Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, and Death: United States, 2022-2023.

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients. RESULTS: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. CONCLUSIONS: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.

Provision of cervical cancer services for women living with HIV, Uganda.

Objective: To describe the scale-up of cervical cancer screening and treatment for women living with human immunodeficiency virus (HIV), aged 25-49 years in Uganda, and to analyse the programme data. Methods: The health ministry targeted existing HIV clinics in a 2-year scale-up of cervical cancer screening services from October 2020. In preparation, we trained health workers to assess women attending HIV clinics for screening eligibility, provided either by human papillomavirus (HPV) testing and/or visual inspection with acetic acid. Clinic staff treated women with precancerous cervical lesions with thermocoagulation or referred women with suspected cancer to external services. We analysed data reported every 6 months for the number of clinics offering screening, screening uptake, the number of positive diagnoses and the number of women who received treatment. Findings: The number of HIV clinics offering cervical cancer screening services increased from 11, before the programme launch, to 1571. During the programme, screening uptake increased from 5.0% (6506/130 293) to 107.3% (151 872/141 527) of targets. The cumulative proportion of positive diagnoses was 5.9% (23 970/407 323) overall, but was much lower for screening offering visual inspection only compared with clinics offering HPV testing. Although the proportion of women receiving treatment if positive increased from 12.8% (53/413) to 84.3% (8087/9592), the World Health Organization target of 90% was not reached. Conclusion: We demonstrated marked increases, potentially replicable by other countries, in screening and treatment. These increases could be improved further by expanding HPV testing and same-day treatment of precancerous lesions.

Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalization Among Immunocompetent Adults Aged ≥18 Years - VISION and IVY Networks, September 2023-January 2024.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.

Interim Estimates of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 U.S. States, February 2022-May 2023.

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.

Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period - IVY Network, 19 U.S. States, February 1, 2022-January 31, 2023.

As of April 2023, the COVID-19 pandemic has resulted in 1.1 million deaths in the United States, with approximately 75% of deaths occurring among adults aged ≥65 years (1). Data on the durability of protection provided by monovalent mRNA COVID-19 vaccination against critical outcomes of COVID-19 are limited beyond the Omicron BA.1 lineage period (December 26, 2021-March 26, 2022). In this case-control analysis, the effectiveness of 2-4 monovalent mRNA COVID-19 vaccine doses was evaluated against COVID-19-associated invasive mechanical ventilation (IMV) and in-hospital death among immunocompetent adults aged ≥18 years during February 1, 2022-January 31, 2023. Vaccine effectiveness (VE) against IMV and in-hospital death was 62% among adults aged ≥18 years and 69% among those aged ≥65 years. When stratified by time since last dose, VE was 76% at 7-179 days, 54% at 180-364 days, and 56% at ≥365 days. Monovalent mRNA COVID-19 vaccination provided substantial, durable protection against IMV and in-hospital death among adults during the Omicron variant period. All adults should remain up to date with recommended COVID-19 vaccination to prevent critical COVID-19-associated outcomes.

Multisystem Inflammatory Syndrome in Adults After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Coronavirus Disease 2019 (COVID-19) Vaccination.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the coronavirus disease 2019 (COVID-19) pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. METHODS: Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. RESULTS: From 14 December 2020 to 30 April 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21-66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11-78 days) before MIS-A onset. All 20 patients had laboratory evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6-45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. CONCLUSIONS: Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring.

