IMPORTANCE: Quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) and adjuvanted recombinant zoster vaccine (RZV) contain novel adjuvants. Data are limited on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of the simultaneous administration of these vaccines. OBJECTIVE: To compare the safety and reactogenicity after simultaneous doses of RZV and aIIV4 administration (opposite arms) with simultaneous doses of RZV with quadrivalent high-dose inactivated influenza vaccine [HD-IIV4]). DESIGN, SETTING, AND PARTICIPANTS: This randomized blinded clinical trial was conducted during the 2021-2022 and 2022-2023 influenza seasons at 2 centers in the US among community-dwelling adults aged 65 years or older. Analysis was performed on an intention-to-treat basis. INTERVENTION: Simultaneous intramuscular administration of RZV dose 1 and aIIV4 or HD-IIV4 in opposite arms after age stratification (65-69 and ≥70 years) and randomization. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportions of participants with 1 or more severe solicited reactions during days 1 to 8, using a noninferiority test (10% noninferiority margin). Additional measures included serious adverse events and adverse events of clinical interest during days 1 to 43 of the study period. RESULTS: A total of 267 adults (median age, 71 years [range, 65-92 years]; 137 men [51.3%]) were randomized; 130 received simultaneous RZV and aIIV4, and 137 received simultaneous RZV and HD-IIV4. The proportion of patients reporting 1 or more severe reactions after simultaneous administration of RZV and aIIV4 (15 of 115 [11.5%]) was noninferior compared with simultaneous RZV and HD-IIV4 (17 of 119 [12.5%]) (absolute difference, -1.0% [95% CI, -8.9% to 7.1%]). There were no significant differences in the number of serious adverse events or adverse events of clinical interest between the groups. CONCLUSIONS AND RELEVANCE: In this clinical trial of simultaneous doses of RZV and aIIV4 compared with simultaneous doses of RZV and HD-IIV4, overall safety findings were similar between groups. From a safety standpoint, this study supports the simultaneous administration of RZV and aIIV4 among older adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05007041.

BACKGROUND: SMS text messaging- and internet-based self-reporting systems can supplement existing vaccine safety surveillance systems, but real-world participation patterns have not been assessed at scale. OBJECTIVE: This study aimed to describe the participation rates of a new SMS text messaging- and internet-based self-reporting system called the Kaiser Permanente Side Effect Monitor (KPSEM) within a large integrated health care system. METHODS: We conducted a prospective cohort study of Kaiser Permanente Southern California (KPSC) patients receiving a COVID-19 vaccination from April 23, 2021, to July 31, 2023. Patients received invitations through flyers, SMS text messages, emails, or patient health care portals. After consenting, patients received regular surveys to assess adverse events up to 5 weeks after each dose. Linkage with medical records provided demographic and clinical data. In this study, we describe KPSEM participation rates, defined as providing consent and completing at least 1 survey within 35 days of COVID-19 vaccination. RESULTS: Approximately, 8% (164,636/2,091,975) of all vaccinated patients provided consent and completed at least 1 survey within 35 days. The lowest participation rates were observed for parents of children aged 12-17 years (1349/152,928, 0.9% participation rate), and the highest participation was observed among older adults aged 61-70 years (39,844/329,487, 12.1%). Persons of non-Hispanic White race were more likely to participate compared with other races and ethnicities (13.1% vs 3.9%-7.5%, respectively; P<.001). In addition, patients residing in areas with a higher neighborhood deprivation index were less likely to participate (5.1%, 16,503/323,122 vs 10.8%, 38,084/352,939 in the highest vs lowest deprivation quintiles, respectively; P<.001). Invitations through the individual's Kaiser Permanente health care portal account and by SMS text message were associated with the highest participation rate (19.2%, 70,248/366,377 and 10.5%, 96,169/914,793, respectively), followed by email (19,464/396,912, 4.9%) and then QR codes on flyers (25,882/2,091,975, 1.2%). SMS text messaging-based surveys demonstrated the highest sustained daily response rates compared with internet-based surveys. CONCLUSIONS: This real-world prospective study demonstrated that a novel digital vaccine safety self-reporting system implemented through an integrated health care system can achieve high participation rates. Linkage with participants' electronic health records is another unique benefit of this surveillance system. We also identified lower participation among selected vulnerable populations, which may have implications when interpreting data collected from similar digital systems.

