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1.
Elife ; 112022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1975326

ABSTRACT

Quantifying the temporal dynamics of infectiousness of individuals infected with SARS-CoV-2 is crucial for understanding the spread of COVID-19 and for evaluating the effectiveness of mitigation strategies. Many studies have estimated the infectiousness profile using observed serial intervals. However, statistical and epidemiological biases could lead to 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 was minimal), and find that the infectiousness profile of the original strain is longer than previously thought. Sensitivity analysis shows our results are robust to model structure, assumed growth rate and potential observational biases. Although unmitigated transmission data is lacking for variants of concern (VOC), previous analyses suggest that the alpha and delta variants have faster within-host kinetics, which we extrapolate to crude estimates of variant-specific unmitigated generation intervals. Knowing the unmitigated infectiousness profile of infected individuals can inform estimates of the effectiveness of isolation and quarantine measures. The framework presented here can help design better quarantine policies in early stages of future epidemics.

2.
N Engl J Med ; 386(23): 2201-2212, 2022 06 09.
Article in English | MEDLINE | ID: covidwho-1864786

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides natural immunity against reinfection. Recent studies have shown waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown. METHODS: Using the Israeli Ministry of Health database, we extracted data for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. We used Poisson regression with adjustment for confounding factors to compare the rates of infection as a function of time since the last immunity-conferring event. RESULTS: The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously. CONCLUSIONS: Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of a second dose of vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.


Subject(s)
COVID-19 , BNT162 Vaccine/immunology , BNT162 Vaccine/therapeutic use , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Humans , Immunity, Innate , Reinfection/immunology , Reinfection/prevention & control , SARS-CoV-2 , Time Factors , Viral Vaccines/immunology , Viral Vaccines/therapeutic use
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337625

ABSTRACT

BACKGROUND The 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. METHODS We 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. RESULTS In 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). CONCLUSIONS A 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.

4.
Nature ; 607(7918): 356-359, 2022 07.
Article in English | MEDLINE | ID: covidwho-1830078

ABSTRACT

The extent to which Omicron infection1-9, with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured the neutralization capacity against variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals in South Africa infected with the Omicron sublineage BA.1 starting at a median of 6 (interquartile range 3-9) days post symptom onset and continuing until last follow-up sample available, a median of 23 (interquartile range 19-27) days post symptoms to allow BA.1-elicited neutralizing immunity time to develop. Fifteen participants were vaccinated with Pfizer's BNT162b2 or Johnson & Johnson's Ad26.CoV2.S and had BA.1 breakthrough infections, and 24 were unvaccinated. BA.1 neutralization increased from a geometric mean 50% focus reduction neutralization test titre of 42 at enrolment to 575 at the last follow-up time point (13.6-fold) in vaccinated participants and from 46 to 272 (6.0-fold) in unvaccinated participants. Delta virus neutralization also increased, from 192 to 1,091 (5.7-fold) in vaccinated participants and from 28 to 91 (3.0-fold) in unvaccinated participants. At the last time point, unvaccinated individuals infected with BA.1 had low absolute levels of neutralization for the non-BA.1 viruses and 2.2-fold lower BA.1 neutralization, 12.0-fold lower Delta neutralization, 9.6-fold lower Beta variant neutralization, 17.9-fold lower ancestral virus neutralization and 4.8-fold lower Omicron sublineage BA.2 neutralization relative to vaccinated individuals infected with BA.1. These results indicate that hybrid immunity formed by vaccination and Omicron BA.1 infection should be protective against Delta and other variants. By contrast, infection with Omicron BA.1 alone offers limited cross-protection despite moderate enhancement.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Cross Protection , SARS-CoV-2 , Vaccination , Ad26COVS1/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , BNT162 Vaccine/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , Cross Protection/immunology , Humans , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Vaccination/statistics & numerical data
5.
Nat Rev Immunol ; 22(5): 267-269, 2022 05.
Article in English | MEDLINE | ID: covidwho-1799587
6.
Front Immunol ; 13: 868915, 2022.
Article in English | MEDLINE | ID: covidwho-1793012

