ABSTRACT
BACKGROUNDThe BNT162b2 (Pfizer-BioNTech) 2-dose vaccine for children and the BNT162b2 3rd dose for adolescents were approved shortly before the Omicron outbreak in Israel. The effects of these vaccines on the rates of Omicron confirmed infection are not yet clear. METHODSWe extracted data for the Omicron-dominated (sub-lineage BA.1) period December 26, 2021 through January 8, 2022. We compared rates of confirmed Covid-19 infection between children 5-10 years old 14-35 days after receiving the 2nd dose to an internal control group of children 3-7 days after receiving the 1st dose (when the vaccine is not yet effective). Similarly, we compared confirmed infection rates in adolescents 12-15 years old 14-60 days after receiving a booster dose to an internal control group of adolescents 3-7 days after receiving the booster dose. We used Poisson regression, adjusting for age, sex, socioeconomic status, calendar week, and exposure. RESULTSIn the 5-10 age group, the estimated rate of confirmed infection was 2.3 fold (95% CI, 2.0 to 2.5) lower in the 2nd dose group than in the internal control group. In adolescents, the third dose decreased confirmed infection rates by 3.3-fold (95% CI, 2.8 to 4.0). CONCLUSIONSA recent 2-dose BNT162b2 vaccination in children and a recent booster dose in adolescents reduced the rate of confirmed infection compared to the respective internal control groups. Future studies are needed to assess the duration of this protection and protection against other outcomes such as PIMS and long-COVID.
ABSTRACT
Following a rise in cases due to the delta variant and evidence of waning immunity after 2 doses of the BNT162b2 vaccine, Israel began administering a third BNT162b2 dose (booster) in July 2021. Recent studies showed that the 3rd dose provides a much lower protection against infection with the omicron variant compared to the delta variant and that this protection wanes quickly. In this study, we used data from Israel to estimate the protection of the 3rd dose against severe disease up to 7 months from receiving the booster dose. The analysis shows that protection conferred by the 3rd dose against omicron did not wane over a 7-month period and that a 4th dose further increased protection, with a severe disease rate approximately 3-fold lower than in the 3-dose cohorts.
ABSTRACT
BACKGROUNDOn January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine (Pfizer-BioNTech) to people aged over 60 years and at-risk populations, who had received a third dose of vaccine at least 4 months earlier. The effect of the fourth dose on confirmed coronavirus 2019 disease (Covid-19) and severe illness are still unclear. METHODSWe extracted data for the Omicron-dominated period January 15 through January 27, 2022, from the Israeli Ministry of Health database regarding 1,138,681 persons aged over 60 years and eligible for the fourth dose. We compared the rate of confirmed Covid-19 and severe illness between those who had received a fourth dose at least 12 days earlier, those who had received only three doses, and those 3 to 7 days after receiving the fourth dose. We used Poisson regression after adjusting for possible confounding factors. RESULTSThe rate of confirmed infection was lower in people 12 or more days after their fourth dose than among those who received only three doses and those 3 to 7 days after vaccination by factors of 2.0 (95% confidence interval [CI], 2.0 to 2.1) and 1.9 (95% CI, 1.8 to 2.0), respectively. The rate of severe illness was lower by factors of 4.3 (95% CI, 2.4 to 7.6) and 4.0 (95% CI, 2.2 to 7.5). CONCLUSIONSRates of confirmed Covid-19 and severe illness were lower following a fourth dose compared to only three doses.
ABSTRACT
BACKGROUNDInfection with SARS-CoV-2 provides substantial natural immunity against reinfection. Recent studies have shown strong waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown. METHODSData on confirmed SARS-CoV-2 infections were extracted from the Israeli Ministry of Health database for the period August to September 2021 regarding all persons previously infected or vaccinated. We compared infection rates as a function of time since the last immunity-conferring event using Poisson regression, adjusting for possible confounding factors. RESULTSConfirmed infection rates increased according to time elapsed since the last immunity-conferring event in all cohorts. For unvaccinated previously infected individuals they increased from 10.5 per 100,000 risk-days for those previously infected 4-6 months ago to 30.2 for those previously infected over a year ago. For individuals receiving a single dose following prior infection they increased from 3.7 per 100,000 person days among those vaccinated in the past two months to 11.6 for those vaccinated over 6 months ago. For vaccinated previously uninfected individuals the rate per 100,000 person days increased from 21.1 for persons vaccinated within the first two months to 88.9 for those vaccinated more than 6 months ago. CONCLUSIONSProtection from reinfection decreases with time since previous infection, but is, nevertheless, higher than that conferred by vaccination with two doses at a similar time since the last immunity-conferring event. A single vaccine dose after infection helps to restore protection.
