Last data update: Oct 28, 2024. (Total: 48004 publications since 2009)
Records 1-30 (of 123 Records) |
Query Trace: Kirking H[original query] |
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School knowledge of infectious diseases in schools: conducting surveillance and on-demand, symptomatic respiratory viral testing in a large pre-kindergarten-12th grade school district
Schuster JE , Chohdry TT , Young CT , Lee BR , Banerjee D , Sasidharan A , Almendares OM , Kirking HL , Porter J , Deliu A , Tilsworth S , Selvarangan R , Goldman JL . Front Public Health 2024 12 1408281 BACKGROUND: Limited data about acute respiratory illness (ARI) and respiratory virus circulation are available in congregate community settings, specifically schools. To better characterize the epidemiology of ARI and respiratory viruses in schools, we developed School Knowledge of Infectious Diseases in Schools (School KIDS). METHODS: School KIDS is a prospective, respiratory viral testing program in a large metropolitan school district (pre-kindergarten-12th grade) in Kansas City, Missouri. During the 2022-2023 school year, all students and staff were eligible to participate in surveillance respiratory viral testing at school by submitting observed self-administered nasal swabs monthly. Participants could also submit a nasal swab for on-demand symptomatic testing when experiencing ≥1 ARI symptom, including cough, fever, nasal congestion, runny nose, shortness of breath, sore throat, and/or wheezing. Swabs were tested in a research laboratory using multipathogen respiratory polymerase chain reaction assays. Participants were evaluated for ongoing viral shedding by collecting two weekly nasal swabs (i.e., convalescent), following initial on-demand symptomatic testing. Participants were asked to complete an electronic survey to capture the presence and type of ARI symptom(s) before the collection of respiratory swabs. RESULTS: From 31 October 2022 to 29 June 2023, School KIDS enrolled 978 participants, including 700 students, representing 3.4% of the district student population, and 278 staff members. Participants submitted a median of six surveillance, one symptomatic, and two convalescent specimens during the study period. A total of 6,315 respiratory specimens, including 4,700 surveillance, 721 on-demand symptomatic, and 894 convalescent specimens, were tested. Overall, a virus was detected in 1,168 (24.9%) surveillance and 363 (50.3%) symptomatic specimens. Of the 5,538 symptom surveys sent to participants before scheduled surveillance testing, 4,069 (73.5%) were completed; ARI symptoms were reported on 1,348 (33.1%) surveys. CONCLUSION: Respiratory surveillance testing in schools is feasible and provides novel information about respiratory virus detections in students and staff attending school. Schools are an important community setting, and better knowledge of respiratory virus circulation in schools may be useful to identify respiratory virus transmission in the community and assess the impact of effective infection prevention measures. |
Symptoms, viral loads, and rebound among COVID-19 outpatients treated with nirmatrelvir/ritonavir compared to propensity score matched untreated individuals
Smith-Jeffcoat SE , Biddle JE , Talbot HK , Morrissey KG , Stockwell MS , Maldonado Y , McLean HQ , Ellingson KD , Bowman NM , Asturias E , Mellis AM , Johnson S , Kirking HL , Rolfes MAR , Olivo V , Merrill L , Battan-Wraith S , Sano E , McLaren SH , Vargas CY , Goodman S , Sarnquist CC , Govindaranjan P , Petrie JG , Belongia EA , Ledezma K , Pryor K , Lutrick K , Bullock A , Yang A , Haehnel Q , Rao S , Zhu Y , Schmitz J , Hart K , Grijalva CG , Salvatore PP . Clin Infect Dis 2024 78 (5) 1175-1184 BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes from coronavirus disease 2019 (COVID-19); however, rebound after treatment has been reported. We compared symptom and viral dynamics in individuals with COVID-19 who completed N/R treatment and similar untreated individuals. METHODS: We identified symptomatic participants who tested severe acute respiratory syndrome coronavirus 2-positive and were N/R eligible from a COVID-19 household transmission study. Index cases from ambulatory settings and their households contacts were enrolled. We collected daily symptoms, medication use, and respiratory specimens for quantitative polymerase chain reaction for 10 days during March 2022-May 2023. Participants who completed N/R treatment (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R treatment completion or 7 days after symptom onset if untreated. RESULTS: Treated (n = 130) and untreated participants (n = 241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; P = .009) and VL rebound (27% vs 7%; P < .001). Average daily symptoms were lower among treated participants without symptom rebound (1.0 vs 1.6; P < .01) but not statistically lower with symptom rebound (3.0 vs 3.4; P = .5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; P < .01) but not statistically lower with VL rebound (4.8 vs 5.1; P = .7). CONCLUSIONS: Individuals who completed N/R treatment experienced fewer symptoms and lower VL but rebound occured more often compared with untreated individuals. Providers should prescribe N/R, when indicated, and communicate rebound risk to patients. |
Detection of a human adenovirus outbreak, including some critical infections, using multipathogen testing at a large university, September 2022-January 2023
Montgomery JP , Marquez JL , Nord J , Stamper AR , Edwards EA , Valentini N , Frank CJ , Washer LL , Ernst RD , Park JI , Price D , Collins J , Smith-jeffcoat sE , Hu f , Knox cL , Khan r , Lu x , Kirking hL , Hsu cH . Open Forum Infect Dis 2024 11 (5) ofae192 BACKGROUND: Human adenoviruses (HAdVs) can cause outbreaks of flu-like illness in university settings. Most infections in healthy young adults are mild; severe illnesses rarely occur. In Fall 2022, an adenovirus outbreak was identified in university students. METHODS: HAdV cases were defined as university students 17-26 years old who presented to the University Health Service or nearby emergency department with flu-like symptoms (eg, fever, cough, headache, myalgia, nausea) and had confirmed adenovirus infections by polymerase chain reaction (PCR). Demographic and clinical characteristics were abstracted from electronic medical records; clinical severity was categorized as mild, moderate, severe, or critical. We performed contact investigations among critical cases. A subset of specimens was sequenced to confirm the HAdV type. RESULTS: From 28 September 2022 to 30 January 2023, 90 PCR-confirmed cases were identified (51% female; mean age, 19.6 years). Most cases (88.9%) had mild illness. Seven cases required hospitalization, including 2 critical cases that required intensive care. Contact investigation identified 44 close contacts; 6 (14%) were confirmed HAdV cases and 8 (18%) reported symptoms but never sought care. All typed HAdV-positive specimens (n = 36) were type 4. CONCLUSIONS: While most students with confirmed HAdV had mild illness, 7 otherwise healthy students had severe or critical illness. Between the relatively high number of hospitalizations and proportion of close contacts with symptoms who did not seek care, the true number of HAdV cases was likely higher. Our findings illustrate the need to consider a wide range of pathogens, even when other viruses are known to be circulating. |
SARS-CoV-2 viral shedding and rapid antigen test performance - Respiratory Virus Transmission Network, November 2022-May 2023
