It is increasingly appreciated that pathogens can spread as infectious units constituted by multiple, genetically diverse genomes, also called collective infectious units or genome collectives. However, genetic characterization of the spatial dynamics of collective infectious units in animal hosts is demanding, and it is rarely feasible in humans. Measles virus (MeV), whose spread in lymphatic tissues and airway epithelia relies on collective infectious units, can, in rare cases, cause subacute sclerosing panencephalitis (SSPE), a lethal human brain disease. In different SSPE cases, MeV acquisition of brain tropism has been attributed to mutations affecting either the fusion or the matrix protein, or both, but the overarching mechanism driving brain adaptation is not understood. Here we analyzed MeV RNA from several spatially distinct brain regions of an individual who succumbed to SSPE. Surprisingly, we identified two major MeV genome subpopulations present at variable frequencies in all 15 brain specimens examined. Both genome types accumulated mutations like those shown to favor receptor-independent cell-cell spread in other SSPE cases. Most infected cells carried both genome types, suggesting the possibility of genetic complementation. We cannot definitively chart the history of the spread of this virus in the brain, but several observations suggest that mutant genomes generated in the frontal cortex moved outwards as a collective and diversified. During diversification, mutations affecting the cytoplasmic tails of both viral envelope proteins emerged and fluctuated in frequency across genetic backgrounds, suggesting convergent and potentially frequency-dependent evolution for modulation of fusogenicity. We propose that a collective infectious unit drove MeV pathogenesis in this brain. Re-examination of published data suggests that similar processes may have occurred in other SSPE cases. Our studies provide a primer for analyses of the evolution of collective infectious units of other pathogens that cause lethal disease in humans.

We analyzed multisystem inflammatory syndrome in children cases by reported COVID-19 vaccination status (2-dose primary series vs. no vaccination). A total of 46% vaccinated versus 58% unvaccinated persons received intensive care unit-level care (P = 0.02); the risk of intensive care unit admission was 23% higher (adjusted relative risk: 1.23; 95% confidence interval: 1.03-1.48) among unvaccinated patients; 21 unvaccinated persons died. Multisystem inflammatory syndrome in children occurs after SARS-CoV-2 infection in vaccinated persons, but may be less severe.

BACKGROUND: The long-term effects of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) or acute COVID-19 are not well known. Our objective was to determine long-term outcomes. METHODS: Children hospitalized with MIS-C or COVID-19 at 3 US hospitals from March 2020, through February 2021 were followed to assess health through 2 years post-hospitalization using medical records and patient surveys. RESULTS: Medical record abstraction was performed for 183 patients hospitalized with MIS-C, 53 of whom participated in surveys, and 97 patients hospitalized with COVID-19, 35 of whom participated in surveys. Patients with MIS-C were younger (median, 9 vs. 14 years of age for COVID-19 patients; P = 0.004), more frequently male (62% vs. 39%; P < 0.001) and had more cardiac (14% vs. 2%; P = 0.001) and neurologic sequelae (8% vs. 1%; P = 0.023). Children with COVID-19 more often had other comorbidities (59% vs. 19%; P < 0.001). Full mental recovery at the time of survey 2 (median, 16 months post-hospitalization for patients with MIS-C and 20 months for patients with COVID-19) was 85% and 88%, respectively; full physical recovery was 87% and 81%, respectively; and nearly all had resumption of normal activities. Patients with MIS-C reported more frequent headache at 1 month (45% vs. 20%; P = 0.037). Patients with COVID-19 were more likely to report cough at 1 month (37% vs. 17%; P = 0.045). Fatigue persisted >1 year in 15%-20% of patients in both groups. CONCLUSIONS: Approximately 20% of children with MIS-C and COVID-19 continued to have symptoms including fatigue and headache >1 year after hospital discharge. The duration of these findings emphasizes the importance of providers following patients until sequelae have resolved.