Multisystem Inflammatory Syndrome in Adults: Case Finding Through Systematic Review of Electronic Medical Records.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a severe condition temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: In this retrospective cohort study, we applied the US Centers for Disease Control and Prevention (CDC) case definition to identify diagnosed and undiagnosed MIS-A cases among adults discharged during April 2020-January 2021 from 4 Atlanta, Georgia hospitals affiliated with a single medical center. Non-MIS-A coronavirus disease 2019 (COVID-19) hospitalizations were identified using International Classification of Diseases, Tenth Revision, Clinical Modification encounter code U07.1. We calculated the ratio of MIS-A to COVID-19 hospitalizations, compared demographic characteristics of the 2 cohorts, and described clinical characteristics of MIS-A patients. RESULTS: We identified 11 MIS-A cases, none of which were diagnosed by the treatment team, and 5755 COVID-19 hospitalizations (ratio 1:523). Compared with patients with COVID-19, patients with MIS-A were more likely to be younger than 50 years (72.7% vs 26.1%, P < .01) and to be non-Hispanic Black (81.8% vs 50.0%, P = .04). Ten patients with MIS-A (90.9%) had at least 1 underlying medical condition. Two MIS-A patients (18.2%) had a previous episode of laboratory-confirmed COVID-19, occurring 37 and 55 days prior to admission. All MIS-A patients developed left ventricular systolic dysfunction. None had documented mucocutaneous involvement. All required intensive care, all received systemic corticosteroids, 8 (72.7%) required mechanical ventilation, 2 (18.2%) required mechanical cardiovascular circulatory support, and none received intravenous immunoglobulin. Two (18.2%) died or were discharged to hospice. CONCLUSIONS: MIS-A is a severe but likely underrecognized complication of SARS-CoV-2 infection. Improved recognition of MIS-A is needed to quantify its burden and identify populations at highest risk.

COVID-19 Vaccine Provider Availability and Vaccination Coverage Among Children Aged 5-11 Years - United States, November 1, 2021-April 25, 2022.

COVID-19 can lead to severe outcomes in children, including multisystem inflammatory syndrome, hospitalization, and death (1,2). On November 2, 2021, the Advisory Committee on Immunization Practices issued an interim recommendation for use of the BNT162b2 (Pfizer-BioNTech) vaccine in children aged 5-11 years for the prevention of COVID-19; however, vaccination coverage in this age group remains low (3). As of June 7, 2022, 36.0% of children aged 5-11 years in the United States had received ≥1 of COVID-19 vaccine (3). Among factors that might influence vaccination coverage is the availability of vaccine providers (4). To better understand how provider availability has affected COVID-19 vaccination coverage among children aged 5-11 years, CDC analyzed data on active COVID-19 vaccine providers and county-level vaccine administration data during November 1, 2021-April 25, 2022. Among 2,586 U.S. counties included in the analysis, 87.5% had at least one active COVID-19 vaccine provider serving children aged 5-11 years. Among the five assessed active provider types, most counties had at least one pharmacy (69.1%) or public health clinic (61.3%), whereas fewer counties had at least one pediatric clinic (29.7%), family medicine clinic (29.0%), or federally qualified health center (FQHC)* (22.8%). Median county-level vaccination coverage was 14.5% (IQR = 8.9%-23.6%). After adjusting for social vulnerability index (SVI)† and urbanicity, the analysis found that vaccination coverage among children aged 5-11 years was higher in counties with at least one active COVID-19 vaccine provider than in counties with no active providers (adjusted rate ratio [aRR] = 1.66). For each provider type, presence of at least one provider in the county was associated with higher coverage; the largest difference in vaccination coverage was observed between counties with and without pediatric clinics (aRR = 1.37). Ensuring broad access to COVID-19 vaccines, in addition to other strategies to address vaccination barriers, could help increase vaccination coverage among children aged 5-11 years.

Effectiveness of Monovalent mRNA Vaccines Against COVID-19-Associated Hospitalization Among Immunocompetent Adults During BA.1/BA.2 and BA.4/BA.5 Predominant Periods of SARS-CoV-2 Omicron Variant in the United States - IVY Network, 18 States, December 26, 2021-August 31, 2022.