ABSTRACT

Background: Immunomodulatory/immunosuppressive activity of multiple sclerosis (MS) disease modifying therapies (DMTs) might affect immune responses to SARS-CoV-2 exposure or vaccination in patients with MS (PwMS). We evaluated the effect of DMTs on humoral and cell-mediated immune responses to 2 and 3 vaccinations and the longevity of SARS-Cov-2 IgG levels in PwMS. Methods: 522 PwMS and 68 healthy controls vaccinated with BNT162b2-Pfizer mRNA vaccine against SARS-CoV-2, or recovering from COVID-19, were recruited in a nation-wide multi-center study. Blood was collected at 3 time-points: 2-16 weeks and ~6 months post 2nd vaccination and 1-16 weeks following 3rd vaccination. Serological responses were measured by quantifying IgG levels against the spike-receptor-binding-domain of SARS-CoV-2, and cellular responses (in a subgroup analysis) by quantifying IFNγ secretion in blood incubated with COVID-19 spike-antigen. Results: 75% PwMS were seropositive post 2nd or 3rd vaccination. IgG levels decreased by 82% within 6 months from vaccination (p<0.0001), but were boosted 10.3 fold by the 3rd vaccination (p<0.0001), and 1.8 fold compared to ≤3m post 2nd vaccination (p=0.025). Patients treated with most DMTs were seropositive post 2nd and 3rd vaccinations, however only 38% and 44% of ocrelizumab-treated patients and 54% and 46% of fingolimod-treated patients, respectively, were seropositive. Similarly, in COVID-19-recovered patients only 54% of ocrelizumab-treated, 75% of fingolimod-treated and 67% of cladribine-treated patients were seropositive. A time interval of ≥5 months between ocrelizumab infusion and vaccination was associated with higher IgG levels (p=0.039 post-2nd vaccination; p=0.036 post-3rd vaccination), and with higher proportions of seropositive patients. Most fingolimod- and ocrelizumab-treated patients responded similarly to 2nd and 3rd vaccination. IFNγ-T-cell responses were detected in 89% and 63% of PwMS post 2nd and 3rd vaccination, however in only 25% and 0% of fingolimod-treated patients, while in 100% and 86% of ocrelizumab-treated patients, respectively. Conclusion: PwMS treated with most DMTs developed humoral and T-cell responses following 2 and 3 mRNA SARS-CoV-2 vaccinations. Fingolimod- or ocrelizumab-treated patients had diminished humoral responses, and fingolimod compromised the cellular responses, with no improvement after a 3rd booster. Vaccination following >5 months since ocrelizumab infusion was associated with better sero-positivity. These findings may contribute to the development of treatment-stratified vaccination guidelines for PwMS.


Subject(s)
COVID-19 , Multiple Sclerosis , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Fingolimod Hydrochloride/therapeutic use , Humans , Immunity, Cellular , Immunoglobulin G/therapeutic use , Israel , Multiple Sclerosis/drug therapy , RNA, Messenger/therapeutic use , SARS-CoV-2 , Vaccination , Vaccines, Synthetic , mRNA Vaccines
7.
Nat Commun ; 13(1): 1971, 2022 04 13.
Article in English | MEDLINE | ID: covidwho-1788288

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 dose 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 (up to 60 days) booster dose with that of a fresh 2-dose vaccine, we took advantage of a quasi-experimental study that compares populations that were eligible to receive the vaccine at different times due to age-dependent policies. Specifically, we compared the confirmed infection rates in adolescents aged 12-14 (215,653 individuals) who received the 2-dose vaccine and in adolescents aged 16-18 (103,454 individuals) who received the booster dose. Our analysis shows that the confirmed infection rate was lower by a factor of 3.7 (95% CI: 2.7 to 5.2) in the booster group.


