Circulation of Rhinoviruses and/or Enteroviruses in Pediatric Patients With Acute Respiratory Illness Before and During the COVID-19 Pandemic in the US.

Importance: Rhinoviruses and/or enteroviruses, which continued to circulate during the COVID-19 pandemic, are commonly detected in pediatric patients with acute respiratory illness (ARI). Yet detailed characterization of rhinovirus and/or enterovirus detection over time is limited, especially by age group and health care setting. Objective: To quantify and characterize rhinovirus and/or enterovirus detection before and during the COVID-19 pandemic among children and adolescents seeking medical care for ARI at emergency departments (EDs) or hospitals. Design, Setting, and Participants: This cross-sectional study used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective surveillance platform, for pediatric patients who sought medical care for fever and/or respiratory symptoms at 7 EDs or hospitals within NVSN across the US between December 2016 and February 2021. Persons younger than 18 years were enrolled in NVSN, and respiratory specimens were collected and tested for multiple viruses. Main Outcomes and Measures: Proportion of patients in whom rhinovirus and/or enterovirus, or another virus, was detected by calendar month and by prepandemic (December 1, 2016, to March 11, 2020) or pandemic (March 12, 2020, to February 28, 2021) periods. Month-specific adjusted odds ratios (aORs) for rhinovirus and/or enterovirus-positive test results (among all tested) by setting (ED or inpatient) and age group (<2, 2-4, or 5-17 years) were calculated, comparing each month during the pandemic to equivalent months of previous years. Results: Of the 38 198 children and adolescents who were enrolled and tested, 11 303 (29.6%; mean [SD] age, 2.8 [3.7] years; 6733 boys [59.6%]) had rhinovirus and/or enterovirus-positive test results. In prepandemic and pandemic periods, rhinoviruses and/or enteroviruses were detected in 29.4% (9795 of 33 317) and 30.9% (1508 of 4881) of all patients who were enrolled and tested and in 42.2% (9795 of 23 236) and 73.0% (1508 of 2066) of those with test positivity for any virus, respectively. Rhinoviruses and/or enteroviruses were the most frequently detected viruses in both periods and all age groups in the ED and inpatient setting. From April to September 2020 (pandemic period), rhinoviruses and/or enteroviruses were detectable at similar or lower odds than in prepandemic years, with aORs ranging from 0.08 (95% CI, 0.04-0.19) to 0.76 (95% CI, 0.55-1.05) in the ED and 0.04 (95% CI, 0.01-0.11) to 0.71 (95% CI, 0.47-1.07) in the inpatient setting. However, unlike some other viruses, rhinoviruses and/or enteroviruses soon returned to prepandemic levels and from October 2020 to February 2021 were detected at similar or higher odds than in prepandemic months in both settings, with aORs ranging from 1.47 (95% CI, 1.12-1.93) to 3.01 (95% CI, 2.30-3.94) in the ED and 1.36 (95% CI, 1.03-1.79) to 2.44 (95% CI, 1.78-3.34) in the inpatient setting, and in all age groups. Compared with prepandemic years, during the pandemic, rhinoviruses and/or enteroviruses were detected in patients who were slightly older, although most (74.5% [1124 of 1508]) were younger than 5 years. Conclusions and Relevance: Results of this study show that rhinoviruses and/or enteroviruses persisted and were the most common respiratory virus group detected across all pediatric age groups and in both ED and inpatient settings. Rhinoviruses and/or enteroviruses remain a leading factor in ARI health care burden, and active ARI surveillance in children and adolescents remains critical for defining the health care burden of respiratory viruses.

Respiratory Virus Surveillance Among Children with Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021.

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years† with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV.

Enterovirus D68-Associated Acute Respiratory Illness ─ New Vaccine Surveillance Network, United States, July-November 2018-2020.

