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.

SARS-CoV-2 Outbreak among Malayan Tigers and Humans, Tennessee, USA, 2020.

We report an outbreak of severe acute respiratory syndrome coronavirus 2 involving 3 Malayan tigers (Panthera tigris jacksoni) at a zoo in Tennessee, USA. Investigation identified naturally occurring tiger-to-tiger transmission; genetic sequence change occurred with viral passage. We provide epidemiologic, environmental, and genomic sequencing data for animal and human infections.

Translocation of an Anteater (Tamandua tetradactyla) Infected with Rabies from Virginia to Tennessee Resulting in Multiple Human Exposures, 2021.

On August 16, 2021, the Tennessee Department of Health (TDH) was notified of a positive rabies test result from a South American collared anteater (Tamandua tetradactyla) in Washington County, Tennessee. Tamanduas, or lesser anteaters, are a species of anteater in which rabies has not previously been reported. The animal was living at a Tennessee zoo and had been recently translocated from a zoo in Virginia. TDH conducted an investigation to confirm the rabies result, characterize the rabies variant, and ascertain an exposure risk assessment among persons who came into contact with the tamandua. Risk assessments for 22 persons were completed to determine the need for rabies postexposure prophylaxis (rPEP); rPEP was recommended for 13 persons, all of whom agreed to receive it. Using phylogenetic results of the virus isolated from the tamandua and knowledge of rabies epidemiology, public health officials determined that the animal was likely exposed to wild raccoons present at the Virginia zoo. This report describes expansion of the wide mammalian species diversity susceptible to rabies virus infection and summarizes the investigation, highlighting coordination among veterinary and human public health partners and the importance of preexposure rabies vaccination for animal handlers and exotic zoo animals.

Disparities in COVID-19 Mortality Rates: Implications for Rural Health Policy and Preparedness.

CONTEXT: It is well established that rural communities face geographic and socioeconomic challenges linked to higher rates of health disparities across the United States, though the coronavirus disease 2019 (COVID-19) impact on rural communities is less certain. OBJECTIVE: To understand the COVID-19 pandemic's impact on rural communities in Tennessee, investigate differences in rural-urban mortality rates after controlling for confounding variables, and inform state pandemic response policy. DESIGN: A cross-sectional analysis of cumulative COVID-19 morality rates. SETTING/PARTICIPANTS: Tennessee county-level COVID-19 mortality data from March 1, 2020, to January 31, 2021, were matched with county-level sociodemographic and health data from public datasets: Agency for Healthcare Research and Quality Social Determinants of Health, PLACES: Local Data for Better Health County Data, and the US Census Bureau. County status was defined using the 2013 National Center for Health Statistics Urban-Rural Classification. MAIN OUTCOME MEASURES: A negative binomial regression model estimated adjusted incidence rate ratio and 95% confidence intervals (CI) for rural compared with urban mortality. Unadjusted rate ratios and rate differences for COVID-19 mortality in rural versus urban counties were compared with those for influenza and pneumonia and all-cause mortality over the past 5 years. RESULTS: During the study period, 9650 COVID-19 deaths occurred across 42 urban and 53 rural counties. Controlling for county-level sociodemographic characteristics, health care access, and comorbidities, incidence rate ratio was 1.13 (95% CI, 1.00-1.28, P < .05) for rural as compared with urban deaths. Unadjusted COVID-19 mortality risk difference between rural and urban counties was greater (61.85, 95% CI, 54.31-69.31) than 5-year influenza and pneumonia rural-urban risk difference (12.57, 95% CI, 11.16-13.00) during 2015-2019. CONCLUSIONS: COVID-19 mortality rates were greater for populations living in Tennessee's rural as compared with urban counties during the study period. This differential impact must be considered in public health decision making to mitigate COVID-19.

Fatal Multisystem Inflammatory Syndrome in Adult after SARS-CoV-2 Natural Infection and COVID-19 Vaccination.

We describe a fatal case of multisystem inflammatory syndrome in an adult with onset 22 days after a second dose of mRNA coronavirus disease vaccine. Serologic and clinical findings indicated severe acute respiratory syndrome coronavirus 2 infection occurred before vaccination. The immunopathology of this syndrome, regardless of vaccination status, remains poorly understood.

Risk of HIV Diagnosis Following Bacterial Sexually Transmitted Infections in Tennessee, 2013-2017.

BACKGROUND: Data on associations between sexually transmitted infections (STIs) and incident human immunodeficiency virus (HIV) diagnoses beyond men who have sex with men (MSM) are lacking. Identifying STIs associated with greatest risk of incident HIV diagnosis could help better target HIV testing and prevention interventions. METHODS: The STI and HIV surveillance data from individuals 13 years or older in Tennessee from January 2013 to December 2017 were cross-matched. Individuals without diagnosed HIV, but with reportable STIs (chlamydia, gonorrhea, syphilis) were followed up from first STI diagnosis until HIV diagnosis or end of study. Cox regression with time-varying STI exposure was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) for subsequent HIV diagnosis; results were stratified by self-reported MSM. RESULTS: We included 148,465 individuals without HIV (3831 MSM; 144,634 non-MSM, including heterosexual men and women) diagnosed with reportable STIs; 473 had incident HIV diagnoses over 377,823 person-years (p-y) of follow-up (median, 2.6 p-y). Controlling for demographic and behavioral factors, diagnoses of gonorrhea, early syphilis, late syphilis, and STI coinfection were independently associated with incident HIV diagnosis compared with chlamydia. Early syphilis was associated with highest HIV diagnosis risk overall (aHR, 5.5; 95% CI, 3.5-5.8); this risk was higher for non-MSM (aHR, 12.3; 95% CI, 6.8-22.3) versus MSM (aHR, 2.9; 95% CI, 1.7-4.7). CONCLUSIONS: While public health efforts often focus on MSM, non-MSM with STIs is also a subgroup at high risk of incident HIV diagnosis. Non-MSM and MSM with any STI, particularly syphilis, should be prioritized for HIV testing and prevention interventions.

DURATION OF ANTIGEN SHEDDING AND DEVELOPMENT OF ANTIBODY TITERS IN MALAYAN TIGERS (PANTHERA TIGRIS JACKSONI) NATURALLY INFECTED WITH SARS-CoV-2.

Natural infection of three captive Malayan tigers (Panthera tigris jacksoni) with SARS-CoV-2 caused mild to moderate symptoms of lethargy, anorexia, and coughing. Each tiger was longitudinally sampled opportunistically via consciously obtained oral, nasal, and/or fecal samples during and after resolution of clinical signs, until 2 wk of negative results were obtained. Persistent shedding of SARS-CoV-2 genetic material was detected via reverse transcription-polymerase chain reaction in feces up to 29 d after initial onset of clinical signs, but not in nasal or oral samples. Tigers became resistant to behavioral training to obtain nasal samples but tolerated longitudinal oral sampling. Serum was obtained from two tigers, and antibody titers revealed a robust antibody response within 9 d of onset of clinical signs, which was sustained for at least 3 mon. The tigers were infected despite the use of masks and gloves by husbandry personnel. No known cause of the outbreak was identified, despite extensive investigational efforts by the regional health department. No forward cross-species transmission was observed in primates housed in nearby enclosures. The increasing regularity of reports of SARS-CoV-2 infection in nondomestic felids warrants further investigations into shedding and immunity.

COVID-19 Case Investigation and Contact Tracing in the US, 2020.

Importance: Contact tracing is a multistep process to limit SARS-CoV-2 transmission. Gaps in the process result in missed opportunities to prevent COVID-19. Objective: To quantify proportions of cases and their contacts reached by public health authorities and the amount of time needed to reach them and to compare the risk of a positive COVID-19 test result between contacts and the general public during 4-week assessment periods. Design, Setting, and Participants: This cross-sectional study took place at 13 health departments and 1 Indian Health Service Unit in 11 states and 1 tribal nation. Participants included all individuals with laboratory-confirmed COVID-19 and their named contacts. Local COVID-19 surveillance data were used to determine the numbers of persons reported to have laboratory-confirmed COVID-19 who were interviewed and named contacts between June and October 2020. Main Outcomes and Measures: For contacts, the numbers who were identified, notified of their exposure, and agreed to monitoring were calculated. The median time from index case specimen collection to contact notification was calculated, as were numbers of named contacts subsequently notified of their exposure and monitored. The prevalence of a positive SARS-CoV-2 test among named and tested contacts was compared with that jurisdiction's general population during the same 4 weeks. Results: The total number of cases reported was 74 185. Of these, 43 931 (59%) were interviewed, and 24 705 (33%) named any contacts. Among the 74 839 named contacts, 53 314 (71%) were notified of their exposure, and 34 345 (46%) agreed to monitoring. A mean of 0.7 contacts were reached by telephone by public health authorities, and only 0.5 contacts per case were monitored. In general, health departments reporting large case counts during the assessment (≥5000) conducted smaller proportions of case interviews and contact notifications. In 9 locations, the median time from specimen collection to contact notification was 6 days or less. In 6 of 8 locations with population comparison data, positive test prevalence was higher among named contacts than the general population. Conclusions and Relevance: In this cross-sectional study of US local COVID-19 surveillance data, testing named contacts was a high-yield activity for case finding. However, this assessment suggests that contact tracing had suboptimal impact on SARS-CoV-2 transmission, largely because 2 of 3 cases were either not reached for interview or named no contacts when interviewed. These findings are relevant to decisions regarding the allocation of public health resources among the various prevention strategies and for the prioritization of case investigations and contact tracing efforts.

Association of T Cell and Macrophage Activation with Arterial Vascular Health in HIV.

HIV-infected individuals are at increased risk of cardiovascular disease (CVD), but the arterial vascular functions affected by persistent innate and cellular immune activation are not well described. We assessed the relationship between immunologic and vascular parameters in 70 HIV-infected adults on efavirenz, tenofovir, and emtricitabine with more than 2 years of virologic suppression and no history of CVD. We measured brachial artery flow-mediated dilation (FMD) using ultrasound and circulating intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) by multiple immunoassay. We also measured circulating naive (CD45RO-CCR7+CD27+), activated (CD38+ and CD38+DR+), exhausted (PD1+), senescent (CD57+), and memory (CD45RO+) CD4+ and CD8+ T cell subsets by flow cytometry, and macrophage activation markers by ELISA and multiple immunoassay. Regression models were adjusted for age, sex, smoking, duration of antiretroviral therapy (ART), and body mass index. Median age was 45 years (IQR 39, 50), median CD4+ count 701 cells/µl (IQR 540, 954), and 43% were female. Lower brachial FMD was associated with a higher percentage of activated CD8+ T cells (p < .01), but not associated with macrophage activation. In contrast, higher ICAM-1 and VCAM-1 were associated with sCD163 (p < = .01 for both), macrophage inflammatory protein-1α (p < = .02 for both), and sCD14 (p = .01 for ICAM-1 only). These findings are consistent with the hypothesis that circulating CD8+ T cell activation may impair arterial smooth muscle relaxation, while macrophage activation has a role in the expression of endothelial cell proteins involved in immune cell translocation. Both innate and cellular immune activation appear to promote arterial vascular disease in HIV-infected persons on ART using differing mechanisms.