The SARS-CoV-2 Omicron variant (B.1.1.529 or BA.1) became predominant in the United States by late December 2021 (1). BA.1 has since been replaced by emerging lineages BA.2 (including BA.2.12.1) in March 2022, followed by BA.4 and BA.5, which have accounted for a majority of SARS-CoV-2 infections since late June 2022 (1). Data on the effectiveness of monovalent mRNA COVID-19 vaccines against BA.4/BA.5-associated hospitalizations are limited, and their interpretation is complicated by waning of vaccine-induced immunity (2-5). Further, infections with earlier Omicron lineages, including BA.1 and BA.2, reduce vaccine effectiveness (VE) estimates because certain persons in the referent unvaccinated group have protection from infection-induced immunity. The IVY Network† assessed effectiveness of 2, 3, and 4 doses of monovalent mRNA vaccines compared with no vaccination against COVID-19-associated hospitalization among immunocompetent adults aged ≥18 years during December 26, 2021-August 31, 2022. During the BA.1/BA.2 period, VE 14-150 days after a second dose was 63% and decreased to 34% after 150 days. Similarly, VE 7-120 days after a third dose was 79% and decreased to 41% after 120 days. VE 7-120 days after a fourth dose was 61%. During the BA.4/BA.5 period, similar trends were observed, although CIs for VE estimates between categories of time since the last dose overlapped. VE 14-150 days and >150 days after a second dose was 83% and 37%, respectively. VE 7-120 days and >120 days after a third dose was 60%and 29%, respectively. VE 7-120 days after the fourth dose was 61%. Protection against COVID-19-associated hospitalization waned even after a third dose. The newly authorized bivalent COVID-19 vaccines include mRNA from the ancestral SARS-CoV-2 strain and from shared mRNA components between BA.4 and BA.5 lineages and are expected to be more immunogenic against BA.4/BA.5 than monovalent mRNA COVID-19 vaccines (6-8). All eligible adults aged ≥18 years§ should receive a booster dose, which currently consists of a bivalent mRNA vaccine, to maximize protection against BA.4/BA.5 and prevent COVID-19-associated hospitalization.

Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Hospitalization Among Immunocompetent Adults Aged ≥65 Years - IVY Network, 18 States, September 8-November 30, 2022.

Monovalent COVID-19 mRNA vaccines, designed against the ancestral strain of SARS-CoV-2, successfully reduced COVID-19-related morbidity and mortality in the United States and globally (1,2). However, vaccine effectiveness (VE) against COVID-19-associated hospitalization has declined over time, likely related to a combination of factors, including waning immunity and, with the emergence of the Omicron variant and its sublineages, immune evasion (3). To address these factors, on September 1, 2022, the Advisory Committee on Immunization Practices recommended a bivalent COVID-19 mRNA booster (bivalent booster) dose, developed against the spike protein from ancestral SARS-CoV-2 and Omicron BA.4/BA.5 sublineages, for persons who had completed at least a primary COVID-19 vaccination series (with or without monovalent booster doses) ≥2 months earlier (4). Data on the effectiveness of a bivalent booster dose against COVID-19 hospitalization in the United States are lacking, including among older adults, who are at highest risk for severe COVID-19-associated illness. During September 8-November 30, 2022, the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network§ assessed effectiveness of a bivalent booster dose received after ≥2 doses of monovalent mRNA vaccine against COVID-19-associated hospitalization among immunocompetent adults aged ≥65 years. When compared with unvaccinated persons, VE of a bivalent booster dose received ≥7 days before illness onset (median = 29 days) against COVID-19-associated hospitalization was 84%. Compared with persons who received ≥2 monovalent-only mRNA vaccine doses, relative VE of a bivalent booster dose was 73%. These early findings show that a bivalent booster dose provided strong protection against COVID-19-associated hospitalization in older adults and additional protection among persons with previous monovalent-only mRNA vaccination. All eligible persons, especially adults aged ≥65 years, should receive a bivalent booster dose to maximize protection against COVID-19 hospitalization this winter season. Additional strategies to prevent respiratory illness, such as masking in indoor public spaces, should also be considered, especially in areas where COVID-19 community levels are high (4,5).

Identification and description of patients with multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection using the Premier Healthcare Database.

Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory illness related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The characteristics of patients with this syndrome and the frequency with which it occurs among patients hospitalised after SARS-CoV-2 infection are unclear. Using the Centers for Disease Control and Prevention case definition for MIS-A, we created ICD-10-CM code and laboratory criteria to identify potential MIS-A patients in the Premier Healthcare Database Special COVID-19 Release, a database containing patient-level information on hospital discharges across the United States. Modified MIS-A criteria were applied to hospitalisations with discharge from March to December 2020. The proportion of hospitalisations meeting electronic health record criteria for MIS-A and descriptive statistics for patients in the potential MIS-A cohort were calculated. Of 34 515 SARS-CoV-2-related hospitalisations with complete clinical and laboratory data, 53 met modified criteria for MIS-A (0.15%). The median age was 62 years (IQR 52-74). Most patients met the severe cardiac illness criterion through either myocarditis (66.0%) or new-onset heart failure (35.8%). A total of 79.2% of patients required ICU admission, while 43.4% of patients in the cohort died. MIS-A appears to be a rare but severe outcome of SARS-CoV-2 infection. Additional studies are needed to investigate how this syndrome differs from severe coronavirus disease 2019 (COVID-19) in adults.

Race, Ethnicity, and Age Trends in Persons Who Died from COVID-19 - United States, May-August 2020.

During February 12-October 15, 2020, the coronavirus disease 2019 (COVID-19) pandemic resulted in approximately 7,900,000 aggregated reported cases and approximately 216,000 deaths in the United States.* Among COVID-19-associated deaths reported to national case surveillance during February 12-May 18, persons aged ≥65 years and members of racial and ethnic minority groups were disproportionately represented (1). This report describes demographic and geographic trends in COVID-19-associated deaths reported to the National Vital Statistics System† (NVSS) during May 1-August 31, 2020, by 50 states and the District of Columbia. During this period, 114,411 COVID-19-associated deaths were reported. Overall, 78.2% of decedents were aged ≥65 years, and 53.3% were male; 51.3% were non-Hispanic White (White), 24.2% were Hispanic or Latino (Hispanic), and 18.7% were non-Hispanic Black (Black). The number of COVID-19-associated deaths decreased from 37,940 in May to 17,718 in June; subsequently, counts increased to 30,401 in July and declined to 28,352 in August. From May to August, the percentage distribution of COVID-19-associated deaths by U.S. Census region increased from 23.4% to 62.7% in the South and from 10.6% to 21.4% in the West. Over the same period, the percentage distribution of decedents who were Hispanic increased from 16.3% to 26.4%. COVID-19 remains a major public health threat regardless of age or race and ethnicity. Deaths continued to occur disproportionately among older persons and certain racial and ethnic minorities, particularly among Hispanic persons. These results can inform public health messaging and mitigation efforts focused on prevention and early detection of infection among disproportionately affected groups.

Factors associated with HIV stigma and the impact of a nonrandomized multi-component video aimed at reducing HIV stigma among a high-risk population in New York City.

We examined characteristics associated with HIV stigma and evaluated a multi-component video designed to normalize HIV and reduce HIV stigma. Three pharmacies located in heavy, drug-active neighborhoods in New York City and registered to sell nonprescription syringes were trained to recruit their nonprescription syringe customers who inject drugs and their under/uninsured customers. Syringe customer participants were trained to recruit up to three of their peers. As part of a larger intervention to increase HIV testing, participants in two of three study arms viewed the "Health Screenings for Life" video and were administered pre/post-video surveys capturing HIV stigma. Participants in the nonvideo arm were administered one assessment of HIV stigma. Log-binomial regression with generalized estimating equations to account for clustering of peer networks was used to: (1) determine factors associated with HIV stigma and (2) determine differences in HIV stigma by study arm. A total of 716 participants were recruited. Factor analyses showed HIV stigma measures loading on two factors: HIV blame and HIV shame. After adjustment, HIV blame was positively associated with younger age (PR: 1.24; 95% CI: 1.07-1.43) and inversely associated with educational attainment (PR: 0.66; 95% CI: 0.58-0.76) and employment (PR: 0.76; 95% CI: 0.60-0.96). HIV shame was inversely associated with educational attainment (PR: 0.75; 95% CI: 0.62-0.92), HIV-positive status (PR: 0.60; 95% CI: 0.39-0.92), and injecting drugs (PR: 0.72; 95% CI: 0.54-0.94) and was positively associated with multiple sex partnerships (PR: 1.24; 95% CI: 1.01-1.52). Those who viewed the video were also less likely to report HIV blame and HIV shame, post-video, compared to those in the nonvideo arm. These data provide evidence of an association between HIV stigma and lower socioeconomic status groups, and between HIV stigma and HIV sexual risk. These data also provide evidence that a multi-component video aimed at normalizing HIV may assist in reducing HIV stigma in heavy, drug-active neighborhoods.

