scholarly journals Identifying and alleviating bias due to differential depletion of susceptible people in post-marketing evaluations of COVID-19 vaccines

Author(s):  
Rebecca Kahn ◽  
Stephanie J Schrag ◽  
Jennifer R Verani ◽  
Marc Lipsitch

Recent studies have provided key information about SARS-CoV-2 vaccines' efficacy and effectiveness (VE). One important question that remains is whether the protection conferred by vaccines wanes over time. However, estimates over time are subject to bias from differential depletion of susceptibles between vaccinated and unvaccinated groups. Here we examine the extent to which biases occur under different scenarios and assess whether serologic testing has the potential to correct this bias. By identifying non-vaccine antibodies, these tests could identify individuals with prior infection. We find that the main determinant of bias is the proportion of the population that has been infected since vaccination began, which is influenced by several factors. In scenarios with high baseline VE, differential depletion of susceptibles creates minimal bias in VE estimates. However, if VE is lower, the bias for leaky vaccines (that reduce individual probability of infection given contact) is larger and should be corrected if the mechanism is known to be leaky. Conducting analyses both unadjusted and adjusted for past infection could give lower and upper bounds for the true VE. Studies of VE should therefore enroll individuals regardless of prior infection history but also collect information, ideally through serologic testing, on this critical variable.

1997 ◽  
Vol 84 (1) ◽  
pp. 176-178
Author(s):  
Frank O'Brien

The author's population density index ( PDI) model is extended to three-dimensional distributions. A derived formula is presented that allows for the calculation of the lower and upper bounds of density in three-dimensional space for any finite lattice.


Author(s):  
S. Yahya Mohamed ◽  
A. Mohamed Ali

In this paper, the notion of energy extended to spherical fuzzy graph. The adjacency matrix of a spherical fuzzy graph is defined and we compute the energy of a spherical fuzzy graph as the sum of absolute values of eigenvalues of the adjacency matrix of the spherical fuzzy graph. Also, the lower and upper bounds for the energy of spherical fuzzy graphs are obtained.


Entropy ◽  
2021 ◽  
Vol 23 (8) ◽  
pp. 940
Author(s):  
Zijing Wang ◽  
Mihai-Alin Badiu ◽  
Justin P. Coon

The age of information (AoI) has been widely used to quantify the information freshness in real-time status update systems. As the AoI is independent of the inherent property of the source data and the context, we introduce a mutual information-based value of information (VoI) framework for hidden Markov models. In this paper, we investigate the VoI and its relationship to the AoI for a noisy Ornstein–Uhlenbeck (OU) process. We explore the effects of correlation and noise on their relationship, and find logarithmic, exponential and linear dependencies between the two in three different regimes. This gives the formal justification for the selection of non-linear AoI functions previously reported in other works. Moreover, we study the statistical properties of the VoI in the example of a queue model, deriving its distribution functions and moments. The lower and upper bounds of the average VoI are also analysed, which can be used for the design and optimisation of freshness-aware networks. Numerical results are presented and further show that, compared with the traditional linear age and some basic non-linear age functions, the proposed VoI framework is more general and suitable for various contexts.


2021 ◽  
Vol 37 (3) ◽  
pp. 919-932
Author(s):  
Byeong Moon Kim ◽  
Byung Chul Song ◽  
Woonjae Hwang

Author(s):  
Megan M Sheehan ◽  
Anita J Reddy ◽  
Michael B Rothberg

Abstract Background Protection afforded from prior disease among patients with coronavirus disease 2019 (COVID-19) infection is unknown. If infection provides substantial long-lasting immunity, it may be appropriate to reconsider vaccination distribution. Methods This retrospective cohort study of 1 health system included 150 325 patients tested for COVID-19 infection via polymerase chain reaction from 12 March 2020 to 30 August 2020. Testing performed up to 24 February 2021 in these patients was included. The main outcome was reinfection, defined as infection ≥90 days after initial testing. Secondary outcomes were symptomatic infection and protection of prior infection against reinfection. Results Of 150 325 patients, 8845 (5.9%) tested positive and 141 480 (94.1%) tested negative before 30 August. A total of 1278 (14.4%) positive patients were retested after 90 days, and 62 had possible reinfection. Of those, 31 (50%) were symptomatic. Of those with initial negative testing, 5449 (3.9%) were subsequently positive and 3191 of those (58.5%) were symptomatic. Protection offered from prior infection was 81.8% (95% confidence interval [CI], 76.6–85.8) and against symptomatic infection was 84.5% (95% CI, 77.9–89.1). This protection increased over time. Conclusions Prior infection in patients with COVID-19 was highly protective against reinfection and symptomatic disease. This protection increased over time, suggesting that viral shedding or ongoing immune response may persist beyond 90 days and may not represent true reinfection. As vaccine supply is limited, patients with known history of COVID-19 could delay early vaccination to allow for the most vulnerable to access the vaccine and slow transmission.


Gut ◽  
2021 ◽  
pp. gutjnl-2021-324789
Author(s):  
Nicholas A Kennedy ◽  
Simeng Lin ◽  
James R Goodhand ◽  
Neil Chanchlani ◽  
Benjamin Hamilton ◽  
...  

ObjectiveDelayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.DesignAntibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3–10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine.ResultsGeometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn’s disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine.ConclusionInfliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab.Trial registration numberISRCTN45176516.


2021 ◽  
Vol 103 (5) ◽  
Author(s):  
Li Peng ◽  
Wen-Bin He ◽  
Stefano Chesi ◽  
Hai-Qing Lin ◽  
Xi-Wen Guan

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