Ischemic Stroke After Bivalent COVID-19 Vaccination: Self-Controlled Case Series Study.

BACKGROUND: The potential association between bivalent COVID-19 vaccination and ischemic stroke remains uncertain, despite several studies conducted thus far. OBJECTIVE: This study aimed to evaluate the risk of ischemic stroke following bivalent COVID-19 vaccination during the 2022-2023 season. METHODS: A self-controlled case series study was conducted among members aged 12 years and older who experienced ischemic stroke between September 1, 2022, and March 31, 2023, in a large health care system. Ischemic strokes were identified using International Classification of Diseases, Tenth Revision codes in emergency departments and inpatient settings. Exposures were Pfizer-BioNTech or Moderna bivalent COVID-19 vaccination. Risk intervals were prespecified as 1-21 days and 1-42 days after bivalent vaccination; all non-risk-interval person-time served as the control interval. The incidence of ischemic stroke was compared in the risk interval and control interval using conditional Poisson regression. We conducted overall and subgroup analyses by age, history of SARS-CoV-2 infection, and coadministration of influenza vaccine. When an elevated risk was detected, we performed a chart review of ischemic strokes and analyzed the risk of chart-confirmed ischemic stroke. RESULTS: With 4933 ischemic stroke events, we found no increased risk within the 21-day risk interval for the 2 vaccines and by subgroups. However, risk of ischemic stroke was elevated within the 42-day risk interval among individuals aged younger than 65 years with coadministration of Pfizer-BioNTech bivalent and influenza vaccines on the same day; the relative incidence (RI) was 2.13 (95% CI 1.01-4.46). Among those who also had a history of SARS-CoV-2 infection, the RI was 3.94 (95% CI 1.10-14.16). After chart review, the RIs were 2.34 (95% CI 0.97-5.65) and 4.27 (95% CI 0.97-18.85), respectively. Among individuals aged younger than 65 years who received Moderna bivalent vaccine and had a history of SARS-CoV-2 infection, the RI was 2.62 (95% CI 1.13-6.03) before chart review and 2.24 (95% CI 0.78-6.47) after chart review. Stratified analyses by sex did not show a significantly increased risk of ischemic stroke after bivalent vaccination. CONCLUSIONS: While the point estimate for the risk of chart-confirmed ischemic stroke was elevated in a risk interval of 1-42 days among individuals younger than 65 years with coadministration of Pfizer-BioNTech bivalent and influenza vaccines on the same day and among individuals younger than 65 years who received Moderna bivalent vaccine and had a history of SARS-CoV-2 infection, the risk was not statistically significant. The potential association between bivalent vaccination and ischemic stroke in the 1-42-day analysis warrants further investigation among individuals younger than 65 years with influenza vaccine coadministration and prior SARS-CoV-2 infection. Furthermore, the findings on ischemic stroke risk after bivalent COVID-19 vaccination underscore the need to evaluate monovalent COVID-19 vaccine safety during the 2023-2024 season.

A Propensity Score Approach and a Partitioned Approach for the Self-Controlled Case Series Design to Evaluate Safety of a 2-dose Vaccine Series: Application to myocarditis/pericarditis following mRNA COVID-19 vaccination.

The assumption that serious adverse events (SAEs) do not affect subsequent exposure might not hold when evaluating 2-dose vaccine safety through a self-controlled case series (SCCS) design. To address this, we developed: 1) propensity score SCCS (PS-SCCS) using a propensity score model involving SAEs during the risk interval after dose 1 (${R}_1\Big)$, and 2) partitioned SCCS (P-SCCS) estimating relative incidence (RI) separately for doses 1 and 2. In simulations, both provided unbiased RIs. Conversely, standard SCCS overestimated RI after dose 2. We applied these approaches to assess myocarditis/pericarditis risks after 2-dose mRNA COVID-19 vaccination in 12-39-year-olds. For BNT162b2, PS-SCCS yielded RIs of 1.85 (95% CI, 0.75-4.59) and 11.05 (95% CI, 6.53-18.68) 14 days after doses 1 and 2 respectively; standard SCCS provided similar RI after dose 1 and RI of 12.92 (95% CI, 7.56-22.09) after dose 2. For mRNA-1273, standard SCCS showed RIs of 1.96 (95% CI, 0.56-6.91) after dose 1 and 7.87 (95% CI, 3.33-18.57) after dose 2. As no mRNA-1273 recipients with SAEs during ${R}_1$ received dose 2, P-SCCS was used, yielding similar RI after dose 1 and RI of 6.48 (95% CI, 2.83-14.83) after dose 2. mRNA vaccines were associated with elevated myocarditis/pericarditis risks following dose 2 in 12-39-year-olds.