BACKGROUND: There are known disparities in U.S. COVID-19 vaccination but there is limited information on national vaccine uptake in a large, racially diverse, all-age population. Here, we describe COVID-19 vaccination coverage in a large U.S. population accessing care in OCHIN (not an acronym), a national network of community-based healthcare organizations. METHODS: Within OCHIN, we identified patients aged 6 months and older with ≥1 completed clinical encounter since becoming age-eligible for the COVID-19 vaccine between December 13, 2020 and December 31, 2022. Patients' COVID-19 vaccination status was assessed from OCHIN's Epic® electronic health record which includes data from state immunization information systems. Patients were considered vaccinated if they received ≥1 dose of a monovalent vaccine product; coverage was categorized by age groups (6 months-4 years; 5-11 years, 12-15 years, 16+ years). Multivariate analyses assessed factors associated with COVID-19 vaccination across age groups. RESULTS: The cohort included 3.3 million Hispanic (37 %), non-Hispanic (NH) White (31 %), NH Black (15 %), and NH Asian (7 %) patients; 45 % of whom were Medicaid-enrolled, 19 % uninsured, and 53 % with a household income below 100 % of the federal poverty level. The proportion with ≥1 COVID-19 vaccine dose increased with age, from 11.7 % (6 months through 4 years) to 72.3 % (65 years and older). The only factors associated with significantly higher COVID-19 vaccine coverage across age groups were prior receipt of an influenza vaccine and having private insurance. In adjusted modeling, when compared to NH whites, COVID-19 vaccine coverage was significantly higher among Hispanic, NH Asian, and NH multiple-race patients aged ≥5 years and significantly lower among NH Black and NH Native Hawaiian/Other Pacific Islander patients aged 6 months-4 years old. CONCLUSIONS: We identified disparities in primary series COVID-19 vaccine coverage by age, race and ethnicity, household income, insurance status, and prior influenza vaccination within this large, diverse population accessing care in community-based healthcare organizations.

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop.

The U.S. COVID-19 vaccination program, which commenced in December 2020, has been instrumental in preventing morbidity and mortality from COVID-19 disease. Safety monitoring has been an essential component of the program. The federal government undertook a comprehensive and coordinated approach to implement complementary safety monitoring systems and to communicate findings in a timely and transparent way to healthcare providers, policymakers, and the public. Monitoring involved both well-established and newly developed systems that relied on both spontaneous (passive) and active surveillance methods. Clinical consultation for individual cases of adverse events following vaccination was performed, and monitoring of special populations, such as pregnant persons, was conducted. This report describes the U.S. government's COVID-19 vaccine safety monitoring systems and programs used by the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the Department of Defense, the Department of Veterans Affairs, and the Indian Health Service. Using the adverse event of myocarditis following mRNA COVID-19 vaccination as a model, we demonstrate how the multiple, complementary monitoring systems worked to rapidly detect, assess, and verify a vaccine safety signal. In addition, longer-term follow-up was conducted to evaluate the recovery status of myocarditis cases following vaccination. Finally, the process for timely and transparent communication and dissemination of COVID-19 vaccine safety data is described, highlighting the responsiveness and robustness of the U.S. vaccine safety monitoring infrastructure during the national COVID-19 vaccination program.

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.

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.

During the COVID-19 pandemic, candidate COVID-19 vaccines were being developed for potential use in the United States on an unprecedented, accelerated schedule. It was anticipated that once available, under U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA) or FDA approval, COVID-19 vaccines would be broadly used and potentially administered to millions of individuals in a short period of time. Intensive monitoring in the post-EUA/licensure period would be necessary for timely detection and assessment of potential safety concerns. To address this, the Centers for Disease Control and Prevention (CDC) convened an Advisory Committee on Immunization Practices (ACIP) work group focused solely on COVID-19 vaccine safety, consisting of independent vaccine safety experts and representatives from federal agencies - the ACIP COVID-19 Vaccine Safety Technical Work Group (VaST). This report provides an overview of the organization and activities of VaST, summarizes data reviewed as part of the comprehensive effort to monitor vaccine safety during the COVID-19 pandemic, and highlights selected actions taken by CDC, ACIP, and FDA in response to accumulating post-authorization safety data. VaST convened regular meetings over the course of 29 months, from November 2020 through April 2023; through March 2023 FDA issued EUAs for six COVID-19 vaccines from four different manufacturers and subsequently licensed two of these COVID-19 vaccines. The independent vaccine safety experts collaborated with federal agencies to ensure timely assessment of vaccine safety data during this time. VaST worked closely with the ACIP COVID-19 Vaccines Work Group; that work group used safety data and VaST's assessments for benefit-risk assessments and guidance for COVID-19 vaccination policy. Safety topics reviewed by VaST included those identified in safety monitoring systems and other topics of scientific or public interest. VaST provided guidance to CDC's COVID-19 vaccine safety monitoring efforts, provided a forum for review of data from several U.S. government vaccine safety systems, and assured that a diverse group of scientists and clinicians, external to the federal government, promptly reviewed vaccine safety data. In the event of a future pandemic or other biological public health emergency, the VaST model could be used to strengthen vaccine safety monitoring, enhance public confidence, and increase transparency through incorporation of independent, non-government safety experts into the monitoring process, and through strong collaboration among federal and other partners.