ABSTRACT
Israel began administering a BNT162b2 booster dose to restore protection following the waning of the 2-dose vaccine. Biological studies have shown that a fresh booster leads to increased antibody levels compared to a fresh 2-dose vaccine, which may suggest increased effectiveness. To compare the real-world effectiveness of a fresh booster dose with that of a fresh 2-dose vaccine, we conduct a quasi-experimental study that compares populations that were eligible to receive the vaccine at different times due to age cutoff policies. Our analysis shows that a fresh booster increases protection against confirmed infection by 3.7 (95% CI: 2.7 to 5.2) fold compared to a fresh 2-dose vaccine.
ABSTRACT
Quantifying the temporal dynamics of infectiousness of individuals infected with SARS-CoV-2 is crucial for understanding the spread of the COVID-19 pandemic and for analyzing the effectiveness of different mitigation strategies. Many studies have tried to use data from the onset of symptoms of infector-infectee pairs to estimate the infectiousness profile of SARS-CoV-2. However, both statistical and epidemiological biases in the data could lead to an underestimation of the duration of infectiousness. We correct for these biases by curating data from the initial outbreak of the pandemic in China (when mitigation steps were still minimal), and find that the infectiousness profile is wider than previously thought. For example, our estimate for the proportion of transmissions occurring 14 days or more after infection is an order of magnitude higher - namely 19% (95% CI 10%-25%). The inferred generation interval distribution is sensitive to the definition of the period of unmitigated transmission, but estimates that rely on later periods are less reliable due to intervention effects. Nonetheless, the results are robust to other factors such as the model, the assumed growth rate and possible bias of the dataset. Knowing the unmitigated infectiousness profile of infected individuals affects estimates of the effectiveness of self-isolation and quarantine of contacts. The framework presented here can help design better quarantine policies in early stages of future epidemics using data from the initial stages of transmission.
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BACKGROUNDFollowing administration to persons 60+ years of age, the booster vaccination campaign in Israel was gradually expanded to younger age groups who received a second dose >5 months earlier. We study the booster effect on COVID-19 outcomes. METHODSWe extracted data for the period July 30, 2021 to October 6, 2021 from the Israeli Ministry of Health database regarding 4,621,836 persons. We compared confirmed Covid-19 infections, severe illness, and death of those who received a booster [≥]12 days earlier (booster group) with a nonbooster group. In a secondary analysis, we compared the rates 3-7 days with [≥]12 days after receiving the booster dose. We used Poisson regressions to estimate rate ratios after adjusting for possible confounding factors. RESULTSConfirmed infection rates were {approx}10-fold lower in the booster versus nonbooster group (ranging 8.8-17.6 across five age groups) and 4.8-11.2 fold lower in the secondary analysis. Severe illness rates in the primary and secondary analysis were 18.7-fold (95% CI, 15.7-22.4) and 6.5-fold (95% CI, 5.1-8.3) lower for ages 60+, and 22.0-fold (95% CI, 10.3-47.0) and 3.2-fold (95% CI, 1.1-9.6) lower for ages 40-60. For ages 60+, COVID-19 associated death rates were 14.7-fold (95% CI, 9.4-23.1) lower in the primary analysis and 4.8-fold (95% CI, 2.8-8.2) lower in the secondary analysis. CONCLUSIONSAcross all age groups, rates of confirmed infection and severe illness were substantially lower among those who received a booster dose of the BNT162b2 vaccine.
ABSTRACT
BackgroundOn July 30, 2021, a third (booster) dose of the Pfizer BNT162b2 vaccine was approved in Israel for individuals 60 years or older who had been fully vaccinated (i.e., received two doses) at least five months previously. Here, we estimate the reduction in relative risk for confirmed infection and severe COVID-19 provided by the booster dose. Methods1,144,690 individuals aged 60y and older who were eligible for a booster dose were followed between July 30 and August 22, 2021. We defined dynamic cohorts where individuals initially belong to the non-booster cohort, leave it when receiving the booster dose and join the booster cohort 12 days later. Rates of infection and severe COVID-19 outcomes per person-days at risk were compared between the cohorts using Poisson regression, adjusting for possible confounding factors. ResultsTwelve days or more after the booster dose we found an 11.4-fold (95% CI: [10.0, 12.9]) decrease in the relative risk of confirmed infection, and a >10-fold decrease in the relative risk of severe illness. Under a conservative sensitivity analysis, we find {approx}5-fold protection against confirmed infection. ConclusionsIn conjunction with safety reports, this study demonstrates the effectiveness of a third vaccine dose in both reducing transmission and severe disease and indicates the great potential of curtailing the Delta variant resurgence by administering booster shots.
