Pathogen-Agnostic Advanced Molecular Diagnostic Testing for Difficult-to-Diagnose Clinical Syndromes-Results of an Emerging Infections Network Survey of Frontline US Infectious Disease Clinicians, May 2023.

During routine clinical practice, infectious disease physicians encounter patients with difficult-to-diagnose clinical syndromes and may order advanced molecular testing to detect pathogens. These tests may identify potential infectious causes for illness and allow clinicians to adapt treatments or stop unnecessary antimicrobials. Cases of pathogen-agnostic disease testing also provide an important window into known, emerging, and reemerging pathogens and may be leveraged as part of national sentinel surveillance. A survey of Emerging Infections Network members, a group of infectious disease providers in North America, was conducted in May 2023. The objective of the survey was to gain insight into how and when infectious disease physicians use advanced molecular testing for patients with difficult-to-diagnose infectious diseases, as well as to explore the usefulness of advanced molecular testing and barriers to use. Overall, 643 providers answered at least some of the survey questions; 478 (74%) of those who completed the survey had ordered advanced molecular testing in the last two years, and formed the basis for this study. Respondents indicated that they most often ordered broad-range 16S rRNA gene sequencing, followed by metagenomic next-generation sequencing and whole genome sequencing; and commented that in clinical practice, some, but not all tests were useful. Many physicians also noted several barriers to use, including a lack of national guidelines and cost, while others commented that whole genome sequencing had potential for use in outbreak surveillance. Improving frontline physician access, availability, affordability, and developing clear national guidelines for interpretation and use of advanced molecular testing could potentially support clinical practice and public health surveillance.

Public Health Surveillance in Electronic Health Records: Lessons From PCORnet.

Introduction: PCORnet, the National Patient-Centered Clinical Research Network, is a large research network of health systems that map clinical data to a standardized data model. In 2018, we expanded existing infrastructure to facilitate use for public health surveillance. We describe benefits and challenges of using PCORnet for surveillance and describe case studies. Methods: In 2018, infrastructure enhancements included addition of a table to store patients' residential zip codes and expansion of a modular program to generate population health statistics across conditions. Chronic disease surveillance case studies conducted in 2019 assessed atrial fibrillation (AF) and cirrhosis. In April 2020, PCORnet established an infrastructure to support COVID-19 surveillance with institutions frequently updating their electronic health record data. Results: By August 2023, 53 PCORnet sites (84%) had a 5-digit zip code available on at least 95% of their patient populations. Among 148,223 newly diagnosed AF patients eligible for oral anticoagulant (OAC) therapy, 43.3% were on any OAC (17.8% warfarin, 28.5% any novel oral anticoagulant) within a year of the AF diagnosis. Among 60,268 patients with cirrhosis (2015-2019), common documented etiologies included unknown (48%), hepatitis C infection (23%), and alcohol use (22%). During October 2022 through December 2023, across 34 institutions, the proportion of COVID-19 patients who were cared for in the inpatient setting was 9.1% among 887,051 adults aged 20 years or older and 6.0% among 139,148 children younger than 20 years. Conclusions: PCORnet provides important data that may augment traditional public health surveillance programs across diverse conditions. PCORnet affords longitudinal population health assessments among large catchments of the population with clinical, treatment, and geographic information, with capabilities to deliver rapid information needed during public health emergencies.

Privacy preserving record linkage for public health action: opportunities and challenges.

