SARS-CoV-2 Exposure Investigations Using Genomic Sequencing Among Healthcare Workers and Patients in A Large Academic Center.

SARS-CoV-2 transmissions among healthcare personnel (HCP) and hospitalized patients are challenging to confirm. Investigation of infected persons often reveals multiple potential risk factors for viral acquisition. We combined exposure investigation with genomic analysis confirming two hospital-based clusters. Prolonged close contact with unmasked, unrecognized infectious, individuals was a common risk.

Healthcare-associated Respiratory Syncytial Virus in Children's Hospitals.

BACKGROUND: Outbreaks of healthcare-associated respiratory syncytial virus (HA-RSV) infections in children are well described, but less is known about sporadic HA-RSV infections. We assessed the epidemiology and clinical outcomes associated with sporadic HA-RSV infections. METHODS: We retrospectively identified hospitalized children <18 years old with HA-RSV infections in six children's hospitals in the United States during the respiratory viral seasons October-April in 2016-2017, 2017-2018, and 2018-2019 and prospectively from October 2020 through November 2021. We evaluated outcomes temporally associated with HA-RSV infections including escalation of respiratory support, transfer to the pediatric intensive care unit (PICU), and in-hospital mortality. We assessed demographic characteristics and comorbid conditions associated with escalation of respiratory support. RESULTS: We identified 122 children (median age 16.0 months [IQR 6, 60 months]) with HA-RSV. The median onset of HA-RSV infections was hospital day 14 (IQR 7, 34 days). Overall, 78 (63.9%) children had two or more comorbid conditions; cardiovascular, gastrointestinal, neurologic/neuromuscular, respiratory, and premature/ neonatal comorbidities were most common. Fifty-five (45.1%) children required escalation of respiratory support and 18 (14.8%) were transferred to the PICU. Five (4.1%) died during hospitalization. In the multivariable analysis, respiratory comorbidities (aOR: 3.36 [CI95 1.41, 8.01]) were associated with increased odds of escalation of respiratory support. CONCLUSIONS: HA-RSV infections cause preventable morbidity and increase healthcare resource utilization. Further study of effective mitigation strategies for HA-respiratory viral infections should be prioritized; this priority is further supported by the impact of the COVID-19 pandemic on seasonal viral infections.

Infection prevention and antibiotic stewardship program needs and practices in 2021: A survey of the Society for Healthcare Epidemiology of America Research Network.

In total, 50 healthcare facilities completed a survey in 2021 to characterize changes in infection prevention and control and antibiotic stewardship practices. Notable findings include sustained surveillance for multidrug-resistant organisms but decreased use of human resource-intensive interventions compared to previous surveys in 2013 and 2018 conducted prior to the COVID-19 pandemic.

Impact of weekly asymptomatic testing for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in inpatients at an academic hospital.

We analyzed the impact of a 7-day recurring asymptomatic SARS-CoV-2 testing protocol for all patients hospitalized at a large academic center. Overall, 40 new cases were identified, and 1 of 3 occurred after 14 days of hospitalization. Recurring testing can identify unrecognized infections, especially during periods of elevated community transmission.

Association of healthcare worker behaviors with coronavirus disease 2019 (COVID-19) risk during four pandemic periods and characteristics associated with high-risk behaviors.

In a large healthcare worker cohort, we quantified the association between behaviors and risk of coronavirus disease 2019 (COVID-19) during different pandemic phases, adjusting for prior infection and vaccination. Individual characteristics, including personal concerns, were associated with these behaviors. Public health messaging should target high-risk populations and behaviors as the pandemic evolves.

Neutralizing SARS-CoV-2 Spike Antibodies against Omicron in Paired Samples after Two or Three Doses of mRNA Vaccine.

SARS-CoV-2 antibody levels wane following two-doses of mRNA vaccination. An mRNA booster dose provides increased protection against hospitalization and death. We demonstrated that a booster dose provides a significant increase in the neutralization of the Beta, Delta and Omicron variants in addition to an increased neutralization of the vaccine strain. The total spike IgG measurements, obtained by using commercial kits that target the spike protein from the vaccine strain, may not reflect serum neutralization against variants of concern. IMPORTANCE This study found little to no neutralizing capability following a 2-dose mRNA vaccine series against the omicron variant, and neutralizing capacity to any variant strain tested was lost by 8-months post 2-dose series. However, the mRNA booster dose eliminated the immune escape observed by the Omicron variant, following the 2-dose series. Even more, the neutralizing titers were significantly higher for all variants post-boost, compared to the titers from the post-two-dose series. Our data are unique, using paired samples that eliminate potential confounders that may impact vaccine response. Notably, as seen after the primary two-dose vaccine series, total antibody levels did not correlate perfectly with variant neutralization activity, suggesting that simply testing titers as a measure of protection may not be a long-term solution. Therefore, it is important to reassess the utility of SARS-CoV-2 antibody testing, as current vaccine strain-based testing may not reliably detect reactive antibodies to Omicron or other variants of concern.

