84]), respectively. In conclusion, HF-specific risk equations (PCP-HF) accurately predict the risk of incident HF in ambulatory and hospitalized patients using routinely available clinical data.

Children unvaccinated against SARS-CoV-2 may still benefit through protection from vaccinated contacts. We estimated the protection provided to children through parental vaccination with the BNT162b2 vaccine. We studied households without prior infection, consisting of two parents and unvaccinated children, estimating the effect of parental vaccination on the risk of infection for unvaccinated children. We studied two periods separately- an early period (January 17, 2021 - March 28, 2021, Alpha variant, two doses vs. no vaccination) and a late period (July 11, 2021 - September 30, 2021, Delta variant, booster dose vs. two-vaccine doses). We found that having a single vaccinated parent was associated with a 26.0% and 20.8% decreased risk, and having two vaccinated parents was associated with a 71.7% and 58.1% decreased risk, in the early and late periods, respectively. To conclude, parental vaccination confers substantial protection for unvaccinated children in the household.