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.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the United States, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations. This case series describes persons aged 12-20 years with MIS-C following COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to CDC. Method(s): We investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's health department-based national MIS-C surveillance, the Vaccine Adverse Event Reporting System (VAERS, co-administered by CDC and the U.S. FDA), and CDC's Clinical Immunization Safety Assessment Project (CISA) from December 14, 2020, to August 31, 2021. We describe cases meeting the CDC MIS-C case definition. Any positive SARS-CoV-2 serology test satisfied the case criteria although anti-nucleocapsid antibody indicates SARS-CoV-2 infection, while anti-spike protein antibody indicates either infection or COVID-19 vaccination. Finding(s): We identified 21 persons with MIS-C after COVID-19 vaccination. Of these 21 persons, median age was 16 years (range, 12-20 years); 13 (62%) were male. All were hospitalized; 12 (57%) had intensive care unit admission, and all were discharged home. Fifteen (71%) of the 21 had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. Through August 2021, 21,335,331 persons aged 12-20 years had received >=1 dose of COVID-19 vaccine, making the overall reporting rate for MIS-C following vaccination 1.0 case per million persons receiving >=1 vaccine dose in this age group. The reporting rate for those without evidence of SARS-CoV-2 infection was 0.3 cases per million vaccinated persons. Interpretation(s): In our case series, we describe a small number of persons with MIS-C who had received >=1 COVID-19 vaccine dose before illness onset. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Importance: Although COVID-19 vaccines protect against infection and severe disease, the role of vaccination in preventing prolonged symptoms in those with subsequent infection is unclear. Objective(s): To determine differences in symptoms stratified by prior vaccination reported by healthcare personnel (HCP) 6 weeks after onset of COVID-19, and whether there were differences in timing of return to work. Design(s): Nested cohort study within a multicenter vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. Setting(s): Health systems in 12 U.S. states. Participant(s): HCP participating in a vaccine effectiveness study were eligible for inclusion if they had confirmed COVID-19 with either verified mRNA vaccination (symptom onset =14 days after two doses) or no prior COVID-19 vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey approximately 6 weeks after illness onset. Exposures: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. Main Outcomes and Measures: Presence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work after COVID-19 illness. Result(s): Among 419 HCP with confirmed COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants (60.6%) compared with unvaccinated participants (60.6% vs. 79.1%; aRR 0.70, 95% CI 0.58-0.84). Vaccinated HCP returned to work a median 2.0 days (95% CI 1.0-3.0) sooner than unvaccinated HCP (aHR 1.37; 95% CI, 1.04-1.79). Conclusion(s): A history of two doses of COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased risk of COVID-like symptoms at 6 weeks and earlier to return to work. Vaccination is associated with improved recovery from COVID-19, in addition to preventing symptomatic infection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a multiorgan hyperinflammatory condition following SARS-CoV-2 infection. Data on COVID-19 vaccine adverse events and vaccine attitudes in children with prior MIS-C are limited. We described characteristics associated with COVID-19 vaccination, vaccine adverse events and vaccine attitudes in children with a history of MIS-C or COVID-19 and their parents/guardians. METHODS: We enrolled children previously hospitalized for MIS-C or COVID-19 from 3 academic institutions. We abstracted charts and interviewed children and parents/guardians regarding vaccine adverse events and acceptability. RESULTS: Of 163 vaccine-eligible children enrolled with a history of MIS-C and 70 with history of COVID-19, 51 (31%) and 34 (49%), respectively, received mRNA COVID-19 vaccine a median of 10 (Interquartile Range 6-13) months after hospital discharge. Among 20 children with MIS-C and parents/guardians who provided interviews, local injection site reaction of brief duration (mean 1.8 days) was most commonly reported; no children required medical care within 2 weeks postvaccination. Vaccine survey results of interviewed, vaccinated children and their parents/guardians: of 20 children with MIS-C and 15 children with COVID-19, 17 (85%) and 13 (87%), respectively, listed doctors in the top 3 most trusted sources for vaccine information; 13 (65%) and 9 (60%) discussed vaccination with their doctor. CONCLUSIONS: COVID-19 vaccination was well tolerated in children with prior MIS-C or COVID-19 participating in our investigation. Parents/guardians regarded their children's doctors as a trusted source of information for COVID-19 vaccines, and most vaccinated children's parents/guardians had discussed COVID-19 vaccination for their child with their doctor.

Multisystem inflammatory syndrome in children (MIS-C) is a complication of SARS-CoV-2 infection; in the U.S., reporting of MIS-C after COVID-19 vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5-11 years on October 29, 2021. Covering a period when ∼7 million children received vaccine, surveillance for MIS-C ≤90 days post-vaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence. During a period with extensive SARS-CoV-2 circulation, MIS-C illness in children after COVID-19 vaccination who lacked evidence of SARS-CoV-2 infection was rare (<1 per million vaccinated children).