Immune escape and attenuated severity associated with the SARS-CoV-2 BA.2.86/JN.1 lineage.

The SARS-CoV-2 BA.2.86 lineage, and its sublineage JN.1 in particular, achieved widespread transmission in the US during winter 2023-24. However, the increase in infections was not accompanied by increases in COVID-19 hospitalizations and mortality commensurate with prior waves. To understand shifts in COVID-19 epidemiology associated with JN.1 emergence, we compared characteristics and clinical outcomes of time-matched cases infected with BA.2.86- derived lineages (predominantly representing JN.1) versus co-circulating XBB-derived lineages in December, 2023 and January, 2024. Cases infected with BA.2.86-derived lineages received greater numbers of COVID-19 vaccine doses, including XBB.1.5-targeted and BA.4/BA.5-targeted boosters, in comparison to cases infected with XBB-derived lineages. Additionally, cases infected with BA.2.86-derived lineages experienced greater numbers of documented prior SARS-CoV-2 infections. These associations of BA.2.86-derived lineages with immune escape were confirmed when comparing cases diagnosed during periods when JN.1 was the predominant circulating lineage to cases diagnosed during November, 2023. Cases infected with BA.2.86-derived lineages, or during periods when JN.1 was the predominant circulating lineage, also experienced lower risk of progression to severe clinical outcomes requiring emergency department consultations or hospital admission. Sensitivity analyses suggested under-ascertainment of prior infections, even if differential between cases infected with BA.2.86-derived lineages and non-BA.2.86 lineages, could not explain this apparent attenuation of severity. Our findings implicate escape from immunity acquired from prior vaccination or infection in the emergence of the JN.1 lineage and suggest infections with this lineage are less likely to experience clinically-severe disease. Monitoring of immune escape and clinical severity in emerging SARS-CoV-2 variants remains a priority to inform responses.

Post-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection.

COVID-19 vaccinations protect against severe illness and death, but associations with post-COVID conditions (PCC) are less clear. We aimed to evaluate the association between prior COVID-19 vaccination and new-onset PCC among individuals with SARS-CoV-2 infection across eight large healthcare systems in the United States. This retrospective matched cohort study used electronic health records (EHR) from patients with SARS-CoV-2 positive tests during March 2021-February 2022. Vaccinated and unvaccinated COVID-19 cases were matched on location, test date, severity of acute infection, age, and sex. Vaccination status was ascertained using EHR and integrated data on externally administered vaccines. Adjusted relative risks (RRs) were obtained from Poisson regression. PCC was defined as a new diagnosis in one of 13 PCC categories 30 days to 6 months following a positive SARS-CoV-2 test. The study included 161,531 vaccinated COVID-19 cases and 161,531 matched unvaccinated cases. Compared to unvaccinated cases, vaccinated cases had a similar or lower risk of all PCC categories except mental health disorders (RR: 1.06, 95% CI: 1.02-1.10). Vaccination was associated with ≥10% lower risk of sensory (RR: 0.90, 0.86-0.95), circulatory (RR: 0.88, 0.83-0.94), blood and hematologic (RR: 0.79, 0.71-0.89), skin and subcutaneous (RR: 0.69, 0.66-0.72), and non-specific COVID-19 related disorders (RR: 0.53, 0.51-0.56). In general, associations were stronger at younger ages but mostly persisted regardless of SARS-CoV-2 variant period, receipt of ≥3 vs. 1-2 vaccine doses, or time since vaccination. Pre-infection vaccination was associated with reduced risk of several PCC outcomes and hence may decrease the long-term consequences of COVID-19.