Association of Frailty, Age, and Biological Sex With Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine-Induced Immunity in Older Adults.

BACKGROUND: Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. METHODS: Plasma samples were collected from older adults (aged 75-98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18-74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). RESULTS: Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. CONCLUSIONS: Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

Differentiation of Individuals Previously Infected with and Vaccinated for SARS-CoV-2 in an Inner-City Emergency Department.

Emergency departments (EDs) can serve as surveillance sites for infectious diseases. The objective of this study was to determine the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to monitor the prevalence of vaccination against coronavirus disease 2019 (COVID-19) among patients attending an urban ED in Baltimore City. Using 1,914 samples of known exposure status, we developed an algorithm to differentiate previously infected, vaccinated, and unexposed individuals using a combination of antibody assays. We applied this testing algorithm to 4,360 samples from ED patients obtained in the spring of 2020 and 2021. Using multinomial logistic regression, we determined factors associated with infection and vaccination. For the algorithm, sensitivity and specificity for identifying vaccinated individuals were 100% and 99%, respectively, and 84% and 100% for previously infected individuals. Among the ED subjects, seroprevalence to SARS-CoV-2 increased from 2% to 24% between April 2020 and March 2021. Vaccination prevalence rose to 11% by mid-March 2021. Marked differences in burden of disease and vaccination coverage were seen by sex, race, and ethnicity. Hispanic patients, though accounting for 7% of the study population, had the highest relative burden of disease (17% of total infections) but with similar vaccination rates. Women and white individuals were more likely to be vaccinated than men or Black individuals. Individuals previously infected with SARS-CoV-2 can often be differentiated from vaccinated individuals using a serologic testing algorithm. The utility of this algorithm can aid in monitoring SARS-CoV-2 exposure and vaccination uptake frequencies and can potentially reflect gender, race, and ethnic health disparities.

In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, variants with enhanced virulence and transmissibility have emerged. Although in vitro systems allow rapid characterization, they do not fully recapitulate the dynamic interaction of virions and neutralizing antibodies in the airway. Here, we demonstrate that the N501Y variant permits respiratory infection in unmodified mice. We utilize N501Y to survey in vivo pseudovirus infection dynamics and susceptibility to reinfection with the L452R (Los Angeles), K417N + E484K (South Africa), and L452R + K417N + E484Q (India) variants. Human coronavirus disease 2019 (COVID-19)+ or vaccinated antibody isotypes, titers, variant receptor binding domain (RBD) binding, and neutralization potential are studied, revealing numerous significant correlations. Immune escape of the K417N + E484K variant is observed because infection can be appreciated in the nasopharynx, but not lungs, of mice transferred with low-antibody-tier plasma. Conversely, near-complete protection is observed in animals receiving high-antibody-tier plasma, a phenomenon that can only be appreciated in vivo.

In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential

Lam et al. develop a model of SARS-CoV-2 infection in laboratory mice. This allows the researchers to study the threat of emerging variants in a more physiological context than cell culture systems. Interactions between SARS-CoV-2 variants and immunity is explored in the airway of mice.

Coronavirus disease 2019 (COVID-19) research agenda for healthcare epidemiology.

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.

Coronavirus Disease 2019 in Pregnancy and Outcomes Among Pregnant Women and Neonates: A Literature Review.

Limited data are available about the outcomes of coronavirus disease 2019 (COVID-19) during pregnancy and risk of vertical transmission in exposed neonates. We reviewed studies published February 1, 2020, through August 15, 2020, on outcomes in pregnant women with COVID-19 and neonates with perinatal exposure. Among pregnant women with COVID-19, 181 (11%) required intensive care unit admission and 123 (8%) required mechanical ventilation. There were 22 maternal deaths. Most infections occurred in the third trimester. Among women who delivered, 28% had a preterm birth, and 57% had a Caesarean section. Sixty-one (4%) of 1222 neonates with reported testing had at least 1 positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test. The most common symptom among neonates was respiratory distress (n = 126; 21%). There were 14 neonatal deaths, one of which occurred in a neonate with positive testing. Further study of COVID-19 in pregnant women and neonates, including standardized reporting of outcomes, testing and treatment protocols, is essential to optimize maternal and neonatal care.

Risk Factors Associated With SARS-CoV-2 Seropositivity Among US Health Care Personnel.