We describe characteristics, clinical features and outcomes of multisystem inflammatory syndrome in children among American Indian and Alaska Native (AI/AN) persons compared with non-Hispanic white persons. AI/AN patients with multisystem inflammatory syndrome in children were younger, more often obese, and from areas of higher social vulnerability. A greater proportion of AI/AN patients had severe respiratory involvement and shock.

THIS REPORT SUMMARIZES THE EVIDENCE AND RATIONALE SUPPORTING THE COMPONENTS OF THE CSTE/CDC MIS-C SURVEILLANCE CASE DEFINITION AND DESCRIBES THE METHODS USED TO DEVELOP THE DEFINITION. THESE METHODS INCLUDED CONVENING MIS-C CLINICAL EXPERTS (I.E., CONSULTANTS): regarding identification of MIS-C and its distinction from other pediatric conditions, a review of available literature comparing MIS-C phenotype with that of pediatric COVID-19 and other hyperinflammatory syndromes, and retrospective application of different criteria to data from MIS-C cases previously reported to CDC.

We describe 2,116 multisystem inflammatory syndrome in children (MIS-C) cases reported to CDC during Delta and Omicron circulation from July 2021-January 2022. Half of MIS-C patients were aged 5-11 years, 52% received ICU-level care, and 1.1% died. Only 3.0% of eligible patients were fully vaccinated prior to MIS-C onset.

BACKGROUND AND OBJECTIVES: Limited post-authorization safety data for BNT-162b2 COVID-19 vaccination among children ages 5-11 years are available, particularly for the adverse event myocarditis, which has been detected in adolescents and young adults. We describe adverse events observed during the first 4 months of the US COVID-19 vaccination program in this age group. METHODS: We analyzed data from 3 US safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health effects; the Vaccine Adverse Events Reporting System (VAERS), the national spontaneous reporting system co-managed by CDC and FDA; and the Vaccine Safety Datalink (VSD), an active surveillance system that monitors electronic health records for prespecified events, including myocarditis. RESULTS: Among 48,795 children ages 5-11 years enrolled in v-safe, most reported reactions were mild-to-moderate, most frequently reported the day after vaccination, and were more common after dose 2. VAERS received 7,578 adverse event reports; 97% were non-serious. On review of 194 serious VAERS reports, 15 myocarditis cases were verified; 8 occurred in males after dose 2 (reporting rate 2.2 per million doses). In VSD, no safety signals were detected in weekly sequential monitoring after administration of 726,820 doses. CONCLUSIONS: Safety findings for BNT-162b2 vaccine from 3 US monitoring systems in children ages 5-11 years show that most reported adverse events were mild and no safety signals were observed in active surveillance. VAERS reporting rates of myocarditis after dose 2 in this age group were substantially lower than those observed among adolescents ages 12-15 years.