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.

PURPOSE: Vaccine-associated enhanced disease (VAED) is a theoretical concern with new vaccines, although trials of authorized vaccines against SARS-CoV-2 have not identified markers for VAED. The purpose of this study was to detect any signals for VAED among adults vaccinated against coronavirus disease 2019 (COVID-19). METHODS: In this cross-sectional study, we assessed COVID-19 severity as a proxy for VAED among 400 adults hospitalized for COVID-19 from March through October 2021 at eight US healthcare systems. Primary outcomes were admission to an intensive care unit (ICU) and severe illness (score ≥6 on the World Health Organization [WHO] Clinical Progression Scale). We compared the risk of outcomes among those who had completed a COVID-19 vaccine primary series versus those who were unvaccinated. We incorporated inverse propensity weights for vaccination status in a doubly robust regression model to estimate the causal average treatment effect. RESULTS: The causal risk ratio in vaccinated versus unvaccinated was 0.36 (95% confidence interval [CI], 0.15-0.94) for ICU admission and 0.46 (95% CI, 0.25-0.76) for severe illness. CONCLUSION: Among hospitalized patients, reduced disease severity in those vaccinated against COVID-19 supports the absence of VAED.

Background In December 2020, two mRNA-based COVID-19 vaccines were authorized for use in the United States. Vaccine safety was monitored using the Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system, and v-safe, an active surveillance system.Methods VAERS and v-safe data during December 14, 2020—June 14, 2021 were analyzed. VAERS reports were categorized as non-serious, serious, or death; reporting rates were calculated. Rates of reported deaths were compared to expected mortality rates by age. Proportions of v-safe participants reporting local and systemic reactions or health impacts the week following doses 1 and 2 were determined.Findings During the analytic period, 298,792,852 doses of mRNA vaccines were administered in the United States. VAERS processed 340,522 reports; 92·1% were non-serious; 6·6%, serious, non-death; and 1·3%, death. Over half of 7,914,583 v-safe participants self-reported local and systemic reactogenicity, more frequently after dose 2. Injection-site pain, fatigue, and headache were commonly reported during days 0–7 following vaccination. Reactogenicity was reported most frequently one day after vaccination; most reactions were mild. More reports of being unable to work or do normal activities occurred after dose 2 (32·1%) than dose 1 (11·9%); &lt;1% of participants reported seeking medical care after vaccination. Rates of deaths reported to VAERS were lower than expected background rates by age group.Interpretation Safety data from &gt;298 million doses of mRNA COVID-19 vaccine administered in the first 6 months of the U.S. vaccination program show the majority of reported adverse events were mild and short in duration.Competing Interest StatementDisclosures: Ruiling Liu- Stock or stock options, Johnson &amp;Johnson50 shares of stocks Moderna20 shares of stocks &amp; Spouse works for Ethicon|Johnson &amp; Johnson, on surgery robotics Funding StatementThis study did not receive any funding.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Both VAERS and v-safe conduct surveillance as a public health function and are exempt from institutional review board review. This analysis was reviewed by the CDC and conducted in accordance with applicable federal law and CDC policy (See: 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C. 552a; 44 U.S.C. 3501 et seq.). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData produced in the present study are available upon reasonable request to the authors

The United States Department of Agriculture (USDA), Division of Agricultural Select Agents and Toxins (DASAT) established a list of biological agents and toxins (Select Agent List) that potentially threaten agricultural health and safety, the procedures governing the transfer of those agents, and training requirements for entities working with them. Every 2 years the USDA DASAT reviews the Select Agent List, using subject matter experts (SMEs) to perform an assessment and rank the agents. To assist the USDA DASAT biennial review process, we explored the applicability of multi-criteria decision analysis (MCDA) techniques and a Decision Support Framework (DSF) in a logic tree format to identify pathogens for consideration as select agents, applying the approach broadly to include non-select agents to evaluate its robustness and generality. We conducted a literature review of 41 pathogens against 21 criteria for assessing agricultural threat, economic impact, and bioterrorism risk and documented the findings to support this assessment. The most prominent data gaps were those for aerosol stability and animal infectious dose by inhalation and ingestion routes. Technical review of published data and associated scoring recommendations by pathogen-specific SMEs was found to be critical for accuracy, particularly for pathogens with very few known cases, or where proxy data (e.g., from animal models or similar organisms) were used to address data gaps. The MCDA analysis supported the intuitive sense that select agents should rank high on the relative risk scale when considering agricultural health consequences of a bioterrorism attack. However, comparing select agents with non-select agents indicated that there was not a clean break in scores to suggest thresholds for designating select agents, requiring subject matter expertise collectively to establish which analytical results were in good agreement to support the intended purpose in designating select agents. The DSF utilized a logic tree approach to identify pathogens that are of sufficiently low concern that they can be ruled out from consideration as a select agent. In contrast to the MCDA approach, the DSF rules out a pathogen if it fails to meet even one criteria threshold. Both the MCDA and DSF approaches arrived at similar conclusions, suggesting the value of employing the two analytical approaches to add robustness for decision making.

