Notes from the Field: Mpox Cluster Caused by Tecovirimat-Resistant Monkeypox Virus - Five States, October 2023-February 2024.

The antiviral drug tecovirimat* has been used extensively to treat U.S. mpox cases since the start of a global outbreak in 2022. Mutations in the mpox viral protein target (F13 or VP37) that occur during treatment can result in resistance to tecovirimat† (1,2). CDC and public health partners have conducted genetic surveillance of monkeypox virus (MPXV) for F13 mutations through sequencing and monitoring of public databases. MPXV F13 mutations associated with resistance have been reported since 2022, typically among severely immunocompromised mpox patients who required prolonged courses of tecovirimat (3-5). A majority of patients with infections caused by MPXV with resistant mutations had a history of tecovirimat treatment; however, spread of tecovirimat-resistant MPXV was reported in California during late 2022 to early 2023 among persons with no previous tecovirimat treatment (3). This report describes a second, unrelated cluster of tecovirimat-resistant MPXV among 18 persons with no previous history of tecovirimat treatment in multiple states.

Possible Exposures Among Mpox Patients Without Reported Male-to-Male Sexual Contact - Six U.S. Jurisdictions, November 1-December 14, 2022.

The extent to which the 2022 mpox outbreak has affected persons without a recent history of male-to-male sexual contact (MMSC) is not well understood. During November 1-December 14, 2022, CDC partnered with six jurisdictional health departments to characterize possible exposures among mpox patients aged ≥18 years who did not report MMSC during the 3 weeks preceding symptom onset. Among 52 patients included in the analysis, 14 (27%) had a known exposure to a person with mpox, including sexual activity and other close intimate contact (eight) and household contact (six). Among 38 (73%) patients with no known exposure to a person with mpox, self-reported activities before illness onset included sexual activity and other close intimate contact (17; 45%), close face-to-face contact (14; 37%), attending large social gatherings (11; 29%), and being in occupational settings involving close skin-to-skin contact (10; 26%). These findings suggest that sexual activity remains an important route of mpox exposure among patients who do not report MMSC.

Detection of SARS-CoV-2 in Neonatal Autopsy Tissues and Placenta.

Severe coronavirus disease in neonates is rare. We analyzed clinical, laboratory, and autopsy findings from a neonate in the United States who was delivered at 25 weeks of gestation and died 4 days after birth; the mother had asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and preeclampsia. We observed severe diffuse alveolar damage and localized SARS-CoV-2 by immunohistochemistry, in situ hybridization, and electron microscopy of the lungs of the neonate. We localized SARS-CoV-2 RNA in neonatal heart and liver vascular endothelium by using in situ hybridization and detected SARS-CoV-2 RNA in neonatal and placental tissues by using reverse transcription PCR. Subgenomic reverse transcription PCR suggested viral replication in lung/airway, heart, and liver. These findings indicate that in utero SARS-CoV-2 transmission contributed to this neonatal death.

Characteristics of JYNNEOS Vaccine Recipients Before and During a Large Multiday LGBTQIA+ Festival - Louisiana, August 9-September 5, 2022.

Since May 2022, 27,558 monkeypox cases have been identified in the United States (1). Gay, bisexual, and other men who have sex with men (MSM) represent the most affected demographic group in the current multinational outbreak (2). As of October 18, 2022, Louisiana had reported 273 monkeypox cases with 187 (68.5%) among residents of the Louisiana Department of Health (LDH) Southeast Region, which includes the city of New Orleans (3).

COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021.

Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status† indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended§ additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged ≥18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),¶ case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and ≥65 years. Eligible persons should stay up to date with COVID-19 vaccinations.

Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status - 13 U.S. Jurisdictions, April 4-July 17, 2021.

COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies.

Early Season Pediatric Influenza B/Victoria Virus Infections Associated with a Recently Emerged Virus Subclade - Louisiana, 2019.