IMPORTANCE: As self-collected home antigen tests become widely available, a better understanding of their performance during the course of SARS-CoV-2 infection is needed. OBJECTIVE: To evaluate the diagnostic performance of home antigen tests compared with reverse transcription-polymerase chain reaction (RT-PCR) and viral culture by days from illness onset, as well as user acceptability. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted from January to May 2021 in San Diego County, California, and metropolitan Denver, Colorado. The convenience sample included adults and children with RT-PCR-confirmed infection who used self-collected home antigen tests for 15 days and underwent at least 1 nasopharyngeal swab for RT-PCR, viral culture, and sequencing. EXPOSURES: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: The primary outcome was the daily sensitivity of home antigen tests to detect RT-PCR-confirmed cases. Secondary outcomes included the daily percentage of antigen test, RT-PCR, and viral culture results that were positive, and antigen test sensitivity compared with same-day RT-PCR and cultures. Antigen test use errors and acceptability were assessed for a subset of participants. RESULTS: This study enrolled 225 persons with RT-PCR-confirmed infection (median [range] age, 29 [1-83] years; 117 female participants [52%]; 10 [4%] Asian, 6 [3%] Black or African American, 50 [22%] Hispanic or Latino, 3 [1%] Native Hawaiian or Other Pacific Islander, 145 [64%] White, and 11 [5%] multiracial individuals) who completed 3044 antigen tests and 642 nasopharyngeal swabs. Antigen test sensitivity was 50% (95% CI, 45%-55%) during the infectious period, 64% (95% CI, 56%-70%) compared with same-day RT-PCR, and 84% (95% CI, 75%-90%) compared with same-day cultures. Antigen test sensitivity peaked 4 days after illness onset at 77% (95% CI, 69%-83%). Antigen test sensitivity improved with a second antigen test 1 to 2 days later, particularly early in the infection. Six days after illness onset, antigen test result positivity was 61% (95% CI, 53%-68%). Almost all (216 [96%]) surveyed individuals reported that they would be more likely to get tested for SARS-CoV-2 infection if home antigen tests were available over the counter. CONCLUSIONS AND RELEVANCE: The results of this cohort study of home antigen tests suggest that sensitivity for SARS-CoV-2 was moderate compared with RT-PCR and high compared with viral culture. The results also suggest that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1 to 2 days later because test sensitivity peaked several days after illness onset and improved with repeated testing.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorisations. We aimed to investigate reports of individuals aged 12-20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC). METHODS: In this surveillance activity, we investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's MIS-C national surveillance system, the Vaccine Adverse Event Reporting System (co-administered by CDC and the US Food and Drug Administration), and CDC's Clinical Immunization Safety Assessment Project. A multidisciplinary team adjudicated cases by use of the CDC MIS-C definition. Any positive SARS-CoV-2 serology test satisfied case criteria; although anti-nucleocapsid antibodies indicate previous SARS-CoV-2 infection, anti-spike protein antibodies indicate either past or recent infection or COVID-19 vaccination. We describe the demographic and clinical features of cases, stratified by laboratory evidence of SARS-CoV-2 infection. To calculate the reporting rate of MIS-C, we divided the count of all individuals meeting the MIS-C case definition, and of those without evidence of SARS-CoV-2 infection, by the number of individuals aged 12-20 years in the USA who received one or more COVID-19 vaccine doses up to Aug 31, 2021, obtained from CDC national vaccine surveillance data. FINDINGS: Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12-20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12-20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals. INTERPRETATION: Here, we describe a small number of individuals with MIS-C who had received one or more doses of a COVID-19 vaccine before illness onset; the contribution of vaccination to these illnesses is unknown. Our findings suggest that MIS-C after COVID-19 vaccination is rare. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. FUNDING: US Centers for Disease Control and Prevention.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory condition in persons aged <21 years associated with antecedent SARS-CoV-2 infection. Our objective was to describe MIS-C cases reported to CDC's national surveillance since the COVID-19 pandemic began. METHODS: We included patients meeting the MIS-C case definition with onset date from February 19, 2020 through July 31, 2021, using CDC's MIS-C case report form, which collects information on demographics, clinical presentation, and laboratory results. Trends over time across 3 MIS-C pandemic waves were assessed using Cochran-Armitage test for categorical and Jonckheere-Terpstra test for continuous variables. RESULTS: Of 4,901 reported cases, 4,470 met inclusion criteria. Median patient age increased over time (P<0.001), with a median of 9 years (interquartile range, 5-13 years) during the most recent (third) wave. Male predominance also increased (62% in third wave, P<0.001). A significant (P<0.001) increase in severe hematologic and gastrointestinal involvement was observed across the study period. Frequency of several cardiovascular complications (i.e., cardiac dysfunction, myocarditis, and shock/ vasopressor receipt) and renal failure declined (P<0.001). Provision of critical care including mechanical ventilation (P<0.001) and extracorporeal membrane oxygenation (ECMO; P=0.046) decreased, as did duration of hospitalization and mortality (each P<0.001). CONCLUSIONS: Over the first 3 pandemic waves of MIS-C in the United States, cardiovascular complications and clinical outcomes including length of hospitalization, receipt of ECMO, and death decreased over time. These data serve as a baseline for monitoring future trends associated with SARS-CoV-2 B.1.617.2 (Delta) or other variants and increased COVID-19 vaccination among children.

Serologic assays developed for SARS-CoV-2 detect different antibody subtypes and are based on different target antigens. Comparison of the performance of a SARS-CoV-2 Spike-Protein ELISA and the nucleocapsid-based Abbott ArchitectTM SARS-CoV-2 IgG assay indicated that the assays had high concordance, with rare paired discordant tests results.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is often asymptomatic or results in only mild disease.1 Data on the extent of transmission of SARS-CoV-2 from children and adolescents in the household setting, including transmission to older persons who are at increased risk for severe disease, are limited.2 After an outbreak of coronavirus disease 2019 (Covid-19) at an overnight camp,3 we conducted a retrospective cohort study involving camp attendees and their household contacts to assess secondary transmission and factors associated with household transmission (additional details are provided in the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org).

