Infectious viral shedding of SARS-CoV-2 Delta following vaccination: A longitudinal cohort study.

The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P = 0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.

Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children's sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.

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.

Outbreaks of Adenovirus-associated Respiratory Illness on 5 College Campuses in the United States, 2018-2019.

BACKGROUND: Human adenoviruses (HAdVs) are commonly associated with acute respiratory illness. HAdV outbreaks are well documented in congregate military training settings, but less is known about outbreaks on college campuses. During fall 2018 and spring 2019, 5 United States (US) colleges reported increases in HAdV-associated respiratory illness. Investigations were performed to better understand HAdV epidemiology in this setting. METHODS: A case was defined as a student at one of the 5 colleges, with acute respiratory illness and laboratory-confirmed HAdV infection during October 2018-December 2018 or March-May 2019. Available respiratory specimens were typed by HAdV type-specific real-time polymerase chain reaction assays, and for a subset, whole genome sequencing was performed. We reviewed available medical records and cases were invited to complete a questionnaire, which included questions on symptom presentation, social history, and absenteeism. RESULTS: We identified 168 HAdV cases. Median age was 19 (range, 17-22) years and 102 cases (61%) were male. Eleven cases were hospitalized, 10 with pneumonia; 2 cases died. Among questionnaire respondents, 80% (75/94) missed ≥ 1 day of class because of their illness. Among those with a type identified (79%), HAdV types 4 and 7 were equally detected, with frequency of each varying by site. Genome types 4a1 and 7d were identified, respectively, by whole genome sequence analysis. CONCLUSIONS: HAdV respiratory illness was associated with substantial morbidity and missed class time among young, generally healthy adults on 5 US college campuses. HAdVs should be considered a cause of respiratory illness outbreaks in congregate settings such as college campuses.

Enterovirus D68 infection among hospitalized children with severe acute respiratory illness in El Salvador and Panama, 2012-2013.

We assessed EV-D68 epidemiology and phylogenetics among children aged ≤9 years hospitalized with severe acute respiratory illnesses at five sites in Panama and El Salvador during 2012-2013. Respiratory specimens positive for enterovirus or rhinovirus were tested by real-time RT-PCR for EV-D68, and partial VP1 gene sequences were determined. Of 715 enrolled children, 17 from sites in both countries were EV-D68-positive and commonly had a history of asthma or wheezing. Phylogenetically, 15 of 16 sequences fell into Clade B1, and one into Clade A2. The Central American EV-D68s were closely related genetically to contemporaneous strains from North America, South America, and the Caribbean.

Lack of Serologic Evidence of Infection Among Health Care Personnel and Other Contacts of First 2 Confirmed Patients With COVID-19 in Illinois, 2020.

OBJECTIVES: Widespread global transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), continues. Many questions remain about asymptomatic or atypical infections and transmission dynamics. We used comprehensive contact tracing of the first 2 confirmed patients in Illinois with COVID-19 and serologic SARS-CoV-2 antibody testing to determine whether contacts had evidence of undetected COVID-19. METHODS: Contacts were eligible for serologic follow-up if previously tested for COVID-19 during an initial investigation or had greater-risk exposures. Contacts completed a standardized questionnaire during the initial investigation. We classified exposure risk as high, medium, or low based on interactions with 2 index patients and use of personal protective equipment (PPE). Serologic testing used a SARS-CoV-2 spike enzyme-linked immunosorbent assay on serum specimens collected from participants approximately 6 weeks after initial exposure to either index patient. The 2 index patients provided serum specimens throughout their illness. We collected data on demographic, exposure, and epidemiologic characteristics. RESULTS: Of 347 contacts, 110 were eligible for serologic follow-up; 59 (17% of all contacts) enrolled. Of these, 53 (90%) were health care personnel and 6 (10%) were community contacts. Seventeen (29%) reported high-risk exposures, 15 (25%) medium-risk, and 27 (46%) low-risk. No participant had evidence of SARS-CoV-2 antibodies. The 2 index patients had antibodies detected at dilutions >1:6400 within 4 weeks after symptom onset. CONCLUSIONS: In serologic follow-up of the first 2 known patients in Illinois with COVID-19, we found no secondary transmission among tested contacts. Lack of seroconversion among these contacts adds to our understanding of conditions (ie, use of PPE) under which SARS-CoV-2 infections might not result in transmission and demonstrates that SARS-CoV-2 antibody testing is a useful tool to verify epidemiologic findings.

Surveillance and Testing for Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, March 2016-March 2019.

During March 2016-March 2019, a total of 200,936 suspected cases of Middle East respiratory syndrome coronavirus infection were identified in Saudi Arabia; infections were confirmed in 698 cases (0.3% [0.7/100,000 population per year]). Continued surveillance is necessary for early case detection and timely infection control response.

Middle East Respiratory Syndrome Coronavirus Transmission.

Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but little evidence suggests the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.

Human parainfluenza virus circulation, United States, 2011-2019.