Smith-Jeffcoat SE , Mellis AM , Grijalva CG , Talbot HK , Schmitz J , Lutrick K , Ellingson KD , Stockwell MS , McLaren SH , Nguyen HQ , Rao S , Asturias EJ , Davis-Gardner ME , Suthar MS , Kirking HL . MMWR Morb Mortal Wkly Rep 2024 73 (16) 365-371 As population immunity to SARS-CoV-2 evolves and new variants emerge, the role and accuracy of antigen tests remain active questions. To describe recent test performance, the detection of SARS-CoV-2 by antigen testing was compared with that by reverse transcription-polymerase chain reaction (RT-PCR) and viral culture testing during November 2022-May 2023. Participants who were enrolled in a household transmission study completed daily symptom diaries and collected two nasal swabs (tested for SARS-CoV-2 via RT-PCR, culture, and antigen tests) each day for 10 days after enrollment. Among participants with SARS-CoV-2 infection, the percentages of positive antigen, RT-PCR, and culture results were calculated each day from the onset of symptoms or, in asymptomatic persons, from the date of the first positive test result. Antigen test sensitivity was calculated using RT-PCR and viral culture as references. The peak percentage of positive antigen (59.0%) and RT-PCR (83.0%) results occurred 3 days after onset, and the peak percentage of positive culture results (52%) occurred 2 days after onset. The sensitivity of antigen tests was 47% (95% CI = 44%-50%) and 80% (95% CI = 76%-85%) using RT-PCR and culture, respectively, as references. Clinicians should be aware of the lower sensitivity of antigen testing compared with RT-PCR, which might lead to false-negative results. This finding has implications for timely initiation of SARS-CoV-2 antiviral treatment, when early diagnosis is essential; clinicians should consider RT-PCR for persons for whom antiviral treatment is recommended. Persons in the community who are at high risk for severe COVID-19 illness and eligible for antiviral treatment should seek testing from health care providers with the goal of obtaining a more sensitive diagnostic test than antigen tests (i.e., an RT-PCR test). |
Deaths associated with pediatric hepatitis of unknown etiology, United States, October 2021-June 2023
Almendares O , Baker JM , Sugerman DE , Parashar UD , Reagan-Steiner S , Kirking HL , Gastañaduy PA , Tate JE . Emerg Infect Dis 2024 30 (4) 644-53 During October 2021-June 2023, a total of 392 cases of acute hepatitis of unknown etiology in children in the United States were reported to Centers for Disease Control and Prevention as part of national surveillance. We describe demographic and clinical characteristics, including potential involvement of adenovirus in development of acute hepatitis, of 8 fatally ill children who met reporting criteria. The children had diverse courses of illness. Two children were immunocompromised when initially brought for care. Four children tested positive for adenovirus in multiple specimen types, including 2 for whom typing was completed. One adenovirus-positive child had no known underlying conditions, supporting a potential relationship between adenovirus and acute hepatitis in previously healthy children. Our findings emphasize the importance of continued investigation to determine the mechanism of liver injury and appropriate treatment. Testing for adenovirus in similar cases could elucidate the role of the virus. |
Identification of large adenovirus infection outbreak at university by multipathogen testing, South Carolina, USA, 2022
Tori ME , Chontos-Komorowski J , Stacy J , Lamson DM , St George K , Lail AT , Stewart-Grant HA , Bell LJ , Kirking HL , Hsu CH . Emerg Infect Dis 2024 30 (2) 358-362 Using multipathogen PCR testing, we identified 195 students with adenovirus type 4 infections on a university campus in South Carolina, USA, during January-May 2022. We co-detected other respiratory viruses in 43 (22%) students. Continued surveillance of circulating viruses is needed to prevent virus infection outbreaks in congregate communities. |
Previous infection and effectiveness of COVID-19 vaccination in middle- and high-school students
Almendares OM , Ruffin JD , Collingwood AH , Nolen LD , Lanier WA , Dash SR , Ciesla AA , Wiegand R , Tate JE , Kirking HL . Pediatrics 2023 152 (6) BACKGROUND AND OBJECTIVES: Understanding the real-world impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mitigation measures, particularly vaccination, in children and adolescents in congregate settings remains important. We evaluated protection against SARS-CoV-2 infection using school-based testing data. METHODS: Using data from Utah middle- and high-school students participating in school-wide antigen testing in January 2022 during omicron (BA.1) variant predominance, log binomial models were fit to estimate the protection of previous SARS-CoV-2 infection and coronavirus disease 2019 vaccination against SARS-CoV-2 infection. RESULTS: Among 17 910 students, median age was 16 years (range: 12-19), 16.7% had documented previous SARS-CoV-2 infection; 55.6% received 2 vaccine doses with 211 median days since the second dose; and 8.6% of students aged 16 to 19 years received 3 vaccine doses with 21 median days since the third dose. Protection from previous infection alone was 35.9% (95% confidence interval [CI]: 12.9%-52.8%) and 23.8% (95% CI: 2.1%-40.7%) for students aged 12 to 15 and 16 to 19 years, respectively. Protection from 2-dose hybrid immunity (previous SARS-CoV-2 infection and vaccination) with <180 days since the second dose was 58.7% (95% CI: 33.2%-74.4%) for students aged 12 to 15 and 54.7% (95% CI: 31.0%-70.3%) for students aged 16 to 19 years. Protection was highest (70.0%, 95% CI: 42.3%-84.5%) among students with 3-dose hybrid immunity, although confidence intervals overlap with 2-dose vaccination. CONCLUSIONS: The estimated protection against infection was strongest for those with hybrid immunity from previous infection and recent vaccination with a third dose. |
Early detection and surveillance of the SARS-CoV-2 variant BA.2.86 - Worldwide, July-October 2023
Lambrou AS , South E , Ballou ES , Paden CR , Fuller JA , Bart SM , Butryn DM , Novak RT , Browning SD , Kirby AE , Welsh RM , Cornforth DM , MacCannell DR , Friedman CR , Thornburg NJ , Hall AJ , Hughes LJ , Mahon BE , Daskalakis DC , Shah ND , Jackson BR , Kirking HL . MMWR Morb Mortal Wkly Rep 2023 72 (43) 1162-1167 Early detection of emerging SARS-CoV-2 variants is critical to guiding rapid risk assessments, providing clear and timely communication messages, and coordinating public health action. CDC identifies and monitors novel SARS-CoV-2 variants through diverse surveillance approaches, including genomic, wastewater, traveler-based, and digital public health surveillance (e.g., global data repositories, news, and social media). The SARS-CoV-2 variant BA.2.86 was first sequenced in Israel and reported on August 13, 2023. The first U.S. COVID-19 case caused by this variant was reported on August 17, 2023, after a patient received testing for SARS-CoV-2 at a health care facility on August 3. In the following month, eight additional U.S. states detected BA.2.86 across various surveillance systems, including specimens from health care settings, wastewater surveillance, and traveler-based genomic surveillance. As of October 23, 2023, sequences have been reported from at least 32 countries. Continued variant tracking and further evidence are needed to evaluate the full public health impact of BA.2.86. Timely genomic sequence submissions to global public databases aided early detection of BA.2.86 despite the decline in the number of specimens being sequenced during the past year. This report describes how multicomponent surveillance and genomic sequencing were used in real time to track the emergence and transmission of the BA.2.86 variant. This surveillance approach provides valuable information regarding implementing and sustaining comprehensive surveillance not only for novel SARS-CoV-2 variants but also for future pathogen threats. |