OBJECTIVES: To understand the landscape of privacy preserving record linkage (PPRL) applications in public health, assess estimates of PPRL accuracy and privacy, and evaluate factors for PPRL adoption. MATERIALS AND METHODS: A literature scan examined the accuracy, data privacy, and scalability of PPRL in public health. Twelve interviews with subject matter experts were conducted and coded using an inductive approach to identify factors related to PPRL adoption. RESULTS: PPRL has a high level of linkage quality and accuracy. PPRL linkage quality was comparable to that of clear text linkage methods (requiring direct personally identifiable information [PII]) for linkage across various settings and research questions. Accuracy of PPRL depended on several components, such as PPRL technique, and the proportion of missingness and errors in underlying data. Strategies to increase adoption include increasing understanding of PPRL, improving data owner buy-in, establishing governance structure and oversight, and developing a public health implementation strategy for PPRL. DISCUSSION: PPRL protects privacy by eliminating the need to share PII for linkage, but the accuracy and linkage quality depend on factors including the choice of PPRL technique and specific PII used to create encrypted identifiers. Large-scale implementations of PPRL linking millions of observations-including PCORnet, National Institutes for Health N3C, and the Centers for Disease Control and Prevention COVID-19 project have demonstrated the scalability of PPRL for public health applications. CONCLUSIONS: Applications of PPRL in public health have demonstrated their value for the public health community. Although gaps must be addressed before wide implementation, PPRL is a promising solution to data linkage challenges faced by the public health ecosystem.

Mortality Surveillance for the COVID-19 Pandemic: Review of the Centers for Disease Control and Prevention's Multiple System Strategy.

Mortality surveillance systems can have limitations, including reporting delays, incomplete reporting, missing data, and insufficient detail on important risk or sociodemographic factors that can impact the accuracy of estimates of current trends, disease severity, and related disparities across subpopulations. The Centers for Disease Control and Prevention used multiple data systems during the COVID-19 emergency response-line-level case‒death surveillance, aggregate death surveillance, and the National Vital Statistics System-to collectively provide more comprehensive and timely information on COVID-19‒associated mortality necessary for informed decisions. This article will review in detail the line-level, aggregate, and National Vital Statistics System surveillance systems and the purpose and use of each. This retrospective review of the hybrid surveillance systems strategy may serve as an example for adaptive informational approaches needed over the course of future public health emergencies. (Am J Public Health. Published online ahead of print July 25, 2024:e1-e10. https://doi.org/10.2105/AJPH.2024.307743).

Deployment of the National Notifiable Diseases Surveillance System during the 2022-23 mpox outbreak in the United States-Opportunities and challenges with case notifications during public health emergencies.

Timely case notifications following the introduction of an uncommon pathogen, such as mpox, are critical for understanding disease transmission and for developing and implementing effective mitigation strategies. When Massachusetts public health officials notified the Centers for Disease Control and Prevention (CDC) about a confirmed orthopoxvirus case on May 17, 2023, which was later confirmed as mpox at CDC, mpox was not a nationally notifiable disease. Because existing processes for new data collections through the National Notifiable Disease Surveillance System were not well suited for implementation during emergency responses at the time of the mpox outbreak, several interim notification approaches were established to capture case data. These interim approaches were successful in generating daily case counts, monitoring disease transmission, and identifying high-risk populations. However, the approaches also required several data collection approvals by the federal government and the Council for State and Territorial Epidemiologists, the use of four different case report forms, and the establishment of complex data management and validation processes involving data element mapping and record-level de-duplication steps. We summarize lessons learned from these interim approaches to inform and improve case notifications during future outbreaks. These lessons reinforce CDC's Data Modernization Initiative to work in close collaboration with state, territorial, and local public health departments to strengthen case-based surveillance prior to the next public health emergency.

Surveillance for Emerging and Reemerging Pathogens Using Pathogen Agnostic Metagenomic Sequencing in the United States: A Critical Role for Federal Government Agencies.

The surveillance and identification of emerging, reemerging, and unknown infectious disease pathogens is essential to national public health preparedness and relies on fluidity, coordination, and interconnectivity between public and private pathogen surveillance systems and networks. Developing a national sentinel surveillance network with existing resources and infrastructure could increase efficiency, accelerate the identification of emerging public health threats, and support coordinated intervention strategies that reduce morbidity and mortality. However, implementing and sustaining programs to detect emerging and reemerging pathogens in humans using advanced molecular methods, such as metagenomic sequencing, requires making large investments in testing equipment and developing networks of clinicians, laboratory scientists, and bioinformaticians. In this study, we sought to gain an understanding of how federal government agencies currently support such pathogen agnostic testing of human specimens in the United States. We conducted a landscape analysis of federal agency websites for publicly accessible information on the availability and type of pathogen agnostic testing and details on flow of clinical specimens and data. The website analysis was supplemented by an expert review of results with representatives from the federal agencies. Operating divisions within the US Department of Health and Human Services and the US Department of Veterans Affairs have developed and sustained extensive clinical and research networks to obtain patient specimens and perform metagenomic sequencing. Metagenomic facilities supported by US agencies were not equally geographically distributed across the United States. Although many entities have work dedicated to metagenomics and/or support emerging infectious disease surveillance specimen collection, there was minimal formal collaboration across agencies.

