Characteristics of Patients With Initial Clostridioides difficile Infection (CDI) That Are Associated With Increased Risk of Multiple CDI Recurrences.

Background: Because interventions are available to prevent further recurrence in patients with recurrent Clostridioides difficile infection (rCDI), we identified predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI). Methods: iCDI was defined as a positive C difficile test in any clinical setting during January 2018-August 2019 in a person aged ≥18 years with no known prior positive test. rCDI was defined as a positive test ≥14 days from the previous positive test within 180 days after iCDI; mrCDI was defined as ≥2 rCDI. We performed multivariable logistic regression analysis. Results: Of 18 829 patients with iCDI, 882 (4.7%) had mrCDI; 437 with mrCDI and 7484 without mrCDI had full chart reviews. A higher proportion of patients with mrCDI than without mrCDI were aged ≥65 years (57.2% vs 40.7%; P < .0001) and had healthcare (59.1% vs 46.9%; P < .0001) and antibiotic (77.3% vs 67.3%; P < .0001) exposures in the 12 weeks preceding iCDI. In multivariable analysis, age ≥65 years (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.55-2.35), chronic hemodialysis (aOR, 2.28; 95% CI, 1.48-3.51), hospitalization (aOR, 1.64; 95% CI, 1.33-2.01), and nitrofurantoin use (aOR, 1.95; 95% CI, 1.18-3.23) in the 12 weeks preceding iCDI were associated with mrCDI. Conclusions: Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use had increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings could aid in clinical decision making and interventional study designs.

Immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination among nursing home residents-Georgia, October 2020-July 2022.

BACKGROUND: Understanding the immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination is important in nursing home (NH) residents, a high-risk population. METHODS: An observational longitudinal evaluation of 37 consenting vaccinated NH residents with/without SARS-CoV-2 infection from October 2020 to July 2022 was conducted to characterize the immune response to spike protein due to infection and/or mRNA COVID-19 vaccine. Antibodies (IgG) to SARS-CoV-2 full-length spike, nucleocapsid, and receptor binding domain protein antigens were measured, and surrogate virus neutralization capacity was assessed using Meso Scale Discovery immunoassays. The participant's spike exposure status varied depending on the acquisition of infection or receipt of a vaccine dose. Longitudinal linear mixed effects modeling was used to describe trajectories based on the participant's last infection or vaccination; the primary series mRNA COVID-19 vaccine was considered two spike exposures. Mean antibody titer values from participants who developed an infection post receipt of mRNA COVID-19 vaccine were compared with those who did not. In a subset of participants (n = 15), memory B cell (MBC) S-specific IgG (%S IgG) responses were assessed using an ELISPOT assay. RESULTS: The median age of the 37 participants at enrollment was 70.5 years; 30 (81%) had prior SARS-CoV-2 infection, and 76% received Pfizer-BioNTech and 24% Moderna homologous vaccines. After an observed augmented effect with each spike exposure, a decline in the immune response, including %S IgG MBCs, was observed over time; the percent decline decreased with increasing spike exposures. Participants who developed an infection at least two weeks post-receipt of a vaccine were observed to have lower humoral antibody levels than those who did not develop an infection post-receipt. CONCLUSIONS: These findings suggest that understanding the durability of immune responses in this vulnerable NH population can help inform public health policy regarding the timing of booster vaccinations as new variants display immune escape.

Monoclonal Antibodies as SARS-CoV-2 Serology Standards: Experimental Validation and Broader Implications for Correlates of Protection.

COVID-19 has highlighted challenges in the measurement quality and comparability of serological binding and neutralization assays. Due to many different assay formats and reagents, these measurements are known to be highly variable with large uncertainties. The development of the WHO international standard (WHO IS) and other pool standards have facilitated assay comparability through normalization to a common material but does not provide assay harmonization nor uncertainty quantification. In this paper, we present the results from an interlaboratory study that led to the development of (1) a novel hierarchy of data analyses based on the thermodynamics of antibody binding and (2) a modeling framework that quantifies the probability of neutralization potential for a given binding measurement. Importantly, we introduced a precise, mathematical definition of harmonization that separates the sources of quantitative uncertainties, some of which can be corrected to enable, for the first time, assay comparability. Both the theory and experimental data confirmed that mAbs and WHO IS performed identically as a primary standard for establishing traceability and bridging across different assay platforms. The metrological anchoring of complex serological binding and neuralization assays and fast turn-around production of an mAb reference control can enable the unprecedented comparability and traceability of serological binding assay results for new variants of SARS-CoV-2 and immune responses to other viruses.