BACKGROUND: On 2/27/2021, FDA authorized Janssen COVID-19 Vaccine (Ad.26.COV2.S) for use in individuals 18 years of age and older. Vaccine safety was monitored using the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system, and v-safe, a smartphone-based surveillance system. METHODS: VAERS and v-safe data from 2/27/2021 to 2/28/2022 were analyzed. Descriptive analyses included sex, age, race/ethnicity, seriousness, AEs of special interest (AESIs), and cause of death. For prespecified AESIs, reporting rates were calculated using the total number of doses of Ad26.COV2.S administered. For myopericarditis, observed-to-expected (O/E) analysis was performed based on the number verified cases, vaccine administration data, and published background rates. Proportions of v-safe participants reporting local and systemic reactions, as well as health impacts, were calculated. RESULTS: During the analytic period, 17,018,042 doses of Ad26.COV2.S were administered in the United States, and VAERS received 67,995 reports of AEs after Ad26.COV2.S vaccination. Most AEs (59,750; 87.9 %) were non-serious and were similar to those observed during clinical trials. Serious AEs included COVID-19 disease, coagulopathy (including thrombosis with thrombocytopenia syndrome; TTS), myocardial infarction, Bell's Palsy, and Guillain-Barré syndrome (GBS). Among AESIs, reporting rates per million doses of Ad26.COV2.S administered ranged from 0.06 for multisystem inflammatory syndrome in children to 263.43 for COVID-19 disease. O/E analysis revealed elevated reporting rate ratios (RRs) for myopericarditis; among adults ages 18-64 years, the RR was 3.19 (95 % CI 2.00, 4.83) within 7 days and 1.79 (95 % CI 1.26, 2.46) within 21 days of vaccination. Of 416,384 Ad26.COV2.S recipients enrolled into v-safe, 60.9 % reported local symptoms (e.g. injection site pain) and 75.9 % reported systemic symptoms (e.g., fatigue, headache). One-third of participants (141,334; 33.9 %) reported a health impact, but only 1.4 % sought medical care. CONCLUSION: Our review confirmed previously established safety risks for TTS and GBS and identified a potential safety concern for myocarditis.

The COVID-19 pandemic has created an unprecedented natural experiment in drug policy, treatment delivery, and harm reduction strategies by exposing wide variation in public health infrastructures and social safety nets around the world. Using qualitative data including ethnographic methods, questionnaires, and semi-structured interviews with people who use drugs (PWUD) and Delphi-method with experts from field sites spanning 13 different countries, this paper compares national responses to substance use during the first wave of the COVID-19 pandemic. Field data was collected by the Substance Use x COVID-19 (SU x COVID) Data Collaborative, an international network of social scientists, public health scientists, and community health practitioners convened to identify and contextualise health service delivery models and social protections that influence the health and wellbeing of PWUD during COVID-19. Findings suggest that countries with stronger social welfare systems pre-COVID introduced durable interventions targeting structural drivers of health. Countries with fragmented social service infrastructures implemented temporary initiatives for PWUD led by non-governmental organisations. The paper summarises the most successful early pandemic responses seen across countries and ends by calling for greater systemic investments in social protections for PWUD, diversion away from criminal-legal systems toward health interventions, and integrated harm reduction, treatment and recovery supports for PWUD.

BACKGROUND: COVID-19 vaccines may be co-administered with other recommended vaccines, including seasonal influenza vaccines. However, few studies have evaluated the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines. OBJECTIVE: To describe reports to the Vaccine Adverse Event Reporting System (VAERS) after co-administration of mRNA COVID-19 and seasonal influenza vaccines. METHODS: We searched the VAERS database for reports of adverse events (AEs) following co-administration of mRNA COVID-19 and seasonal influenza vaccines and following a first booster dose mRNA COVID-19 vaccine alone, during July 1, 2021-June 30, 2022. We assessed the characteristics of these reports and described the most frequently reported MedDRA preferred terms (PTs). Clinicians reviewed available medical records for serious reports and reports of adverse events of special interest (AESI) and categorized the main diagnosis by system organ class. RESULTS: From July 1, 2021 through June 30, 2022, VAERS received 2,449 reports of adverse events following co-administration of mRNA COVID-19 and seasonal influenza vaccines. Median age of vaccinees was 48 years (IQR: 31, 66); 387 (15.8%) were classified as serious. Most reports (1,713; 69.3%) described co-administration of a first booster dose of an mRNA COVID-19 vaccine with seasonal influenza vaccine. The most common AEs among non-serious reports were injection site reactions (193; 14.5%), headache (181; 13.6%), and pain (171; 12.8%). The most common AEs among reports classified as serious were dyspnea (38; 14.9%), COVID-19 infection (32; 12.6%), and chest pain (27; 10.6%). DISCUSSION: This review of reports to VAERS following co-administration of mRNA COVID-19 and seasonal influenza vaccines did not reveal any unusual or unexpected patterns of AEs. Increased reporting of certain events (e.g., COVID-19 disease) was expected. CDC will continue to monitor the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines, including co-administration involving bivalent mRNA COVID-19 booster vaccines that have been recommended for people ages ≥ 6 months in the United States.