Attitudes Toward COVID-19 Vaccines Among Pregnant and Recently Pregnant Individuals.

Importance: Pregnant people and infants are at high risk of severe COVID-19 outcomes. Understanding changes in attitudes toward COVID-19 vaccines among pregnant and recently pregnant people is important for public health messaging. Objective: To assess attitudinal trends regarding COVID-19 vaccines by (1) vaccination status and (2) race, ethnicity, and language among samples of pregnant and recently pregnant Vaccine Safety Datalink (VSD) members from 2021 to 2023. Design, Setting, and Participants: This cross-sectional surveye study included pregnant or recently pregnant members of the VSD, a collaboration of 13 health care systems and the US Centers for Disease Control and Prevention. Unvaccinated, non-Hispanic Black, and Spanish-speaking members were oversampled. Wave 1 took place from October 2021 to February 2022, and wave 2 took place from November 2022 to February 2023. Data were analyzed from May 2022 to September 2023. Exposures: Self-reported or electronic health record (EHR)-derived race, ethnicity, and preferred language. Main Outcomes and Measures: Self-reported vaccination status and attitudes toward monovalent (wave 1) or bivalent Omicron booster (wave 2) COVID-19 vaccines. Sample- and response-weighted analyses assessed attitudes by vaccination status and 3 race, ethnicity, and language groupings of interest. Results: There were 1227 respondents; all identified as female, the mean (SD) age was 31.7 (5.6) years, 356 (29.0%) identified as Black race, 555 (45.2%) identified as Hispanic ethnicity, and 445 (36.3%) preferred the Spanish language. Response rates were 43.5% for wave 1 (652 of 1500 individuals sampled) and 39.5% for wave 2 (575 of 1456 individuals sampled). Respondents were more likely than nonrespondents to be White, non-Hispanic, and vaccinated per EHR. Overall, 76.8% (95% CI, 71.5%-82.2%) reported 1 or more COVID-19 vaccinations; Spanish-speaking Hispanic respondents had the highest weighted proportion of respondents with 1 or more vaccination. Weighted estimates of somewhat or strongly agreeing that COVID-19 vaccines are safe decreased from wave 1 to 2 for respondents who reported 1 or more vaccinations (76% vs 50%; χ21 = 7.8; P < .001), non-Hispanic White respondents (72% vs 43%; χ21 = 5.4; P = .02), and Spanish-speaking Hispanic respondents (76% vs 53%; χ21 = 22.8; P = .002). Conclusions and Relevance: Decreasing confidence in COVID-19 vaccine safety in a large, diverse pregnant and recently pregnant insured population is a public health concern.

Influenza vaccination accuracy among adults: Self-report compared with electronic health record data.

OBJECTIVE: To assess the validity of electronic health record (EHR)-based influenza vaccination data among adults in a multistate network. METHODS: Following the 2018-2019 and 2019-2020 influenza seasons, surveys were conducted among a random sample of adults who did or did not appear influenza-vaccinated (per EHR data) during the influenza season. Participants were asked to report their influenza vaccination status; self-report was treated as the criterion standard. Results were combined across survey years. RESULTS: Survey response rate was 44.7% (777 of 1740) for the 2018-2019 influenza season and 40.5% (505 of 1246) for the 2019-2020 influenza season. The sensitivity of EHR-based influenza vaccination data was 75.0% (95% confidence interval [CI] 68.1, 81.1), specificity 98.4% (95% CI 92.9, 99.9), and negative predictive value 73.9% (95% CI 68.0, 79.3). CONCLUSIONS: In a multistate research network across two recent influenza seasons, there was moderate concordance between EHR-based vaccination data and self-report.

Mortality risk after COVID-19 vaccination: A self-controlled case series study.

BACKGROUND: Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination. METHODS: We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models. RESULTS: For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58-1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60-1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1. CONCLUSION: Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US.

Latent Tuberculosis Infection Testing Practices in a Large US Integrated Healthcare System.