BACKGROUND: To better understand SARS-CoV-2 shedding duration and infectivity, we estimated SARS-CoV-2 RNA shedding duration, described characteristics associated with viral RNA shedding resolution1, and determined if replication-competent viruses could be recovered ≥10 days after symptom onset among individuals with mild to moderate COVID-19. METHODS: We collected serial nasopharyngeal specimens at various time points from 109 individuals with rRT-PCR-confirmed COVID-19 in Utah and Wisconsin. We calculated probability of viral RNA shedding resolution using the Kaplan-Meier estimator and evaluated characteristics associated with shedding resolution using Cox proportional hazards regression. We attempted viral culture for 35 rRT-PCR-positive nasopharyngeal specimens collected ≥10 days after symptom onset. RESULTS: The likelihood of viral RNA shedding resolution at 10 days after symptom onset was approximately 3%. Time to shedding resolution was shorter among participants aged <18 years (adjusted hazards ratio [aHR]: 3.01; 95% CI: 1.6-5.6) and longer among those aged ≥50 years (aHR: 0.50; 95% CI: 0.3-0.9) compared to participants aged 18-49 years. No replication-competent viruses were recovered. CONCLUSIONS: Although most patients were positive for SARS-CoV-2 for ≥10 days after symptom onset, our findings suggest that individuals with mild to moderate COVID-19 are unlikely to be infectious ≥10 days after symptom onset.

OBJECTIVES: In late June 2020, a large outbreak of coronavirus disease 2019 (COVID-19) occurred at a sleep-away youth camp in Georgia, affecting primarily persons </=21 years. We conducted a retrospective cohort study among campers and staff (attendees) to determine the extent of the outbreak and assess factors contributing to transmission. METHODS: Attendees were interviewed to ascertain demographic characteristics, known exposures to COVID-19 and community exposures, and mitigation measures before, during, and after attending camp. COVID-19 case status was determined for all camp attendees on the basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results and reported symptoms. We calculated attack rates and instantaneous reproduction numbers and sequenced SARS-CoV-2 viral genomes from the outbreak. RESULTS: Among 627 attendees, the median age was 15 years (interquartile range: 12-16 years); 56% (351 of 627) of attendees were female. The attack rate was 56% (351 of 627) among all attendees. On the basis of date of illness onset or first positive test result on a specimen collected, 12 case patients were infected before arriving at camp and 339 case patients were camp associated. Among 288 case patients with available symptom information, 45 (16%) were asymptomatic. Despite cohorting, 50% of attendees reported direct contact with people outside their cabin cohort. On the first day of camp session, the instantaneous reproduction number was 10. Viral genomic diversity was low. CONCLUSIONS: Few introductions of SARS-CoV-2 into a youth congregate setting resulted in a large outbreak. Testing strategies should be combined with prearrival quarantine, routine symptom monitoring with appropriate isolation and quarantine, cohorting, social distancing, mask wearing, and enhanced disinfection and hand hygiene. Promotion of mitigation measures among younger populations is needed.

BACKGROUND: Although many viral respiratory illnesses are transmitted within households, the evidence base for SARS-CoV-2 is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission. METHODS: We recruited laboratory-confirmed COVID-19 patients and their household contacts in Utah and Wisconsin during March 22-April 25, 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 rRT-PCR and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (OR) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. RESULTS: Thirty-two (55%) of 58 households had evidence of secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI]: 23-36%) overall, 42% among children (<18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions had increased odds of infection (OR: 15.9, 95% CI: 2.4-106.9). Household contacts who themselves had diabetes mellitus had increased odds of infection (OR: 7.1, 95% CI: 1.2-42.5). CONCLUSIONS: We found substantial evidence of secondary infections among household contacts. People with COVID-19, particularly those with immunocompromising conditions or those with household contacts with diabetes, should take care to promptly self-isolate to prevent household transmission.

