The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long ...term effectiveness is still unknown. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection between June 1 and July 27, the date of analysis. After controlling for potential confounders as age and comorbidities, we found a significant 1.51 fold (95% CI, 1.38-1.66) increased risk for infection for early vaccinees compared to those vaccinated later that was similar across all ages groups. The increased risk reached 2.26- fold (95% CI, 1.80-3.01) when comparing those who were vaccinated in January to those vaccinated in April. This preliminary finding of vaccine waning as a factor of time from vaccince should prompt further investigations into long-term protection against different strains.
The duration of protection of the third (booster) dose of the BioNTech/Pfizer BNT162b2 mRNA Coronavirus Disease 2019 vaccine has been the subject of recent investigations, as global discussions ...around the necessity and effectiveness of a fourth dose are already underway. By conducting a retrospective study implementing a test-negative case-control design, analyzing 546,924 PCR tests performed throughout January 2022 by 389,265 persons who received at least two doses, we find that the effectiveness in each month-since-vaccination decreases significantly. Compared to those vaccinated five months prior to the outcome period, on August 2021, relative protection against infection waned from 53.4% a month after vaccination to 16.5% three months after vaccination. These results suggest that there is a significant waning of vaccine effectiveness against the Omicron variant of the third dose of the BNT162b2 vaccine within a few months after administration. Additional information could assist to comprehensively estimate the effectiveness of the three-dose-strategy.
Abstract
Background
Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by 2 doses of the BNT162b2 vaccine begins shortly after ...inoculation and becomes substantial within 4 months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity.
Methods
A retrospective observational study of 124 500 persons, compared 2 groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes—infection, symptomatic disease (coronavirus disease 2019 COVID-19), hospitalization, and death—between 1 June and 14 August 2021, when the Delta variant was dominant in Israel.
Results
SARS-CoV-2-naive vaccinees had a 13.06-fold (95% confidence interval CI, 8.08–21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 and February 2021, evidence of waning naturally acquired immunity was demonstrated, although SARS-CoV-2 naive vaccinees still had a 5.96-fold (95% CI: 4.85–7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI: 5.51–9.21) increased risk for symptomatic disease.
Conclusions
Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 2-dose vaccine-indued immunity.
The first real-world analysis of naturally acquired immunity versus vaccine induced immunity against SARS-CoV-2. Our findings illustrate that naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity.
Data regarding women infected with SARS-CoV-2 during early trimesters are scarce. We aimed to assess preterm birth (PTB) and small-for-gestational-age (SGA) rates in a large and unselected cohort by ...trimester at infection and overall. A retrospective cohort study including all women with a positive SARS-CoV-2 RT-PCR test during a non-ectopic singleton pregnancy between February 21.sup.st 2020 and July 2.sup.nd 2021 (N = 2753). Each infected woman was matched to a non-infected pregnant woman by age, last menstruation date, sector, and socioeconomic status. Logistic regression was conducted to assess the risks of PTB and SGA including an interaction between group and trimester of infection. Multivariable models included underlying diseases, previous abortions and null parity. Subgroup analyses were conducted on symptomatic infected women and matched non-infected women. A total of 2753 /2789 (98.7%) eligible women that were infected during pregnancy could be matched, among them, 17.4% and 48.4% were infected during the first and third trimesters, respectively. While first and second trimester infections were not associated with PTB (p>0.8), third trimester infections and in particular after 34 weeks of gestation had a greater risk of PTB with adjusted ORs of 2.76 (95% CI 1.63-4.67) and 7.10 (95% CI 2.44-20.61), respectively. PTB risk was further heightened in symptomatic third trimester infections (OR = 4.28, 95% CI 1.94-9.25). SGA risk was comparable between study groups across all trimesters of infection. Pregnancy loss incidence was similar in both groups (adjusted OR = 1.16; 95% CI 0.90-1.50). SARS-CoV-2 infection was associated with increased risk of PTB only among women infected during late pregnancy, particularly among symptomatic women.
Red blood cell distribution width (RDW) has been assessed during COVID-19 patient hospitalization, however, further research should be done to evaluate RDW from routine community blood tests, before ...infection, as a risk factor for COVID-19 related hospitalization and mortality.
RDW was measured as a predictor along with age, sex, chronic illnesses, and BMI in logistic regressions to predict hospitalization and mortality. Hospitalization and mortality odds ratios (ORs) were estimated with 95% confidence intervals (CI). RDW was evaluated separately as continuous and discrete (High RDW ≥ 14.5) variables.
