Introduction: COVID-19 vaccines significantly reduce SARS-CoV-2 (SCoV2)-related hospitalization and mortality in randomized controlled clinical trials, as well as in real-world effectiveness against different circulating SCoV2-lineages. However, some vaccine recipients show breakthrough infection and it remains unknown, which host and viral factors contribute to this risk and how many resulted in severe outcomes. Our aim was to identify demographic and clinical risk factors for SCoV2 breakthrough infections and severe disease in fully vaccinated individuals and to compare patient characteristics in breakthrough infections caused by SCoV2 Alpha or Delta variant. Methods: We conducted an exploratory retrospective case-control study from 28th of December to 25th of October 2021 dominated by the Delta SCoV2 variant. All cases of infection had to be reported by law to the local health authorities. Vaccine recipients data was anonymously available from the national Vaccination Monitoring Data Lake and the main local vaccine center. We compared anonymized patients characteristics of breakthrough infection (n=492) to two overlapping control groups including all vaccine recipients from the Canton of Basel-City (group 1 n=126586 and group 2 n=109382). We also compared patients with breakthrough infection caused by the Alpha to Delta variant. We used different multivariate generalized linear models (GLM). Results: We found only 492/126586 (0.39%) vaccine recipients with a breakthrough infection after vaccination during the 10 months observational period. Most cases were asymptomatic or mild (478/492 97.2%) and only very few required hospitalization (14/492, 2.8%). The time to a positive SCoV2 test shows that most breakthrough infections occurred between a few days to about 170 days after full vaccination, with a median of 78 days (interquartile range, IQR 47-124 days). Factors associated with a lower odds for breakthrough infection were: age (OR 0.987, 95%CI 0.983-0.992), previous COVID-19 infection prior to vaccination (OR 0.296, 95%CI 0.117-0.606), and (self-declared) serious side-effects from previous vaccines (OR 0.289, 95%CI 0.033-1.035). Factors associated with a higher odds for breakthrough infection were: vaccination with the Pfizer/BioNTech vaccine (OR 1.459, 95%CI 1.238-1.612), chronic disease as vaccine indication (OR 2.109, 95%CI 1.692-2.620), and healthcare workers (OR 1.404, 95%CI 1.042-1.860). We did not observe a significantly increased risk for immunosuppressed patients (OR 1.248, 95% CI 0.806-1.849). Conclusions: Our study shows that breakthrough infections are rare and show mild illness, but that it occurs early after vaccination with more than 50% of cases within 70 to 80 days post-full vaccination. This clearly implies that boost vaccination should be much earlier initiated compared to the currently communicated 180-day threshold. This has important implications especially for risk groups associated with more frequent breakthrough infections such as healthcare workers, and people in high-risk care facilities. Due to changes in the epidemiological dynamic with new variants emerging, continuous monitoring of breakthrough infections is helpful to provide evidence on booster vaccines and patient groups at risk for potential complications.
(1) Background: Some COVID-19 vaccine recipients show breakthrough infection. It remains unknown, which factors contribute to risks and severe outcomes. Our aim was to identify risk factors for SCoV2 breakthrough infections in fully vaccinated individuals. (2) Methods: We conducted a retrospective case-control study from 28 December 2020 to 25 October 2021. Data of all patients with breakthrough infection was compared to data of all vaccine recipients in the Canton of Basel-City, Switzerland. Further, breakthrough infections by Alpha- and Delta-variants were compared. (3) Results: Only 0.39% (488/126,586) of all vaccine recipients suffered from a breakthrough infection during the observational period, whereof most cases were asymptomatic or mild (97.2%). Breakthrough infections after full vaccination occurred in the median after 78 days (IQR 47-123.5). Factors with lower odds for breakthrough infection were age (OR 0.987) and previous COVID-19 infection prior to vaccination (OR 0.296). Factors with higher odds for breakthrough infection included vaccination with Pfizer/BioNTech instead of Moderna (OR 1.459), chronic disease (OR 2.109), and healthcare workers (OR 1.404). (4) Conclusions: Breakthrough infections are rare and mild but can occur early after vaccination. This implies that booster vaccination might be initiated earlier, especially for risk groups. Due to new variants emerging repeatedly, continuous monitoring of breakthrough infections is crucial.
The effect of iron on resistance to Salmonella typhimurium was investigated in mice inoculated with vaccines prepared from live and avirulent (SL3770) or killed and virulent (SR11 or LT2) bacteria. It has been found that mice vaccinated with SL3770 vaccine develop an immunity which can be neutralized with iron. Iron promoted the development of lethal infections by serving as a growth-essential nutrilite for infecting bacteria and by neutralizing the acquired immunity. The titration of this dual effect of iron showed that more iron was needed to neutralize the immunity in vaccinated animals than to promote bacterial growth in normal animals. In the presence of a sufficient amount of exogenous iron, as few as 10 bacteria caused lethal infections in normal and immune mice with the same effectiveness. This iron-sensitive immunity could be changed to iron-resistant immunity by the immunological stimulation of SL3770-vaccinated mice with a sonicated vaccine prepared from heat-killed SR11 or LT2 bacteria. In distinction to iron-sensitive immunity, iron-resistant immunity could be transferred from SR11or LT2-stimulated to normal mice with serum. Although effective in the transfer of antibacterial immunity, sera of SR11or LT2-stimulated mice supported the growth of virulent bacteria as well as did sera of normal mice. The absorption of immune serum with either SR11 or LT2 bacteria removed its protective quality, but the sensitized bacteria remained as infectious as untreated bacteria for iron-treated normal mice. Only in SL3770-vaccinated mice were the immune serum-sensitized bacteria not able to cause the infection in spite of daily treatment with iron. These results suggest that iron-resistant immunity is due to the synergistic action of specific antibody and phagocytes of immunologically stimulated animals.
AimsThe study objective was to explore how upper extremity impairments (UEIs) affect the everyday life and work‐life of people with type 1 diabetes (T1D) and to compare them to a control group without T1D to determine if there are diabetes‐specific consequences of UEIs.MethodsIn a controlled cross‐sectional study, a survey was distributed across all regions of Denmark. A total of 2174 people with T1D and 827 controls were included in the study population. The survey addressed UEI symptoms, employment status, functional disability, mental well‐being and diabetes distress. Data were analysed using multivariable logistic and linear regression.ResultsUpper extremity impairments were associated with a higher rate of work absence and modification, but no more so for people with T1D than for the control group. Among people with T1D, UEIs were significantly associated with worse mental well‐being and diabetes distress, and across all outcomes including functional disability, additive effects were found with an increasing number of coexisting impairments. The impact of UEIs on functional disability was more severe for the T1D group than the control group, but this was primarily due to differences in the number of coexisting impairments.ConclusionsUpper extremity impairments have significant negative implications for the work‐life and everyday life of people with T1D, and interventions to reduce UEIs and their impact among this group are highly relevant.
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