Antigenic Characterization of Circulating and Emerging SARS-CoV-2 Variants in the U.S. throughout the Delta to Omicron Waves.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

Comparison of mRNA vaccine effectiveness against COVID-19-associated hospitalization by vaccination source: Immunization information systems, electronic medical records, and self-report-IVY Network, February 1-August 31, 2022.

BACKGROUND: Accurate determination of COVID-19 vaccination status is necessary to produce reliable COVID-19 vaccine effectiveness (VE) estimates. Data comparing differences in COVID-19 VE by vaccination sources (i.e., immunization information systems [IIS], electronic medical records [EMR], and self-report) are limited. We compared the number of mRNA COVID-19 vaccine doses identified by each of these sources to assess agreement as well as differences in VE estimates using vaccination data from each individual source and vaccination data adjudicated from all sources combined. METHODS: Adults aged ≥18 years who were hospitalized with COVID-like illness at 21 hospitals in 18 U.S. states participating in the IVY Network during February 1-August 31, 2022, were enrolled. Numbers of COVID-19 vaccine doses identified by IIS, EMR, and self-report were compared in kappa agreement analyses. Effectiveness of mRNA COVID-19 vaccines against COVID-19-associated hospitalization was estimated using multivariable logistic regression models to compare the odds of COVID-19 vaccination between SARS-CoV-2-positive case-patients and SARS-CoV-2-negative control-patients. VE was estimated using each source of vaccination data separately and all sources combined. RESULTS: A total of 4499 patients were included. Patients with ≥1 mRNA COVID-19 vaccine dose were identified most frequently by self-report (n = 3570, 79 %), followed by IIS (n = 3272, 73 %) and EMR (n = 3057, 68 %). Agreement was highest between IIS and self-report for 4 doses with a kappa of 0.77 (95 % CI = 0.73-0.81). VE point estimates of 3 doses against COVID-19 hospitalization were substantially lower when using vaccination data from EMR only (VE = 31 %, 95 % CI = 16 %-43 %) than when using all sources combined (VE = 53 %, 95 % CI = 41 %-62%). CONCLUSION: Vaccination data from EMR only may substantially underestimate COVID-19 VE.

Clinical Characteristics of Multisystem Inflammatory Syndrome in Adults: A Systematic Review.

IMPORTANCE: Multisystem inflammatory syndrome in adults (MIS-A) has not been well described. Improved diagnosis and treatment of MIS-A might mitigate COVID-19 morbidity and mortality. OBJECTIVE: To summarize the descriptive epidemiology and clinical characteristics of MIS-A. EVIDENCE REVIEW: This systematic review identified patients with MIS-A using 3 strategies: (1) literature review from May 1, 2020, to May 25, 2021, by searching MEDLINE, Embase, Global Health, CAB Abstracts, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Academic Search Complete, Scopus, World Health Organization Global COVID-19 Literature Database, and Google Scholar; (2) voluntary reports of MIS-A to the Centers for Disease Control and Prevention (CDC); and (3) reports among persons aged 18 to 20 years in the CDC surveillance system for MIS in children. FINDINGS: Of 221 patients with MIS-A, the median age was 21 (interquartile range [IQR], 19-34) years, and 154 of 219 (70%) with data available were men. Sixty of 169 patients (36%) were non-Hispanic Black individuals, and 122 of 209 (58%) had no underlying comorbidity. One hundred two of 149 patients (68%) noted a previous symptomatic COVID-19-like illness (median, 28 [IQR, 20-36] days previously). Most patients with MIS-A presented with fever (197 of 205 [96%]), hypotension (133 of 220 [60%]), cardiac dysfunction (114 of 210 [54%]), shortness of breath (102 of 198 [52%]), and/or diarrhea (102 of 197 [52%]). The median number of organ systems involved was 5 (IQR, 4-6). Median hospital stay was 8 (IQR, 5-12) days; 115 of 201 patients (57%) were admitted to the intensive care unit; 101 of 213 (47%) required respiratory support, and 15 of 220 (7%) died. Most patients (176 of 195 [90%]) had elevated markers of coagulopathy and/or inflammation and a positive SARS-CoV-2 serologic finding (139 of 194 [72%]). Ten patients with MIS-A presented with Kawasaki disease. CONCLUSIONS AND RELEVANCE: These findings suggest that MIS-A is a serious hyperinflammatory condition that presents approximately 4 weeks after onset of acute COVID-19 with extrapulmonary multiorgan dysfunction.