Subject(s)
COVID-19 , Adolescent , COVID-19/prevention & control , Humans , Immunization, Secondary , Israel , SARS-CoV-2
8.
N Engl J Med ; 386(18): 1712-1720, 2022 05 05.
Article in English | MEDLINE | ID: covidwho-1774020

ABSTRACT

BACKGROUND: On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19). METHODS: Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day. RESULTS: The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks. CONCLUSIONS: Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Israel/epidemiology
9.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327341

ABSTRACT

BACKGROUND On 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. METHODS We 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. RESULTS The 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). CONCLUSIONS Rates of confirmed Covid-19 and severe illness were lower following a fourth dose compared to only three doses.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-306311

ABSTRACT

Accurate numbers are needed to understand and predict viral dynamics. Curation of high-quality literature values for the infectious period duration or household secondary attack rate, for example, is especially pressing currently because these numbers inform decisions about how and when to lockdown or reopen societies. We aim to provide a curated source for the key numbers that help us understand the virus driving our current global crisis. This compendium focuses solely on COVID-19 epidemiology. The numbers reported in summary format are substantiated by annotated references. For each property, we provide a concise definition, description of measurement and inference methods, and associated caveats. We hope this compendium will make essential numbers more accessible and avoid common sources of confusion for the many newcomers to the field such as using the incubation period to denote and quantify the latent period or using the hospitalization duration for the infectiousness period duration. This document will be repeatedly updated and the community is invited to participate in improving it.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-306310

ABSTRACT

Modeling the spread of COVID-19 is crucial for informing public health policy. All models for COVID-19 epidemiology rely on parameters describing the dynamics of the infection process. The meanings of epidemiological parameters like R_0, R_t, the "serial interval" and "generation interval" can be challenging to understand, especially as these and other parameters are conceptually overlapping and sometimes confusingly named. Moreover, the procedures used to estimate these parameters make various assumptions and use different mathematical approaches that should be understood and accounted for when relying on parameter values and reporting them to the public. Here, we offer several insights regarding the derivation of commonly-reported epidemiological parameters, and describe how mitigation measures like lockdown are expected to affect their values. We aim to present these quantitative relationships in a manner that is accessible to the widest audience possible. We hope that better communicating the intricacies of epidemiological models will improve our collective understanding of their strengths and weaknesses, and will help avoid possible pitfalls when using them.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-306309

ABSTRACT

The current SARS-CoV-2 pandemic is a harsh reminder of the fact that, whether in a single human host or a wave of infection across continents, viral dynamics is often a story about the numbers. In this snapshot, our aim is to provide a one-stop, curated graphical source for the key numbers that help us understand the virus driving our current global crisis. The discussion is framed around two broad themes: 1) the biology of the virus itself and 2) the characteristics of the infection of a single human host. Our one-page summary provides the key numbers pertaining to SARS-CoV-2, based mostly on peer-reviewed literature. The numbers reported in summary format are substantiated by the annotated references below. Readers are urged to remember that much uncertainty remains and knowledge of this pandemic and the virus driving it is rapidly evolving. In the paragraphs below we provide "back of the envelope" calculations that exemplify the insights that can be gained from knowing some key numbers and using quantitative logic. These calculations serve to improve our intuition through sanity checks, but do not replace detailed epidemiological analysis.

13.
Current Trends in Neurology ; 15:39, 2021.
Article in English | ProQuest Central | ID: covidwho-1651701

ABSTRACT

More than a year into the pandemic of severe acute respiratory syndrome-related Corona virus-2 (SARS-Cov-2), there is a growing body of evidence for the involvement of the virus in the nervous system by different mechanisms. Here we report on a previously healthy 39-year-old man who presented with clinical symptoms suggesting encephalitis including fever, impaired consciousness, confusion, and seizures. Cerebrospinal fluid analysis confirmed the diagnosis. Repeated serological tests were positive for IgM and IgG to SARS-Cov-2 despite negative polymerase chain reaction (PCR) test result for the virus in the nasopharyngeal swabs and CSF samples. An extensive work-up for other infectious, inflammatory, or paraneoplastic causes was negative. The patient was intubated and sedated due to impaired consciousness and received supportive treatment. The patient was extubated after 3 days and recovered gradually over 3 weeks. This case suggests the development of post-infectious encephalitis due to previous Covid-19 infection, like the development of post-infectious encephalitis after infection with other viruses.