Paediatric acute hepatitis of unknown aetiology: a national surveillance investigation in the USA during 2021 and 2022
Cates J , Baker JM , Almendares O , Balachandran N , McKeever ER , Kambhampati AK , Cubenas C , Vinjé J , Cannon JL , Chhabra P , Freeman B , Reagan-Steiner S , Bhatnagar J , Gastañaduy PA , Kirking HL , Sugerman D , Parashar UD , Tate JE . Lancet Child Adolesc Health 2023 7 (11) 773-785 BACKGROUND: Adenovirus is a known cause of hepatitis in immunocompromised children, but not in immunocompetent children. In April, 2022, following multiple reports of hepatitis of unknown aetiology and adenovirus viraemia in immunocompetent children in the USA and UK, the US Centers for Disease Control and Prevention (CDC) and jurisdictional health departments initiated national surveillance of paediatric acute hepatitis of unknown aetiology. We aimed to describe the clinical and epidemiological characteristics of children identified with hepatitis of unknown aetiology between Oct 1, 2021, and Sept 30, 2022, in the USA and to compare characteristics of those who tested positive for adenovirus with those who tested negative. METHODS: In this national surveillance investigation in the USA, children were identified for investigation if they were younger than 10 years with elevated liver transaminases (>500 U/L) who had an unknown cause for their hepatitis and onset on or after Oct 1, 2021. We reviewed medical chart abstractions, which included data on demographics, underlying health conditions, signs and symptoms of illness, laboratory results, vaccination history, radiological and liver pathology findings, diagnoses and treatment received, and outcomes. Caregiver interviews were done to obtain information on symptoms and health-care utilisation for the hepatitis illness, medical history, illness in close contacts or at school or daycare, diet, travel, and other potential exposures. Blood, stool, respiratory, and tissue specimens were evaluated according to clinician discretion and available specimens were submitted to CDC for additional laboratory testing or pathology evaluation. FINDINGS: Surveillance identified 377 patients from 45 US jurisdictions with hepatitis of unknown aetiology with onset from Oct 1, 2021, to Sept 30, 2022. The median age of patients was 2·8 years (IQR 1·2-5·0) and 192 (51%) were male, 184 (49%) were female, and one patient had sex unknown. Only 22 (6%) patients had a notable predisposing underlying condition. 347 patients (92%) were admitted to hospital, 21 (6%) subsequently received a liver transplant, and nine (2%) died. Among the 318 patients without notable underlying conditions, 275 were tested for adenovirus. Of these 116 (42%) had at least one positive specimen, and species F type 41 was the most frequent type identified (19 [73%] of 26 typed specimens were HAdV-41). Proportions of patients who had acute liver failure, received a liver transplant, and died were similar between those who tested positive for adenovirus compared with those who tested negative. Adenovirus species F was detected by polymerase chain reaction in nine pathology liver evaluations, but not by immunohistochemistry in seven of the nine with adequate liver tissue available. Interviews with caregivers yielded no common exposures. INTERPRETATION: Adenovirus, alone or in combination with other factors, might play a potential role in acute hepatitis among immunocompetent children identified in this investigation, but the pathophysiologic mechanism of liver injury is unclear. To inform both prevention and intervention measures, more research is warranted to determine if and how adenovirus might contribute to hepatitis risk and the potential roles of other pathogens and host factors. FUNDING: None. |
One Health Investigation of SARS-CoV-2 Infection and Seropositivity among Pets in Households with Confirmed Human COVID-19 Cases — Utah and Wisconsin, 2020 (preprint)
Goryoka GW , Cossaboom CM , Gharpure R , Dawson P , Tansey C , Rossow J , Mrotz V , Rooney J , Torchetti M , Loiacono CM , Killian ML , Jenkins-Moore M , Lim A , Poulsen K , Christensen D , Sweet E , Peterson D , Sangster AL , Young EL , Oakeson KF , Taylor D , Price A , Kiphibane T , Klos R , Konkle D , Bhattacharyya S , Dasu T , Chu VT , Lewis NM , Queen K , Zhang J , Uehara A , Dietrich EA , Tong S , Kirking HL , Doty JB , Murrell LS , Spengler JR , Straily A , Wallace R , Barton Behravesh C . bioRxiv 2021 2021.04.11.439379 Background Approximately 67% of U.S. households have pets. Limited data are available on SARS-CoV-2 in pets. We assessed SARS-CoV-2 infection in pet cohabitants as a sub-study of an ongoing COVID-19 household transmission investigation.Methods Mammalian pets from households with ≥1 person with laboratory-confirmed COVID-19 were eligible for inclusion from April–May 2020. Demographic/exposure information, oropharyngeal, nasal, rectal, and fur swabs, feces, and blood were collected from enrolled pets and tested by rRT-PCR and virus neutralization assays.Findings We enrolled 37 dogs and 19 cats from 34 of 41 eligible households. All oropharyngeal, nasal, and rectal swabs tested negative by rRT-PCR; one dog’s fur swabs (2%) tested positive by rRT-PCR at the first animal sampling. Among 47 pets with serological results from 30 households, eight (17%) pets (4 dogs, 4 cats) from 6 (20%) households had detectable SARS-CoV-2 neutralizing antibodies. In households with a seropositive pet, the proportion of people with laboratory-confirmed COVID-19 was greater (median 79%; range: 40–100%) compared to households with no seropositive pet (median 37%; range: 13–100%) (p=0.01). Thirty-three pets with serologic results had frequent daily contact (≥1 hour) with the human index patient before the person’s COVID-19 diagnosis. Of these 33 pets, 14 (42%) had decreased contact with the human index patient after diagnosis and none (0%) were seropositive; of the 19 (58%) pets with continued contact, 4 (21%) were seropositive.Interpretations Seropositive pets likely acquired infection from humans, which may occur more frequently than previously recognized. People with COVID-19 should restrict contact with animals.Funding Centers for Disease Control and Prevention, U.S. Department of AgricultureCompeting Interest StatementThe authors have declared no competing interest. |
Performance of Repeat BinaxNOW SARS-CoV-2 Antigen Testing in a Community Setting, Wisconsin, November-December 2020 (preprint)
Shah MM , Salvatore PP , Ford L , Kamitani E , Whaley MJ , Mitchell K , Currie DW , Morgan CN , Segaloff HE , Lecher S , Somers T , Van Dyke ME , Bigouette JP , Delaney A , DaSilva J , O'Hegarty M , Boyle-Estheimer L , Abdirizak F , Karpathy SE , Meece J , Ivanic L , Goffard K , Gieryn D , Sterkel A , Bateman A , Kahrs J , Langolf K , Zochert T , Knight NW , Hsu CH , Kirking HL , Tate JE . medRxiv 2021 2021.04.05.21254834 Repeating the BinaxNOW antigen test for SARS-CoV-2 by two groups of readers within 30 minutes resulted in high concordance (98.9%) in 2,110 encounters. BinaxNOW test sensitivity was 77.2% (258/334) compared to real-time reverse transcription-polymerase chain reaction. Repeating antigen testing on the same day did not significantly improve test sensitivity while specificity remained high.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was funded by the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. See e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C. 552a; 44 U.S.C. 3501 et seq.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData will be made available upon reasonable request. |
Quantitative Comparison of SARS-CoV-2 Nucleic Acid Amplification Test and Antigen Testing Algorithms: A Decision Analysis Simulation Model (preprint)