Using Colonization to Understand the Burden of Antimicrobial Resistance Across Low- and Middle-Income Countries.

Understanding the burden of antibiotic resistance globally is hindered by incomplete surveillance, particularly across low-resource settings. The Antibiotic Resistance in Communities and Hospitals (ARCH) consortium encompasses sites across 6 resource-limited settings and is intended to address these gaps. Supported by the Centers for Disease Control and Prevention, the ARCH studies seek to characterize the burden of antibiotic resistance by examining colonization prevalence at the community and hospital level and to evaluate for risk factors that are associated with colonization. In this supplement, 7 articles present results from these initial studies. Though future studies identifying and evaluating prevention strategies will be critical to mitigate spreading resistance and its impact on populations, the findings from these studies address important questions surrounding the epidemiology of antibiotic resistance.

Vital Signs: Health Disparities in Hemodialysis-Associated Staphylococcus aureus Bloodstream Infections - United States, 2017-2020.

INTRODUCTION: Racial and ethnic minorities are disproportionately affected by end-stage kidney disease (ESKD). ESKD patients on dialysis are at increased risk for Staphylococcus aureus bloodstream infections, but racial, ethnic, and socioeconomic disparities associated with this outcome are not well described. METHODS: Surveillance data from the 2020 National Healthcare Safety Network (NHSN) and the 2017-2020 Emerging Infections Program (EIP) were used to describe bloodstream infections among patients on hemodialysis (hemodialysis patients) and were linked to population-based data sources (CDC/Agency for Toxic Substances and Disease Registry [ATSDR] Social Vulnerability Index [SVI], United States Renal Data System [USRDS], and U.S. Census Bureau) to examine associations with race, ethnicity, and social determinants of health. RESULTS: In 2020, 4,840 dialysis facilities reported 14,822 bloodstream infections to NHSN; 34.2% were attributable to S. aureus . Among seven EIP sites, the S. aureus bloodstream infection rate during 2017-2020 was 100 times higher among hemodialysis patients (4,248 of 100,000 person-years) than among adults not on hemodialysis (42 of 100,000 person-years). Unadjusted S. aureus bloodstream infection rates were highest among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) hemodialysis patients. Vascular access via central venous catheter was strongly associated with S. aureus bloodstream infections (NHSN: adjusted rate ratio [aRR] = 6.2; 95% CI = 5.7-6.7 versus fistula; EIP: aRR = 4.3; 95% CI = 3.9-4.8 versus fistula or graft). Adjusting for EIP site of residence, sex, and vascular access type, S. aureus bloodstream infection risk in EIP was highest in Hispanic patients (aRR = 1.4; 95% CI = 1.2-1.7 versus non-Hispanic White [White] patients), and patients aged 18-49 years (aRR = 1.7; 95% CI = 1.5-1.9 versus patients aged ≥65 years). Areas with higher poverty levels, crowding, and lower education levels accounted for disproportionately higher proportions of hemodialysis-associated S. aureus bloodstream infections. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Disparities exist in hemodialysis-associated S. aureus infections. Health care providers and public health professionals should prioritize prevention and optimized treatment of ESKD, identify and address barriers to lower-risk vascular access placement, and implement established best practices to prevent bloodstream infections.

Pandemic Demand for SARS-CoV-2 Testing Led to Critical Supply and Workforce Shortages in U.S. Clinical and Public Health Laboratories.

COVID-19 has brought unprecedented challenges to clinical and public health laboratories. While U.S. laboratories have continued striving to provide quality test results during the pandemic, the uncertainty and lack of supplies became a significant hurdle, hindering day-to-day laboratory operations and the ability to increase testing capacity for both SARS-CoV-2 and non-COVID-19 testing. In addition, long-standing laboratory workforce shortages became apparent, hindering the ability of clinical and public health laboratories to rapidly increase testing. The American Society for Microbiology, the College of American Pathologists, the National Coalition of STD Directors, and the Emerging Infections Network independently conducted surveys in 2020 and early 2021 to assess the capacity of the nation's clinical laboratories to respond to the increase in demand for testing during the COVID-19 pandemic. The results of these surveys highlighted the shortages of crucial supplies for SARS-CoV-2 testing and supplies for other routine laboratory diagnostics, as well as a shortage of trained personnel to perform testing. The conclusions are based on communications, observations, and the survey results of the clinical laboratory, public health, and professional organizations represented here. While the results of each survey considered separately may not be representative of the entire community, when considered together they provide remarkably similar results, further validating the findings and highlighting the importance of laboratory supply chains and the personnel capable of performing these tests for any response to a large-scale public health emergency.

Use of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Tests by US Infectious Disease Physicians: Results of an Emerging Infections Network Survey, March 2022.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests have had limited recommended clinical application during the coronavirus disease 2019 (COVID-19) pandemic. To inform clinical practice, an understanding is needed of current perspectives of United States-based infectious disease (ID) physicians on the use, interpretation, and need for SARS-CoV-2 antibody tests. Methods: In March 2022, members of the Emerging Infections Network (EIN), a national network of practicing ID physicians, were surveyed on types of SARS-CoV-2 antibody assays ordered, interpretation of test results, and clinical scenarios for which antibody tests were considered. Results: Of 1867 active EIN members, 747 (40%) responded. Among the 583 who managed or consulted on COVID-19 patients, a majority (434/583 [75%]) had ordered SARS-CoV-2 antibody tests and were comfortable interpreting positive (452/578 [78%]) and negative (405/562 [72%]) results. Antibody tests were used for diagnosing post-COVID-19 conditions (61%), identifying prior SARS-CoV-2 infection (60%), and differentiating prior infection and response to COVID-19 vaccination (37%). Less than a third of respondents had used antibody tests to assess need for additional vaccines or risk stratification. Lack of sufficient evidence for use and nonstandardized assays were among the most common barriers for ordering tests. Respondents indicated that statements from professional societies and government agencies would influence their decision to order SARS-CoV-2 antibody tests for clinical decision making. Conclusions: Practicing ID physicians are using SARS-CoV-2 antibody tests, and there is an unmet need for clarifying the appropriate use of these tests in clinical practice. Professional societies and US government agencies can support clinicians in the community through the creation of appropriate guidance.

Vital Signs: Health Disparities in Hemodialysis-Associated Staphylococcus aureus Bloodstream Infections - United States, 2017-2020.

Introduction: Racial and ethnic minorities are disproportionately affected by end-stage kidney disease (ESKD). ESKD patients on dialysis are at increased risk for Staphylococcus aureus bloodstream infections, but racial, ethnic, and socioeconomic disparities associated with this outcome are not well described. Methods: Surveillance data from the 2020 National Healthcare Safety Network (NHSN) and the 2017-2020 Emerging Infections Program (EIP) were used to describe bloodstream infections among patients on hemodialysis (hemodialysis patients) and were linked to population-based data sources (CDC/Agency for Toxic Substances and Disease Registry [ATSDR] Social Vulnerability Index [SVI], United States Renal Data System [USRDS], and U.S. Census Bureau) to examine associations with race, ethnicity, and social determinants of health. Results: In 2020, 4,840 dialysis facilities reported 14,822 bloodstream infections to NHSN; 34.2% were attributable to S. aureus. Among seven EIP sites, the S. aureus bloodstream infection rate during 2017-2020 was 100 times higher among hemodialysis patients (4,248 of 100,000 person-years) than among adults not on hemodialysis (42 of 100,000 person-years). Unadjusted S. aureus bloodstream infection rates were highest among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) hemodialysis patients. Vascular access via central venous catheter was strongly associated with S. aureus bloodstream infections (NHSN: adjusted rate ratio [aRR] = 6.2; 95% CI = 5.7-6.7 versus fistula; EIP: aRR = 4.3; 95% CI = 3.9-4.8 versus fistula or graft). Adjusting for EIP site of residence, sex, and vascular access type, S. aureus bloodstream infection risk in EIP was highest in Hispanic patients (aRR = 1.4; 95% CI = 1.2-1.7 versus non-Hispanic White [White] patients), and patients aged 18-49 years (aRR = 1.7; 95% CI = 1.5-1.9 versus patients aged ≥65 years). Areas with higher poverty levels, crowding, and lower education levels accounted for disproportionately higher proportions of hemodialysis-associated S. aureus bloodstream infections. Conclusions and implications for public health practice: Disparities exist in hemodialysis-associated S. aureus infections. Health care providers and public health professionals should prioritize prevention and optimized treatment of ESKD, identify and address barriers to lower-risk vascular access placement, and implement established best practices to prevent bloodstream infections.