Literature Review of Pathogen Agnostic Molecular Testing of Clinical Specimens From Difficult-to-Diagnose Patients: Implications for Public Health.

To better identify emerging or reemerging pathogens in patients with difficult-to-diagnose infections, it is important to improve access to advanced molecular testing methods. This is particularly relevant for cases where conventional microbiologic testing has been unable to detect the pathogen and the patient's specimens test negative. To assess the availability and utility of such testing for human clinical specimens, a literature review of published biomedical literature was conducted. From a corpus of more than 4,000 articles, a set of 34 reports was reviewed in detail for data on where the testing was being performed, types of clinical specimens tested, pathogen agnostic techniques and methods used, and results in terms of potential pathogens identified. This review assessed the frequency of advanced molecular testing, such as metagenomic next generation sequencing that has been applied to clinical specimens for supporting clinicians in caring for difficult-to-diagnose patients. Specimen types tested were from cerebrospinal fluid, respiratory secretions, and other body tissues and fluids. Publications included case reports and series, and there were several that involved clinical trials, surveillance studies, research programs, or outbreak situations. Testing identified both known human pathogens (sometimes in new sites) and previously unknown human pathogens. During this review, there were no apparent coordinated efforts identified to develop regional or national reports on emerging or reemerging pathogens. Therefore, development of a coordinated sentinel surveillance system that applies advanced molecular methods to clinical specimens which are negative by conventional microbiological diagnostic testing would provide a foundation for systematic characterization of emerging and underdiagnosed pathogens and contribute to national biodefense strategy goals.

Association between SARS-CoV-2 infection and select symptoms and conditions 31 to 150 days after testing among children and adults.

BACKGROUND: An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results. METHODS: We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020-May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test. RESULTS: After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions. CONCLUSIONS: Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection.

Who Gets Sick From COVID-19? Sociodemographic Correlates of Severe Adult Health Outcomes During Alpha- and Delta-Variant Predominant Periods: September 2020-November 2021.

BACKGROUND: Because COVID-19 case data do not capture most SARS-CoV-2 infections, the actual risk of severe disease and death per infection is unknown. Integrating sociodemographic data into analysis can show consequential health disparities. METHODS: Data were merged from September 2020 to November 2021 from 6 national surveillance systems in matched geographic areas and analyzed to estimate numbers of COVID-19-associated cases, emergency department visits, and deaths per 100 000 infections. Relative risks of outcomes per infection were compared by sociodemographic factors in a data set including 1490 counties from 50 states and the District of Columbia, covering 71% of the US population. RESULTS: Per infection with SARS-CoV-2, COVID-19-related morbidity and mortality were higher among non-Hispanic American Indian and Alaska Native persons, non-Hispanic Black persons, and Hispanic or Latino persons vs non-Hispanic White persons; males vs females; older people vs younger; residents in more socially vulnerable counties vs less; those in large central metro areas vs rural; and people in the South vs the Northeast. DISCUSSION: Meaningful disparities in COVID-19 morbidity and mortality per infection were associated with sociodemography and geography. Addressing these disparities could have helped prevent the loss of tens of thousands of lives.

Monoclonal Antibodies as SARS-CoV-2 Serology Standards: Experimental Validation and Broader Implications for Correlates of Protection.