BACKGROUND: Tuberculosis (TB) is a public health threat, with >80% of active TB in the United States occurring due to reactivation of latent TB infection (LTBI). We may be underscreening those with high risk for LTBI and overtesting those at lower risk. A better understanding of gaps in current LTBI testing practices in relation to LTBI test positivity is needed. METHODS: This study, conducted between 1 January 2008 and 31 December 2019 at Kaiser Permanente Southern California, included individuals aged ≥18 years without a history of active TB. We examined factors associated with LTBI testing and LTBI positivity. RESULTS: Among 3 816 884 adults (52% female, 37% White, 37% Hispanic, mean age 43.5 years [standard deviation, 16.1]), 706 367 (19%) were tested for LTBI, among whom 60 393 (9%) had ≥1 positive result. Among 1 211 971 individuals who met ≥1 screening criteria for LTBI, 210 025 (17%) were tested for LTBI. Factors associated with higher adjusted odds of testing positive included male sex (1.32; 95% confidence interval, 1.30-1.35), Asian/Pacific Islander (2.78, 2.68-2.88), current smoking (1.24, 1.20-1.28), diabetes (1.13, 1.09-1.16), hepatitis B (1.45, 1.34-1.57), hepatitis C (1.54, 1.44-1.66), and birth in a country with an elevated TB rate (3.40, 3.31-3.49). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing. CONCLUSIONS: Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to refine and implement screening guidelines that appropriately target testing for those at highest risk for LTBI.

Factors associated with uptake of bivalent mRNA COVID-19 vaccines in a large US health care system.

BACKGROUND: Bivalent mRNA COVID-19 vaccines were developed to provide protection against the original SARS-CoV-2 strain and Omicron BA.4/BA.5 variants, but uptake in the United States has been low. Sociodemographic disparities in COVID-19 vaccine uptake have been documented, but it is unclear if similar disparities persist among individuals who previously completed a primary series of monovalent COVID-19 vaccine. METHODS: We conducted a retrospective cohort study at Kaiser Permanente Southern California (KPSC) including youth aged 5-17 years and adults aged ≥18 years who were KPSC members and had completed a primary series of monovalent COVID-19 vaccine. Individuals were followed from index date (date of eligibility for bivalent vaccine) to 03/31/2023 to ascertain receipt of any dose of bivalent mRNA COVID-19 vaccine or until disenrollment from KPSC or death. Multivariable robust Poisson regression was conducted to assess the adjusted relative risk and 95 % confidence intervals of factors associated with receipt of bivalent vaccine. RESULTS: The final cohorts included 305,339 youth and 2,534,619 adults, of whom 19.5 % and 30.7 %, respectively, had received bivalent COVID-19 vaccine. Factors associated with being more likely to receive bivalent COVID-19 vaccine included older age, Asian race, more prior year outpatient and virtual visits, Charlson score ≥1, and immunocompromised status. Factors associated with being less likely to receive a bivalent COVID-19 vaccine included age 12-17 vs 5-11 years, Hispanic and non-Hispanic Black race/ethnicity, ≥1 prior year inpatient or emergency department visits, prior history of SARS-CoV-2 infection (adults only), Medicaid insurance, and higher neighborhood deprivation index. CONCLUSION: Even among youth and adults who had previously received a primary series of monovalent COVID-19 vaccine, sociodemographic and clinical disparities were observed in receipt of bivalent COVID-19 vaccine. These findings are critical to inform equitable strategies for the implementation of the updated monovalent COVID-19 vaccine targeting the Omicron XBB strain.

Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States: The contribution of vaccine-related attitudes.