BACKGROUND: Studies combining data from digital surveys and electronic health records (EHR) can be used to conduct comprehensive assessments on COVID-19 vaccine safety. METHODS: We conducted an observational study using data from a digital survey and EHR of children aged 5-11 years vaccinated with Pfizer-BioNTech COVID-19 mRNA vaccine across Kaiser Permanente Southern California during November 4, 2021-February 28, 2022. Parents/guardians who enrolled their children were sent a 14-day survey on reactions. Survey results were combined with EHR, and medical encounters were described for children whose parents or guardians indicated seeking medical care for vaccine-related symptoms. This study describes self-reported reactions (local and systemic) and additional symptoms (chest pain, tachycardia, and pre-syncope). RESULTS: The study recruited 7,077 participants aged 5-11 years who received the Pfizer-BioNTech COVID-19 mRNA vaccine. Of 6,247 participants with survey responses after dose 1, 2,176 (35 %) reported at least one systemic reaction, and 1,076 (32 %) of 3,401 respondents following dose 2 reported at least one systemic reaction. Local reactions were reported less frequently following dose 2 (1,113, 33 %) than dose 1 (3,140, 50 %). The most frequently reported reactions after dose 1 were pain at the injection site (48 %), fatigue (20 %), headache (12 %), myalgia (9 %) and fever (5 %). The most frequently reported symptoms after dose 2 were also pain at the injection site (30 %), fatigue (19 %), headache (13 %), myalgia (10 %) and fever (9 %). Post-vaccination reactions occurred most frequently-one day following vaccination. Chest pain or tachycardia were reported infrequently (1 %). EHR demonstrated that parents rarely sought care for post-vaccination symptoms, and among those seeking care, the most common symptoms documented in EHR were fever and nausea, comprising<0.5 % of children. No encounters were related to myocarditis. CONCLUSION: While post-vaccination reactions to the Pfizer-BioNTech COVID-19 mRNA vaccine were common in children aged 5-11 years, our data showed that in most cases they were transient and did not require medical care.

BACKGROUND: Studying the safety of travel vaccines poses challenges since recipients may be traveling during the risk window for adverse events and the identification of a suitable comparison group can also be difficult. The examination of traveler characteristics, travel vaccination patterns, and health care utilization using electronic health record (EHR) data can inform the feasibility of future travel vaccine safety studies. METHODS: A retrospective cohort study of health plan members in the Vaccine Safety Datalink Project aged 9 months and older who had a travel-related encounter or received a travel vaccine from 2009 to 2018 was performed. Travel regions visited, travel duration, type of travel vaccine received (typhoid, yellow fever, Japanese encephalitis, rabies, and cholera), and timing of vaccination date before departure date were described. Sociodemographic information, clinical characteristics, and health care utilization were compared between travelers who received travel vaccines and travelers who did not. RESULTS: A total of 1,026,822 unique travelers departing from the United States were identified; 612,795 travelers received 898,196 doses of travel vaccines. The most commonly administered travel vaccine was typhoid vaccine and 77% of all travel vaccines were given more than one week prior to departure. Compared with travelers without travel vaccines, travelers with travel vaccines were overall similar but as a group were slightly younger, healthier, and had lower Hispanic representation. Health care utilization dramatically decreased during travel. Outpatient visits decreased from 294.8 visits per 10,000 person-days before travel to 24.2 visits per 10,000 person-days during reported travel dates. CONCLUSIONS: Through the EHR information from almost a million travelers, a departure date and duration of travel were successfully captured for the majority of travelers with corresponding health care utilization data. Time after vaccination and prior to departure can potentially be used in the future to compare travelers who receive travel vaccines with travelers who do not receive travel vaccines when looking at adverse events of interest after vaccination.