COVID-19 has highlighted challenges in the measurement quality and comparability of serological binding and neutralization assays. Due to many different assay formats and reagents, these measurements are known to be highly variable with large uncertainties. The development of the WHO international standard (WHO IS) and other pool standards have facilitated assay comparability through normalization to a common material but does not provide assay harmonization nor uncertainty quantification. In this paper, we present the results from an interlaboratory study that led to the development of (1) a novel hierarchy of data analyses based on the thermodynamics of antibody binding and (2) a modeling framework that quantifies the probability of neutralization potential for a given binding measurement. Importantly, we introduced a precise, mathematical definition of harmonization that separates the sources of quantitative uncertainties, some of which can be corrected to enable, for the first time, assay comparability. Both the theory and experimental data confirmed that mAbs and WHO IS performed identically as a primary standard for establishing traceability and bridging across different assay platforms. The metrological anchoring of complex serological binding and neuralization assays and fast turn-around production of an mAb reference control can enable the unprecedented comparability and traceability of serological binding assay results for new variants of SARS-CoV-2 and immune responses to other viruses.

Increased Hospitalizations Involving Fungal Infections during COVID-19 Pandemic, United States, January 2020-December 2021.

Hospitalizations involving fungal infections increased 8.5% each year in the United States during 2019-2021. During 2020-2021, patients hospitalized with COVID-19-associated fungal infections had higher (48.5%) in-hospital mortality rates than those with non-COVID-19-associated fungal infections (12.3%). Improved fungal disease surveillance is needed, particularly during respiratory virus pandemics.

Severity Outcomes among Adult Patients with Primary Immunodeficiency and COVID-19 Seen in Emergency Departments, United States, April 2020-August 2021.

Primary immunodeficiencies (PIs) are a group of diseases that increase susceptibility to infectious diseases. Few studies have examined the relationship between PI and COVID-19 outcomes. In this study, we used Premier Healthcare Database, which contains information on inpatient discharges, to analyze COVID-19 outcomes among 853 adult PI and 1,197,430 non-PI patients who visited the emergency department. Hospitalization, intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and death had higher odds in PI patients than in non-PI patients (hospitalization aOR: 2.36, 95% CI: 1.87-2.98; ICU admission aOR: 1.53, 95% CI: 1.19-1.96; IMV aOR: 1.41, 95% CI: 1.15-1.72; death aOR: 1.37, 95% CI: 1.08-1.74), and PI patients spent on average 1.91 more days in the hospital than non-PI patients when adjusted for age, sex, race/ethnicity, and chronic conditions associated with severe COVID-19. Of the largest four PI groups, selective deficiency of the immunoglobulin G subclass had the highest hospitalization frequency (75.2%). This large study of United States PI patients provides real-world evidence that PI is a risk factor for adverse COVID-19 outcomes.

Potential for Recurrent Mpox Outbreaks Among Gay, Bisexual, and Other Men Who Have Sex with Men - United States, 2023.

More than 30,000 monkeypox (mpox) cases have been diagnosed in the United States since May 2022, primarily among gay, bisexual, and other men who have sex with men (MSM) (1,2). In recent months, diagnoses have declined to one case per day on average. However, mpox vaccination coverage varies regionally, suggesting variable potential risk for mpox outbreak recurrence (3). CDC simulated dynamic network models representing sexual behavior among MSM to estimate the risk for and potential size of recurrent mpox outbreaks at the jurisdiction level for 2023 and to evaluate the benefits of vaccination for preparedness against mpox reintroduction. The risk for outbreak recurrence after mpox reintroduction is linearly (inversely) related to the proportion of MSM who have some form of protective immunity: the higher the population prevalence of immunity (from vaccination or natural infection), the lower the likelihood of recurrence in that jurisdiction across all immunity levels modeled. In contrast, the size of a potential recurrent outbreak might have thresholds: very small recurrences are predicted for jurisdictions with mpox immunity of 50%-100%; exponentially increasing sizes of recurrences are predicted for jurisdictions with 25%-50% immunity; and linearly increasing sizes of recurrences are predicted for jurisdictions with <25% immunity. Among the 50 jurisdictions examined, 15 are predicted to be at minimal risk for recurrence because of their high levels of population immunity. This analysis underscores the ongoing need for accessible and sustained mpox vaccination to decrease the risk for and potential size of future mpox recurrences.