Multiple genetically distinct influenza B/Victoria lineage viruses have cocirculated in the United States recently, circulating sporadically during the 2018-19 season and more frequently early during the 2019-20 season (1). The beginning of the 2019-20 influenza season in Louisiana was unusually early and intense, with infections primarily caused by influenza B/Victoria lineage viruses. One large pediatric health care facility in New Orleans (facility A) reported 1,268 laboratory-confirmed influenza B virus infections, including 23 hospitalizations from July 31 to November 21, 2019, a time when influenza activity is typically low. During this period, Louisiana also reported one pediatric death associated with influenza B virus infection. An investigation of the influenza B virus infections in Louisiana, including medical and vaccine record abstraction on 198 patients, primarily from facility A, with sporadic cases from other facilities in the state, found that none of the patients had received 2019-20 seasonal influenza vaccine, in part because influenza activity began before influenza vaccination typically occurs. Among 83 influenza B viruses sequenced from 198 patients in Louisiana, 81 (98%) belonged to the recently emerged B/Victoria V1A.3 genetic subclade. Nationally, to date, B/Victoria viruses are the most commonly reported influenza viruses among persons aged <25 years (2). Of the 198 patients in the investigation, 95% were aged <18 years. Although most illnesses were uncomplicated, the number of hospitalizations, clinical complications, and the reported pediatric death in Louisiana serve as a reminder that, even though influenza B viruses are less common than influenza A viruses in most seasons, influenza B virus infection can be severe in children. All persons aged ≥6 months should receive an annual influenza vaccination if they have not already received it (3). Antiviral treatment of influenza is recommended as soon as possible for all hospitalized patients and for outpatients at high risk for influenza complications (including children aged <2 years and persons with underlying medical conditions) (4).

Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection - United Kingdom and United States, March-August 2020.

During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe and the United States (1-3). Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (1). Since June 2020, several case reports have described a similar syndrome in adults; this review describes in detail nine patients reported to CDC, seven from published case reports, and summarizes the findings in 11 patients described in three case series in peer-reviewed journals (4-6). These 27 patients had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and concurrently received positive test results for SARS-CoV-2, the virus that causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating recent infection. Reports of these patients highlight the recognition of an illness referred to here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults. Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2 infections, interventions that prevent COVID-19 might prevent MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this newly described condition.

SARS-CoV-2-Associated Deaths Among Persons Aged <21 Years - United States, February 12-July 31, 2020.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED).† These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers.

Characteristics of Persons Who Died with COVID-19 - United States, February 12-May 18, 2020.

During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City).

Severe Respiratory Illness Outbreak Associated with Human Coronavirus NL63 in a Long-Term Care Facility.

We describe an outbreak of severe respiratory illness associated with human coronavirus NL63 in a long-term care facility in Louisiana in November 2017. Six of 20 case-patients were hospitalized with pneumonia, and 3 of 20 died. Clinicians should consider human coronavirus NL63 for patients in similar settings with respiratory disease.

Oseltamivir-resistant influenza A(H1N1)pdm09 viruses, United States, 2013-14.

We report characteristics of oseltamivir-resistant influenza A(H1N1)pdm09 viruses and patients infected with these viruses in the United States. During 2013-14, fifty-nine (1.2%) of 4,968 analyzed US influenza A(H1N1)pdm09 viruses had the H275Y oseltamivir resistance-conferring neuraminidase substitution. Our results emphasize the need for local surveillance for neuraminidase inhibitor susceptibility among circulating influenza viruses.

Intensity of Influenza-Like Illness (ILI) and Congestive Heart Failure (CHF) Deaths: A Correlation Study in Louisiana, 2000-2012.

Influenza infection has been linked to significant morbidity and mortality, especially in vulnerable populations including the elderly and those with chronic disease, such as congestive heart failure (CHF). This correlation analysis used influenza surveillance data and vital statistics mortality data to assess the correlation between influenza-like illness (ILI) and CHF deaths in Louisiana from 2000-2012 on a weekly level and at the seasonal level. The correlation between ILI proportion and mean number of deaths for the entire study period was 0.23. The comparisons made at the seasonal level showed some association between season's intensity and CHF mortality. The clinical implication of this study is that ILI surveillance can be used to issue alert to clinicians who treat CHF patient in order to stress measures aimed at preventing deaths from CHF.

Severe Acute Respiratory Illness (SARI) Surveillance in Louisiana, 2013-2014.