Four thousand one hundred and sixty-eight patients were included in this study, where 824 patients (19.8%) had a high RDW value ≥14.5% (High RDW: 64.7% were female, mean age 58 years ±22 vs. Normal RDW: 60.2% female, mean age 46 years ±19). Eight hundred and twenty-nine patients had a hospitalization, where the median time between positive PCR and hospital entry was 5 IQR 1-18 days. Models were analyzed with RDW (continuous) and adjusted for age, sex, comorbidities, and BMI suggested an OR of 1.242 95% CI = 1.187-2.688 for hospitalization and an OR of 2.911 95% CI = 1.928-4.395 for mortality (p < .001). RDW (discrete) with the same adjustments presented an OR of 2.232 95% CI = 1.853-1.300 for hospitalization and an OR of 1.263 95% CI = 1.166-1.368 for mortality (p < .001).
High RDW values obtained from community blood tests are associated with greater odds of hospitalization and mortality for patients with COVID-19.
KEY MESSAGES
RDW measures before SARS-CoV-2 infection is a predictive factor for hospitalization and mortality.
RDW threshold of 14.5% provides high sensitivity and specificity for COVID-19 related mortality, comparatively to other blood tests.
Patient records should be accessed by clinicians for prior RDW results, if available, followed by further monitoring.
Halting the rapid clinical deterioration, marked by arterial hypoxemia, is among the greatest challenges clinicians face when treating COVID-19 patients in hospitals. While it is clear that oxygen ...measures and treatment procedures describe a patient’s clinical condition at a given time point, the potential predictive strength of the duration and extent of oxygen supplementation methods over the entire course of hospitalization for a patient death from COVID-19 has yet to be assessed. In this study, we aim to develop a prediction model for COVID-19 mortality in hospitals by utilizing data on oxygen supplementation modalities of patients. We analyzed the data of 545 patients hospitalized with COVID-19 complications admitted to Assuta Ashdod Medical Center, Israel, between 7 March 2020, and 16 March 2021. By solely analyzing the daily data on oxygen supplementation modalities in 182 random patients, we could identify that 75% (9 out of 12) of individuals supported by reservoir oxygen masks during the first two days died 3–30 days following hospital admission. By contrast, the mortality rate was 4% (4 out of 98) among those who did not require any oxygenation supplementation. Then, we combined this data with daily blood test results and clinical information of 545 patients to predict COVID-19 mortality. Our Random Forest model yielded an area under the receiver operating characteristic curve (AUC) score on the test set of 82.5%, 81.3%, and 83.0% at admission, two days post-admission, and seven days post-admission, respectively. Overall, our results could essentially assist clinical decision-making and optimized treatment and management for COVID-19 hospitalized patients with an elevated risk of mortality.
To examine the relative effectiveness of a fourth dose of the Pfizer-BioNTech mRNA (BNT162b2) vaccine compared with three vaccine doses over the span of 10 weeks.
Retrospective, test negative, ...case-control study, with a matched analysis and an unmatched multiple tests analysis.
Nationally centralised database of Maccabi Healthcare Services, an Israeli national health fund for 2.5 million people; from 10 January 2022 (seven days after the fourth dose was first given to eligible individuals) to 13 March 2022, an omicron dominant period in Israel.
97 499 Maccabi Healthcare Services members aged 60 years and older, who were eligible to receive a fourth vaccine dose and obtained at least one polymerase chain reaction (PCR) test during the study.
Breakthrough SARS-CoV-2 infection, defined as a positive PCR test performed seven or more days after inoculation with the BNT162b2 vaccine; and breakthrough SARS-CoV-2 infection resulting in severe covid-19 disease, defined as hospital admission or death related to covid-19.
27 876 participants received the fourth BNT162b2 vaccine dose and 69 623 received three doses only. Of 106 participants who died during the follow-up period, 77 had had their third doses only and 23 had had their fourth doses during the first three weeks after inoculation. In the first three weeks, a fourth dose provided additional protection against both SARS-CoV-2 infection and severe disease relative to three doses of the vaccine. However, relative vaccine effectiveness against infection quickly decreased over time, peaking during the third week at 65.1% (95% confidence interval 63.0% to 67.1%) and falling to 22.0% (4.9% to 36.1%) by the end of the 10 week follow-up period. Unlike relative effectiveness against SARS-CoV-2 infection, the relative effectiveness of a fourth dose against severe covid-19 was maintained at a high level (>72%) throughout follow-up. However, severe disease was a relatively rare event, occurring in <1% of study participants who received four doses or three doses only.
A fourth dose of the BNT162b2 vaccine appears to have provided additional protection against both SARS-CoV-2 infection and severe covid-19 disease relative to three vaccine doses. However, relative effectiveness of the fourth dose against infection appears to wane sooner than that of the third dose.
To evaluate the duration of protection against reinfection conferred by a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents.