The CDC Domestic Mpox Response - United States, 2022-2023.

Monkeypox (mpox) is a serious viral zoonosis endemic in west and central Africa. An unprecedented global outbreak was first detected in May 2022. CDC activated its emergency outbreak response on May 23, 2022, and the outbreak was declared a Public Health Emergency of International Concern on July 23, 2022, by the World Health Organization (WHO),* and a U.S. Public Health Emergency on August 4, 2022, by the U.S. Department of Health and Human Services.† A U.S. government response was initiated, and CDC coordinated activities with the White House, the U.S. Department of Health and Human Services, and many other federal, state, and local partners. CDC quickly adapted surveillance systems, diagnostic tests, vaccines, therapeutics, grants, and communication systems originally developed for U.S. smallpox preparedness and other infectious diseases to fit the unique needs of the outbreak. In 1 year, more than 30,000 U.S. mpox cases were reported, more than 140,000 specimens were tested, >1.2 million doses of vaccine were administered, and more than 6,900 patients were treated with tecovirimat, an antiviral medication with activity against orthopoxviruses such as Variola virus and Monkeypox virus. Non-Hispanic Black (Black) and Hispanic or Latino (Hispanic) persons represented 33% and 31% of mpox cases, respectively; 87% of 42 fatal cases occurred in Black persons. Sexual contact among gay, bisexual, and other men who have sex with men (MSM) was rapidly identified as the primary risk for infection, resulting in profound changes in our scientific understanding of mpox clinical presentation, pathogenesis, and transmission dynamics. This report provides an overview of the first year of the response to the U.S. mpox outbreak by CDC, reviews lessons learned to improve response and future readiness, and previews continued mpox response and prevention activities as local viral transmission continues in multiple U.S. jurisdictions (Figure).

Epidemiologic and Clinical Features of Mpox-Associated Deaths - United States, May 10, 2022-March 7, 2023.

As of March 7, 2023, a total of 30,235 confirmed and probable monkeypox (mpox) cases were reported in the United States,† predominantly among cisgender men§ who reported recent sexual contact with another man (1). Although most mpox cases during the current outbreak have been self-limited, cases of severe illness and death have been reported (2-4). During May 10, 2022-March 7, 2023, 38 deaths among persons with probable or confirmed mpox¶ (1.3 per 1,000 mpox cases) were reported to CDC and classified as mpox-associated (i.e., mpox was listed as a contributing or causal factor). Among the 38 mpox-associated deaths, 94.7% occurred in cisgender men (median age = 34 years); 86.8% occurred in non-Hispanic Black or African American (Black) persons. The median interval from symptom onset to death was 68 days (IQR = 50-86 days). Among 33 decedents with available information, 93.9% were immunocompromised because of HIV. Public health actions to prevent mpox deaths include integrated testing, diagnosis, and early treatment for mpox and HIV, and ensuring equitable access to both mpox and HIV prevention and treatment, such as antiretroviral therapy (ART) (5).

Tracking COVID-19 in the United States With Surveillance of Aggregate Cases and Deaths.

Early during the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) leveraged an existing surveillance system infrastructure to monitor COVID-19 cases and deaths in the United States. Given the time needed to report individual-level (also called line-level) COVID-19 case and death data containing detailed information from individual case reports, CDC designed and implemented a new aggregate case surveillance system to inform emergency response decisions more efficiently, with timelier indicators of emerging areas of concern. We describe the processes implemented by CDC to operationalize this novel, multifaceted aggregate surveillance system for collecting COVID-19 case and death data to track the spread and impact of the SARS-CoV-2 virus at national, state, and county levels. We also review the processes established to acquire, process, and validate the aggregate number of cases and deaths due to COVID-19 in the United States at the county and jurisdiction levels during the pandemic. These processes include time-saving tools and strategies implemented to collect and validate authoritative COVID-19 case and death data from jurisdictions, such as web scraping to automate data collection and algorithms to identify and correct data anomalies. This topical review highlights the need to prepare for future emergencies, such as novel disease outbreaks, by having an event-agnostic aggregate surveillance system infrastructure in place to supplement line-level case reporting for near-real-time situational awareness and timely data.