14.
N Engl J Med ; 385(26): 2421-2430, 2021 12 23.
Article in English | MEDLINE | ID: covidwho-1562194

ABSTRACT

BACKGROUND: After promising initial results from the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) to persons 60 years of age or older, the booster campaign in Israel was gradually expanded to persons in younger age groups who had received a second dose at least 5 months earlier. METHODS: We extracted data for the period from July 30 to October 10, 2021, from the Israel Ministry of Health database regarding 4,696,865 persons 16 years of age or older who had received two doses of BNT162b2 at least 5 months earlier. In the primary analysis, we compared the rates of confirmed coronavirus disease 2019 (Covid-19), severe illness, and death among those who had received a booster dose at least 12 days earlier (booster group) with the rates among those who had not received a booster (nonbooster group). In a secondary analysis, we compared the rates in the booster group with the rates among those who had received a booster 3 to 7 days earlier (early postbooster group). We used Poisson regression models to estimate rate ratios after adjusting for possible confounding factors. RESULTS: The rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of approximately 10 (range across five age groups, 9.0 to 17.2) and was lower in the booster group than in the early postbooster group by a factor of 4.9 to 10.8. The adjusted rate difference ranged from 57.0 to 89.5 infections per 100,000 person-days in the primary analysis and from 34.4 to 38.3 in the secondary analysis. The rates of severe illness in the primary and secondary analyses were lower in the booster group by a factor of 17.9 (95% confidence interval [CI], 15.1 to 21.2) and 6.5 (95% CI, 5.1 to 8.2), respectively, among those 60 years of age or older and by a factor of 21.7 (95% CI, 10.6 to 44.2) and 3.7 (95% CI, 1.3 to 10.2) among those 40 to 59 years of age. The adjusted rate difference in the primary and secondary analyses was 5.4 and 1.9 cases of severe illness per 100,000 person-days among those 60 years of age or older and 0.6 and 0.1 among those 40 to 59 years of age. Among those 60 years of age or older, mortality was lower by a factor of 14.7 (95% CI, 10.0 to 21.4) in the primary analysis and 4.9 (95% CI, 3.1 to 7.9) in the secondary analysis. The adjusted rate difference in the primary and secondary analyses was 2.1 and 0.8 deaths per 100,000 person-days. CONCLUSIONS: Across the age groups studied, rates of confirmed Covid-19 and severe illness were substantially lower among participants who received a booster dose of the BNT162b2 vaccine than among those who did not.


Subject(s)
COVID-19/epidemiology , Immunization, Secondary , Patient Acuity , /statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/prevention & control , Female , Humans , Israel/epidemiology , Male , Middle Aged , Young Adult
15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294817

ABSTRACT

BACKGROUND Infection 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. METHODS Data 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. RESULTS Confirmed 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. CONCLUSIONS Protection 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.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294199

ABSTRACT

Research in Economics on COVID-19 posits an economy subject to disease dynamics, which are often seriously misspecified in terms of speed and scale. Using a social planner problem, we show that such misspecifications lead to misguided policy. Erroneously characterizing a relatively slow-moving disease engenders dramatically higher death tolls and excessive output loss relative to the correct benchmark. We delineate the latter, employing epidemiological evidence on the timescales of COVID-19 transmission and clinical progression. The resulting sound model is simple, transparent, and novel in Economics.

17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293587

ABSTRACT

BACKGROUND Infection 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. METHODS Data 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. RESULTS Confirmed 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. CONCLUSIONS Protection 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.

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293109

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.