BACKGROUND: Human parainfluenza viruses (HPIVs) cause upper and lower respiratory tract illnesses, most frequently among infants and young children, but also in the elderly. While seasonal patterns of HPIV types 1-3 have been described, less is known about national patterns of HPIV-4 circulation. OBJECTIVES: To describe patterns of HPIVs circulation in the United States (US). STUDY DESIGN: We used data from the National Respiratory and Enteric Virus Surveillance System (NREVSS), a voluntary passive laboratory-based surveillance system, to characterize the epidemiology and circulation patterns of HPIVs in the US during 2011-2019. We summarized the number of weekly aggregated HPIV detections nationally and by US census region, and used a subset of data submitted to NREVSS from public health laboratories and several clinical laboratories during 2015-2019 to analyze differences in patient demographics. RESULTS: During July 2011 - June 2019, 2,700,135 HPIV tests were reported; 122,852 (5 %) were positive for any HPIV including 22,446 for HPIV-1 (18 %), 17,474 for HPIV-2 (14 %), 67,649 for HPIV-3 (55 %), and 15,283 for HPIV-4 (13 %). HPIV testing increased substantially each year. The majority of detections occurred in children aged ≤ 2 years (36 %) with fluctuations in the distribution of age by type. CONCLUSIONS: HPIVs were detected year-round during 2011-2019, with type-specific year-to-year variations in circulation patterns. Among HPIV detections where age was known, the majority were aged ≤ 2 years. HPIV-4 exhibited an annual fall-winter seasonality, both nationally and regionally. Continued surveillance is needed to better understand national patterns of HPIV circulation.

Outbreak of Respiratory Illness Associated With Human Adenovirus Type 7 Among Persons Attending Officer Candidates School, Quantico, Virginia, 2017.

A respiratory outbreak associated with human adenovirus type 7 (HAdV-7) occurred among unvaccinated officer candidates attending initial military training. Respiratory infections associated with HAdV-7 can be severe, resulting in significant morbidity. Genomic sequencing revealed HAdV-7d, a genome type recently remerging in the United States as a significant respiratory pathogen, following reports from Southeast Asia. Twenty-nine outbreak cases were identified; this likely represents an underestimate. Although the HAdV type 4 and 7 vaccine is currently given to US military enlisted recruit trainees, it is not routinely given to officer candidates. Administration of the HAdV type 4 and 7 vaccine may benefit this cohort.

Diabetes Mellitus, Hypertension, and Death among 32 Patients with MERS-CoV Infection, Saudi Arabia.

Diabetes mellitus and hypertension are recognized risk factors for severe clinical outcomes, including death, associated with Middle East respiratory syndrome coronavirus infection. Among 32 virus-infected patients in Saudi Arabia, severity of illness and frequency of death corresponded closely with presence of multiple and more severe underlying conditions.

Severe Human Metapneumovirus and Group A Streptococcus Pneumonia in an Immunocompetent Adult.

An immunocompetent adult with asthma developed severe human metapneumovirus (HMPV) illness complicated by group A Streptococcus coinfection, progressing to acute respiratory distress syndrome and shock. Several coworkers had less severe HMPV infection. HMPV can cause severe respiratory illness in healthy adults and should be considered as a potential cause of community respiratory outbreaks.

Isolation and growth characterization of novel full length and deletion mutant human MERS-CoV strains from clinical specimens collected during 2015.

Middle East respiratory syndrome (MERS) is a viral respiratory illness first reported in Saudi Arabia in September 2012 caused by the human coronavirus (CoV), MERS-CoV. Using full-genome sequencing and phylogenetic analysis, scientists have identified three clades and multiple lineages of MERS-CoV in humans and the zoonotic host, dromedary camels. In this study, we have characterized eight MERS-CoV isolates collected from patients in Saudi Arabia in 2015. We have performed full-genome sequencing on the viral isolates, and compared them to the corresponding clinical specimens. All isolates were clade B, lineages 4 and 5. Three of the isolates carry deletions located on three independent regions of the genome in the 5'UTR, ORF1a and ORF3. All novel MERS-CoV strains replicated efficiently in Vero and Huh7 cells. Viruses with deletions in the 5'UTR and ORF1a exhibited impaired viral release in Vero cells. These data emphasize the plasticity of the MERS-CoV genome during human infection.

Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, 2017-2018.

We characterized exposures and demographics of Middle East respiratory syndrome coronavirus cases reported to the Saudi Arabia Ministry of Health during July 1-October 31, 2017, and June 1-September 16, 2018. Molecular characterization of available specimens showed that circulating viruses during these periods continued to cluster within lineage 5.

Picornavirus etiology of acute infections among hospitalized infants.