Use of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Tests by US Infectious Disease Physicians: Results of an Emerging Infections Network Survey, March 2022.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests have had limited recommended clinical application during the coronavirus disease 2019 (COVID-19) pandemic. To inform clinical practice, an understanding is needed of current perspectives of United States-based infectious disease (ID) physicians on the use, interpretation, and need for SARS-CoV-2 antibody tests. Methods: In March 2022, members of the Emerging Infections Network (EIN), a national network of practicing ID physicians, were surveyed on types of SARS-CoV-2 antibody assays ordered, interpretation of test results, and clinical scenarios for which antibody tests were considered. Results: Of 1867 active EIN members, 747 (40%) responded. Among the 583 who managed or consulted on COVID-19 patients, a majority (434/583 [75%]) had ordered SARS-CoV-2 antibody tests and were comfortable interpreting positive (452/578 [78%]) and negative (405/562 [72%]) results. Antibody tests were used for diagnosing post-COVID-19 conditions (61%), identifying prior SARS-CoV-2 infection (60%), and differentiating prior infection and response to COVID-19 vaccination (37%). Less than a third of respondents had used antibody tests to assess need for additional vaccines or risk stratification. Lack of sufficient evidence for use and nonstandardized assays were among the most common barriers for ordering tests. Respondents indicated that statements from professional societies and government agencies would influence their decision to order SARS-CoV-2 antibody tests for clinical decision making. Conclusions: Practicing ID physicians are using SARS-CoV-2 antibody tests, and there is an unmet need for clarifying the appropriate use of these tests in clinical practice. Professional societies and US government agencies can support clinicians in the community through the creation of appropriate guidance.

JYNNEOS Vaccination Coverage Among Persons at Risk for Mpox - United States, May 22, 2022-January 31, 2023.

From May 2022 through the end of January 2023, approximately 30,000 cases of monkeypox (mpox) have been reported in the United States and >86,000 cases reported internationally.* JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended for subcutaneous administration to persons at increased risk for mpox (1,2) and has been demonstrated to provide protection against infection (3-5). To increase the total number of vaccine doses available, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) on August 9, 2022, recommending administration of the vaccine intradermally (0.1 mL per dose) for persons aged ≥18 years who are recommended to receive it (6); intradermal administration can generate an equivalent immune response to that achieved through subcutaneous injection using approximately one fifth the subcutaneous dose (7). CDC analyzed JYNNEOS vaccine administration data submitted to CDC from jurisdictional immunization information systems (IIS)† to assess the impact of the EUA and to estimate vaccination coverage among the population at risk for mpox. During May 22, 2022-January 31, 2023, a total of 1,189,651 JYNNEOS doses (734,510 first doses and 452,884 second doses)§ were administered. Through the week of August 20, 2022, the predominant route of administration was subcutaneous, after which intradermal administration became predominant, in accordance with FDA guidance. As of January 31, 2023, 1-dose and 2-dose (full vaccination) coverage among persons at risk for mpox is estimated to have reached 36.7% and 22.7%, respectively. Despite a steady decline in mpox cases from a 7-day daily average of more than 400 cases on August 1, 2022, to five cases on January 31, 2023, vaccination for persons at risk for mpox continues to be recommended (1). Targeted outreach and continued access to and availability of mpox vaccines to persons at risk are important to help prevent and minimize the impact of a resurgence of mpox.

Neurologic Manifestations of Common Variable Immunodeficiency: Impact on Quality of Life.