BACKGROUND AND OBJECTIVES: Limited data exist on severe acute respiratory syndrome coronavirus 2 in children. We described infection rates and symptom profiles among pediatric household contacts of individuals with coronavirus disease 2019. METHODS: We enrolled individuals with coronavirus disease 2019 and their household contacts, assessed daily symptoms prospectively for 14 days, and obtained specimens for severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction and serology testing. Among pediatric contacts (<18 years), we described transmission, assessed the risk factors for infection, and calculated symptom positive and negative predictive values. We compared secondary infection rates and symptoms between pediatric and adult contacts using generalized estimating equations. RESULTS: Among 58 households, 188 contacts were enrolled (120 adults; 68 children). Secondary infection rates for adults (30%) and children (28%) were similar. Among households with potential for transmission from children, child-to-adult transmission may have occurred in 2 of 10 (20%), and child-to-child transmission may have occurred in 1 of 6 (17%). Pediatric case patients most commonly reported headache (79%), sore throat (68%), and rhinorrhea (68%); symptoms had low positive predictive values, except measured fever (100%; 95% confidence interval [CI]: 44% to 100%). Compared with symptomatic adults, children were less likely to report cough (odds ratio [OR]: 0.15; 95% CI: 0.04 to 0.57), loss of taste (OR: 0.21; 95% CI: 0.06 to 0.74), and loss of smell (OR: 0.29; 95% CI: 0.09 to 0.96) and more likely to report sore throat (OR: 3.4; 95% CI: 1.04 to 11.18). CONCLUSIONS: Children and adults had similar secondary infection rates, but children generally had less frequent and severe symptoms. In two states early in the pandemic, we observed possible transmission from children in approximately one-fifth of households with potential to observe such transmission patterns.

There is increasing evidence that children and adolescents can efficiently transmit SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1-3). During July-August 2020, four state health departments and CDC investigated a COVID-19 outbreak that occurred during a 3-week family gathering of five households in which an adolescent aged 13 years was the index and suspected primary patient; 11 subsequent cases occurred.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.

BACKGROUND: Improved understanding of SARS-CoV-2 spectrum of disease is essential for clinical and public health interventions. There are limited data on mild or asymptomatic infections, but recognition of these individuals is key as they contribute to viral transmission. We describe the symptom profiles from individuals with mild or asymptomatic SARS-CoV-2 infection. METHODS: From March 22 to April 22, 2020 in Wisconsin and Utah, we enrolled and prospectively observed 198 household contacts exposed to SARS-CoV-2. We collected and tested nasopharyngeal (NP) specimens by RT-PCR two or more times during a 14-day period. Contacts completed daily symptom diaries. We characterized symptom profiles on the date of first positive RT-PCR test and described progression of symptoms over time. RESULTS: We identified 47 contacts, median age 24 (3-75) years, with detectable SARS-CoV-2 by RT-PCR. The most commonly reported symptoms on the day of first positive RT-PCR test were upper respiratory (n=32, 68%) and neurologic (n=30, 64%); fever was not commonly reported (n=9, 19%). Eight (17%) individuals were asymptomatic at the date of first positive RT-PCR collection; two (4%) had preceding symptoms that resolved and six (13%) subsequently developed symptoms. Children less frequently reported lower respiratory symptoms (age <18: 21%, age 18-49: 60%, age 50+ years: 69%; p=0.03). CONCLUSIONS: Household contacts with lab-confirmed SARS-CoV-2 infection reported mild symptoms. When assessed at a single time-point, several contacts appeared to have asymptomatic infection; however, over time all developed symptoms. These findings are important to inform infection control, contact tracing, and community mitigation strategies.

Limited data are available about transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), among youths. During June 17-20, an overnight camp in Georgia (camp A) held orientation for 138 trainees and 120 staff members; staff members remained for the first camp session, scheduled during June 21-27, and were joined by 363 campers and three senior staff members on June 21. Camp A adhered to the measures in Georgia's Executive Order* that allowed overnight camps to operate beginning on May 31, including requiring all trainees, staff members, and campers to provide documentation of a negative viral SARS-CoV-2 test ≤12 days before arriving. Camp A adopted most(†) components of CDC's Suggestions for Youth and Summer Camps(§) to minimize the risk for SARS-CoV-2 introduction and transmission. Measures not implemented were cloth masks for campers and opening windows and doors for increased ventilation in buildings. Cloth masks were required for staff members. Camp attendees were cohorted by cabin and engaged in a variety of indoor and outdoor activities, including daily vigorous singing and cheering. On June 23, a teenage staff member left camp A after developing chills the previous evening. The staff member was tested and reported a positive test result for SARS-CoV-2 the following day (June 24). Camp A officials began sending campers home on June 24 and closed the camp on June 27. On June 25, the Georgia Department of Public Health (DPH) was notified and initiated an investigation. DPH recommended that all attendees be tested and self-quarantine, and isolate if they had a positive test result.

Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously(1-3). Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness.