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.

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.

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.

Comparison of total and neutralizing SARS-CoV-2 spike antibodies against omicron and other variants in paired samples after two or three doses of mRNA vaccine.

Recognizing that anti-SARS-CoV-2 antibody levels wane over time following the 2-dose SARS-CoV-2 mRNA series, the FDA approved a booster dose for people greater than 12 years old. Limited data exist on whether a booster dose of the mRNA vaccine results in greater antibody protection than the primary series. We examined total and neutralizing antibodies to the spike protein of SARS-CoV-2, and neutralizing antibodies against Washington-1 (WA-1) and variants of concern (VOC) including Beta, Delta and Omicron in a longitudinal cohort. Healthcare workers (HWs) were included in the analysis if serum was collected 1) within 14-44 days post-dose2 of an mRNA SARS-CoV-2 vaccine (Timepoint 1, TP1), or 2) at least 8 months post-dose2 (Timepoint 2, TP2), or 3) within 14-44 days following mRNA booster (Timepoint 3, TP3). HWs with prior covid-positive PCR were excluded. We found that there is little to no neutralizing capability following a 2-dose mRNA vaccine series against the omicron variant, and neutralizing capacity to any variant strain tested has been lost by 8-months post two-dose vaccination series. However, the mRNA booster series eliminates the immune escape observed by the omicron variant with the two-dose series. Neutralizing titers were significantly higher for all variants post-boost compared to the titers post two-dose series. The longitudinal nature of our cohort facilitated the analysis of paired samples pre and post boost, showing a greater than 15-fold increase in neutralization against omicron post-boost in these paired samples. An mRNA booster dose provides greater quantity and quality of antibodies compared to a two-dose regimen and is critical to provide any protection against the omicron variant.

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.

Differentiation of SARS-CoV-2 naturally infected and vaccinated individuals in an inner-city emergency department.

BACKGROUND: Emergency Departments (EDs) can serve as surveillance sites for infectious diseases. Our purpose was to determine the burden of SARS-CoV-2 infection and prevalence of vaccination against COVID-19 among patients attending an urban ED in Baltimore City. METHODS: Using 1914 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 4360 samples ED patients obtained in the springs of 2020 and 2021. Using multinomial logistic regression, we determined factors associated with infection and vaccination. RESULTS: For the algorithm, sensitivity and specificity for identifying vaccinated individuals was 100% and 99%, respectively, and 84% and 100% for naturally 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 7% of the study population, had the highest relative burden of disease (17% of total infections) but similar vaccination rates. Women and White individuals were more likely to be vaccinated than men or Black individuals (adjusted odds ratios [aOR] 1.35 [95% CI: 1.02, 1.80] and aOR 2.26 [95% CI: 1.67, 3.07], respectively). CONCLUSIONS: Individuals previously infected with SARS-CoV-2 can be differentiated from vaccinated individuals using a serologic testing algorithm. SARS-CoV-2 exposure and vaccination uptake frequencies reflect gender, race and ethnic health disparities in this urban context. SUMMARY: Using an antibody testing algorithm, we distinguished between immune responses from SARS-CoV-2-infected and vaccinated individuals. When applied to blood samples from an emergency department in Baltimore, disparities in disease burden and vaccine uptake by sex, race, and ethnicity were identified.