OBJECTIVE: Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States have been documented. This study assessed the contribution of vaccine-related attitudes to coverage disparities. METHODS: Surveys were conducted following the 2019-2020 and 2020-2021 influenza seasons in a US research network. Using electronic health record data to identify pregnant women, random samples were selected for surveying; non-Hispanic Black women and influenza-unvaccinated women were oversampled. Regression-based decomposition analyses were used to assess the contribution of vaccine-related attitudes to racial and ethnic differences in influenza vaccination. Data were combined across survey years, and analyses were weighted and accounted for survey design. RESULTS: Survey response rate was 41.2% (721 of 1748) for 2019-2020 and 39.3% (706 of 1798) for 2020-2021. Self-reported influenza vaccination was higher among non-Hispanic White respondents (79.4% coverage, 95% CI 73.1%-85.7%) than Hispanic (66.2% coverage, 95% CI 52.5%-79.9%) and non-Hispanic Black (55.8% coverage, 95% CI 50.2%-61.4%) respondents. For all racial and ethnic groups, a high proportion (generally >80%) reported being seen for care, recommended for influenza vaccination, and offered vaccination. In decomposition analyses, vaccine-related attitudes (e.g., worry about vaccination causing influenza; concern about vaccine safety and effectiveness) explained a statistically significant portion of the observed racial and ethnic disparities in vaccination. Maternal age, education, and health status were not significant contributors after controlling for vaccine-related attitudes. CONCLUSIONS: In a setting with relatively high influenza vaccination coverage among pregnant women, racial and ethnic disparities in coverage were identified. Vaccine-related attitudes were associated with the disparities observed.

Prior Screening for Latent Tuberculosis Among Patients Diagnosed With Tuberculosis Disease: Missed Opportunities?

Background: California has the largest number of tuberculosis (TB) disease cases in the United States. This study in a large California health system assessed missed opportunities for latent tuberculosis (LTBI) screening among patients with TB disease. Methods: Kaiser Permanente Southern California patients who were ≥18 years old with membership for ≥24 months during the study period from 1 January 2008 to 31 December 2019 were included. Prior LTBI test (tuberculin skin test or interferon-γ release assay) or diagnosis code prior to TB disease diagnosis was assessed among patients with observed TB disease (confirmed by polymerase chain reaction and/or culture). In the absence of current treatment practices, more patients screened for LTBI may have developed TB disease. We estimated hypothetical TB disease cases prevented by multiplying LTBI progression rates by the number of LTBI-positive patients prescribed treatment. Results: A total of 1289 patients with observed TB disease were identified; 148 patients were LTBI positive and 84 were LTBI negative. Patients not prescreened for LTBI made up 82.0% of observed TB disease cases (1057/1289). Adding the hypothetical maximum estimate for prevented cases decreased the percentage of patients who were not prescreened for LTBI to 61.7% [1057/(1289 + 424)]. Conclusions: One-fifth of patients were screened for LTBI prior to their active TB diagnosis. Assuming the upper bound of cases prevented through current screening, almost 62% of TB disease patients were never screened for LTBI. Future work to elucidate gaps in LTBI screening practices and to identify opportunities to improve screening guidelines is needed.

Risk Factors for Not Completing a 2-Dose Primary Series of Messenger RNA COVID-19 Vaccination in a Large Health Care System in Southern California: Retrospective Cohort Study.