Salvatore PP , Shah MM , Ford L , Delaney A , Hsu CH , Tate JE , Kirking HL . medRxiv 2021 2021.03.15.21253608 Background Antigen tests for SARS-CoV-2 offer advantages over nucleic acid amplification tests (NAATs, such as RT-PCR), including lower cost and rapid return of results, but show reduced sensitivity. Public health organizations continue to recommend different strategies for utilizing NAATs and antigen tests in various settings. There has not yet been a quantitative comparison of the expected performance of these strategies.Methods We utilized a decision analysis approach to simulate the expected outcomes of six algorithms for implementing NAAT and antigen testing, analogous to testing strategies recommended by public health organizations. Each algorithm was simulated 50,000 times for four SARS-CoV-2 infection prevalence levels ranging from 5% to 20% in a population of 100000 persons seeking testing. Primary outcomes were number of missed cases, number of false-positive diagnoses, and total test volumes. Outcome medians and 95% uncertainty ranges (URs) were reported.Results Algorithms that use NAATs to confirm all negative antigen results minimized missed cases but required high NAAT capacity: 92,200 (95% UR: 91,200-93,200) tests (in addition to 100,000 antigen tests) at 10% prevalence. Substituting repeat antigen testing in lieu of NAAT confirmation of all initial negative antigen tests resulted in 2,280 missed cases (95% UR: 1,507-3,067) at 10% prevalence. Selective use of NAATs to confirm antigen results when discordant with symptom status (e.g., symptomatic persons with negative antigen results) resulted in the most efficient use of NAATs, with 25 NAATs (95% UR: 13-57) needed to detect one additional case at 10% prevalence compared to exclusive use of antigen tests.Conclusions No single SARS-CoV-2 testing algorithm is likely to be optimal across settings with different levels of prevalence and for all programmatic priorities; each presents a trade-off between prioritized outcomes and resource constraints. This analysis provides a framework for selecting setting-specific strategies to achieve acceptable balances and trade-offs between programmatic priorities and constraints.Disclaimer The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was funded by the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. See e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C. 552a; 44 U.S.C. 3501 et seq.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesCode for the algorithm simulations can be found on the CDC Epidemic Prediction Initiative GitHub site (https://github.com/cdcepi). |
Characteristics of children and antigen test performance at a SARS-CoV-2 community testing site (preprint)
Ford L , Whaley MJ , Shah MM , Salvatore PP , Segaloff HE , Delaney A , Currie DW , Boyle-Estheimer L , O'Hegarty M , Morgan CN , Meece J , Ivacic L , Thornburg NJ , Tamin A , Harcourt JL , Folster JM , Medrzycki M , Jain S , Wong P , Goffard K , Gieryn D , Kahrs J , Langolf K , Zochert T , Tate JE , Hsu CH , Kirking HL . medRxiv 2021 2021.07.06.21259792 Background Performance characteristics of SARS-CoV-2 antigen tests among children are limited despite the need for point-of-care testing in school and childcare settings. We describe children seeking SARS-CoV-2 testing at a community site and compare antigen test performance to real-time reverse transcription-polymerase chain reaction (RT-PCR) and viral culture.Methods Two anterior nasal specimens were self-collected for BinaxNOW antigen and RT-PCR testing, along with demographics, symptoms, and exposure information from individuals ≥5 years at a community testing site. Viral culture was attempted on residual antigen or RT-PCR positive specimens. Demographic and clinical characteristics, and the performance of SARS-CoV-2 antigen tests, were compared among children (<18 years) and adults.Results About one in ten included specimens were from children (225/2110); 16.4% (37/225) were RT-PCR positive. Cycle threshold values were similar among RT-PCR positive specimens from children and adults (22.5 vs 21.3, p=0.46) and among specimens from symptomatic and asymptomatic children (22.5 vs 23.2, p=0.39). Sensitivity of antigen test compared to RT-PCR was 73.0% (27/37) among specimens from children and 80.8% (240/297) among specimens from adults; among specimens from children, specificity was 100% (188/188), positive and negative predictive value were 100% (27/27) and 94.9% (188/198) respectively. Virus was isolated from 51.4% (19/37) of RT-PCR positive pediatric specimens; all 19 had positive antigen test results.Conclusions With lower sensitivity relative to RT-PCR, antigen tests may not diagnose all positive COVID-19 cases; however, antigen testing identified children with live SARS-CoV-2 virus.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. See e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C. 552a; 44 U.S.C. 3501 et seq.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request. |
Description of a University COVID-19 Outbreak and Interventions to Disrupt Transmission, Wisconsin, August – October 2020 (preprint)
Currie DW , Moreno GK , Delahoy MJ , Pray IW , Jovaag A , Braun KM , Cole D , Shechter T , Fajardo GC , Griggs C , Yandell BS , Goldstein S , Bushman D , Segaloff HE , Kelly GP , Pitts C , Lee C , Grande KM , Kita-Yarbro A , Grogan B , Mader S , Baggott J , Bateman AC , Westergaard RP , Tate JE , Friedrich TC , Kirking HL , O'Connor DH , Killerby ME . medRxiv 2021 2021.05.07.21256834 University settings have demonstrated potential for COVID-19 outbreaks, as they can combine congregate living, substantial social activity, and a young population predisposed to mild illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin (UW)–Madison. During August – October 2020, 3,485 students tested positive, including 856/6,162 students living in residence halls. Case counts began rising during move-in week for on-campus students (August 25-31, 2020), then rose rapidly during September 1-11, 2020. UW-Madison initiated multiple prevention efforts, including quarantining two residence halls; a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, where UW-Madison is located, did not find evidence of transmission from a large cluster of cases in the two residence halls quarantined during the outbreak. Coordinated implementation of prevention measures can effectively reduce SARS-CoV-2 spread in university settings and may limit spillover to the community surrounding the university.Competing Interest StatementThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention.Clinical TrialN/A.Funding StatementG.K.M. is supported by an NLM training grant to the Computation and Informatics in Biology and Medicine Training Program (NLM 5T15LM007359). This work was funded in part by the U.S. Centers for Disease Control and Prevention Contract #75D30120C09870: Defining the Role of College Students in SARS-CoV-2 Spread in the Upper Midwest.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:A waiver of HIPAA Authorization was obtained by the Western Institutional Review Board (WIRB #1-1290953-1) to obtain the clinical specimens for whole genome sequencing. This analysis was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. These activities were determined to be non-research public health surveillance by the Institutional Review Board at UW-Madison.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll sequencing data is available on www.gisaid.org. Scripts for sequence data analysis is available at https://github.com/gagekmoreno/SARS-CoV-2-at-UW_Madison. https://github.com/gagekmoreno/SARS-CoV-2-at-UW_Madison |
Loss of Taste and Smell as Distinguishing Symptoms of COVID-19 (preprint)