Selective and Cascade Reporting of Antimicrobial Susceptibility Testing Results and Its Impact on Antimicrobial Resistance Surveillance-National Healthcare Safety Network, April 2020 to March 2021.

Selective or cascade reporting (SR/CR) of antimicrobial susceptibility testing (AST) results is a strategy for antimicrobial stewardship. SR/CR is often achieved by suppressing AST results of secondary drugs in electronic laboratory reports. We assessed the extent of SR/CR and its impact on cumulative antibiograms (CAs) in a large cohort of U.S. hospitals submitting AST data to the CDC's National Healthcare Safety Network (NHSN) through electronic data exchange. The NHSN calls for hospitals to extract AST data from their electronic systems. We analyzed the AST reported for Escherichia coli (blood and urine) and Staphylococcus aureus (blood and lower respiratory tract [LRT]) isolates from April 2020 to March 2021, used AST reporting patterns to assign SR/CR reporting status for hospitals, and compared their CAs. Sensitivity analyses were done to account for those potentially extracted complete data. At least 35% and 41% of the hospitals had AST data that were suppressed in more than 20% blood isolates for E. coli and S. aureus isolates, respectively. At least 63% (blood) and 50% (urine) routinely reported ciprofloxacin or levofloxacin for E. coli isolates; and 60% (blood) and 59% (LRT) routinely reported vancomycin for S. aureus isolates. The distribution of CAs for many agents differed between high SR/CR and low- or non-SR/CR hospitals. Hospitals struggled to obtain complete AST data through electronic data exchange because of data suppression. Use of SR/CR can bias CAs if incomplete data are used. Technical solutions are needed for extracting complete AST results for public health surveillance. IMPORTANCE This study is the first to assess the extent of using selective and/or cascade antimicrobial susceptibility reporting for antimicrobial stewardship among U.S. hospitals and its impact on cumulative antibiograms in the context of electronic data exchange for national antimicrobial resistance surveillance.

SARS-CoV-2 Antibody Responses to the Ancestral SARS-CoV-2 Strain and Omicron BA.1 and BA.4/BA.5 Variants in Nursing Home Residents After Receipt of Bivalent COVID-19 Vaccine - Ohio and Rhode Island, September-November 2022.

Introduction of monovalent COVID-19 mRNA vaccines in late 2020 helped to mitigate disproportionate COVID-19-related morbidity and mortality in U.S. nursing homes (1); however, reduced effectiveness of monovalent vaccines during the period of Omicron variant predominance led to recommendations for booster doses with bivalent COVID-19 mRNA vaccines that include an Omicron BA.4/BA.5 spike protein component to broaden immune response and improve vaccine effectiveness against circulating Omicron variants (2). Recent studies suggest that bivalent booster doses provide substantial additional protection against SARS-CoV-2 infection and severe COVID-19-associated disease among immunocompetent adults who previously received only monovalent vaccines (3).* The immunologic response after receipt of bivalent boosters among nursing home residents, who often mount poor immunologic responses to vaccines, remains unknown. Serial testing of anti-spike protein antibody binding and neutralizing antibody titers in serum collected from 233 long-stay nursing home residents from the time of their primary vaccination series and including any subsequent booster doses, including the bivalent vaccine, was performed. The bivalent COVID-19 mRNA vaccine substantially increased anti-spike and neutralizing antibody titers against Omicron sublineages, including BA.1 and BA.4/BA.5, irrespective of previous SARS-CoV-2 infection or previous receipt of 1 or 2 booster doses. These data, in combination with evidence of low uptake of bivalent booster vaccination among residents and staff members in nursing homes (4), support the recommendation that nursing home residents and staff members receive a bivalent COVID-19 booster dose to reduce associated morbidity and mortality (2).