Biological response modifiers (BRM), also known as immunomodulators or cytokine inhibitors, are immunosuppressive substances that are increasingly being used to treat various autoimmune diseases,1 including during pregnancy. Some BRM are actively transported across the placenta barrier and can remain in infants for up to 12 months after birth,2,3 raising concerns that infants exposed to BRM in utero may be at increased risk of infections and adverse events after immunization with live attenuated vaccines.

Pregnant women with symptomatic coronavirus disease 2019 (Covid-19) have a higher risk of adverse outcomes than do women who are not pregnant.1,2 In part because of these findings, Covid-19 vaccination has been recommended for pregnant women. However, uptake has been lower in pregnant women than among women who are not pregnant.3,4 The concern of many women regarding safety remains a barrier to maternal vaccination.

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.

The Vaccine Safety Datalink (VSD) conducts active surveillance and vaccine safety research studies. Since the start of the U.S. COVID-19 vaccination program, the VSD has conducted near real-time safety surveillance of COVID-19 vaccines using Rapid Cycle Analysis. VSD investigators developed an internal dashboard to facilitate visualization and rapid reviews of large weekly automated vaccine safety surveillance data. Dashboard development and maintenance was informed by vaccine surveillance data users and vaccine safety partners. Key metrics include population demographics, vaccine uptake, pre-specified safety outcomes, sequential analyses results, and descriptive data on potential vaccine safety signals. Dashboard visualizations are used to provide situational awareness on dynamic vaccination coverage and the status of multiple safety analyses conducted among the VSD population. This report describes the development and implementation of the internal VSD COVID-19 Vaccine Dashboard, including metrics used to develop the dashboard, which may have application across various other public health settings.

BACKGROUND: Enteric pathogens are often associated with exposure to food, water, animals, and feces from infected individuals. However, in sexual networks of men who have sex with men (MSM), transmission of enteric pathogens may occur during direct or indirect oral-anal contact. METHODS: We performed a scoping review of the literature for studies prior to July 2019 with key terms for gastrointestinal syndromes ("proctitis," "enteritis," "proctocolitis"), enteric pathogens or sexually transmitted infections (STIs), and outbreaks using multiple electronic databases. RESULTS: We identified 5861 records through database searches, bibliography reviews, and keyword searches, of which 117 references were included in the pathogen-specific reviews. CONCLUSIONS: The strength of observational data describing enteric pathogens in MSM and possible sexual transmission of enteric pathogens varies by pathogen; however, a robust body of literature describes the sexual transmission of Campylobacter, Giardia lamblia, and Shigella (particularly antimicrobial-resistant strains) in sexual networks of MSM. Providers are encouraged to consider enteritis or proctocolitis in MSM as possibly having been sexually transmitted and encourage targeted STI testing. Risk/harm reduction and prevention messages should also be incorporated, though there is an acknowledged paucity of evidence with regards to effective strategies. Further research is needed to understand the transmission and prevention of enteric pathogens in MSM.

OBJECTIVES: To determine whether children aged 4-7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD. METHODS: The study included children born between 1995-2012, aged 4-7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions. RESULTS: The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58-1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63-2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80-1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59-1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD. CONCLUSION: Children with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.

BACKGROUND: In December, 2020, two mRNA-based COVID-19 vaccines were authorised for use in the USA. We aimed to describe US surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), a passive system, and v-safe, a new active system, during the first 6 months of the US COVID-19 vaccination programme. METHODS: In this observational study, we analysed data reported to VAERS and v-safe during Dec 14, 2020, to June 14, 2021. VAERS reports were categorised as non-serious, serious, or death. Reporting rates were calculated using numbers of COVID-19 doses administered as the denominator. We analysed v-safe survey reports from days 0-7 after vaccination for reactogenicity, severity (mild, moderate, or severe), and health impacts (ie, unable to perform normal daily activities, unable to work, or received care from a medical professional). FINDINGS: During the study period, 298 792 852 doses of mRNA vaccines were administered in the USA. VAERS processed 340 522 reports: 313 499 (92·1%) were non-serious, 22 527 (6·6%) were serious (non-death), and 4496 (1·3%) were deaths. Over half of 7 914 583 v-safe participants self-reported local and systemic reactogenicity, more frequently after dose two (4 068 447 [71·7%] of 5 674 420 participants for local reactogenicity and 4 018 920 [70·8%] for systemic) than after dose one (4 644 989 [68·6%] of 6 775 515 participants for local reactogenicity and 3 573 429 [52·7%] for systemic). Injection-site pain (4 488 402 [66·2%] of 6 775 515 participants after dose one and 3 890 848 [68·6%] of 5 674 420 participants after dose two), fatigue (2 295 205 [33·9%] participants after dose one and 3 158 299 participants [55·7%] after dose two), and headache (1 831 471 [27·0%] participants after dose one and 2 623 721 [46·2%] participants after dose two) were commonly reported during days 0-7 following vaccination. Reactogenicity was reported most frequently the day after vaccination; most reactions were mild. More reports of being unable to work, do normal activities, or of seeking medical care occurred after dose two (1 821 421 [32·1%]) than after dose one (808 963 [11·9%]); less than 1% of participants reported seeking medical care after vaccination (56 647 [0·8%] after dose one and 53 077 [0·9%] after dose two). INTERPRETATION: Safety data from more than 298 million doses of mRNA COVID-19 vaccine administered in the first 6 months of the US vaccination programme show that most reported adverse events were mild and short in duration. FUNDING: US Centers for Disease Control and Prevention.