BACKGROUND AND OBJECTIVES: Common variable immunodeficiency is a systemic disease and not solely a disease of humoral immunity. Neurologic symptoms associated with common variable immunodeficiency are underrecognized and warrant further study. This work aimed to characterize the neurologic symptoms reported by people living with common variable immunodeficiency. METHODS: We conducted a single academic medical center study of neurologic symptoms reported by adults previously diagnosed with common variable immunodeficiency. We used a survey of common neurologic symptoms to determine the prevalence of these symptoms in a population with common variable immunodeficiency and further assessed these patient-reported symptoms with validated questionnaires and compared symptom burden with other neurologic conditions. RESULTS: A volunteer sample of adults (aged 18 years or older) previously diagnosed with common variable immunodeficiency at the University of Utah Clinical Immunology/Immune Deficiency Clinic who were able to read and comprehend English and willing and able to answer survey-based questions were recruited. Of 148 eligible participants identified, 80 responded and 78 completed the surveys. The mean age of respondents was 51.3 years (range 20-78 years); 73.1% female and 94.8% White. Patients with common variable immunodeficiency reported many common neurologic symptoms (mean 14.6, SD 5.9, range 1-25), with sleep issues, fatigue, and headache reported by more than 85%. Validated questionnaires addressing specific neurologic symptoms supported these results. T-scores on Neuro QoL questionnaires for sleep (mean 56.4, SD 10.4) and fatigue (mean 54.1, SD 11) were higher, indicating more dysfunction, than in the reference clinical population (p < 0.005). The Neuro QoL questionnaire for cognitive function showed a lower T-score (mean 44.8, SD 11.1) than that in the reference general population (p < 0.005), indicating worse function in this domain. DISCUSSION: Among survey respondents, there is a marked burden of neurologic symptoms. Given the impact of neurologic symptoms on health-related quality-of-life measures, clinicians should screen patients with common variable immunodeficiency for the presence of these symptoms and offer referral to neurologists and/or symptomatic treatment when indicated. Frequently prescribed neurologic medications may also affect the immune system, and neurologists should consider screening patients for immune deficiency before prescribing them.

Relative Effectiveness of Coronavirus Disease 2019 Vaccination and Booster Dose Combinations Among 18.9 Million Vaccinated Adults During the Early Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Period-United States, 1 January 2022 to 31 March 2022.

BACKGROUND: Small sample sizes have limited prior studies' ability to capture severe COVID-19 outcomes, especially among Ad26.COV2.S vaccine recipients. This study of 18.9 million adults aged ≥18 years assessed relative vaccine effectiveness (rVE) in three recipient cohorts: (1) primary Ad26.COV2.S vaccine and Ad26.COV2.S booster (2 Ad26.COV2.S), (2) primary Ad26.COV2.S vaccine and mRNA booster (Ad26.COV2.S+mRNA), (3) two doses of primary mRNA vaccine and mRNA booster (3 mRNA). METHODS: We analyzed two de-identified datasets linked using privacy-preserving record linkage (PPRL): insurance claims and retail pharmacy COVID-19 vaccination data. We assessed the presence of COVID-19 diagnosis during January 1-March 31, 2022 in: (1) any claim, (2) outpatient claim, (3) emergency department (ED) claim, (4) inpatient claim, and (5) inpatient claim with intensive care unit (ICU) admission. rVE for each outcome comparing three recipient cohorts (reference: two Ad26.COV2.S doses) was estimated from adjusted Cox proportional hazards models. RESULTS: Compared with two Ad26.COV2.S doses, Ad26.COV2.S+mRNA and three mRNA doses were more effective against all COVID-19 outcomes, including 57% (95% CI: 52-62) and 62% (95% CI: 58-65) rVE against an ED visit; 44% (95% CI: 34-52) and 54% (95% CI: 48-59) rVE against hospitalization; and 48% (95% CI: 22-66) and 66% (95% CI: 53-75) rVE against ICU admission, respectively. CONCLUSIONS: This study demonstrated that Ad26.COV2.S + mRNA doses were as good as three doses of mRNA, and better than two doses of Ad26.COV2.S. Vaccination continues to be an important preventive measure for reducing the public health impact of COVID-19.