Importance: Risks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care personnel (HCP) are unclear. Objective: To evaluate the risk factors associated with SARS-CoV-2 seropositivity among HCP with the a priori hypothesis that community exposure but not health care exposure was associated with seropositivity. Design, Setting, and Participants: This cross-sectional study was conducted among volunteer HCP at 4 large health care systems in 3 US states. Sites shared deidentified data sets, including previously collected serology results, questionnaire results on community and workplace exposures at the time of serology, and 3-digit residential zip code prefix of HCP. Site-specific responses were mapped to a common metadata set. Residential weekly coronavirus disease 2019 (COVID-19) cumulative incidence was calculated from state-based COVID-19 case and census data. Exposures: Model variables included demographic (age, race, sex, ethnicity), community (known COVID-19 contact, COVID-19 cumulative incidence by 3-digit zip code prefix), and health care (workplace, job role, COVID-19 patient contact) factors. Main Outcome and Measures: The main outcome was SARS-CoV-2 seropositivity. Risk factors for seropositivity were estimated using a mixed-effects logistic regression model with a random intercept to account for clustering by site. Results: Among 24 749 HCP, most were younger than 50 years (17 233 [69.6%]), were women (19 361 [78.2%]), were White individuals (15 157 [61.2%]), and reported workplace contact with patients with COVID-19 (12 413 [50.2%]). Many HCP worked in the inpatient setting (8893 [35.9%]) and were nurses (7830 [31.6%]). Cumulative incidence of COVID-19 per 10 000 in the community up to 1 week prior to serology testing ranged from 8.2 to 275.6; 20 072 HCP (81.1%) reported no COVID-19 contact in the community. Seropositivity was 4.4% (95% CI, 4.1%-4.6%; 1080 HCP) overall. In multivariable analysis, community COVID-19 contact and community COVID-19 cumulative incidence were associated with seropositivity (community contact: adjusted odds ratio [aOR], 3.5; 95% CI, 2.9-4.1; community cumulative incidence: aOR, 1.8; 95% CI, 1.3-2.6). No assessed workplace factors were associated with seropositivity, including nurse job role (aOR, 1.1; 95% CI, 0.9-1.3), working in the emergency department (aOR, 1.0; 95% CI, 0.8-1.3), or workplace contact with patients with COVID-19 (aOR, 1.1; 95% CI, 0.9-1.3). Conclusions and Relevance: In this cross-sectional study of US HCP in 3 states, community exposures were associated with seropositivity to SARS-CoV-2, but workplace factors, including workplace role, environment, or contact with patients with known COVID-19, were not. These findings provide reassurance that current infection prevention practices in diverse health care settings are effective in preventing transmission of SARS-CoV-2 from patients to HCP.

Community-Onset Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Young Infants: A Systematic Review.

OBJECTIVE: To summarize and evaluate current reports on community-onset severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young infants. STUDY DESIGN: We performed a systematic review to identify reports published from November 1, 2019, until June 15, 2020, on laboratory-confirmed community-onset SARS-CoV-2 infection in infants younger than 3 months of age. We excluded studies reporting neonates with perinatal coronavirus disease 2019 (COVID-19) exposure and diagnosis before hospital discharge and hospital-onset disease, as well as clinically diagnosed cases without confirmation. Two independent reviewers performed study screening, data abstraction, and risk of bias assessment. Variables of interest included patient age, exposure to COVID-19, medical history, clinical symptoms, SARS-CoV-2 testing, laboratory findings, clinical course, and disposition. RESULTS: In total, 38 publications met inclusion criteria, including 23 single case reports, 14 case series, and 1 cohort study, describing 63 infants younger than 3 months of age with laboratory-confirmed SARS-CoV-2 infection. Most cases were mild to moderate. Fever, respiratory, gastrointestinal, cardiac, and neurologic findings were reported. Laboratory abnormalities included neutropenia, lymphopenia, and elevated serum levels of inflammatory markers and aminotransferases. Fifty-eight (92%) infants were hospitalized, 13 (21%) were admitted to the intensive care unit, and 2 (3%) required mechanical ventilation. No death was reported. CONCLUSIONS: Among young infants with laboratory-confirmed SARS-CoV-2 infection, most cases were mild to moderate and improved with supportive care. Our results demonstrate a need for a high index of suspicion for SARS-CoV-2 infection in young infants presenting with generalized symptoms such as fever or decreased feeding, even in the absence of respiratory symptoms.

Transforming a PICU Into an Adult ICU During the Coronavirus Disease 2019 Pandemic: Meeting Multiple Needs.

We describe the process converting half of our 40-bed PICU into a negative-pressure biocontainment ICU dedicated to adult coronavirus disease 2019 patients within a 1,003-bed academic quaternary hospital. We outline the construction, logistics, supplies, provider education, staffing, and operations. We share lessons learned of working with a predominantly pediatric staff blended with adult expertise staff while maintaining elements of family-centered care typical of pediatric critical care medicine. Critically ill coronavirus disease 2019 adult patients may be cared for in a PICU and care may be augmented by implementing elements of holistic, family-centered PICU practice.