19.
N Engl J Med ; 385(24): e85, 2021 12 09.
Article in English | MEDLINE | ID: covidwho-1493320

ABSTRACT

BACKGROUND: In December 2020, Israel began a mass vaccination campaign against coronavirus disease 2019 (Covid-19) by administering the BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a resurgent Covid-19 outbreak began in mid-June 2021. Possible reasons for the resurgence were reduced vaccine effectiveness against the delta (B.1.617.2) variant and waning immunity. The extent of waning immunity of the vaccine against the delta variant in Israel is unclear. METHODS: We used data on confirmed infection and severe disease collected from an Israeli national database for the period of July 11 to 31, 2021, for all Israeli residents who had been fully vaccinated before June 2021. We used a Poisson regression model to compare rates of confirmed SARS-CoV-2 infection and severe Covid-19 among persons vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors. RESULTS: Among persons 60 years of age or older, the rate of infection in the July 11-31 period was higher among persons who became fully vaccinated in January 2021 (when they were first eligible) than among those fully vaccinated 2 months later, in March (rate ratio, 1.6; 95% confidence interval [CI], 1.3 to 2.0). Among persons 40 to 59 years of age, the rate ratio for infection among those fully vaccinated in February (when they were first eligible), as compared with 2 months later, in April, was 1.7 (95% CI, 1.4 to 2.1). Among persons 16 to 39 years of age, the rate ratio for infection among those fully vaccinated in March (when they were first eligible), as compared with 2 months later, in May, was 1.6 (95% CI, 1.3 to 2.0). The rate ratio for severe disease among persons fully vaccinated in the month when they were first eligible, as compared with those fully vaccinated in March, was 1.8 (95% CI, 1.1 to 2.9) among persons 60 years of age or older and 2.2 (95% CI, 0.6 to 7.7) among those 40 to 59 years of age; owing to small numbers, the rate ratio could not be calculated among persons 16 to 39 years of age. CONCLUSIONS: These findings indicate that immunity against the delta variant of SARS-CoV-2 waned in all age groups a few months after receipt of the second dose of vaccine.


Subject(s)
Antibodies, Neutralizing/blood , COVID-19/epidemiology , Immunogenicity, Vaccine , SARS-CoV-2 , Adolescent , Adult , Aged , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/prevention & control , Female , Humans , Immunization, Secondary , Israel/epidemiology , Male , Middle Aged , Patient Acuity , Poisson Distribution , Regression Analysis , Socioeconomic Factors , Time Factors
20.
N Engl J Med ; 385(15): 1393-1400, 2021 10 07.
Article in English | MEDLINE | ID: covidwho-1410382

ABSTRACT

BACKGROUND: On July 30, 2021, the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) was approved in Israel for persons who were 60 years of age or older and who had received a second dose of vaccine at least 5 months earlier. Data are needed regarding the effect of the booster dose on the rate of confirmed coronavirus 2019 disease (Covid-19) and the rate of severe illness. METHODS: We extracted data for the period from July 30 through August 31, 2021, from the Israeli Ministry of Health database regarding 1,137,804 persons who were 60 years of age or older and had been fully vaccinated (i.e., had received two doses of BNT162b2) at least 5 months earlier. In the primary analysis, we compared the rate of confirmed Covid-19 and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (nonbooster group). In a secondary analysis, we evaluated the rate of infection 4 to 6 days after the booster dose as compared with the rate at least 12 days after the booster. In all the analyses, we used Poisson regression after adjusting for possible confounding factors. RESULTS: At least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% confidence interval [CI], 10.4 to 12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9 to 29.5). In a secondary analysis, the rate of confirmed infection at least 12 days after vaccination was lower than the rate after 4 to 6 days by a factor of 5.4 (95% CI, 4.8 to 6.1). CONCLUSIONS: In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Immunization, Secondary , Aged , Aged, 80 and over , COVID-19/epidemiology , Databases, Factual , Female , Humans , Israel/epidemiology , Male , Middle Aged , Patient Acuity , Poisson Distribution , SARS-CoV-2
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