COVID-19 vaccines are recommended during pregnancy to prevent severe maternal morbidity and adverse birth outcomes; however, vaccination coverage among pregnant women has been low (1). Concerns among pregnant women regarding vaccine safety are a persistent barrier to vaccine acceptance during pregnancy. Previous studies of maternal COVID-19 vaccination and birth outcomes have been limited by small sample size (2) or lack of an unvaccinated comparison group (3). In this retrospective cohort study of live births from eight Vaccine Safety Datalink (VSD) health care organizations, risks for preterm birth (<37 weeks' gestation) and small-for-gestational-age (SGA) at birth (birthweight <10th percentile for gestational age) after COVID-19 vaccination (receipt of ≥1 COVID-19 vaccine doses) during pregnancy were evaluated. Risks for preterm and SGA at birth among vaccinated and unvaccinated pregnant women were compared, accounting for time-dependent vaccine exposures and propensity to be vaccinated. Single-gestation pregnancies with estimated start or last menstrual period during May 17-October 24, 2020, were eligible for inclusion. Among 46,079 pregnant women with live births and gestational age available, 10,064 (21.8%) received ≥1 COVID-19 vaccine doses during pregnancy and during December 15, 2020-July 22, 2021; nearly all (9,892; 98.3%) were vaccinated during the second or third trimester. COVID-19 vaccination during pregnancy was not associated with preterm birth (adjusted hazard ratio [aHR] = 0.91; 95% CI = 0.82-1.01). Among 40,627 live births with birthweight available, COVID-19 vaccination in pregnancy was not associated with SGA at birth (aHR = 0.95; 95% CI = 0.87-1.03). Results consistently showed no increased risk when stratified by mRNA COVID-19 vaccine dose, or by second or third trimester vaccination, compared with risk among unvaccinated pregnant women. Because of the small number of first-trimester exposures, aHRs for first-trimester vaccination could not be calculated. These data add to the evidence supporting the safety of COVID-19 vaccination during pregnancy. To reduce the risk for severe COVID-19-associated illness, CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future (4).

BACKGROUND: Cisgender women have been underrepresented in antibiotic-resistant gonorrhea (ARGC) surveillance systems. Three of 8 project sites (City of Milwaukee [MIL], Guilford County [GRB], Denver County [DEN]), funded under the Centers for Disease Control and Prevention's Strengthening the US Response to Resistant Gonorrhea (SURRG), focused efforts to better include cisgender women in ARGC surveillance. METHODS: MIL, GRB, and DEN partnered with diverse health care settings and developed gonorrhea culture criteria to facilitate urogenital specimen collection in cisgender women and men. Regional laboratories within the Antibiotic Resistance Laboratory Network performed agar dilution antibiotic susceptibility testing (AST) of gonococcal isolates. Data from 2018 and 2019 were analyzed. RESULTS: In SURRG, 90.5% (11,464 of 12,667) of the cisgender women from whom urogenital culture specimens were collected were from MIL, GRB, and DEN. Of women in SURRG whose gonococcal isolates underwent AST, 70% were from these 3 sites. In these 3 sites, a substantial proportion of cisgender women with positive urogenital cultures and AST were from health care settings other than sexually transmitted disease (STD) clinics (non-STD clinics; MIL, 56.0%; GRB, 80.4%; and DEN, 23.5%). Isolates with AST were obtained from 5.1%, 10.2%, and 2.4% of all diagnosed gonorrhea cases among cisgender women in MIL, GRB, and DEN, respectively, and were more often susceptible to all antibiotics than those from cisgender men from each of these sites. CONCLUSIONS: With focused efforts and partnerships with non-STD clinics, 3 SURRG sites were able to include robust ARGC surveillance from cisgender women. These findings may guide further efforts to improve gender equity in ARGC surveillance.

