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: 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.

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.

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: Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.

METHODS: We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.

RESULTS: In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.

CONCLUSIONS: In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

BACKGROUND: Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.

METHODS: We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.

RESULTS: In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.

CONCLUSIONS: In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).