Kendall B Knuth

Background: This exploratory study compares self-reported COVID-19 vaccine side effects and breakthrough infections in people who described themselves as having diabetes with those who did not identify as having diabetes. Objective: The study uses person-reported data to evaluate differences in the perception of COVID-19 vaccine side effects between adults with diabetes and those who did not report having diabetes. Methods: This is a retrospective cohort study conducted using data provided online by adults aged 18 years and older residing in the United States. The participants who voluntarily self-enrolled between March 19, 2021, and July 16, 2022, in the IQVIA COVID-19 Active Research Experience project reported clinical and demographic information, COVID-19 vaccination, whether they had experienced any side effects, test-confirmed infections, and consented to linkage with prescription claims. No distinction was made for this study to differentiate prediabetes or type 1 and type 2 diabetes nor to verify reports of positive COVID-19 tests. Person-reported medication use was validated using pharmacy claims and a subset of the linked data was used for a sensitivity analysis of medication effects. Multivariate logistic regression was used to estimate the adjusted odds ratios of vaccine side effects or breakthrough infections by diabetic status, adjusting for age, gender, education, race, ethnicity (Hispanic or Latino), BMI, smoker, receipt of an influenza vaccine, vaccine manufacturer, and all medical conditions. Evaluations of diabetes medication-specific vaccine side effects are illustrated graphically to support the examination of the magnitude of side effect differences for various medications and combinations of medications used to manage diabetes. Results: People with diabetes (n=724) reported experiencing fewer side effects within 2 weeks of vaccination for COVID-19 than those without diabetes (n=6417; mean 2.7, SD 2.0 vs mean 3.1, SD 2.0). The adjusted risk of having a specific side effect or any side effect was lower among those with diabetes, with significant reductions in fatigue and headache but no differences in breakthrough infections over participants’ maximum follow-up time. Diabetes medication use did not consistently affect the risk of specific side effects, either using self-reported medication use or using only diabetes medications that were confirmed by pharmacy health insurance claims for people who also reported having diabetes. Conclusions: People with diabetes reported fewer vaccine side effects than participants not reporting having diabetes, with a similar risk of breakthrough infection. Trial Registration: ClinicalTrials.gov NCT04368065; https://clinicaltrials.gov/study/NCT04368065

Objective To describe cognitive symptoms in people not hospitalised at study enrolment for SARS-CoV-2 infection and associated demographics, medical history, other neuropsychiatric symptoms and SARS-CoV-2 vaccination. Design Longitudinal observational study. Setting Direct-to-participant registry with community-based recruitment via email and social media including Google, Facebook and Reddit, targeting adult US residents. Demographics, medical history, COVID-19-like symptoms, tests and vaccinations were collected through enrolment and follow-up surveys. Participants Participants who reported positive COVID-19 test results between 15 December 2020 and 13 December 2021. Those with cognitive symptoms were compared with those not reporting such symptoms. Main outcome measure Self-reported cognitive symptoms (defined as ‘feeling disoriented or having trouble thinking’ from listed options or related written-in symptoms) Results Of 3908 participants with a positive COVID-19 test result, 1014 (25.9%) reported cognitive symptoms at any time point during enrolment or follow-up, with approximately half reporting moderate/severe symptoms. Cognitive symptoms were associated with other neuropsychiatric symptoms, including dysgeusia, anosmia, trouble waking up, insomnia, headache, anxiety and depression. In multivariate analyses, female sex (OR, 95% CI): 1.7 (1.3 to 2.2), age (40–49 years (OR: 1.5 (1.2–1.9) compared with 18–29 years), history of autoimmune disease (OR: 1.5 (1.2–2.1)), lung disease (OR: 1.7 (1.3–2.2)) and depression (OR: 1.4 (1.1–1.7)) were associated with cognitive symptoms. Conversely, black race (OR: 0.6 (0.5–0.9)) and COVID-19 vaccination before infection (OR: 0.6 (0.4–0.7)) were associated with reduced occurrence of cognitive symptoms. Conclusions In this study, cognitive symptoms among COVID-19-positive participants were associated with female gender, age, autoimmune disorders, lung disease and depression. Vaccination and black race were associated with lower occurrence of cognitive symptoms. A constellation of neuropsychiatric and psychological symptoms occurred with cognitive symptoms. Our findings suggest COVID-19’s full health and economic burden may be underestimated. Trial registration number NCT04368065.