Reference Susceptibility Testing and Genomic Surveillance of Clostridioides difficile, United States, 2012-17.

BACKGROUND: Antimicrobial susceptibility testing (AST) is not routinely performed for Clostridioides difficile and data evaluating minimum inhibitory concentrations (MICs) are limited. We performed AST and whole genome sequencing (WGS) for 593 C. difficile isolates collected between 2012 and 2017 through the Centers for Disease Control and Prevention's Emerging Infections Program. METHODS: MICs to 6 antimicrobial agents (ceftriaxone, clindamycin, meropenem, metronidazole, moxifloxacin, and vancomycin) were determined using the reference agar dilution method according to Clinical and Laboratory Standards Institute guidelines. Whole genome sequencing was performed on all isolates to detect the presence of genes or mutations previously associated with resistance. RESULTS: Among all isolates, 98.5% displayed a vancomycin MIC ≤2 µg/mL and 97.3% displayed a metronidazole MIC ≤2 µg/mL. Ribotype 027 (RT027) isolates displayed higher vancomycin MICs (MIC50: 2 µg/mL; MIC90: 2 µg/mL) than non-RT027 isolates (MIC50: 0.5 µg/mL; MIC90: 1 µg/mL) (P < .01). No vanA/B genes were detected. RT027 isolates also showed higher MICs to clindamycin and moxifloxacin and were more likely to harbor associated resistance genes or mutations. CONCLUSIONS: Elevated MICs to antibiotics used for treatment of C. difficile infection were rare, and there was no increase in MICs over time. The lack of vanA/B genes or mutations consistently associated with elevated vancomycin MICs suggests there are multifactorial mechanisms of resistance. Ongoing surveillance of C. difficile using reference AST and WGS to monitor MIC trends and the presence of antibiotic resistance mechanisms is essential.

Endotracheal Intubation Strategy, Success, and Adverse Events Among Emergency Department Patients During the COVID-19 Pandemic.

STUDY OBJECTIVE: To describe endotracheal intubation practices in emergency departments by staff intubating patients early in the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Multicenter prospective cohort study of endotracheal intubations conducted at 20 US academic emergency departments from May to December 2020, stratified by known or suspected COVID-19 status. We used multivariable regression to measure the association between intubation strategy, COVID-19 known or suspected status, first-pass success, and adverse events. RESULTS: There were 3,435 unique emergency department endotracheal intubations by 586 participating physicians or advanced practice providers; 565 (18%) patients were known or suspected of having COVID-19 at the time of endotracheal intubation. Compared with patients not known or suspected of COVID-19, endotracheal intubations of patients with known or suspected COVID-19 were more often performed using video laryngoscopy (88% versus 82%, difference 6.3%; 95% confidence interval [CI], 3.0% to 9.6%) and passive nasal oxygenation (44% versus 39%, difference 5.1%; 95% CI, 0.9% to 9.3%). First-pass success was not different between those who were and were not known or suspected of COVID-19 (87% versus 86%, difference 0.6%; 95% CI, -2.4% to 3.6%). Adjusting for patient characteristics and procedure factors in those with low anticipated airway difficulty (n=2,374), adverse events (most commonly hypoxia) occurred more frequently in patients with known or suspected COVID-19 (35% versus 19%, adjusted odds ratio 2.4; 95% CI, 1.7 to 3.3). CONCLUSION: Compared with patients not known or suspected of COVID-19, endotracheal intubation of those confirmed or suspected to have COVID-19 was associated with a similar first-pass intubation success rate but higher risk-adjusted adverse events.

Longitudinal serologic and viral testing post-SARS-CoV-2 infection and post-receipt of mRNA COVID-19 vaccine in a nursing home cohort-Georgia, October 2020‒April 2021.

There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. We conducted a prospective longitudinal evaluation of 11 consenting SARS-CoV-2-positive nursing home residents to evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination. The evaluation included nine visits over 150 days from October 25, 2020, through April 1, 2021. Visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOW™ COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. We evaluated quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). The median age among participants was 74 years; one participant was immunocompromised. Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies, and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive, but none were culture- positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation ≤90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents.