Dawson P , Rabold EM , Laws RL , Conners EE , Gharpure R , Yin S , Buono SA , Dasu T , Bhattacharyya S , Westergaard RP , Pray IW , Ye D , Nabity SA , Tate JE , Kirking HL . medRxiv 2020 2020.05.13.20101006 Olfactory and taste dysfunctions have emerged as symptoms of COVID-19. Among individuals with COVID-19 enrolled in a household study, loss of taste and/or smell was the fourth most commonly reported symptom (26/42; 62%), and among household contacts, it had the highest positive predictive value (83%; 95% CI: 55–95%) for COVID-19. These findings support consideration of loss of taste and/or smell in possible case identification and testing prioritization for COVID-19.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData presented in the current study may be available from the corresponding author on request. |
Enhanced Contact Investigations for Nine Early Travel-Related Cases of SARS-CoV-2 in the United States (preprint)
Burke RM , Balter S , Barnes E , Barry V , Bartlett K , Beer KD , Benowitz I , Biggs HM , Bruce H , Bryant-Genevier J , Cates J , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu VT , Clark S , Cody SH , Cohen M , Conners EE , Dasari V , Dawson P , DeSalvo T , Donahue M , Dratch A , Duca L , Duchin J , Dyal JW , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Freeman-Ponder B , Fry AM , Gant J , Gautom R , Ghinai I , Gounder P , Grigg CT , Gunzenhauser J , Hall AJ , Han GS , Haupt T , Holshue M , Hunter J , Ibrahim MB , Jacobs MW , Jarashow MC , Joshi K , Kamali T , Kawakami V , Kim M , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Lang M , Layden J , Leidman E , Lindquist S , Lindstrom S , Link-Gelles R , Marlow M , Mattison CP , McClung N , McPherson TD , Mello L , Midgley CM , Novosad S , Patel MT , Pettrone K , Pillai SK , Pray IW , Reese HE , Rhodes H , Robinson S , Rolfes M , Routh J , Rubin R , Rudman SL , Russell D , Scott S , Shetty V , Smith-Jeffcoat SE , Soda EA , Spitters C , Stierman B , Sunenshine R , Terashita D , Traub E , Vahey GM , Verani JR , Wallace M , Westercamp M , Wortham J , Xie A , Yousaf A , Zahn M . medRxiv 2020 2020.04.27.20081901 Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData may be available upon reasonable request. |
Performance of Existing and Novel Symptom- and Antigen Testing-Based COVID-19 Case Definitions in a Community Setting (preprint)
Lee S , Almendares O , Prince-Guerra JL , Heilig CM , Tate JE , Kirking HL . medRxiv 2022 10 Point-of-care antigen tests are an important tool for SARS-CoV-2 detection, but they are less clinically sensitive than real-time reverse-transcription PCR (RT-PCR), impacting their efficacy as screening procedures. Our goal in this study was to see whether we could improve this sensitivity by considering antigen test results in combination with other relevant information, namely exposure status and reported symptoms. In November of 2020, we collected 3,419 paired upper respiratory specimens tested by RT-PCR and the Abbott BinaxNOW antigen test at two community testing sites in Pima County, Arizona. We used symptom, exposure, and antigen testing data to evaluate the sensitivity and specificity of various symptom definitions in predicting RT-PCR positivity. Our analysis yielded 6 novel multi-symptom case definitions with and without antigen test results, the best of which overall achieved a Youden's J index of 0.66, as compared with 0.52 for antigen testing alone. Using a random forest as a guide, we show that this definition, along with our others, does not lose the ability to generalize well to new data despite achieving optimal performance in our sample. Our methodology is broadly applicable, and we have made our code publicly available to aid public health practitioners in developing or fine-tuning their own screening rules. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Transmission potential of vaccinated and unvaccinated persons infected with the SARS-CoV-2 Delta variant in a federal prison, July-August 2021 (preprint)
Salvatore PP , Lee CC , Sleweon S , McCormick DW , Nicolae L , Knipe K , Dixon T , Banta R , Ogle I , Young C , Dusseau C , Salmonson S , Ogden C , Godwin E , Ballom T , Ross T , Wynn NT , David E , Bessey TK , Kim G , Suppiah S , Tamin A , Harcourt JL , Sheth M , Lowe L , Browne H , Tate JE , Kirking HL , Hagan LM . medRxiv 2021 19 Background The extent to which vaccinated persons who become infected with SARS-CoV-2 contribute to transmission is unclear. During a SARS-CoV-2 Delta variant outbreak among incarcerated persons with high vaccination rates in a federal prison, we assessed markers of viral shedding in vaccinated and unvaccinated persons. Methods Consenting incarcerated persons with confirmed SARS-CoV-2 infection provided mid-turbinate nasal specimens daily for 10 consecutive days and reported symptom data via questionnaire. Real-time reverse transcription-polymerase chain reaction (RT-PCR), viral whole genome sequencing, and viral culture was performed on these nasal specimens. Duration of RT-PCR positivity and viral culture positivity was assessed using survival analysis. Results A total of 978 specimens were provided by 95 participants, of whom 78 (82%) were fully vaccinated and 17 (18%) were not fully vaccinated. No significant differences were detected in duration of RT-PCR positivity among fully vaccinated participants (median: 13 days) versus those not fully vaccinated (median: 13 days; p=0.50), or in duration of culture positivity (medians: 5 days and 5 days; p=0.29). Among fully vaccinated participants, overall duration of culture positivity was shorter among Moderna vaccine recipients versus Pfizer (p=0.048) or Janssen (p=0.003) vaccine recipients. Conclusions As this field continues to develop, clinicians and public health practitioners should consider vaccinated persons who become infected with SARS-CoV-2 to be no less infectious than unvaccinated persons. These findings are critically important, especially in congregate settings where viral transmission can lead to large outbreaks. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Notes from the field: Multipathogen respiratory virus testing among primary and secondary school students and staff members in a large metropolitan school district - Missouri, November 2, 2022-April 19, 2023
Goldman JL , Lee BR , Porter J , Deliu A , Tilsworth S , Almendares OM , Sleweon S , Kirking HL , Selvarangan R , Schuster JE . MMWR Morb Mortal Wkly Rep 2023 72 (28) 772-774 Respiratory virus infections are common in school-aged children (1). Although children spend most of their awake hours in the school setting, few data are available on the prevalence of respiratory viruses in schools. Surveillance for respiratory viruses other than SARS-CoV-2 has not been widely conducted in primary and secondary schools (2). | | Prospective Surveillance and Preliminary Results | To determine the prevalence of respiratory viruses in school students and staff members, prospective surveillance was implemented in a large metropolitan school district in Kansas City, Missouri with 33 pre-Kindergarten (pre-K)–grade 12 schools during the 2022–23 school year. All district students and staff members were eligible to enroll in opt-in respiratory virus testing and symptom surveys irrespective of the presence of symptoms; enrollment information was sent by the school district using existing communication channels. Self-collected anterior nasal swabs were obtained monthly and tested using multiplex viral polymerase chain reaction.* Thirty-six hours before each scheduled monthly test, an electronic survey was sent to enrolled participants (or their parent or guardian) inquiring about respiratory virus infection symptoms during the preceding 7 days.† Logistic regression models were used to compare positivity across age groups. Regression models accounted for clustering within schools when calculating cluster-robust SEs. Percentile-based bootstrapped CIs were calculated using Stata 17 software (version 17.0; StataCorp). The goal of this report is to share timely virus testing results during ongoing surveillance. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§ |
