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BackgroundVaccines are highly effective in preventing severe disease and death from COVID-19, and new medications that can reduce severity of disease have been approved. However, many countries are facing limited supply of vaccine doses and medications. A model estimating the probabilities for hospitalization and mortality according to individual risk factors and vaccine doses received could help prioritize vaccination and yet scarce medications to maximize lives saved and reduce the burden on hospitalization facilities. MethodsElectronic health records from 101,039 individuals infected with SARS-CoV-2, since the beginning of the pandemic and until November 30, 2021 were extracted from a national healthcare organization in Israel. Logistic regression models were built to estimate the risk for subsequent hospitalization and death based on the number of BNT162b2 mRNA vaccine doses received and few major risk factors (age, sex, body mass index, hemoglobin A1C, kidney function, and presence of hypertension, pulmonary disease and malignancy). ResultsThe models built predict the outcome of newly infected individuals with remarkable accuracy: area under the curve was 0.889 for predicting hospitalization, and 0.967 for predicting mortality. Even when a breakthrough infection occurs, having received three vaccination doses significantly reduces the risk of hospitalization by 66% (OR=0.339) and of death by 78% (OR=0.223). ConclusionsThe models enable rapid identification of individuals at high risk for hospitalization and death when infected. These patients can be prioritized to receive booster vaccination and the yet scarce medications. A calculator based on these models is made publicly available on http://covidest.web.app
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BackgroundImmune protection following either vaccination or infection with SARS-CoV-2 decreases over time. ObjectiveTo determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals. MethodsAntibody titers were measured between January 31, 2021, and July 31, 2021 in two mutually exclusive groups: i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and ii) SARS-CoV-2 convalescents who had not received the vaccine. ResultsA total of 2,653 individuals fully vaccinated by two doses of vaccine during the study period and 4,361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8-5644.6]) after the second vaccination, than in convalescent individuals (median 355.3 AU/mL IQR [141.2-998.7]; p<0.001). In vaccinated subjects, antibody titers decreased by up to 40% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection. ConclusionsThis study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group. FundingThis research was internally funded by Leumit Health Services (LHS) and was supported in part by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Impact statementLarge scale study display the kinetics of SARS-CoV-2 IgG antibodies present in individuals vaccinated with two doses of mRNA vaccine vs. unvaccinated patients who had recovered from the disease: initial levels of antibody are much higher in vaccinated patients, but decrease faster.
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ImportanceIsrael was among the first countries to launch a large-scale COVID-19 vaccination campaign, and quickly vaccinated its population, achieving early control over the spread of the virus. However, the number of COVID-19 cases is now rapidly increasing, which may indicate that vaccine protection decreases over time. ObjectiveTo determine whether time elapsed since the second BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) injection is significantly associated with the risk of post-vaccination COVID-19 infection. DesignThis is a retrospective cohort study performed in a large state-mandated health care organization in Israel. ParticipantsAll fully vaccinated adults who have received a RT-PCR test between May 15, 2021 and July 26, 2021, at least two weeks after their second vaccine injection were included. Patients with a history of past COVID-19 infection were excluded. Main Outcome and MeasurePositive result for the RT-PCR test. ResultsThe cohort included 33,993 fully vaccinated adults, 49% women, with a mean age of 47 years (SD, 17 years), who received an RT-PCR test for SARS-CoV-2 during the study period. The median time between the second dose of the vaccine and the RT-PCR test was 146 days, interquartile range [121-167] days. 608 (1.8%) patients had positive test results. There was a significantly higher rate of positive results among patients who received their second vaccine dose at least 146 days before the RT-PCR test compared to patients who have received their vaccine less than 146 days before: odds ratio for infection was 3.00 for patients aged over 60 (95% CI 1.86-5.11); 2.29 for patients aged between 40 and 59 (95% CI 1.67-3.17); and 1.74 for patients aged between 18 and 39 (95% CI 1.27-2.37); P<0.001 in each age group. Conclusions and RelevanceIn this large population study of patients tested for SARS-CoV-2 by RT-PCR following two doses of mRNA BNT162b2 vaccine, we observe a significant increase of the risk of infection in individuals who received their last vaccine dose since at least 146 days ago, particularly among patients older than 60.
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AimTo evaluate associations of plasma 25(OH)D status with the likelihood of coronavirus disease (COVID-19) infection and hospitalization. MethodsThe study population included the 14,000 members of Leumit Health Services who were tested for COVID-19 infection from February 1st to April 30th 2020, and who had at least one previous blood test for plasma 25(OH)D level. "Suboptimal" or "low" plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below 30 ng/mL. ResultsOf 7,807 individuals, 782 (10.1%) were COVID-19-positive, and 7,025 (89.9%) COVID-19-negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 [19.00 ng/mL (95% confidence interval [CI] 18.41-19.59) vs. 20.55 (95% CI 20.32-20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24-2.01, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI 1.01-4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (95% CI 1.08-1.95, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [1.95 (95% CI 0.98-4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low-medium socioeconomic status were also positively associated with the risk of COVID-19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID-19. ConclusionLow plasma 25(OH)D level appears to be an independent risk factor for COVID-19 infection and hospitalization.