We applied 2 ...complementary approaches: a matched test-negative, case-control design and a retrospective cohort design. A total of 458 959 unvaccinated individuals aged 5-18 years were included. The analyses focused on the period July 1, 2021, to December 13, 2021, a period of Delta variant dominance in Israel. We evaluated 3 SARS-CoV-2–related outcomes: documented polymerase chain reaction–confirmed infection or reinfection, symptomatic infection or reinfection, and SARS-CoV-2–related hospitalization or death.
Overall, children and adolescents who were previously infected acquired durable protection against reinfection with SARS-CoV-2 for at least 18 months. Importantly, no SARS-CoV-2–related deaths were recorded in either the SARS-CoV-2–naïve group or the previously infected group. The effectiveness of naturally acquired immunity against a recurrent infection reached 89.2% (95% CI, 84.7%-92.4%) at 3-6 months after the first infection and declined slightly to 82.5% (95% CI, 79.1%-85.3%) by 9-12 months after infection, with a slight nonsignificant waning trend seen up to 18 months after infection. Additionally, children aged 5-11 years exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in those aged 12-18 years was more prominent but still mild.
Children and adolescents who were previously infected with SARS-CoV-2 remain protected to a high degree for 18 months. Further research is needed to examine naturally acquired immunity against Omicron and newer emerging variants.
There is insufficient evidence regarding the magnitude and durability of protection conferred by a combined effect of naturally acquired immunity after SARS-CoV-2 infection and vaccine-induced ...immunity.
To compare the incidence rate of SARS-CoV-2 reinfection in previously infected persons to that of previously infected persons who subsequently received a single dose of BNT162b2 messenger RNA vaccine.
A retrospective cohort study emulating a randomized controlled target trial through a series of nested trials.
Nationally centralized database of Maccabi Healthcare Services, Israel.
Persons with documented SARS-CoV-2 infection who did not receive subsequent SARS-CoV-2 vaccination were compared with persons with documented SARS-CoV-2 infection who received a single dose of the BNT162b2 vaccine at least 3 months after infection.
Forty-one randomized controlled trials were emulated, in which 107 413 Maccabi Healthcare Services' members aged 16 years and older were eligible for at least 1 trial.
SARS-CoV-2-related outcomes of infection, symptomatic disease, hospitalization, and death, between 2 March and 13 December 2021.
A statistically significant decreased risk (hazard ratio, 0.18 95% CI, 0.15 to 0.20) for reinfection was found among persons who were previously infected and then vaccinated versus those who were previously infected but remained unvaccinated. In addition, there was a decreased risk for symptomatic disease (hazard ratio, 0.24 CI, 0.20 to 0.29) among previously infected and vaccinated persons compared with those who were not vaccinated after infection. No COVID-19-related mortality cases were found.
Hybrid protection against non-Delta variants could not be inferred.
Persons previously infected with SARS-CoV-2 gained additional protection against reinfection and COVID-19 from a subsequent single dose of the BNT162b2 vaccine. Nonetheless, even without a subsequent vaccination, reinfection appeared relatively rare.
None.
Abstract
Background
Although BNT162b2 vaccine-efficacy analyses have been published, the effectiveness of the vaccine in preventing coronavirus disease 2019 given confirmed exposure has not been ...previously demonstrated, even though it has policy implications, such as the need for self-quarantine when exposure has occurred.
Methods
In a retrospective cohort study, we used data collected between 20 December 2020 and 17 March 2021 from the second largest healthcare provider in Israel to analyze the probability of an additional household infection occurring within 10 days after an index infection. In model 1, vaccine effectiveness was described for Fully Vaccinated individuals (7 or more days from second dose) vs either Unvaccinated individuals or those Recently Vaccinated Once (0–7 days from the first dose, presumably still unprotected). Secondary analyses included correction for differing testing rates. In model 2, we conducted a separate analysis of households comprised of only adults with the same vaccination status.
Results
A total of 173 569 households were included, of which 6351 had an index infection (mean standard deviation age, 58.9 13.5 years); 50% were women. Adjusted vaccine effectiveness of Fully Vaccinated compared with Unvaccinated participants was 80.3% (95% confidence interval CI, 73.5–85.4) and 82.0% (95% CI, 75.6–86.8) compared with those Recently Vaccinated Once.
Conclusions
The BNT162b2 vaccine is effective in high-risk real-life exposure scenarios, but the protection afforded in these settings is lower than that previously described. Individuals with a confirmed significant exposure to severe acute respiratory syndrome are still at risk of being infected even if fully vaccinated.
We evaluated BNT162b2 vaccine effectiveness against infection in high-risk exposure settings by analyzing vaccinated and unvaccinated household members of individuals with SARS-CoV-2. The vaccine is effective in high-risk real-life exposure scenarios but not as effective as in the general population.
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