The first two COVID-19 vaccines, both of which contain messenger RNA (mRNA), BNT162b2 from Pfizer Inc/BioNTech and mRNA-1273 from Moderna and a third containing a recombinant replication-incompetent adenovirus type 26 (Ad26) vector, Ad26.COV2.S from Janssen Pharmaceuticals Companies of Johnson & Johnson, were authorized for emergency use in the United States by the Food and Drug Administration (FDA) in mid-December 2020 and at the end of February 2021, respectively [Citation1–3]. In the pre-emergency use authorization clinical trials for these vaccines, local and systemic reactions were the main types of adverse events (AE) observed. The Centers for Disease Control and Prevention (CDC) uses three systems to monitor the safety of COVID-19 vaccines: 1) the Vaccine Adverse Event Reporting System (VAERS), which is the front-line, national, spontaneous surveillance system [Citation4]; 2) v-safe, a new smartphone and Internet survey-based, after-vaccination health checker for people who receive COVID-19 vaccines [Citation5]; there is also the associated v-safe pregnancy registry which collects detailed pregnancy and medical history information from v-safe participants who report being pregnant around the time of vaccination [Citation6]; and 3) the Vaccine Safety Datalink (VSD) which is a large linked database system used for active surveillance and traditional epidemiologic research [Citation7]. These complementary systems are being used to actively monitor the safety of COVID-19 vaccines in the United States [Citation8]. The results of this unprecedented and comprehensive effort are communicated through frequent presentations at the meetings of the Advisory Committee on Immunization Practices (ACIP) and in several fast-tracked published reports.

We used wastewater surveillance to identify 2 coronavirus disease outbreaks at a college in Maine, USA. Cumulative increases of >1 log(10) severe acute respiratory syndrome coronavirus 2 RNA in consecutive 24-hour composite samples preceded the outbreaks. For 76% of cases, RNA was identified in grab samples from residence halls <7 days before case discovery.

BACKGROUND: Disease intervention specialists (DIS) provide partner services (PS) for sexually transmitted infections (STI). We assessed an expansion of DIS services for clients with HIV and/or syphilis, and contacts within their social and sexual networks. METHODS: Black and Latinx cisgender men and transgender women who have sex with men diagnosed with HIV and/or syphilis in four urban North Carolina (NC) counties were referred to designated DIS, who were trained to recruit clients as "seeds" for chain-referral sampling of sociosexual network "peers." All received HIV/STI testing and care; referrals for pre-exposure prophylaxis (PrEP) and social, behavioral, and non-STI medical services were offered. Participants completed baseline, 1 month, and 3 month computerized surveys. RESULTS: Of 213 cases referred to DIS from May 2018 to February 2020, 42 seeds (25 with syphilis, 17 with HIV) and 50 peers participated. Median age was 27 years; 93% were Black and 86% were cisgender men. Most peers came from seeds' social networks: 66% were friends, 20% were relatives, and 38% were cisgender women. Incomes were low, 41% were uninsured, and 10% experienced recent homelessness. More seeds than peers had baseline PrEP awareness; attitudes were favorable but utilization was poor. Thirty-seven participants were referred for PrEP 50 times; 17 (46%) accessed PrEP by month 3. Thirty-nine participants received 129 non-PrEP referrals, most commonly for housing assistance, primary care, Medicaid navigation, and food insecurity. CONCLUSIONS: Chain-referral sampling from PS clients allowed DIS to access persons with significant medical and social service needs, demonstrating that DIS can support marginalized communities beyond STI intervention.

BACKGROUND: In 2016, CDC initiated Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) in multiple jurisdictions to enhance antibiotic resistant gonorrhea rapid detection and response infrastructure and evaluate the impact of key strategies. METHODS: Eight jurisdictions were funded to establish or enhance local gonococcal culture specimen collection in STD and community clinics, conduct rapid antimicrobial susceptibility testing (AST) in local laboratories, modify systems for enhanced data collection and rapid communication of results, and initiate enhanced partner services among patients with gonorrhea demonstrating elevated minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime or azithromycin. RESULTS: Grantees incorporated genital, pharyngeal, and rectal gonococcal culture collection from all genders at participating clinics. During 2018-2019, grantees collected 58,441 culture specimens from 46,822 patients and performed AST on 10,814 isolates (representing 6.8% (3,412) and 8.9% (4,883) of local reported cases in 2018 and 2019 respectively). Of isolates that underwent AST, 11% demonstrated elevated azithromycin MICs; fewer than 0.5% demonstrated elevated ceftriaxone or cefixime MICs. Among patients whose infections demonstrated elevated MICs, 81.7% were interviewed for partner elicitation; however, limited new cases were identified among partners and contacts. CONCLUSIONS: As a public health model to build capacity to slow the spread of emerging resistance, SURRG successfully expanded culture collection, implemented rapid AST, and implemented an enhanced partner services investigation approach in participating jurisdictions. Findings from SURRG may enhance preparedness efforts and inform a longer-term, comprehensive, and evidence-based public health response to emerging gonococcal resistance. Continued development of innovative approaches to address emerging resistance is needed.