BACKGROUND: COVID-19 vaccination is crucial in combating the COVID-19 pandemic. Messenger RNA COVID-19 vaccines were initially authorized as a 2-dose primary series and have been widely used in the United States; completing the 2-dose primary series offers protection against infection, severe illness, and death. Understanding the risk factors for not completing the 2-dose primary series is critical to evaluate COVID-19 vaccination programs and promote completion of the 2-dose primary series. OBJECTIVE: This study examined potential risk factors for not completing a 2-dose primary series of mRNA COVID-19 vaccination. METHODS: We conducted a retrospective cohort study among members aged ≥18 years from a large integrated health care system, Kaiser Permanente Southern California, from December 14, 2020, to June 30, 2022. Noncompletion of the 2-dose primary series was defined as not completing the second dose within 6 months after receipt of the first dose. Crude noncompletion rates were estimated overall and by demographic characteristics, health care use patterns, comorbidity, and community-level socioeconomic factors. A Poisson regression model was fit to examine associations of individual-level and community-level risk factors with noncompletion of the 2-dose primary series. RESULTS: Among 2.5 million recipients of ≥1 dose of mRNA COVID-19 vaccines, 3.3% (n=81,202) did not complete the second dose within 6 months. Members aged 25-44 years, 65-74 years, and ≥75 years were less likely to not complete the 2-dose primary series than those aged 18-24 years, while members aged 45-64 years were more likely to not complete the 2-dose primary series (adjusted risk ratio [aRR] 1.13, 95% CI 1.10-1.15). Male sex was associated with a higher risk of noncompletion (aRR 1.17, 95% CI 1.15-1.19). Hispanic and non-Hispanic Black race/ethnicity were associated with a lower risk of noncompletion (range aRR 0.78-0.91). Having Medicaid and prior influenza vaccination were associated with a higher risk of noncompletion. Having SARS-CoV-2 infection, experiencing an adverse event, or having an inpatient and emergency department visit during the minimum recommended dose intervals were associated with a higher risk of not completing the 2-dose primary series (aRR 1.98, 95% CI 1.85-2.12; 1.99, 95% CI 1.43-2.76; and 1.85, 95% CI 1.77-1.93, respectively). Those who received the first dose after June 30, 2021, were more likely to not complete the 2-dose primary series within 6 months of receipt of the first dose. CONCLUSIONS: Despite limitations such as being a single-site study and the inability to consider social factors such as employment and vaccine attitudes, our study identified several risk factors for not completing a 2-dose primary series of mRNA vaccination, including being male; having Medicaid coverage; and experiencing SARS-CoV-2 infection, adverse events, or inpatient and emergency department visits during the minimum recommended dose intervals. These findings can inform future efforts in developing effective strategies to enhance vaccination coverage and improve the completion rate of necessary doses.

Multidrug Resistance of Escherichia coli From Outpatient Uncomplicated Urinary Tract Infections in a Large United States Integrated Healthcare Organization.

Background: Urinary tract infections (UTIs) cause significant disease and economic burden. Uncomplicated UTIs (uUTIs) occur in otherwise healthy individuals without underlying structural abnormalities, with uropathogenic Escherichia coli (UPEC) accounting for 80% of cases. With recent transitions in healthcare toward virtual visits, data on multidrug resistance (MDR) (resistant to ≥3 antibiotic classes) by care setting are needed to inform empiric treatment decision making. Methods: We evaluated UPEC resistance over time by care setting (in-person vs virtual), in adults who received outpatient care for uUTI at Kaiser Permanente Southern California between January 2016 and December 2021. Results: We included 174 185 individuals who had ≥1 UPEC uUTI (233 974 isolates) (92% female, 46% Hispanic, mean age 52 years [standard deviation 20]). Overall, prevalence of UPEC MDR decreased during the study period (13% to 12%) both in virtual and in-person settings (P for trend <.001). Resistance to penicillins overall (29%), coresistance to penicillins and trimethoprim-sulfamethoxazole (TMP-SMX) (12%), and MDR involving the 2 plus ≥1 antibiotic class were common (10%). Resistance to 1, 2, 3, and 4 antibiotic classes was found in 19%, 18%, 8%, and 4% of isolates, respectively; 1% were resistant to ≥5 antibiotic classes, and 50% were resistant to none. Similar resistance patterns were observed over time and by care setting. Conclusions: We observed a slight decrease in both class-specific antimicrobial resistance and MDR of UPEC overall, most commonly involving penicillins and TMP-SMX. Resistance patterns were consistent over time and similar in both in-person and virtual settings. Virtual healthcare may expand access to UTI care.

Risk of herpes zoster following mRNA COVID-19 vaccine administration.