The objectives of this article are to describe the severe acute respiratory illness (SARI) surveillance implemented in Louisiana during the 2013-2014 influenza season, present the epidemiology of reported SARI cases, and identify ways to improve this system by incorporating formal SARI surveillance into the influenza surveillance program. Of the 212 SARI cases, 181 (85%) had at least one underlying medical condition, 54 (25.7%) had two conditions, 43 (20.3%) had three conditions, and 25 (11.8%) reported four or more. The most common four underlying conditions were: obesity (43.4%), chronic cardiac conditions (39.6%), diabetes (29.7%), and chronic pulmonary conditions (26.9%). While obesity was the most reported underlying condition, it was three times more likely to be reported in less than 65 years old rather than those >65. Continuation of SARI data collection in future seasons will allow comparisons regarding severity, populations affected, and identify risk factors most commonly associated with severe illness. Reporting of SARI cases also increased influenza-associated adult mortality reporting to the Office of Public Health's Office of Infectious Diseases Epidemiology (ID Epi). Though all influenza-associated mortality is reportable in Louisiana, adult mortality was reported rarely prior to the 2013-2014 season.

Outbreak of Francisella novicida bacteremia among inmates at a louisiana correctional facility.

BACKGROUND: Francisella novicida is a rare cause of human illness despite its close genetic relationship to Francisella tularensis, the agent of tularemia. During April-July 2011, 3 inmates at a Louisiana correctional facility developed F. novicida bacteremia; 1 inmate died acutely. METHODS: We interviewed surviving inmates; reviewed laboratory, medical, and housing records; and conducted an environmental investigation. Clinical and environmental samples were tested by culture, real-time polymerase chain reaction (PCR), and multigene sequencing. Isolates were typed by pulsed-field gel electrophoresis (PFGE). RESULTS: Clinical isolates were identified as F. novicida based on sequence analyses of the 16S ribosomal RNA, pgm, and pdpD genes. PmeI PFGE patterns for the clinical isolates were indistinguishable. Source patients were aged 40-56 years, male, and African American, and all were immunocompromised. Two patients presented with signs of bacterial peritonitis; the third had pyomyositis of the thigh. The 3 inmates had no contact with one another; their only shared exposures were consumption of municipal water and of ice that was mass-produced at the prison in an unenclosed building. Swabs from one set of ice machines and associated ice scoops yielded evidence of F. novicida by PCR and sequencing. All other environmental specimens tested negative. CONCLUSIONS: To our knowledge, this is the first reported common-source outbreak of F. novicida infections in humans. Epidemiological and laboratory evidence implicate contaminated ice as the likely vehicle of transmission; liver disease may be a predisposing factor. Clinicians, laboratorians, and public health officials should be aware of the potential for misidentification of F. novicida as F. tularensis.

In-field detection and characterization of B/Victoria lineage deletion variant viruses causing early influenza activity and an outbreak in Louisiana, 2019.

Background: In 2019, the Louisiana Department of Health reported an early influenza B/Victoria (B/VIC) virus outbreak. Method: As it was an atypically large outbreak, we deployed to Louisiana to investigate it using genomics and a triplex real-time RT-PCR assay to detect three antigenically distinct B/VIC lineage variant viruses. Results: The investigation indicated that B/VIC V1A.3 subclade, containing a three amino acid deletion in the hemagglutinin and known to be antigenically distinct to the B/Colorado/06/2017 vaccine virus, was the most prevalent circulating virus within the specimens evaluated (86/88 in real-time RT-PCR). Conclusion: This work underscores the value of portable platforms for rapid, onsite pathogen characterization.

Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic.