Epidemiology of SARS-CoV-2 transmission and superspreading in Salt Lake County, Utah, March-May 2020
Walker J , Tran T , Lappe B , Gastanaduy P , Paul P , Kracalik IT , Fields VL , Lopez A , Schwartz A , Lewis NM , Tate JE , Kirking HL , Hall AJ , Pevzner E , Khong H , Smithee M , Lowry J , Dunn A , Kiphibane T , Tran CH . PLoS One 2023 18 (6) e0275125 BACKGROUND: Understanding the drivers of SARS-CoV-2 transmission can inform the development of interventions. We evaluated transmission identified by contact tracing investigations between March-May 2020 in Salt Lake County, Utah, to quantify the impact of this intervention and identify risk factors for transmission. METHODS: RT-PCR positive and untested symptomatic contacts were classified as confirmed and probable secondary case-patients, respectively. We compared the number of case-patients and close contacts generated by different groups, and used logistic regression to evaluate factors associated with transmission. RESULTS: Data were collected on 184 index case-patients and up to six generations of contacts. Of 1,499 close contacts, 374 (25%) were classified as secondary case-patients. Decreased transmission odds were observed for contacts aged <18 years (OR = 0.55 [95% CI: 0.38-0.79]), versus 18-44 years, and for workplace (OR = 0.36 [95% CI: 0.23-0.55]) and social (OR = 0.44 [95% CI: 0.28-0.66]) contacts, versus household contacts. Higher transmission odds were observed for case-patient's spouses than other household contacts (OR = 2.25 [95% CI: 1.52-3.35]). Compared to index case-patients identified in the community, secondary case-patients identified through contract-tracing generated significantly fewer close contacts and secondary case-patients of their own. Transmission was heterogeneous, with 41% of index case-patients generating 81% of directly-linked secondary case-patients. CONCLUSIONS: Given sufficient resources and complementary public health measures, contact tracing can contain known chains of SARS-CoV-2 transmission. Transmission is associated with age and exposure setting, and can be highly variable, with a few infections generating a disproportionately high share of onward transmission. |
Assessment of anti-SARS-CoV-2 antibody levels among university students vaccinated with different COVID-19 primary and booster doses - fall 2021, Wisconsin
DeJonge PM , Lambrou AS , Segaloff HE , Bateman A , Sterkel A , Griggs C , Baggott J , Kelly P , Thornburg N , Epperson M , Desamu-Thorpe R , Abedi G , Hsu CH , Nakayama JY , Ruffin J , Turner-Harper D , Matanock A , Almendares O , Whaley M , Chakrabarti A , DeGruy K , Daly M , Westergaard R , Tate JE , Kirking HL . BMC Infect Dis 2023 23 (1) 374 BACKGROUND: University students commonly received COVID-19 vaccinations before returning to U.S. campuses in the Fall of 2021. Given likely immunologic variation among students based on differences in type of primary series and/or booster dose vaccine received, we conducted serologic investigations in September and December 2021 on a large university campus in Wisconsin to assess anti-SARS-CoV-2 antibody levels. METHODS: We collected blood samples, demographic information, and COVID-19 illness and vaccination history from a convenience sample of students. Sera were analyzed for both anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibody levels using World Health Organization standardized binding antibody units per milliliter (BAU/mL). Levels were compared across categorical primary COVID-19 vaccine series received and binary COVID-19 mRNA booster status. The association between anti-S levels and time since most recent vaccination dose was estimated by mixed-effects linear regression. RESULTS: In total, 356 students participated, of whom 219 (61.5%) had received a primary vaccine series of Pfizer-BioNTech or Moderna mRNA vaccines and 85 (23.9%) had received vaccines from Sinovac or Sinopharm. Median anti-S levels were significantly higher for mRNA primary vaccine series recipients (2.90 and 2.86 log [BAU/mL], respectively), compared with those who received Sinopharm or Sinovac vaccines (1.63 and 1.95 log [BAU/mL], respectively). Sinopharm and Sinovac vaccine recipients were associated with a significantly faster anti-S decline over time, compared with mRNA vaccine recipients (P <.001). By December, 48/172 (27.9%) participants reported receiving an mRNA COVID-19 vaccine booster, which reduced the anti-S antibody discrepancies between primary series vaccine types. CONCLUSIONS: Our work supports the benefit of heterologous boosting against COVID-19. COVID-19 mRNA vaccine booster doses were associated with increases in anti-SARS-CoV-2 antibody levels; following an mRNA booster dose, students with both mRNA and non-mRNA primary series receipt were associated with comparable levels of anti-S IgG. |
Tuberculosis Infection in Children
Stewart RJ , Wortham J , Parvez F , Bamrah Morris S , Kirking HL , Hatzenbuehler Cameron L , Cruz AT . J Nurse Pract 2020 16 (9) 673-678 Globally, tuberculosis (TB) is the leading cause of infectious disease mortality; however, clinicians in the United States are increasingly unfamiliar with TB and the recommended tests and treatment for latent TB infection. Compared with adults, children who develop TB more often develop severe disease, and children < 2 years are particularly susceptible to developing TB disease after initial infection. Nurse practitioners who work in primary care are on the front lines of identifying children at high risk and obtaining testing and treatment. This article reviews the clinical course for identifying children at risk for TB and provides updated guidelines for testing and treatment. |
Adeno-associated virus type 2 in US children with acute severe hepatitis.
Servellita V , Gonzalez AS , Lamson DM , Foresythe A , Huh HJ , Bazinet AL , Bergman NH , Bull RL , Garcia KY , Goodrich JS , Lovett SP , Parker K , Radune D , Hatada A , Pan CY , Rizzo K , Bertumen JB , Morales C , Oluniyi PE , Nguyen J , Tan J , Stryke D , Jaber R , Leslie MT , Lyons Z , Hedman HD , Parashar U , Sullivan M , Wroblewski K , Oberste MS , Tate JE , Baker JM , Sugerman D , Potts C , Lu X , Chhabra P , Pediatric Hepatitis of Unknown Etiology Working Group , Ingram LA , Shiau H , Britt W , Sanchez LHG , Ciric C , Rostad CA , Vinjé J , Kirking HL , Wadford DA , Raborn RT , St George K , Chiu CY . Nature 2023 As of August 2022, clusters of acute severe hepatitis of unknown etiology in children have been reported from 35 countries, including the United States(1,2). Previous studies have found human adenoviruses (HAdVs) in the blood from cases in Europe and the United States(3-7), although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment based sequencing, and agnostic metagenomic sequencing to analyze samples from 16 HAdV-positive cases from October 1, 2021 to May 22, 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P<0.001) and to 0 of 30 patients with hepatitis of defined etiology (P<0.001). In controls, HAdV-41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P<0.001). Co-infections by Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and/or enterovirus A71 (EV-A71) were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P<0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses. |
Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak - United States, December 31, 2019-February 4, 2020.