ABSTRACT
BackgroundStarting December 2020, Israel began a mass vaccination campaign against coronavirus administering the Pfizer BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no SARS-CoV-2 infections, a resurgent COVID-19 outbreak initiated mid June 2021. Possible reasons for the breakthrough were reduced vaccine effectiveness against the Delta variant, and waning immunity. The aim of this study was to quantify the extent of waning immunity using Israels national-database. MethodsData on all PCR positive test results between July 11-31, 2021 of Israeli residents who became fully vaccinated before June 2021 were used in this analysis. Infection rates and severe COVID-19 outcomes were compared between individuals who were vaccinated in different time periods using a Poisson regression, stratifying by age group and adjusting for possible confounding factors. ResultsThe rates of both documented SARS-CoV-2 infections and severe COVID-19 exhibit a statistically significant increase as time from second vaccine dose elapsed. Elderly individuals (60+) who received their second dose in March 2021 were 1.6 (CI: [1.3, 2]) times more protected against infection and 1.7 (CI: [1.0, 2.7]) times more protected against severe COVID-19 compared to those who received their second dose in January 2021. Similar results were found for different age groups. ConclusionsThese results indicate a strong effect of waning immunity in all age groups after six months. Quantifying the effect of waning immunity on vaccine effectiveness is critical for policy makers worldwide facing the dilemma of administering booster vaccinations.
ABSTRACT
With the development of high-efficacy vaccines against SARS-CoV-2, an urgent open question is whether currently available vaccines protect with similar efficacy against infection with SARS-CoV-2 variants of concern (VOC). Recent reports quantifying the extent by which VOC can evade vaccine immunity resulted in a range of estimates for the same VOC, which makes them difficult to interpret. One possible explanation for the discrepancies between different studies is an inconsistency in terms of the time post-vaccination of the sampled population. Here we present a model based on the observed correlation between antibody neutralization levels and vaccine efficacy, which demonstrates the impact of time post-vaccination on the comparison of the vaccine efficacy for VOC versus non-VOC infections. Our model predicts and exemplifies several possible consequences for vaccine efficacy in VOC infections: 1) a delay in the onset of vaccine efficacy against VOC; 2) a transient increase in susceptibility to breakthrough infection with VOC compared to non-VOC as a function of time after vaccination. We review preliminary data indicating that such phenomena are observed in studies of the B.1.1.7 and B.1.351 variants. We find that ignoring the strong dependence on the time post-vaccination can lead to contradictory reports of relative efficacy against VOC versus non-VOC, with implications on mitigation strategies against VOC and the design of vaccine efficacy studies.
ABSTRACT
Quantitatively describing the time course of the SARS-CoV-2 infection within an infected individual is important for understanding the current global pandemic and possible ways to combat it. Here we integrate the best current knowledge about the typical viral load of SARS-CoV-2 in bodily fluids and host tissues to estimate the total number and mass of SARS-CoV-2 virions in an infected person. We estimate that each infected person carries 109-1011 virions during peak infection, with a total mass in the range of 1-100 g, which curiously implies that all SARS-CoV-2 virions currently circulating within human hosts have a collective mass of only 0.1-10 kg. We combine our estimates with the available literature on host immune response and viral mutation rates to demonstrate how antibodies markedly outnumber the spike proteins and the genetic diversity of virions in an infected host covers all possible single nucleotide substitutions. SignificanceKnowing the absolute numbers of virions in an infection promotes better understanding of the disease dynamics and the response of the immune system. Here we use the best current knowledge on the concentrations of virions in infected individuals to estimate the total number and mass of SARS-CoV-2 virions in an infected person. Although each infected person carries an estimated 1-100 billion virions during peak infection, their total mass is no more than 0.1 mg. This curiously implies that all SARS-CoV-2 virions currently in all human hosts have a mass of between 100 gram and 10 kilogram. Combining the known mutation rate and our estimate of the number of infectious virions we quantify the formation rate of genetic variants.
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Many countries have applied lockdown that helped suppress COVID-19, but with devastating economic consequences. Here we propose exit strategies from lockdown that provide sustainable, albeit reduced, economic activity. We use mathematical models to show that a cyclic schedule of 4-day work and 10-day lockdown, or similar variants, can prevent resurgence of the epidemic while providing part-time employment. The cycle pushes the reproduction number R below one by reduced exposure time and by exploiting the virus latent period: those infected during work days reach peak infectiousness during lockdown days. The number of work days can be adapted in response to observations. Throughout, full epidemiological measures need to continue including hygiene, physical distancing, compartmentalization, testing and contact tracing. This conceptual framework, when combined with other interventions to control the epidemic, can offer the beginnings of predictability to many economic sectors.