Importance: Multiple inflammatory syndrome in children (MIS-C) occurs in association with the COVID-19 pandemic. Objective: To describe the clinical characteristics and geographic and temporal distribution of the largest cohort of patients with MIS-C in the United States to date. Design, Setting, and Participants: Cross-sectional analysis was conducted on clinical and laboratory data collected from patients with MIS-C. The analysis included patients with illness onset from March 2020 to January 2021 and met MIS-C case definition. Main Outcomes and Measures: Geographic and temporal distribution of MIS-C was compared with that of COVID-19 nationally, by region, and level of urbanicity by county. Clinical and laboratory findings and changes over time were described by age group and by presence or absence of preceding COVID-19. Results: A total of 1733 patients with MIS-C were identified; 994 (57.6%) were male and 1117 (71.3%) were Hispanic or non-Hispanic Black. Gastrointestinal symptoms, rash, and conjunctival hyperemia were reported by 53% (n = 931) to 67% (n = 1153) of patients. A total of 937 patients (54%) had hypotension or shock, and 1009 (58.2%) were admitted for intensive care. Cardiac dysfunction was reported in 484 patients (31.0%), pericardial effusion in 365 (23.4%), myocarditis in 300 (17.3%), and coronary artery dilatation or aneurysms in 258 (16.5%). Patients aged 0 to 4 years had the lowest proportion of severe manifestations, although 171 patients (38.4%) had hypotension or shock and 197 (44.3%) were admitted for intensive care. Patients aged 18 to 20 years had the highest proportions with myocarditis (17 [30.9%]), pneumonia (20 [36.4%]), acute respiratory distress syndrome (10 [18.2%]), and polymerase chain reaction positivity (39 [70.9%]). These older adolescents also had the highest proportion reporting preceding COVID-19-like illness (63%). Nationally, the first 2 MIS-C peaks followed the COVID-19 peaks by 2 to 5 weeks. The cumulative MIS-C incidence per 100 000 persons younger than 21 years was 2.1 and varied from 0.2 to 6.3 by state. Twenty-four patients (1.4%) died. Conclusions and Relevance: In this cross-sectional study of a large cohort of patients with MIS-C, 2 peaks that followed COVID-19 peaks by 2 to 5 weeks were identified. The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection. The clinical manifestations varied by age and by presence or absence of preceding COVID-19.

Media Reports as a Tool for Timely Monitoring of COVID-19-Related Deaths Among First Responders-United States, April 2020.

We aimed to describe coronavirus disease 2019 (COVID-19) deaths among first responders early in the COVID-19 pandemic. We used media reports to gather timely information about COVID-19-related deaths among first responders during March 30-April 30, 2020, and evaluated the sensitivity of media scanning compared with traditional surveillance. We abstracted information about demographic characteristics, occupation, underlying conditions, and exposure source. Twelve of 19 US public health jurisdictions with data on reported deaths provided verification, and 7 jurisdictions reported whether additional deaths had occurred; we calculated the sensitivity of media scanning among these 7 jurisdictions. We identified 97 COVID-19-related first-responder deaths during the study period through media and jurisdiction reports. Participating jurisdictions reported 5 deaths not reported by the media. Sixty-six decedents worked in law enforcement, and 31 decedents worked in fire/emergency medical services. Media reports rarely noted underlying conditions. The media scan sensitivity was 88% (95% CI, 73%-96%) in the subset of 7 jurisdictions. Media reports demonstrated high sensitivity in documenting COVID-19-related deaths among first responders; however, information on risk factors was scarce. Routine collection of data on industry and occupation could improve understanding of COVID-19 morbidity and mortality among all workers.

Deaths in Children and Adolescents Associated With COVID-19 and MIS-C in the United States.

OBJECTIVES: To describe the demographics, clinical characteristics, and hospital course among persons <21 years of age with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated death. METHODS: We conducted a retrospective case series of suspected SARS-CoV-2-associated deaths in the United States in persons <21 years of age during February 12 to July 31, 2020. All states and territories were invited to participate. We abstracted demographic and clinical data, including laboratory and treatment details, from medical records. RESULTS: We included 112 SARS-CoV-2-associated deaths from 25 participating jurisdictions. The median age was 17 years (IQR 8.5-19 years). Most decedents were male (71, 63%), 31 (28%) were Black (non-Hispanic) persons, and 52 (46%) were Hispanic persons. Ninety-six decedents (86%) had at least 1 underlying condition; obesity (42%), asthma (29%), and developmental disorders (22%) were most commonly documented. Among 69 hospitalized decedents, common complications included mechanical ventilation (75%) and acute respiratory failure (82%). The sixteen (14%) decedents who met multisystem inflammatory syndrome in children (MIS-C) criteria were similar in age, sex, and race and/or ethnicity to decedents without MIS-C; 11 of 16 (69%) had at least 1 underlying condition. CONCLUSIONS: SARS-CoV-2-associated deaths among persons <21 years of age occurred predominantly among Black (non-Hispanic) and Hispanic persons, male patients, and older adolescents. The most commonly reported underlying conditions were obesity, asthma, and developmental disorders. Decedents with coronavirus disease 2019 were more likely than those with MIS-C to have underlying medical conditions.