BACKGROUND: Adverse events following mRNA COVID-19 vaccines, including herpes zoster (HZ), have been reported. We conducted a cohort study to evaluate the association between mRNA COVID-19 vaccination and subsequent HZ at Kaiser Permanente Southern California (KPSC). RESEARCH DESIGN AND METHODS: The vaccinated cohort consisted of KPSC members who received their first dose of mRNA COVID-19 vaccine (mRNA-1273 and BNT162b2) during 12/2020-05/2021 and were matched to unvaccinated individuals on age and sex. Incident HZ cases occurring within 90 days of follow-up were identified by diagnosis codes and antiviral medications. Cox proportional hazards models estimated adjusted hazard ratios (aHR), comparing HZ incidence between the vaccinated and unvaccinated cohorts. RESULTS: Cohort included 1,052,362 mRNA-1273 recipients, 1,055,461 BNT162b2 recipients, and 1,020,334 comparators. Compared to unvaccinated individuals, aHR for HZ up to 90 days after the second dose of mRNA-1273 and BNT162b2 was 1.14 (1.05-1.24) and 1.12 (1.03-1.22), respectively. In those aged ≥50 years not vaccinated with zoster vaccine, aHR was also increased after the second dose of mRNA-1273 (1.18 [1.06-1.33]) and BNT162b2 (1.15 [1.02-1.29]) vaccine vs. unvaccinated individuals. CONCLUSIONS: Our findings suggest a potential increased risk of HZ after a second dose of mRNA vaccines, potentially driven by the increased risk in individuals aged ≥50 years without history of zoster vaccination.

Increased vaccine sensitivity of an emerging SARS-CoV-2 variant.

Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with enhancements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and ≥5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater point estimates of protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of ≥4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and ≥2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses.

Decision-Making about COVID-19 Vaccines among Health Care Workers and Their Adolescent Children.

Health care workers promote COVID-19 vaccination for adolescent patients, and as parents, may influence their own children to get vaccinated. We conducted virtual, semi-structured qualitative interviews with vaccinated health care workers and their adolescent children to explore their decision-making process for COVID-19 vaccination. In total, 21 health care workers (physicians, nurses, and medical staff) and their adolescent children (N = 17) participated in interviews. The following three themes described parent-adolescent decision-making for COVID-19 vaccination: (1) family anticipation and hesitation about COVID-19 vaccine approval; (2) parents' or adolescents' choice: the decision maker for adolescent COVID-19 vaccination; and (3) leveraging one's vaccination status to encourage others to get vaccinated. Nurses encouraged adolescent autonomy in decisions for COVID-19 vaccination while physicians viewed vaccination as the parent's decision. Health care workers and their adolescent children used role-modeling to motivate unvaccinated peers and may model their decision-making process for adolescent COVID-19 vaccination with their own children to support their patients' and parents' vaccine decisions.

Effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system.

BACKGROUND: In the USA, oral nirmatrelvir-ritonavir is authorised for use in patients aged 12 years or older with mild-to-moderate COVID-19 who are at risk of progression to severe disease and hospitalisation. We aimed to establish the effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and death in people with COVID-19 in an outpatient prescribing context in the USA. METHODS: In this matched observational outpatient cohort study in the Kaiser Permanente Southern California (CA, USA) health-care system, data were extracted from electronic health records of non-hospitalised patients aged 12 years or older who received a positive SARS-CoV-2 PCR test result (their index test) between April 8 and Oct 7, 2022, and had not received another positive test result within the preceding 90 days. We compared outcomes between people who received nirmatrelvir-ritonavir and those who did not receive nirmatrelvir-ritonavir by matching cases by date, age, sex, clinical status (including care received, the presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), vaccination history, comorbidities, health-care seeking during the previous year, and BMI. Our primary endpoint was the estimated effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions or death within 30 days of a positive test for SARS-CoV-2. FINDINGS: 7274 nirmatrelvir-ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75·2%) treatment recipients and 84 657 (67·1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir-ritonavir had an overall estimated effectiveness of 53·6% (95% CI 6·6-77·0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79·6% (33·9-93·8) when nirmatrelvir-ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir-ritonavir was 89·6% (50·2-97·8). INTERPRETATION: In a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir-ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test. FUNDING: US Centers for Disease Control and Prevention and US National Institutes of Health.

Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome.