BACKGROUND This exploratory study compares self-reported COVID-19 vaccine side effects and breakthrough infections in people who described themselves as having diabetes with those who did not identify as having diabetes. OBJECTIVE The study uses person-reported data to evaluate differences in the perception of COVID-19 vaccine side effects between adults with diabetes and those who did not report having diabetes. METHODS This is a retrospective cohort study conducted using data provided online by adults aged 18 years and older residing in the United States. The participants who voluntarily self-enrolled between March 19, 2021, and July 16, 2022, in the IQVIA COVID-19 Active Research Experience project reported clinical and demographic information, COVID-19 vaccination, whether they had experienced any side effects, test-confirmed infections, and consented to linkage with prescription claims. No distinction was made for this study to differentiate prediabetes or type 1 and type 2 diabetes nor to verify reports of positive COVID-19 tests. Person-reported medication use was validated using pharmacy claims and a subset of the linked data was used for a sensitivity analysis of medication effects. Multivariate logistic regression was used to estimate the adjusted odds ratios of vaccine side effects or breakthrough infections by diabetic status, adjusting for age, gender, education, race, ethnicity (Hispanic or Latino), BMI, smoker, receipt of an influenza vaccine, vaccine manufacturer, and all medical conditions. Evaluations of diabetes medication-specific vaccine side effects are illustrated graphically to support the examination of the magnitude of side effect differences for various medications and combinations of medications used to manage diabetes. RESULTS People with diabetes (n=724) reported experiencing fewer side effects within 2 weeks of vaccination for COVID-19 than those without diabetes (n=6417; mean 2.7, SD 2.0 vs mean 3.1, SD 2.0). The adjusted risk of having a specific side effect or any side effect was lower among those with diabetes, with significant reductions in fatigue and headache but no differences in breakthrough infections over participants’ maximum follow-up time. Diabetes medication use did not consistently affect the risk of specific side effects, either using self-reported medication use or using only diabetes medications that were confirmed by pharmacy health insurance claims for people who also reported having diabetes. CONCLUSIONS People with diabetes reported fewer vaccine side effects than participants not reporting having diabetes, with a similar risk of breakthrough infection. CLINICALTRIAL ClinicalTrials.gov NCT04368065; https://clinicaltrials.gov/study/NCT04368065

Corrigendum for the article COVID-19 Vaccination Breakthrough Infections in a Real-World Setting: Using Community Reporters to Evaluate Vaccine Effectiveness

Purpose: Coronavirus disease 2019 (COVID-19) has highlighted the need for new methods of pharmacovigilance. Here, we use adult community volunteers to obtain systematic information on vaccine effectiveness and the nature and severity of breakthrough infections. Methods: Between December 15, 2020 and September 16, 2021, 11,826 unpaid community-based volunteers reported the following information to an on-line registry: COVID-19 test results, vaccination (Pfizer, Moderna, or Johnson & Johnson) and COVID-19 symptoms. COVID-19 infections were described based on vaccination status at the time of infection: 1) fully vaccinated, 2) partially vaccinated (received first of two-dose vaccines or were < 14 days post-final dose), or 3) unvaccinated. Results: Among 8554 participants who received any COVID-19 vaccine, COVID-19 infections were reported by 74 (1.0%) of those who were fully vaccinated and 198 (2.3%) of those who were partially vaccinated at the time of infection. Among the 74 participants who reported a breakthrough infection after full vaccination, the median time from vaccination to reported positive test result was 104.5 days (interquartile range: 77– 135 days), with no difference among vaccine manufacturers. One quarter (25.7%) of breakthrough infections in the fully vaccinated cases were asymptomatic and most (> 97%) fully vaccinated participants reported no symptoms or only mild symptoms compared to 89.3% of the unvaccinated cases. Only 1.4% of fully vaccinated participants reported experiencing at least 3 moderate-to-severe symptoms compared to 7.8% in the unvaccinated. Conclusion: Person-generated health data, also referred to as patient-reported outcomes, is a useful approach for quantifying breakthrough infections and their severity and for comparing vaccines. Trial Registration: Clinicaltrials.gov NCT04368065, EU PAS Register EUPAS36240.

Background COVID-19 has highlighted the need for new methods of pharmacovigilance. Here we use community volunteers to obtain systematic information on vaccine effectiveness and the nature and severity of breakthrough infections. Methods Between December 15, 2020 to September 16, 2021, 10,412 unpaid community-based participants reported the following information to an on-line registry: COVID-19 test results, vaccination (Pfizer, Moderna, or Johnson & Johnson), COVID-19 symptoms and perceived severity using a 4-point scale. COVID-19 infections were described for those who were 1) fully vaccinated, 2) partially vaccinated (received first of two dose vaccines or were Results Of 8,554 who were vaccinated, COVID-19 infections were reported by 74 (1.0%) of those who were fully vaccinated and 198 (2.3%) of those who were partially vaccinated. Among the 74 participants who reported a breakthrough infection after full vaccination, the median time to reported positive test result was 104.5 days (Interquartile range: 77-135 days), with no difference among vaccine manufactures. One quarter (25.7%) of breakthrough infections in the fully vaccinated cases were asymptomatic. More than 97% of fully vaccinated participants reported no moderate/severe symptoms compared to 89.3% of the unvaccinated cases; and only 1.4% of fully vaccinated participants reported experiencing at least 3 moderate to severe symptoms compared to 7.8% in the unvaccinated. Conclusion Person-generated health data, also referred to as patient-reported outcomes, is a useful resource for quantifying breakthrough infections and their severity, showing here that fully vaccinated participants report no or very mild COVID-19 symptoms. Trial registration Clinicaltrials.gov NCT04368065, EU PAS Register EUPAS36240