BACKGROUND: Enteroviruses (EV) and parechoviruses (PeV) are ubiquitous viruses that cause a range of illness, including acute illness in children aged <1 year. OBJECTIVES: We describe EV and PeV infections among children from 2 US study sites aged <1 year and hospitalized with acute infections. For EV- and PeV-negative case-patients, we explored other viral etiologies. METHODS: Participants were aged <1 year, hospitalized during 2016, and had cerebrospinal fluid (CSF) collected for routine diagnostic testing. Demographic and clinical data were abstracted from medical charts, and residual specimens were sent to CDC for confirmatory testing and typing. RESULTS: Of 472 eligible case-patients, CSF specimen was available for 319 (67.6%). Among those, 13 (4.1%) were positive for EV and 11 (3.4%) for PeV. Most case-patients (86.8%, n = 277) were aged <2 months, as were all EV- or PeV-positive case-patients. None of the positive case-patients had underlying conditions, and the chief complaint for 91.7% (n = 22) was fever. Twelve positive case-patients were admitted to intensive care (ICU) and had brief hospital stays (median 2 days). Sequencing revealed a variety of EV types and the predominance of PeV-A3 among the PeV-positive case-patients. CONCLUSIONS: A range of EV and PeV types were associated with acute febrile illnesses leading to hospitalization in children aged <2 months. Approximately half of EV and PeV case-patients were admitted to ICU, but length of hospital stay was brief and illnesses were generally self-limiting. Clinicians should consider EV and PeV infections in infants presenting with febrile illness.

Risk Factors for MERS-CoV Seropositivity among Animal Market and Slaughterhouse Workers, Abu Dhabi, United Arab Emirates, 2014-2017.

Camel contact is a recognized risk factor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Because specific camel exposures associated with MERS-CoV seropositivity are not fully understood, we investigated worker-camel interactions and MERS-CoV seroprevalence. We assessed worker seroprevalence in 2 slaughterhouses and 1 live-animal market in Abu Dhabi, United Arab Emirates, during 2014-2017 and administered an epidemiologic survey in 2016 and 2017. Across 3 sampling rounds during 2014-2017, we sampled 100-235 workers, and 6%-19% were seropositive for MERS-CoV at each sampling round. One (1.4%) of 70 seronegative workers tested at multiple rounds seroconverted. On multivariable analyses, working as a camel salesman, handling live camels or their waste, and having diabetes were associated with seropositivity among all workers, whereas handling live camels and either administering medications or cleaning equipment was associated with seropositivity among market workers. Characterization of high-risk exposures is critical for implementation of preventive measures.

Middle East Respiratory Syndrome Coronavirus Infection Dynamics and Antibody Responses among Clinically Diverse Patients, Saudi Arabia.

Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV-positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics.

Enterovirus D68-Associated Acute Respiratory Illness - New Vaccine Surveillance Network, United States, July-October, 2017 and 2018.

In the fall of 2014, an outbreak of enterovirus D68 (EV-D68)-associated acute respiratory illness (ARI) occurred in the United States (1,2); before 2014, EV-D68 was rarely reported to CDC (2,3). In the United States, reported EV-D68 detections typically peak during late summer and early fall (3). EV-D68 epidemiology is not fully understood because testing in clinical settings seldom has been available and detections are not notifiable to CDC. To better understand EV-D68 epidemiology, CDC recently established active, prospective EV-D68 surveillance among pediatric patients at seven U.S. medical centers through the New Vaccine Surveillance Network (NVSN) (4). This report details a preliminary characterization of EV-D68 testing and detections among emergency department (ED) and hospitalized patients with ARI at all NVSN sites during July 1-October 31, 2017, and the same period in 2018. Among patients with ARI who were tested, EV-D68 was detected in two patients (0.8%) in 2017 and 358 (13.9%) in 2018. Continued active, prospective surveillance of EV-D68-associated ARI is needed to better understand EV-D68 epidemiology in the United States.

Respiratory Illness Associated With Emergent Human Adenovirus Genome Type 7d, New Jersey, 2016-2017.

BACKGROUND: Human adenoviruses (HAdVs) are known causes of respiratory illness outbreaks in congregate settings, but cases and clusters are less well described from community settings in the United States. During December 2016-February 2017, the New Jersey Department of Health received reports of HAdV infections from 3 sources in 3 adjacent counties. We investigated to characterize the epidemiologic, laboratory, and clinical features of this HAdV outbreak. METHODS: A case was defined as a New Jersey resident with acute respiratory illness during December 1, 2016-March 31, 2017 with laboratory identification of HAdV genome type 7d (HAdV-7d). Human adenovirus was detected by real-time and conventional polymerase chain reaction and molecular typed by partial hexon capsid protein gene sequencing. The HAdV genome type was identified by whole genome sequencing analysis. Available medical, public health, and surveillance records were reviewed. RESULTS: We identified 12 cases, including 3 treatment facility patients, 7 college students, and 2 cases at a tertiary-care hospital. Four cases died; all had underlying comorbidities. Nine HAdV-7d whole genome sequences obtained from all 3 sites were nearly identical. CONCLUSIONS: Transmission of HAdV-7d occurred in community and congregate settings across 3 counties and resulted in severe morbidity and mortality in some cases with underlying comorbidities. Clinicians and local and state health departments should consider HAdV in patients with severe respiratory infection.