Emergency department personnel patient care-related COVID-19 risk.

OBJECTIVES: Emergency department (ED) health care personnel (HCP) are at risk of exposure to SARS-CoV-2. The objective of this study was to determine the attributable risk of SARS-CoV-2 infection from providing ED care, describe personal protective equipment use, and identify modifiable ED risk factors. We hypothesized that providing ED patient care increases the probability of acquiring SARS-CoV-2 infection. METHODS: We conducted a multicenter prospective cohort study of 1,673 ED physicians, advanced practice providers (APPs), nurses, and nonclinical staff at 20 U.S. centers over 20 weeks (May to December 2020; before vaccine availability) to detect a four-percentage point increased SARS-CoV-2 incidence among HCP related to direct patient care. Participants provided monthly nasal and serology specimens and weekly exposure and procedure information. We used multivariable regression and recursive partitioning to identify risk factors. RESULTS: Over 29,825 person-weeks, 75 participants (4.5%) acquired SARS-CoV-2 infection (31 were asymptomatic). Physicians/APPs (aOR 1.07; 95% CI 0.56-2.03) did not have higher risk of becoming infected compared to nonclinical staff, but nurses had a marginally increased risk (aOR 1.91; 95% CI 0.99-3.68). Over 99% of participants used CDC-recommended personal protective equipment (PPE), but PPE lapses occurred in 22.1% of person-weeks and 32.1% of SARS-CoV-2-infected patient intubations. The following factors were associated with infection: household SARS-CoV-2 exposure; hospital and community SARS-CoV-2 burden; community exposure; and mask non-use in public. SARS-CoV-2 intubation was not associated with infection (attributable risk fraction 13.8%; 95% CI -2.0-38.2%), and nor were PPE lapses. CONCLUSIONS: Among unvaccinated U.S. ED HCP during the height of the pandemic, the risk of SARS-CoV-2 infection was similar in nonclinical staff and HCP engaged in direct patient care. Many identified risk factors were related to community exposures.

SARS-CoV-2 Convalescent Sera Binding and Neutralizing Antibody Concentrations Compared with COVID-19 Vaccine Efficacy Estimates against Symptomatic Infection.

Previous COVID-19 vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during 27 July 2020 to 27 August 2020 from COVID-19-unvaccinated persons with detectable anti-SARS-CoV-2 antibodies. Neutralizing and binding antibody concentrations were severalfold lower in the unvaccinated study population compared to published concentrations at 28 days postvaccination. In this convenience sample, ~88% of neutralizing and ~63 to 86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection; ~30% of neutralizing and 1 to 14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. Our study not only supports observations of infection-induced immunity and current recommendations for vaccination postinfection to maximize protection against COVID-19, but also provides a large data set of pre-COVID-19 vaccination anti-SARS-CoV-2 antibody concentrations that will serve as an important comparator in the current setting of vaccine-induced and hybrid immunity. As new SARS-CoV-2 variants emerge and displace circulating virus strains, we recommend that standardized binding antibody assays that include spike protein-based antigens be utilized to estimate antibody concentrations correlated with protection from COVID-19. These estimates will be helpful in informing public health guidance, such as the need for additional COVID-19 vaccine booster doses to prevent symptomatic infection. IMPORTANCE Although COVID-19 vaccine efficacy (VE) studies have estimated antibody concentrations that correlate with protection from COVID-19, how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. We assessed quantitative neutralizing and binding antibody concentrations using standardized assays on serum specimens collected from COVID-19-unvaccinated persons with detectable antibodies. We found that most unvaccinated persons with qualitative antibody evidence of prior infection had quantitative antibody concentrations that met or exceeded concentrations associated with 70% VE against COVID-19. However, only a small proportion had antibody concentrations that met or exceeded concentrations associated with 90% VE, suggesting that persons with prior COVID-19 would benefit from vaccination to maximize protective antibody concentrations against COVID-19.

Development and Validation of an Enzyme Immunoassay for Detection and Quantification of SARS-CoV-2 Salivary IgA and IgG.