Patel A , Jernigan DB , 2019-nCOV CDC Response Team , Abdirizak Fatuma , Abedi Glen , Aggarwal Sharad , Albina Denise , Allen Elizabeth , Andersen Lauren , Anderson Jade , Anderson Megan , Anderson Tara , Anderson Kayla , Bardossy Ana Cecilia , Barry Vaughn , Beer Karlyn , Bell Michael , Berger Sherri , Bertulfo Joseph , Biggs Holly , Bornemann Jennifer , Bornstein Josh , Bower Willie , Bresee Joseph , Brown Clive , Budd Alicia , Buigut Jennifer , Burke Stephen , Burke Rachel , Burns Erin , Butler Jay , Cantrell Russell , Cardemil Cristina , Cates Jordan , Cetron Marty , Chatham-Stephens Kevin , Chatham-Stevens Kevin , Chea Nora , Christensen Bryan , Chu Victoria , Clarke Kevin , Cleveland Angela , Cohen Nicole , Cohen Max , Cohn Amanda , Collins Jennifer , Conners Erin , Curns Aaron , Dahl Rebecca , Daley Walter , Dasari Vishal , Davlantes Elizabeth , Dawson Patrick , Delaney Lisa , Donahue Matthew , Dowell Chad , Dyal Jonathan , Edens William , Eidex Rachel , Epstein Lauren , Evans Mary , Fagan Ryan , Farris Kevin , Feldstein Leora , Fox LeAnne , Frank Mark , Freeman Brandi , Fry Alicia , Fuller James , Galang Romeo , Gerber Sue , Gokhale Runa , Goldstein Sue , Gorman Sue , Gregg William , Greim William , Grube Steven , Hall Aron , Haynes Amber , Hill Sherrasa , Hornsby-Myers Jennifer , Hunter Jennifer , Ionta Christopher , Isenhour Cheryl , Jacobs Max , Jacobs Slifka Kara , Jernigan Daniel , Jhung Michael , Jones-Wormley Jamie , Kambhampati Anita , Kamili Shifaq , Kennedy Pamela , Kent Charlotte , Killerby Marie , Kim Lindsay , Kirking Hannah , Koonin Lisa , Koppaka Ram , Kosmos Christine , Kuhar David , Kuhnert-Tallman Wendi , Kujawski Stephanie , Kumar Archana , Landon Alexander , Lee Leslie , Leung Jessica , Lindstrom Stephen , Link-Gelles Ruth , Lively Joana , Lu Xiaoyan , Lynch Brian , Malapati Lakshmi , Mandel Samantha , Manns Brian , Marano Nina , Marlow Mariel , Marston Barbara , McClung Nancy , McClure Liz , McDonald Emily , McGovern Oliva , Messonnier Nancy , Midgley Claire , Moulia Danielle , Murray Janna , Noelte Kate , Noonan-Smith Michelle , Nordlund Kristen , Norton Emily , Oliver Sara , Pallansch Mark , Parashar Umesh , Patel Anita , Patel Manisha , Pettrone Kristen , Pierce Taran , Pietz Harald , Pillai Satish , Radonovich Lewis , Reagan-Steiner Sarah , Reel Amy , Reese Heather , Rha Brian , Ricks Philip , Rolfes Melissa , Roohi Shahrokh , Roper Lauren , Rotz Lisa , Routh Janell , Sakthivel Senthil Kumar Sarmiento Luisa , Schindelar Jessica , Schneider Eileen , Schuchat Anne , Scott Sarah , Shetty Varun , Shockey Caitlin , Shugart Jill , Stenger Mark , Stuckey Matthew , Sunshine Brittany , Sykes Tamara , Trapp Jonathan , Uyeki Timothy , Vahey Grace , Valderrama Amy , Villanueva Julie , Walker Tunicia , Wallace Megan , Wang Lijuan , Watson John , Weber Angie , Weinbaum Cindy , Weldon William , Westnedge Caroline , Whitaker Brett , Whitaker Michael , Williams Alcia , Williams Holly , Willams Ian , Wong Karen , Xie Amy , Yousef Anna . Am J Transplant 2020 20 (3) 889-895 This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance. |
Is Symptom Screening Useful for Identifying COVID-19 Infection in School Settings? Georgia, USA.
Swanson M , Hast M , Burnett E , Oraka E , Kimball A , Morris E , Marcet PL , Almendares O , Franklin R , Mehari L , McCloud J , Kirking HL , Tate JE , Scott C . J Sch Nurs 2021 37 (6) 503-512 This study's goal was to characterize the utility of symptom screening in staff and students for COVID-19 identification and control of transmission in a school setting. We conducted a secondary analysis of cross-sectional data for staff, students and associated household members in a Georgia school district exposed to COVID-19 cases who received RT-PCR testing and symptom monitoring. Among positive contacts, 30/49 (61%) of students and 1/6 (17%) of staff reported no symptoms consistent with COVID-19. Symptom sensitivity was 30% in elementary students and 42% in middle/high students. Fifty-three percent (10/19) of symptomatic positive contacts had at least one household member test positive for SARS-CoV-2 compared with 50% (10/20) of asymptomatic positive contacts. The absence of symptoms in children is not indicative of a lack of SARS-CoV-2 infection or reduced risk of infection for associated household members. Testing all close contacts of people with COVID-19 in schools is needed to interrupt transmission networks. |
Evaluation of Correctional Facility COVID-19 Outbreaks With Layered Mitigation Strategies Including Vaccination: Colorado, 2020-2021.