Enterovirus D68 (EV-D68) is associated with a broad spectrum of illnesses, including mild to severe acute respiratory illness (ARI) and acute flaccid myelitis (AFM). Enteroviruses, including EV-D68, are typically detected in the United States during late summer through fall, with year-to-year fluctuations. Before 2014, EV-D68 was infrequently reported to CDC (1). However, numbers of EV-D68 detection have increased in recent years, with a biennial pattern observed during 2014-2018 in the United States, after the expansion of surveillance and wider availability of molecular testing. In 2014, a national outbreak of EV-D68 was detected (2). EV-D68 was also reported in 2016 via local (3) and passive national (4) surveillance. EV-D68 detections were limited in 2017, but substantial circulation was observed in 2018 (5). To assess recent levels of circulation, EV-D68 detections in respiratory specimens collected from patients aged <18 years* with ARI evaluated in emergency departments (EDs) or admitted to one of seven U.S. medical centers† within the New Vaccine Surveillance Network (NVSN) were summarized. This report provides a provisional description of EV-D68 detections during July-November in 2018, 2019 and 2020, and describes the demographic and clinical characteristics of these patients. In 2018, a total of 382 EV-D68 detections in respiratory specimens obtained from patients aged <18 years with ARI were reported by NVSN; the number decreased to six detections in 2019 and 30 in 2020. Among patients aged <18 years with EV-D68 in 2020, 22 (73%) were non-Hispanic Black (Black) persons. EV-D68 detections in 2020 were lower than anticipated based on the biennial circulation pattern observed since 2014. The circulation of EV-D68 in 2020 might have been limited by widespread COVID-19 mitigation measures; how these changes in behavior might influence the timing and levels of circulation in future years is unknown. Ongoing monitoring of EV-D68 detections is warranted for preparedness for EV-D68-associated ARI and AFM.

Surface‒Aerosol Stability and Pathogenicity of Diverse Middle East Respiratory Syndrome Coronavirus Strains, 2012‒2018.

Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. Although some mutations found in camel-derived MERS-CoV strains have been characterized, most natural variation found across MERS-CoV isolates remains unstudied. We report on the environmental stability, replication kinetics, and pathogenicity of several diverse isolates of MERS-CoV, as well as isolates of severe acute respiratory syndrome coronavirus 2, to serve as a basis of comparison with other stability studies. Although most MERS-CoV isolates had similar stability and pathogenicity in our experiments, the camel-derived isolate C/KSA/13 had reduced surface stability, and another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that although betacoronaviruses might have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the need for continual global viral surveillance.

Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021.

Importance: People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain. Objective: To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population. Design, Setting, and Participants: In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021. Exposure: Calendar time. Main Outcomes and Measures: Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates. Results: Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred. Conclusions and Relevance: Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population.

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 in the United States.

BACKGROUND: The evidence base for severe acute respiratory syndrome coronavirus-2 (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 patients with laboratory-confirmed SARS-CoV-2 infection and their household contacts in Utah and Wisconsin during 22 March 2020-25 April 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 real-time reverse-transcription polymerase chain reaction (rRT-PCR) and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (ORs) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. RESULTS: Thirty-two (55%) of 58 households secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI], 23%-36%) overall, 42% among children (aged <18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions and household contacts who themselves had diabetes mellitus had increased odds of infection with ORs 15.9 (95% CI, 2.4-106.9) and 7.1 (95% CI: 1.2-42.5), respectively. 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.

Shedding of Culturable Virus, Seroconversion, and 6-Month Follow-up Antibody Responses in the First 14 Confirmed Cases of Coronavirus Disease 2019 in the United States.

We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to 6 months after symptom onset, among 14 early patients with coronavirus disease 2019 in the United States. We isolated viable severe acute respiratory syndrome coronavirus 2 from real-time reverse-transcription polymerase chain reaction-positive respiratory specimens collected during days 0-8 after onset, but not after. All 13 patients with 2 or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at 6 months after onset; all retained detectable anti-spike immunoglobulin G, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at 6 months.

Animal Reservoirs and Hosts for Emerging Alphacoronaviruses and Betacoronaviruses.