Oral fluids offer a noninvasive sampling method for the detection of Abs. Quantification of IgA and IgG Abs in saliva allows studies of the mucosal and systemic immune response after natural infection or vaccination. We developed and validated an enzyme immunoassay (EIA) to detect and quantify salivary IgA and IgG Abs against the prefusion-stabilized form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein expressed in suspension-adapted HEK-293 cells. Normalization against total Ab isotype was performed to account for specimen differences, such as collection time and sample volume. Saliva samples collected from 187 SARS-CoV-2 confirmed cases enrolled in 2 cohorts and 373 prepandemic saliva samples were tested. The sensitivity of both EIAs was high (IgA, 95.5%; IgG, 89.7%) without compromising specificity (IgA, 99%; IgG, 97%). No cross-reactivity with endemic coronaviruses was observed. The limit of detection for SARS-CoV-2 salivary IgA and IgG assays were 1.98 ng/ml and 0.30 ng/ml, respectively. Salivary IgA and IgG Abs were detected earlier in patients with mild COVID-19 symptoms than in severe cases. However, severe cases showed higher salivary Ab titers than those with a mild infection. Salivary IgA titers quickly decreased after 6 wk in mild cases but remained detectable until at least week 10 in severe cases. Salivary IgG titers remained high for all patients, regardless of disease severity. In conclusion, EIAs for both IgA and IgG had high specificity and sensitivity for the confirmation of current or recent SARS-CoV-2 infections and evaluation of the IgA and IgG immune response.

Descriptive evaluation of antibody responses to severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in plasma and gingival crevicular fluid in a nursing home cohort-Arkansas, June-August 2020.

OBJECTIVE: To characterize and compare severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-specific immune responses in plasma and gingival crevicular fluid (GCF) from nursing home residents during and after natural infection. DESIGN: Prospective cohort. SETTING: Nursing home. PARTICIPANTS: SARS-CoV-2-infected nursing home residents. METHODS: A convenience sample of 14 SARS-CoV-2-infected nursing home residents, enrolled 4-13 days after real-time reverse transcription polymerase chain reaction diagnosis, were followed for 42 days. After diagnosis, plasma SARS-CoV-2-specific pan-Immunoglobulin (Ig), IgG, IgA, IgM, and neutralizing antibodies were measured at 5 time points, and GCF SARS-CoV-2-specific IgG and IgA were measured at 4 time points. RESULTS: All participants demonstrated immune responses to SARS-CoV-2 infection. Among 12 phlebotomized participants, plasma was positive for pan-Ig and IgG in all 12 participants. Neutralizing antibodies were positive in 11 participants; IgM was positive in 10 participants, and IgA was positive in 9 participants. Among 14 participants with GCF specimens, GCF was positive for IgG in 13 participants and for IgA in 12 participants. Immunoglobulin responses in plasma and GCF had similar kinetics; median times to peak antibody response were similar across specimen types (4 weeks for IgG; 3 weeks for IgA). Participants with pan-Ig, IgG, and IgA detected in plasma and GCF IgG remained positive throughout this evaluation, 46-55 days after diagnosis. All participants were viral-culture negative by the first detection of antibodies. CONCLUSIONS: Nursing home residents had detectable SARS-CoV-2 antibodies in plasma and GCF after infection. Kinetics of antibodies detected in GCF mirrored those from plasma. Noninvasive GCF may be useful for detecting and monitoring immunologic responses in populations unable or unwilling to be phlebotomized.

Associations of facility-level antibiotic use and hospital-onset Clostridioides difficile infection in US acute-care hospitals, 2012-2018.

Previously reported associations between hospital-level antibiotic use and hospital-onset Clostridioides difficile infection (HO-CDI) were reexamined using 2012-2018 data from a new cohort of US acute-care hospitals. This analysis revealed significant positive associations between total, third-generation, and fourth-generation cephalosporin, fluoroquinolone, carbapenem, and piperacillin-tazobactam use and HO-CDI rates, confirming previous findings.

Repeated antigen testing among severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive nursing home residents.

Repeated antigen testing of 12 severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive nursing home residents using Abbott BinaxNOW identified 9 of 9 (100%) culture-positive specimens up to 6 days after initial positive test. Antigen positivity lasted 2-24 days. Antigen positivity might last beyond the infectious period, but it was reliable in residents with evidence of early infection.