COVID-19 Case Surveillance: Trends in Person-Level Case Data Completeness, United States, April 5-September 30, 2020.

OBJECTIVES: To obtain timely and detailed data on COVID-19 cases in the United States, the Centers for Disease Control and Prevention (CDC) uses 2 data sources: (1) aggregate counts for daily situational awareness and (2) person-level data for each case (case surveillance). The objective of this study was to describe the sensitivity of case ascertainment and the completeness of person-level data received by CDC through national COVID-19 case surveillance. METHODS: We compared case and death counts from case surveillance data with aggregate counts received by CDC during April 5-September 30, 2020. We analyzed case surveillance data to describe geographic and temporal trends in data completeness for selected variables, including demographic characteristics, underlying medical conditions, and outcomes. RESULTS: As of November 18, 2020, national COVID-19 case surveillance data received by CDC during April 5-September 30, 2020, included 4 990 629 cases and 141 935 deaths, representing 72.7% of the volume of cases (n = 6 863 251) and 71.8% of the volume of deaths (n = 197 756) in aggregate counts. Nationally, completeness in case surveillance records was highest for age (99.9%) and sex (98.8%). Data on race/ethnicity were complete for 56.9% of cases; completeness varied by region. Data completeness for each underlying medical condition assessed was <25% and generally declined during the study period. About half of case records had complete data on hospitalization and death status. CONCLUSIONS: Incompleteness in national COVID-19 case surveillance data might limit their usefulness. Streamlining and automating surveillance processes would decrease reporting burdens on jurisdictions and likely improve completeness of national COVID-19 case surveillance data.

The association between neighborhood socioeconomic disadvantage and high-risk injection behavior among people who inject drugs.

BACKGROUND: Although much research has been conducted on the determinants of HIV risk behavior among people who inject drugs (PWID), the influence of the neighborhood context on high-risk injection behavior remains understudied. To address this gap in the literature, we measured associations between neighborhood socioeconomic disadvantage and high-risk injection behavior, and determined whether these associations were modified by drug-related police activity and syringe exchange program (SEP) accessibility. METHODS: Our sample was comprised of 484 pharmacy-recruited PWID in New York City. Measures of neighborhood socioeconomic disadvantage were created using data from the 2006-2010 American Community Survey. Associations with high-risk injection behavior were estimated using multivariable Poisson regression. Effect modification by drug-related police activity and SEP accessibility was assessed by entering cross-product terms into adjusted models of high-risk injection behavior. RESULTS: Neighborhood socioeconomic disadvantage was associated with decreased receptive syringe sharing and unsterile syringe use. In neighborhoods with high drug-related police activity, associations between neighborhood disadvantage and unsterile syringe use were attenuated to the null. In neighborhoods with high SEP accessibility, neighborhood disadvantage was associated with decreased acquisition of syringes from an unsafe source. CONCLUSIONS: PWID in disadvantaged neighborhoods reported safer injection behaviors than their counterparts in neighborhoods that were relatively better off. The contrasting patterns of effect modification by SEP accessibility and drug-related police activity support the use of harm reduction approaches over law enforcement-based strategies for the control of blood borne virus transmission among PWID in disadvantaged urban areas.