The ongoing global pandemic caused by coronavirus disease has once again demonstrated the role of the family Coronaviridae in causing human disease outbreaks. Because severe acute respiratory syndrome coronavirus 2 was first detected in December 2019, information on its tropism, host range, and clinical manifestations in animals is limited. Given the limited information, data from other coronaviruses might be useful for informing scientific inquiry, risk assessment, and decision-making. We reviewed endemic and emerging infections of alphacoronaviruses and betacoronaviruses in wildlife, livestock, and companion animals and provide information on the receptor use, known hosts, and clinical signs associated with each host for 15 coronaviruses detected in humans and animals. This information can be used to guide implementation of a One Health approach that involves human health, animal health, environmental, and other relevant partners in developing strategies for preparedness, response, and control to current and future coronavirus disease threats.

Severe Acute Respiratory Syndrome Coronavirus 2 Infections in Children: Multicenter Surveillance, United States, January-March 2020.

Previous reports of coronavirus disease 2019 among children in the United States have been based on health jurisdiction reporting. We performed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing on children enrolled in active, prospective, multicenter surveillance during January-March 2020. Among 3187 children, only 4 (0.1%) SARS-CoV-2-positive cases were identified March 20-31 despite evidence of rising community circulation.

Investigation and Serologic Follow-Up of Contacts of an Early Confirmed Case-Patient with COVID-19, Washington, USA.

We describe the contact investigation for an early confirmed case of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the United States. Contacts of the case-patient were identified, actively monitored for symptoms, interviewed for a detailed exposure history, and tested for SARS-CoV-2 infection by real-time reverse transcription PCR (rRT-PCR) and ELISA. Fifty contacts were identified and 38 (76%) were interviewed, of whom 11 (29%) reported unprotected face-to-face interaction with the case-patient. Thirty-seven (74%) had respiratory specimens tested by rRT-PCR, and all tested negative. Twenty-three (46%) had ELISA performed on serum samples collected ≈6 weeks after exposure, and none had detectable antibodies to SARS-CoV-2. Among contacts who were tested, no secondary transmission was identified in this investigation, despite unprotected close interactions with the infectious case-patient.

First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. METHODS: Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient's symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested. FINDINGS: Patient 1-a woman in her 60s-returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2. INTERPRETATION: Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected. FUNDING: None.

First Case of 2019 Novel Coronavirus in the United States.

An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.

Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020.

In December 2019, a cluster of cases of pneumonia emerged in Wuhan City in central China's Hubei Province. Genetic sequencing of isolates obtained from patients with pneumonia identified a novel coronavirus (2019-nCoV) as the etiology (1). As of February 4, 2020, approximately 20,000 confirmed cases had been identified in China and an additional 159 confirmed cases in 23 other countries, including 11 in the United States (2,3). On January 17, CDC and the U.S. Department of Homeland Security's Customs and Border Protection began health screenings at U.S. airports to identify ill travelers returning from Wuhan City (4). CDC activated its Emergency Operations Center on January 21 and formalized a process for inquiries regarding persons suspected of having 2019-nCoV infection (2). As of January 31, 2020, CDC had responded to clinical inquiries from public health officials and health care providers to assist in evaluating approximately 650 persons thought to be at risk for 2019-nCoV infection. Guided by CDC criteria for the evaluation of persons under investigation (PUIs) (5), 210 symptomatic persons were tested for 2019-nCoV; among these persons, 148 (70%) had travel-related risk only, 42 (20%) had close contact with an ill laboratory-confirmed 2019-nCoV patient or PUI, and 18 (9%) had both travel- and contact-related risks. Eleven of these persons had laboratory-confirmed 2019-nCoV infection. Recognizing persons at risk for 2019-nCoV is critical to identifying cases and preventing further transmission. Health care providers should remain vigilant and adhere to recommended infection prevention and control practices when evaluating patients for possible 2019-nCoV infection (6). Providers should consult with their local and state health departments when assessing not only ill travelers from 2019-nCoV-affected countries but also ill persons who have been in close contact with patients with laboratory-confirmed 2019-nCoV infection in the United States.