Martinez HE , Marshall KE , Showell VW , Tate JE , Kirking HL , Broudy M , Matzinger SR , Burakoff A , Deng L , Payne DC , Fleming-Dutra K , Jervis RH . J Correct Health Care 2023 29 (3) 198-205 In 2020-2021, a Colorado corrections facility experienced four COVID-19 outbreaks. Case counts, attack rates (ARs) in people who are detained or incarcerated (PDI), and mitigation measures used in each outbreak were compared to evaluate effects of combined strategies. Serial PCR testing, isolation/quarantine, and masking were implemented in outbreak 1. Daily staff antigen testing began in outbreak 2. Facility-wide COVID-19 vaccination started in outbreak 3 and coverage increased by the end of outbreak 4 (PDI: <1% to 59%, staff: 27% to 40%). Despite detection of variants of concern, outbreaks 3 and 4 had 97% lower PDI ARs (both 1%) than outbreak 2 (29%). Daily staff testing and increasing vaccination coverage, with other outbreak mitigation strategies, are important to reduce COVID-19 transmission in congregate settings. |
Behaviors associated with household transmission of SARS-CoV-2 in California and Colorado, January 2021-April 2021
Namageyo-Funa A , Ruffin JD , Killerby ME , Jalloh MF , Scott C , Lindell K , Silver M , Matanock A , Soto RA , Donnelly MAP , Schwartz NG , Chuey MR , Chu VT , Beatty ME , Totten SE , Hudziec MM , Tate JE , Kirking HL , Hsu CH . AJPM Focus 2022 1 (1) 100004 INTRODUCTION: Mitigation behaviors are key to preventing SARS-CoV-2 transmission. We identified the behaviors associated with secondary transmission from confirmed SARS-CoV-2 primary cases to household contacts and described the characteristics associated with reporting these behaviors. METHODS: Households with confirmed SARS-CoV-2 infections were recruited in California and Colorado from January to April 2021. Self-reported behaviors and demographics were collected through interviews. We investigated behaviors associated with transmission and individual and household characteristics associated with behaviors using univariable and multivariable logistic regression with generalized estimating equations to account for household clustering. RESULTS: Among household contacts of primary cases, 43.3% (133 of 307) became infected with SARS-CoV-2. When an adjusted analysis was conducted, household contacts who slept in the same bedroom with the primary case (AOR=2.19; 95% CI=1.25, 3.84) and ate food prepared by the primary case (AOR=1.98; 95% CI=1.02, 3.87) had increased odds of SARS-CoV-2 infection. Household contacts in homes 2,000 square feet had increased odds of sleeping in the same bedroom as the primary case compared with those in homes >2,000 square feet (AOR=3.97; 95% CI=1.73, 9.10). Parents, siblings, and other relationships (extended family, friends, or roommates) of the primary case had decreased odds of eating food prepared by the primary case compared with partners. CONCLUSIONS: Sleeping in the same bedroom as the primary case and eating food prepared by the primary case were associated with secondary transmission. Household dimension and relationship to the primary case were associated with these behaviors. Our findings encourage innovative means to promote adherence to mitigation measures that reduce household transmission. |
Modelling the impact of CD4 testing on mortality from TB and cryptococcal meningitis among patients with advanced HIV disease in nine countries
Oboho IK , Paulin H , Corcoran C , Hamilton M , Jordan A , Kirking HL , Agyemang E , Podewils LJ , Pretorius C , Greene G , Chiller T , Desai M , Bhatkoti R , Shiraishi RW , Shah NS . J Int AIDS Soc 2023 26 (3) e26070 INTRODUCTION: Despite antiretroviral therapy (ART) scale-up among people living with HIV (PLHIV), those with advanced HIV disease (AHD) (defined in adults as CD4 count <200 cells/mm(3) or clinical stage 3 or 4), remain at high risk of death from opportunistic infections. The shift from routine baseline CD4 testing towards viral load testing in conjunction with "Test and Treat" has limited AHD identification. METHODS: We used official estimates and existing epidemiological data to project deaths from tuberculosis (TB) and cryptococcal meningitis (CM) among PLHIV-initiating ART with CD4 <200 cells/mm(3) , in the absence of select World Health Organization recommended diagnostic or therapeutic protocols for patients with AHD. We modelled the reduction in deaths, based on the performance of screening/diagnostic testing and the coverage and efficacy of treatment/preventive therapies for TB and CM. We compared projected TB and CM deaths in the first year of ART from 2019 to 2024, with and without CD4 testing. The analysis was performed for nine countries: South Africa, Kenya, Lesotho, Mozambique, Nigeria, Uganda, Zambia, Zimbabwe and the Democratic Republic of Congo. RESULTS: The effect of CD4 testing comes through increased identification of AHD and consequent eligibility for protocols for AHD prevention, diagnosis and management; algorithms for CD4 testing avert between 31% and 38% of deaths from TB and CM in the first year of ART. The number of CD4 tests required per death averted varies widely by country from approximately 101 for South Africa to 917 for Kenya. CONCLUSIONS: This analysis supports retaining baseline CD4 testing to avert deaths from TB and CM, the two most deadly opportunistic infections among patients with AHD. However, national programmes will need to weigh the cost of increasing CD4 access against other HIV-related priorities and allocate resources accordingly. |
Transmission potential of vaccinated and unvaccinated persons infected with the SARS-CoV-2 Delta variant in a federal prison, July-August 2021.
Salvatore PP , Lee CC , Sleweon S , McCormick DW , Nicolae L , Knipe K , Dixon T , Banta R , Ogle I , Young C , Dusseau C , Salmonson S , Ogden C , Godwin E , Ballom T , Rhodes T , Wynn NT , David E , Bessey TK , Kim G , Suppiah S , Tamin A , Harcourt JL , Sheth M , Lowe L , Browne H , Tate JE , Kirking HL , Hagan LM . Vaccine 2022 41 (11) 1808-1818 BACKGROUND: The extent to which vaccinated persons who become infected with SARS-CoV-2 contribute to transmission is unclear. During a SARS-CoV-2 Delta variant outbreak among incarcerated persons with high vaccination rates in a federal prison, we assessed markers of viral shedding in vaccinated and unvaccinated persons. METHODS: Consenting incarcerated persons with confirmed SARS-CoV-2 infection provided mid-turbinate nasal specimens daily for 10 consecutive days and reported symptom data via questionnaire. Real-time reverse transcription-polymerase chain reaction (RT-PCR), viral whole genome sequencing, and viral culture was performed on these nasal specimens. Duration of RT-PCR positivity and viral culture positivity was assessed using survival analysis. RESULTS: A total of 957 specimens were provided by 93 participants, of whom 78 (84 %) were vaccinated and 17 (16 %) were unvaccinated. No significant differences were detected in duration of RT-PCR positivity among vaccinated participants (median: 13 days) versus those unvaccinated (median: 13 days; p = 0.50), or in duration of culture positivity (medians: 5 days and 5 days; p = 0.29). Among vaccinated participants, overall duration of culture positivity was shorter among Moderna vaccine recipients versus Pfizer (p = 0.048) or Janssen (p = 0.003) vaccine recipients. In post-hoc analyses, Moderna vaccine recipients demonstrated significantly shorter duration of culture positivity compared to unvaccinated participants (p = 0.02). When restricted to participants without reported prior infection, the difference between Moderna vaccine recipients and unvaccinated participants was more pronounced (medians: 3 days and 6 days, p = 0.002). CONCLUSIONS: Infectious periods for vaccinated and unvaccinated persons who become infected with SARS-CoV-2 are similar and can be highly variable, though some vaccinated persons are likely infectious for shorter durations. These findings are critically important, especially in congregate settings where viral transmission can lead to large outbreaks. In such settings, clinicians and public health practitioners should consider vaccinated, infected persons to be no less infectious than unvaccinated, infected persons. |
SARS-CoV-2 viral shedding in vaccinated and unvaccinated persons: A case series.
McCormick DW , Hagan LM , Salvatore PP , Magleby R , Lee C , Sleweon S , Nicolae L , Dixon T , Banta R , Ogle I , Young C , Dusseau C , Ogden C , Browne H , Michael Metz J , Chen MH , Solano MI , Rogers S , Burgin A , Sheth M , Bankamp B , Tamin A , Harcourt JL , Tate JE , Kirking HL . Vaccine 2022 41 (11) 1769-1773 The preclinical time course of SARS-CoV-2 shedding is not well-described. Understanding this time course will help to inform risk of SARS-CoV-2 transmission. During an outbreak in a congregate setting, we collected paired mid-turbinate nasal swabs for antigen testing and reverse-transcription polymerase chain reaction (RT-PCR) every other day from all consenting infected and exposed persons. Among 12 persons tested prospectively before and during SARS-CoV-2 infection, ten of 12 participants (83%) had completed a primary COVID-19 vaccination series prior to the outbreak. We recovered SARS-CoV-2 in viral culture from 9/12 (75%) of participants. All three persons from whom we did not recover SARS-CoV-2 in viral culture had completed their primary vaccination series. We recovered SARS-CoV-2 from viral culture in 6/9 vaccinated persons and before symptom onset in 3/6 symptomatic persons. These findings underscore the need for both non-pharmaceutical interventions and vaccination to mitigate transmission. |
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