Expansion of the SARS-CoV-2 BA.4 and BA.5 Omicron subvariants in populations with prevalent immunity from prior infection and vaccination, and associated burden of severe COVID-19, has raised concerns about epidemiologic characteristics of these lineages including their association with immune escape or severe clinical outcomes. Here we show that BA.4/BA.5 cases in a large US healthcare system had at least 55% (95% confidence interval: 43-69%) higher adjusted odds of prior documented infection than time-matched BA.2 cases, as well as 15% (9-21%) and 38% (27-49%) higher adjusted odds of having received 3 and ≥4 COVID-19 vaccine doses, respectively. However, after adjusting for differences in epidemiologic characteristics among cases with each lineage, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held in sensitivity analyses correcting for potential exposure misclassification resulting from unascertained prior infections. Our results demonstrate that the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages, relative to the Delta variant, has persisted with BA.4/BA.5, despite the association of BA.4/BA.5 with increased risk of breakthrough infection among previously vaccinated or infected individuals.

Adolescent Self-Consent for COVID-19 Vaccination: Views of Healthcare Workers and Their Adolescent Children on Vaccination Autonomy.

PURPOSE: This study explored the perceptions of healthcare worker parents (physicians, nurses, and staff) and their adolescents (aged 12-17 years) on adolescent self-consent to COVID-19 vaccination by applying the concept of positive deviance of those already vaccinated against COVID-19. METHODS: We used a qualitative descriptive design to conduct individual, semi-structured interviews with COVID-19-vaccinated healthcare workers in Southern California and their vaccinated adolescent children. Separate interviews were conducted with parents and adolescents from November to December 2021 using digital phone conferencing software. All interviews were recorded and transcribed. Thematic and constant comparative analysis techniques were used to identify relevant themes and subthemes. RESULTS: Twenty one healthcare workers (9 nurses, one nurse practitioner, one technologist, and 10 physicians) and their adolescents (N = 17) participated. Three overarching themes were identified to describe participants' perspectives about adolescent self-consent for COVID-19 vaccination: (1) Family values and practices around adolescent vaccination; (2) Differences in parent and adolescent support for vaccine self-consent laws; and (3) Parent and adolescent uncertainty on readiness for vaccine self-consent laws. Adolescents largely supported self-consent while parents supported the policy if they would be able to have a discussion with their adolescent prior to the decision. DISCUSSION: Parents and adolescents supported adolescent self-consent for COVID-19 vaccination, with the reservation that adolescents should discuss the decision alongside their parents to exercise their medical autonomy with supportive guidance. Greater adolescent involvement in making decisions and providing self-consent for healthcare, including vaccines, could prepare adolescents to have a greater sense of autonomy over their health and contribute to population health measures.

Influenza Vaccination Among Pregnant Women: Self-report Compared With Vaccination Data From Electronic Health Records, 2018-2020 Influenza Seasons.

OBJECTIVES: Having accurate influenza vaccination coverage estimates can guide public health activities. The objectives of this study were to (1) validate the accuracy of electronic health record (EHR)-based influenza vaccination data among pregnant women compared with survey self-report and (2) assess whether survey respondents differed from survey nonrespondents by demographic characteristics and EHR-based vaccination status. METHODS: This study was conducted in the Vaccine Safety Datalink, a network of 8 large medical care organizations in the United States. Using EHR data, we identified all women pregnant during the 2018-2019 or 2019-2020 influenza seasons. Surveys were conducted among samples of women who did and did not appear vaccinated for influenza according to EHR data. Separate surveys were conducted after each influenza season, and respondents reported their influenza vaccination status. Analyses accounted for the stratified design, sampling probability, and response probability. RESULTS: The survey response rate was 50.5% (630 of 1247) for 2018-2019 and 41.2% (721 of 1748) for 2019-2020. In multivariable analyses combining both survey years, non-Hispanic Black pregnant women had 3.80 (95% CI, 2.13-6.74) times the adjusted odds of survey nonresponse; odds of nonresponse were also higher for Hispanic pregnant women and women who had not received (per EHR data) influenza vaccine during current or prior influenza seasons. The sensitivity, specificity, and positive predictive value of EHR documentation of influenza vaccination compared with self-report were ≥92% for both survey years combined. The negative predictive value of EHR-based influenza vaccine status was 80.5% (95% CI, 76.7%-84.0%). CONCLUSIONS: EHR-based influenza vaccination data among pregnant women were generally concordant with self-report. New data sources and novel approaches to mitigating nonresponse bias may be needed to enhance influenza vaccination surveillance efforts.